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    Disorders of sex development in children
    Changes of serum unsaturated free fatty acid profiles in girls with idiopathic central precocious puberty and their correlations with body mass index and sex hormones
    Lin-lin LI, Shao-hua HU, Xiao-qin YIN, Pin LI
    2021, 41 (11):  1405-1411. 
    doi: 10.3969/j.issn.1674-8115.2021.11.001

    Abstract ( 113 )   HTML ( 49 )   PDF (1206KB) ( 79 )  
    Objective

    ·To analyze the changes of unsaturated free fatty acid profiles and their correlations with body mass index (BMI) and sex hormones in idiopathic central precocious puberty (ICPP) girls.

    Methods

    ·Fifty-six ICPP girls who were hospitalized in Children's Hospital of Shanghai Jiao Tong University from August 2020 to January 2021 and 46 normal undeveloped girls at the same age were selected, respectively included in the ICPP group and the control group. The height and weight of the two groups were collected, and the BMI and body mass index standard deviation score (BMI SDS) were calculated. The concentration of serum unsaturated free fatty acid profiles of all the girls as well as the basic and peak values of serum luteinizing hormone (LH) and follicle stimulating hormone (FSH), estradiol (E2), sex hormone-binding globulin (SHBG), and insulin-like growth factor-1 (IGF-1) in ICPP girls were detected. The girls who received gonadotropin releasing-hormone analogues (GnRHa) treatment were followed up for 3 months. Finally, 48 ICPP girls were enrolled in the follow-up study. The concentrations of serum unsaturated free fatty acid profiles before and after treatment in 48 ICPP girls who completed the follow-up were compared. Multivariate stepwise regression was used to analyze the correlation between serum unsaturated free fatty acid profiles and various indicators.

    Results

    ·①BMI and BMI SDS of the ICPP group were higher than those of the control group (P<0.05), but there was no correlation between the levels of various unsaturated free fatty acids and BMI(P>0.05). ②Compared with the control group, the levels of arachidonic acid (AA, P=0.001), n-6 docosapentenoic acid (n-6DPA, P=0.000), n-3 docosapentaenoic acid (n-3DPA, P=0.005), eicosapentaenoic acid (EPA, P=0.010), docosapentaenoic acid (DHA, P=0.003) and total n-6 polyunsaturated fatty acids (n-6PUFA, P=0.049) were significantly reduced. ③The levels of oleic acid (C18:1n-9, P=0.036), gondoic acid (C20:1n-9, P=0.030), linoleic acid (LA, P=0.020), γ-Linolenic acid (GLA, P=0.010), α-linolenic acid (ALA, P=0.009) and total n-6PUFA (P=0.041) were positively correlated with the peak values of LH. The levels of EPA (P=0.049) and DHA (P=0.046) were negatively correlated with the basic values of LH. The levels of EPA (P=0.020, P=0.002), n-3DPA (P=0.003, P=0.001), DHA (P=0.007, P=0.028) ), and total n-3PUFA (P=0.012, P=0.011) were negatively correlated with the basic values of FSH and E2. The ratio of total n-6PUFA/total n-3PUFA was positively correlated with the basic values of FSH (P=0.002). The peak vaules of FSH, SHBG, and IGF-1 had no correlation with various unsaturated free fatty acids (all P>0.05). ④After 3 months of GnRHa treatment, the levels of C16:1 (P=0.001), C18:1 (P=0.001), C20:1 (P=0.001), LA (P=0.013), GLA (P= 0.013), and ALA (P=0.032) in ICPP girls were significantly lower than those before treatment, while the levels of AA (P=0.001), EPA (P=0.000), and DHA (P=0.025) were significantly higher than those before treatment.

    Conclusion

    ·ICPP girls were generally overweight or obese, but there was no correlation between the levels of various unsaturated free fatty acids and BMI. Sexual development and GnRHa treatment could affect the metabolism of unsaturated free fatty acids in ICPP girls, and sex hormones were related to a variety of unsaturated free fatty acids.

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    Analysis of gender assignment in children with 46, XY disorders of sex development
    Yan LIANG, Yi-qing LÜ, Hua XIE, Yi-chen HUANG, Xiao-xi LI, Pin LI, Yi-qun XI
    2021, 41 (11):  1412-1416. 
    doi: 10.3969/j.issn.1674-8115.2021.11.002

    Abstract ( 121 )   HTML ( 38 )   PDF (999KB) ( 50 )  
    Objective

    ·To explore the results of gender assignment of the patients with 46,XY disorders of sex development (DSD), and provide reference for clinical decision-making of similar patients.

    Methods

    ·The clinical data of 46,XY DSD patients who were treated in Children's Hospital of Shanghai Jiao Tong University from 2015 to 2018 were collected. All the patients completed comprehensive assessments in the Department of Pediatric Endocrinology. Gender assignment was carried out after multidisciplinary treatment team discussion and full communication with the patients and/or the family members. The gender assignment results of these patients with different conditions were analyzed. The follow-up began 1 month after operation until 18 years old. Psychological assessment was performed after puberty.

    Results

    ·A total of 52 patients with 46,XY DSD were collected. Before admission, 26 cases were female and 26 cases were male. Thirteen female patients were assigned to the same gender, among whom 6 cases were diagnosed as having complete androgen insensitivity syndrome, 2 cases diagnosed as having 17α-hydroxylase deficiency with extremely poor testicular function, 1 diagnosed as having complete gonadal dysplasia, and 4 diagnosed as having testicular dysfunction; otherwise 13 female patients changed gender to male, because 3 patients had partial androgen insensitive syndrome, 4 patients had 5α-reductase deficiency, 2 patients had androgen synthesis disorder, and the etiology of 4 patients was unknown (gonadal biopsy showed that both gonads of the patients were testicular tissues). All the 26 male patients were assigned to the same gender, among whom 11 cases were diagnosed as having 5α-reductase deficiency, 6 diagnosed as having partial androgen insensitivity syndrome, 4 diagnosed as having androgen synthesis disorder, and 5 cases with unknown etiology (gonadal biopsy showed bilateral testicular tissues in 2 cases and unilateral gonadal dysplasia with contralateral testicular tissue in 3 cases). Thirteen patients who reached the age of psychological evaluation did not exist gender identity confusion.

    Conclusion

    ·The 46,XY DSD patients with complete gonadal dysplasia, complete androgen insensitivity syndrome or testicular dysfunction can be considered for female gender assignment. The patients with 5α-reductase deficiency or partial androgen insensitivity syndrome can be considered for male selection. For the children with unknown etiology, it should be considered comprehensively according to the specific phenotype and the actual situation of children's families.

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    Clinical features of 23 patients with 45,X/46,XY mosaicism
    Xiu-li CHEN, Hai-ying WU, Ming-cui FU, Hong-ying WANG, Ou XU, Lin-qi CHEN
    2021, 41 (11):  1417-1424. 
    doi: 10.3969/j.issn.1674-8115.2021.11.003

    Abstract ( 100 )   HTML ( 27 )   PDF (2017KB) ( 39 )  
    Objective

    ·To analyze the clinical features of the patients with 45,X/46,XY mosaicism, and improve the understanding, diagnosis and treatment of the disease.

    Methods

    ·The clinical manifestations, the level of sex hormones, and the gonads pathology of the patients with 45,X/46,XY mosaicism diagnosed by G-banding karyotype analysis and fluorescence in situ hybridization (FISH) were retrospectively analyzed, who were admitted in Children's Hospital of Soochow University from January 2014 to December 2020.

    Results

    ·Twenty-three patients with 45,X/46,XY mosaicism were included, among whom 11 cases were the female phenotype, and 12 cases were the male phenotype. In these patients, 12 patients were diagnosed by G-banding karyotype analysis, 10 patients were diagnosed by FISH, and only 1 patient was diagnosed by array-based comparative genomic hybridization. The age of the first diagnosis was 0.3?14.9 years. The mean age of the patients with the female phenotype was (9.3±3.9) years, which was bigger than that of the male phenotype [(4.4±3.7) years, P<0.05]. All the patients above 1 year old had different degrees of short stature, especially in the female phenotype patients. In the female phenotype patients, three patients had clitoromegaly, while the other patients had no masculine appearance of external genitalia. The external masculinisation scores (EMS) of the patients with the female phenotype were 0?2.5. Twelve patients with the male phenotype were in pre-adolescent state, among whom 4 patients had hypospadias combined with cryptorchidism, 3 patients had hypospadias, 3 patients had small testicles, and 2 patients had normal external genitalia. The EMS of them ranged from 4 to 12, with a mean score of 10.5. All the patients with the female phenotype had hypergonadotropic hypogonadism, while most of the patients with the male phenotype had gonadotropin levels matched with their age. There were 3 patients with the female phenotype having gonadoblastomas.

    Conclusion

    ·The 45,X/46,XY mosaicism patients present a wide spectrum of manifestations. The risk of gonadal malignancy onset should be emphasized. EMS has guiding significance for clinical evaluation of these patients.

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    Report of 3 cases of 47,XXX syndrome with growth retardation
    YANG-Li, Ya-qin FENG, Yu YANG, Li-ling XIE, Di-lan WANG, Hui HUANG
    2021, 41 (11):  1425-1428. 
    doi: 10.3969/j.issn.1674-8115.2021.11.004

    Abstract ( 139 )   HTML ( 22 )   PDF (1104KB) ( 78 )  

    To analyze the clinical data of 3 children with growth retardation, including height, chromosome karyotype, and the levels of growth hormone, insulin-like growth factor-1 and gonadal development. All the 3 cases of children were found to be slow in growth rate, no special face, and normal level of insulin-like growth factor-1; the 3 cases all underwent growth hormone provocation test, of which 1 case was partial growth hormone deficiency and 2 cases were idiopathic short; 3 cases of chromosomal karyotypes were 47, XXX, in line with the diagnosis of super-female syndrome.

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    Basic research
    Study on differentially expressed microRNA as a biomarker of polycystic ovary syndrome
    Yu-huan WANG, Yi-cen DING, Yao-yu CAI, Ya-ni KANG
    2021, 41 (11):  1429-1435. 
    doi: 10.3969/j.issn.1674-8115.2021.11.005

    Abstract ( 148 )   HTML ( 33 )   PDF (2597KB) ( 50 )  
    Objective

    ·To explore microRNAs (miRNAs) as biomarkers of polycystic ovary syndrome (PCOS) and the biological significance in the pathogenesis of PCOS.

    Methods

    ·Five patients with PCOS from January 2019 to October 2019 in Renji Hospital, Shanghai Jiao Tong University School of Medicine were selected as the observation group, and 5 healthy women were selected as the control group. Granulosa cells from 2 groups were collected and RNA was extracted by TRIzol method. TruSeq Small RNA Library Prep Kit was used to construct miRNA-Seq library. After the quality inspection of the library, NextSeq500 was used for high-throughput sequencing. Bioinformatics data analysis was performed on the sequencing results. RT-qPCR was used to verify the differential expression of candidate miRNA markers.

    Results

    ·We finally got 20 differentially expressed miRNAs (all P<0.05). Among them, miR-196a-5p, miR-10a-5p and miR-451a were significantly up-regulated, while miR-877-5p and miR-2355-5p were significantly down-regulated. These differentially expressed miRNAs and their target genes may be involved in the transcriptional regulation mechanism of PCOS occurrence and development.

    Conclusion

    ·Differentially expressed miRNAs have potential as PCOS biomarkers and are involved in the occurrence and development of PCOS.

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    Construction and application value of prognosis-associated miRNA prediction model in gastric cancer patients
    Ben YUE, Gao-ming WANG, Lu-di YANG, Ran CUI, Feng-rong YU
    2021, 41 (11):  1436-1445. 
    doi: 10.3969/j.issn.1674-8115.2021.11.006

    Abstract ( 144 )   HTML ( 31 )   PDF (4151KB) ( 49 )  
    Objective

    ·To construct a prognosis-associated microRNA (miRNA) prediction model in gastric cancer patients based on bioinformatics analysis and evaluate its application value.

    Methods

    ·The clinicopathological data of gastric cancer patients were downloaded from the Cancer Genome Atlas (TCGA). There were 258 males and 139 females with a median age of 67 years. Three hundred and fifty-six of the 397 patients had complete clinicopathological data. The 397 patients were allocated into training cohort consisting of 278 patients and validation cohort consisting of 119 patients using the random sampling method, with a ratio of 7∶3. A miRNA sequencing dataset GSE93415 containing 20 pairs of gastric cancer and corresponding adjacent normal tissue was downloaded from Gene Expression Omnibus database. The candidate miRNAs were selected from differentially expressed miRNAs in gastric cancer and adjacent tissue. A prognosis associated miRNA prediction model was constructed upon survival-associated miRNAs which were selected from candidate miRNAs through LASSO-Cox regression analysis. The performance of prognosis-associated miRNA prediction model was validated in the training cohort and validation cohort. The reliability of the model was evaluated by using Log-Rank test, and the accuracy of the model was evaluated by using the area under curve (AUC) of the receiver operating characteristic curves. Gene expression profiles and algorithms in the pRRophetic package were utilized to predict patients' sensitivity to chemotherapy drugs. Calibration curves were used to verify the accuracy of the nomogram. Consistency index (C-index) was used to check the consistency of the nomogram and other factors. Decision curve analysis (DCA) was employed to predict the contribution of candidate factors to clinical decision making.

    Results

    ·① There was no significant difference in the baseline and overall survival between the training cohort and validation cohort (P>0.05). ② There were 111 differentially expressed miRNAs calculated from GSE93415 dataset, of which 20 were up-regulated in tumor tissue while 91 were down-regulated. Fifty-nine miRNAs were selected as candidate miRNAs after filtration. ③ Among the 59 candidate miRNAs, 5 survival-associated miRNAs were selected, including let-7i-5p, let-7f-5p, miR-708-5p, miR-135b-5p and miR-100-5p. The differential expression patterns of gastric cancer to adjacent tissue were all down-regulation, with the fold change of 2.55, 2.78, 2.17, 3.08 and 3.26. Risk score = (-0.049×let-7i-5p expression level -0.033 2×let-7f-5p expression level +0.202 9×miR-708-5p expression level -0.088 9×miR-135b-5p expression level +0.016 3×miR-100-5p expression level). ④ In the training cohort and the validation cohort, the overall survival rate of patients in the high-risk group was lower, and the difference was statistically significant (P<0.05) . The AUC of the prognosis-associated miRNA model for 1-, 3- and 5-year survival prediction was 0.640, 0.763 and 0.853, and was 0.631, 0.735 and 0.750 in validation cohort. ⑤Results of univariate analysis showed that age, tumor pathological stage, T stage, N stage, M stage and prognosis-associated miRNA model score were related factors for prognosis of gastric cancer patients (HR=1.017, 1.633, 1.353, 1.346, 2.652, 15.874; 95%CI 1.002?1.033, 1.333?2.001, 1.109?1.650, 1.169?1.548, 1.553?4.529, 5.729?43.985; P<0.05). Results of multivariate analysis showed that age, M stage and prognosis-associated miRNA model score were independent risk factors for prognosis of gastric cancer patients (HR=1.03, 2.27, 18.72; 95%CI 1.01?1.05, 1.09?4.70, 5.96?58.77; P<0.05). ⑥The AUC of the prognosis-associated miRNA model for 5-year survival prediction was 0.818 in 356 gastric cancer patients with complete clinicopathological data, higher than that of age, gender, tumor pathological stage, T stage, N stage, M stage and merged clinical factors. ⑦The results of Calibration curves, C-index, and DCA all indicated that patients with gastric cancer may get more net benefits from the prognostic nomogram than age, gender and tumor pathological stage.

    Conclusion

    ·A prognosis-associated miRNA prediction model that can be used to predict the survival of gastric cancer patients is constructed based on 5 miRNAs, which has a certain predictive ability to distinguish the survival status and prognosis of gastric cancer patients and can provide reference for clinical treatment.

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    Effect of PDSORBS2 peptide on H9C2 cell apoptosis induced by hypoxia and reoxygenation
    Lu-lu CHEN, Xun-long XU, Wan-lan CHEN, Zhao-hui QIU
    2021, 41 (11):  1446-1453. 
    doi: 10.3969/j.issn.1674-8115.2021.11.007

    Abstract ( 135 )   HTML ( 27 )   PDF (2084KB) ( 50 )  
    Objective

    ·To explore the inhibitory effect and its mechanism of the PDSORBS2 peptide on H9C2 cell apoptosis induced by hypoxia and reoxygenation (H/R).

    Methods

    ·In the previous work of this study, a new peptide PDSORBS2 (LPASLNS) was discovered from rat cardiomyocytes after ischemia. Cell counting kit-8 (CCK-8) was used to detect cell viability to select the appropriate concentration of PDSORBS2 peptide and the appropriate time for H/R treatment. The cells were randomly divided into normal control group (NC group), NC+PDSORBS2 group, H/R group and H/R+PDSORBS2 group. A fluorescence microscope was used to observe the changes in the nucleus morphology. The degree of apoptosis and cell cycle was analyzed by flow cytometry. A kit was used to detect the content of reactive oxygen species (ROS) in cells. The expression levels of apoptosis-related proteins including poly ADP-ribose polymerase (PARP), cleaved-caspase3, B-cell lymphoma-2 (Bcl-2), and BCL2-associated X (Bax), extracellular regulated protein kinases (ERK), protein kinase B (AKT), cyclin-dependent kinases 2 (CDK2), and p27Kip1 protein were analyzed by Western blotting in H9C2 cells.

    Results

    ·Compared with the NC group, 6 h of hypoxia and 2 h of reoxygenation significantly decreased the viability of H9C2 cells, while 50 μmol/L PDSORBS2 significantly increased the viability of H9C2 cells induced by H/R (P=0.004). Compared with the H/R group, the pretreatment of PDSORBS2 improved the morphology of H9C2 nuclei induced by H/R and reduced the apoptotic rate of H9C2 cells (P=0.000), cell cycle arrest (P=0.000), and intracellular ROS content (P=0.005). The expression levels of pro-apoptotic proteins (PARP, Bax and cleaved-caspase3) and p27Kip1 protein were down-regulated, and the expression levels of Bcl-2, phospho-extracellular regulated protein kinases (P-ERK), phospho-protein kinase B (P-AKT), CDK2 etc. increased.

    Conclusion

    ·The PDSORBS2 may inhibit H/R-induced apoptosis of H9C2 cells through the ERK/AKT/CDK2/p27Kip1 signaling pathway.

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    Effects of knockdown of immunoregulatory protein B7-H3 gene on malignant proliferation, invasion and stem cell-like characteristics of bladder cancer cells
    Xiao-han WANG, Yun-lin YE, Kang-hua XIAO, Zhi-xin ZHAO, Jing-ya WU
    2021, 41 (11):  1454-1460. 
    doi: 10.3969/j.issn.1674-8115.2021.11.008

    Abstract ( 141 )   HTML ( 21 )   PDF (2429KB) ( 53 )  
    Objective

    ·To investigate the effect of gene interfering with immune regulatory protein B7-H3 on malignant proliferation and stemness characteristics of bladder cancer J82 cells.

    Methods

    ·Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect shRNA interference efficiency. The proliferation of J82 cells was detected by clone formation assay. Cell apoptosis was detected by flow cytometry. Cell invasion was detected using Transwell asssay. The tumor-cloning ability was observed using tumor sphere formation experiment. Apoptosis, invasion, and expression and stemness-related proteins were detected by Western blotting.

    Results

    ·B7-H3 is highly expressed in bladder cancer tissues and bladder cancer cell lines (P=0.000). shRNA2 was identified as the most efficient interference with B7-H3 gene in three shRNAs (P=0.000). The interference of B7-H3 inhibited the proliferation, invasion, tumor cloning ability and stem cell-like characteristics of J82 cells (P=0.000). Furthermore, B7-H3 interference promoted the apoptosis of J82 cells (P=0.000).

    Conclusion

    ·The gene interference of immunoregulatory protein B7-H3 can inhibit the malignant proliferation, invasion and stemness characteristics of bladder cancer J82 cells, providing a new possibility and effective evidence for the treatment of bladder cancer.

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    Influence of optimization of chromatographic and mass spectrometric parameters on the quantitative sensitivity of immunosuppressive drugs
    Shuang MENG, Li ZHOU, Qin FU, Li XIA, Li-yuan MENG
    2021, 41 (11):  1461-1469. 
    doi: 10.3969/j.issn.1674-8115.2021.11.009

    Abstract ( 91 )   HTML ( 15 )   PDF (4712KB) ( 37 )  
    Objective

    ·To investigate the influence of mobile phase in chromatographic conditions and mass spectrometry ion source parameters on the quantitative results of four common immunosuppressant drugs including cyclosporine A (CsA), tacrolimus (TaC), sirolimus (SiR) and everolimus (EvE) by liquid chromatography-mass spectrometry.

    Methods

    ·Based on ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) technology, the effect on peak shape and response under different parameter settings were evaluated by changing the mobile phase and ion source parameters; the sensitivity of the method under different ion source temperatures was detected by linearity of the standard curve and limit of quantitation (LOQ).

    Results

    ·The narrower peak width was obtained when methanol was used as organic phase; the addition of ammonium formate (AF) to the aqueous phase observably improved the peak response but inhibited partly when the concentration of AF excessed; therefore, 5 mmol/L AF was chosen as the mobile phase modifier. The optimization of the ion source temperature significantly improved the chromatographic peak shape and quantitative sensitivity. The quantitative method had nice linearity (r2>0.99) and sensitivity (LOQ=0.05 ng/mL) under 250 ℃ ion source temperature.

    Conclusion

    ·A simultaneous quantitative analytical method for four immunosuppressant drugs is established based on UPLC-MS/MS technology and the quantitative sensitivity has been conveniently and significantly improved by optimizing the mobile phase and ion source parameters. The addition of AF in the mobile phase and the ion source temperature are key parameters that affect the quantitative analysis and provide new ideas for the development and optimization of high-sensitivity quantitative methods for other compounds based on liquid chromatography-mass spectrometry.

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    Clinical research
    Surgical approach and prognosis evaluation of primary benign and aggressive bone tumors involving the acetabulum
    Zhu-sheng ZHANG, Qi LIU, Qi-yuan BAO, Yu-hui SHEN, Wei-bin ZHANG, Rong WAN
    2021, 41 (11):  1470-1477. 
    doi: 10.3969/j.issn.1674-8115.2021.11.010

    Abstract ( 119 )   HTML ( 8 )   PDF (1709KB) ( 43 )  
    Objective

    ·To summarize the general characteristics, management principles and prognosis of benign and aggressive bone tumors (BABT) involving the acetabulum.

    Methods

    ·A total of 88 cases of primary acetabular lesions were collected, including 41 cases of BABTs. The demographic data of the patients, the surgical procedures and the prognosis of the patients were analyzed.

    Results

    ·The median follow-up time of the 41 cases of BABTs was 42.6 months. Lesion curettage with bone grafting was performed in 30 cases, followed by curettage with cement reconstruction (n=2), enbloc resection with endoprosthesis reconstruction (n=8), and hemi-pelvic amputation (n=1). Postoperative pathology confirmed a benign tumor in 23 cases, 8 of which were accompanied by bone cortical damage (34.8%), and only 2 patients had local recurrence. Postoperative pathology demonstrated an aggressive histology in 18 cases, 14 cases of which were accompanied by bone cortical damage (77.8%), and a total of 5 cases had local recurrence. Of the 7 giant cell tumors of bone, one recurred (14.3%), in comparison to 3 local recurrence (75.0%) of the 4 cases of atypical cartilage hyperplasia.

    Conclusion

    ·Benign acetabular tumors without cortical bone damage have a low recurrence rate following lesion curettage. Aggressive tumors and/or tumors with cortical bone damage have a higher recurrence rate following simple curettage, and the surgical margin needs to be strictly determined prior to surgery. Specifically, lesion curettage with bone cement or enbloc resection with endoprosthesis reconstruction could be an appropriate option for giant cell tumor of bone, while enbloc resection with endoprosthesis reconstruction should be always recommended for atypical cartilage tumor.

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    Exploration of the predictive value of myocardial strain on ventricular remodeling after acute ST-segment elevation myocardial infarction
    Ya-jie GAO, Wen-kun MA, Cheng-jie GAO, Yi ZHOU, Jing-wei PAN
    2021, 41 (11):  1478-1484. 
    doi: 10.3969/j.issn.1674-8115.2021.11.011

    Abstract ( 104 )   HTML ( 8 )   PDF (1086KB) ( 53 )  
    Objective

    ·To investigate the predictive value of myocardial strain in left ventricular remodeling (LVR) after acute ST-segment elevation myocardial infarction (STEMI).

    Methods

    ·Forty-seven patients with STEMI who were admitted to Department of Cardiology of Shanghai Sixth People's Hospital, Shanghai Jiao Tong University from December 2018 to December 2019 and successfully received emergency primary percutaneous coronary intervention were included. Cardiac magnetic resonance (CMR) was performed at the acute stage of STEMI and 1 year later. Left ventricular stroke volume(LVSV), left ventricular mass index (LVMI), global longitudinal strain (GLS), global circumferential strain (GCS) and global radial strain (GRS) were analyzed. Biochemical indexes such as peak hypersensitive serum cardiac troponin I (hs-cTnI) and peak brain natriuretic peptide precursor (proBNP) and clinical data such as age, sex, blood pressure, heart rate (HR) were collected. LVR was defined as the following 2 models. The first one was that the left ventricular end diastolic volume (LVEDV) increased by ≥20% after 1 year of STEMI compared with the baseline. The second one was that the left ventricular end systolic volume (LVESV) increased by ≥15% after 1 year of STEMI compared with the baseline. Patients with STEMI were divided into LVR group and non-LVR group according to the above two models. The differences of CMR index, biochemical index and clinical data between the two groups were compared. Logistic regression was performed and receiver operating characteristic curve was drawn.

    Results

    ·In the model where LVEDV increased by ≥20% 1 year after the acute stage of STEMI, the LVR group and the non-LVR group had statistically significant differences in baseline HR (P=0.003), LVSV (P=0.034), LVMI (P=0.029), GLS (P=0.003), GCS (P=0.016) and GRS (P=0.019). Logistic regression analysis showed that baseline HR and GLS were significantly correlated with LVR (β=-0.070, OR=0.932, P=0.043; β=-0.334, OR=0.716, P=0.031). When the cut-off value of GLS was -9.835, the sensitivity and specificity of LVR prediction were 75.0% and 71.0%, respectively. In the model where LVESV increased by≥15% 1 year after the acute stage of STEMI, there were statistically significant differences in peak hs-cTnI (P=0.035), peak proBNP (P=0.044), LVMI (P=0.034) and GLS (P=0.010) between the LVR group and the non-LVR group. Logistic regression analysis showed that peak hs-cTnI and baseline GLS were significantly correlated with LVR (β=-0.017, OR=0.982, P=0.024; β=-0.304, OR=0.738, P=0.041). When the cut-off value of GLS was -11.145, the sensitivity and specificity for LVR prediction were 94.1% and 50.0%, respectively.

    Conclusion

    ·In patients with STEMI, baseline GLS has a good predictive value for LVR, while GCS and GRS have no significant predictive value.

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    Analysis of pregnancy complications and adverse pregnancy outcomes of elderly primiparas
    Jin-mei ZENG, Ri-ling CHEN, Jie-yun HE, Dong-mei LIANG, Ting-yu LIAN, Ming-juan YIN, Jia-wei RAO, Jin-dong NI
    2021, 41 (11):  1485-1490. 
    doi: 10.3969/j.issn.1674-8115.2021.11.012

    Abstract ( 101 )   HTML ( 7 )   PDF (976KB) ( 42 )  
    Objective

    ·To explore the pregnancy complications and adverse pregnancy outcomes, and summarize the pregnancy characteristics of elderly primiparas.

    Methods

    ·A total of 300 elderly primiparas who delivered in Shunde Women's and Children's Hospital Affiliated to Guangdong Medical University from January 2017 to December 2018 were selected to form the elderly primipara group, and a total of 2 138 elderly multiparae who gave birth to their second child in the same period were selected to form the elderly multipara group. A total of 2 088 primiparas at the appropriate age were randomly selected according to the discharge date to form the appropriate age primipara group, and 1 839 multiparae at the appropriate age who gave birth to their second child were randomly selected to form the appropriate age multipara group. Univariate analysis was performed by χ2 test and analysis of variance, and multivariate analysis was performed by Logistic regression analysis. The differences among the four groups were compared and analyzed, including gestational diabetes mellitus, gestational hypertension, premature delivery, postpartum hemorrhage, and so on.

    Results

    ·Multivariate Logistic regression analysis showed that the elderly primiparas group had the highest risk of gestational diabetes mellitus (aOR=2.938, 95%CI 2.240?3.853), gestational hypertension (aOR=8.579, 95%CI 3.082?23.887), eclampsia (aOR=6.139, 95%CI 2.400?15.985), placenta previa (aOR=3.642; 95%CI 1.551?8.552), turbid amniotic fluid (aOR=4.318, 95%CI 1.852?10.069), premature delivery (aOR=2.573, 95%CI 1.710?3.871), cesarean section (aOR=2.589, 95%CI 1.988?3.373), low birth weight (aOR=3.317, 95%CI 2.111?5.214), neonatal asphyxia (aOR=8.175, 95%CI 2.907?22.992) and respiratory distress syndrome (aOR=10.936, 95%CI 4.400?27.316), compared with the appropriate age multiparae group. The appropriate age primipara group had highest risk of premature rupture of membranes (aOR=1.635, 95%CI 1.337?1.999) and hydramnios/oligohydramnios (aOR=1.730, 95%CI 1.317?2.271), compared with the appropriate age multipara group. The elderly multipara group had the highest risk of developing pelvic adhesions (aOR=1.754, 95%CI 1.030?2.988) compared with the appropriate age multipara group, whereas the appropriate age primipara group had the lowest risk of developing pelvic adhesions (aOR=0.148, 95%CI 0.050?0.439).

    Conclusion

    ·Elderly primiparas confer the highest risks of gestational diabetes mellitus, gestational hypertension, eclampsia, placenta previa, turbid amniotic fluid, premature delivery, cesarean section, low birth weight, neonatal asphyxia and respiratory distress syndrome. Attention should be paid to the perinatal care of elderly primiparas, so that they can receive standardized antenatal visits to improve the quality of their delivery.

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    A new rebleeding prediction model and scoring system for patients with acute nonvariceal upper gastrointestinal bleeding
    Li-ting XI, Jin-zhou ZHU, Chen-yan YU, Liu-jing NI, Chun-fang XU, Ai-rong WU
    2021, 41 (11):  1491-1497. 
    doi: 10.3969/j.issn.1674-8115.2021.11.013

    Abstract ( 101 )   HTML ( 13 )   PDF (1283KB) ( 35 )  
    Objective

    ·To explore independent risk factors of rebleeding and construct a prediction model and risk scoring system of acute nonvariceal upper gastrointestinal bleeding (ANVUGIB).

    Methods

    ·A total of 686 patients with ANVUGIB admitted to the First Affiliated Hospital of Soochow University from January 1, 2016 to December 31, 2019 were collected. The general conditions, clinical characteristics, laboratory results, endoscopic findings and prognosis were recorded. The Baylor score, Rockall score, Glasgow Blatchford Score (GBS), Cedars-Sinai Medical Center Predictive Index(CSMCPI), AIMS65 and MAP (ASH) for each patient were calculated. The collected data were randomly divided into a training set (n=481) and a validation set (n=205). A new prediction model for rebleeding was established by binary Logistic regression based on the training set data. The discrimination and calibration of the training and validation set were evaluated respectively, and then the model was transformed into a risk scoring system. The comparisons between the receiver operating characteristics (ROC) curves were based on the Delong test.

    Results

    ·Binary Logistic regression analysis showed that low systolic blood pressure, low hemoglobin level, American Society of Anesthesiologists (ASA) grade>3, and endoscopic findings of clots, visible vessels and active bleeding were independent risk factors for rebleeding. The area under the curve (AUC) of the prediction model was 0.892 (95% CI 0.838?0.946, P=0.001), Hosmer-Lemeshow test P=0.934. The validation set AUC=0.915 (95% CI 0.851?0.980, P=0.001), Hosmer-Lemeshow test P=0.871. The scoring system (AUC=0.882, 95% CI 0.823?0.942) was better at predicting rebleeding than all other scores mentioned except MAP (ASH) score (P<0.05).

    Conclusion

    ·The scoring system could predict rebleeding after ANVUGIB, which could be an option in clinical practice.

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    Clinical effect of recombinant human granulocyte-macrophage colony stimulating factor gel on donor site after medium to thickness skin transplantation in patients with diabetes
    Wei-dong XIA, Guang-yi CHEN, Wen-tong DAI, Sheng ZHAO, Su LI, Cai LIN
    2021, 41 (11):  1498-1501. 
    doi: 10.3969/j.issn.1674-8115.2021.11.014

    Abstract ( 65 )   HTML ( 9 )   PDF (781KB) ( 32 )  
    Objective

    ·To explore the effect of recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) gel on the donor site of patients with diabetic skin ulcer after medium to thickness skin transplantation.

    Methods

    ·Seventy-four patients with diabetic skin ulcer who were admitted to the Burn Wound Center, the First Affiliated Hospital of Wenzhou Medical University from March 2016 to April 2021 and underwent medium to thickness skin transplantation were analyzed retrospectively. All patients were given active monitoring, drug control of blood glucose, appropriate symptomatic and supportive treatment such as anti-inflammatory, fluid rehydration and nutrition. According to the different treatment methods of the donor site, patients treated with rhGM-CSF gel in the skin donor sites were assigned to the rhGM-CSF group (38 cases); patients treated with routine dressing change in the skin donor sites were assigned to the control group (36 cases). The healing rate and the complete healing time of the donor site on the 8th and 14th day after treatment were calculated respectively in the two groups, and the changes of laboratory examination results before and after treatment in the rhGM-CSF group were compared.

    Results

    ·There were no significant differences in age, pre-treatment albumin level, glycated hemoglobin level and the area of donor site between the two groups. On the 8th and 14th day after treatment, the wound healing rates of the rhGM-CSF group were (53±19) % and (92±14) %, respectively, which were significantly higher than (35±18) % and (77±20) % of the control group, and the difference was statistically significant (t=-4.159, P=0.000; t=-3.462, P=0.000). The complete healing time of the donor site in the rhGM-CSF group was (14±3) d, which was shorter than (16±3) d in the control group (t=3.452, P=0.000). There was no significant difference in platelet count, the levels of hemoglobin, glutamic-pyruvic transaminase, and creatinine. Leukocyte count after treatment was lower than before treatment (Z=-3.491, P=0.000), but both of them were in the normal reference range and had no clinical significance.

    Conclusion

    ·The application of rhGM-CSF gel to the donor site after medium to thickness skin transplantation in diabetic skin ulcer patients can promote the healing of wounds, shorten the wound healing time, and has certain safety. It is worthy of application and popularization.

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    Evidence-based medicine
    Meta-analysis of the relationship between sleep duration and the risk of diabetic retinopathy
    Jie LIU, Xin-min XIE, Xue-mei ZHI, Jing-yi LU
    2021, 41 (11):  1502-1508. 
    doi: 10.3969/j.issn.1674-8115.2021.11.015

    Abstract ( 83 )   HTML ( 6 )   PDF (1807KB) ( 40 )  
    Objective

    ·To explore the relationship between sleep duration and the risk of diabetic retinopathy (DR) by performing a meta-analysis.

    Methods

    ·The databases of Cochrane Library, PubMed, Embase, Web of Science, SinoMed, CNKI, VIP, and WanFang were searched for eligible studies regarding the relationship between sleep duration and the risk of DR up to April 2021. English search terms included "sleep" "sleep duration" "sleep time" "sleeping habit" "quantity of sleep diabetic retinopathy" and "retinal diseases". Chinese search terms included "睡眠" "睡眠时间" and "糖尿病性视网膜病变". The type of literature was observational studies, including cross-sectional studies, case-control studies, and cohort studies. Two researchers independently screened the literature and extracted data. The extracted data included the first author, country, publication time, study type, sample size, mean age, exposure assessment, sleep duration, outcome assessment, adjusted variables. The Newcastle-Qttawa Scale (NOS) was used to evaluate the quality of the included studies and a meta-analysis was performed by using R 4.0.4 software.

    Results

    ·A total of 1 146 documents were retrieved, and 5 met the inclusion criteria, including 5 627 study subjects. Results showed that long sleep duration was positively correlated with the risk of any DR [the combined odds ratio(OR) in the fixed-effect model and random-effect model both were 2.05, 95% confidence interval (CI) 1.37?3.05) ], while short sleep duration was not associated with the risk of any DR (OR in the fixed-effect model and random-effect model were 0.89, 95%CI 0.72?1.10 and 0.98, 95%CI 0.71?1.37, respectively], but it was related to the risk of moderate DR (OR in the fixed-effect model and random-effect model were2.07, 95%CI 1.29?3.33 and 2.06, 95% CI 1.18?3.58, respectively). Short sleep duration was not associated with the risk of vision-threatening diabetic retinopathy (OR in the fixed-effect model and random-effect model both were 0.92, 95%CI 0.58?1.47).

    Conclusion

    ·Sleep duration is significantly associated with the risk of DR, in which too much sleep is a risk factor, while short sleep is to be further determined by research. As a modifiable factor at the individual level, the role of sleep intervention in the management of DR should be further emphasized.

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    Review
    Classification and treatment progress of MMRd-related endometrial cancer
    Qian YIN, Yin-cheng TENG
    2021, 41 (11):  1509-1513. 
    doi: 10.3969/j.issn.1674-8115.2021.11.016

    Abstract ( 114 )   HTML ( 18 )   PDF (891KB) ( 52 )  

    Endometrial carcinoma is a very heterogeneous gynecological cancer. According to the latest molecular classification, endometrial carcinoma is divided into mismatch repair deficiency (MMRd)-related EC and non-MMRd-related EC. And MMRd-related EC is divided into three subtypes according to the characteristics of mutation: MLH1-hypermethylationged endometrial carcinoma (EC-met); Lynch syndrome-related endometrial carcinoma (EC-ls) and mismatch repair gene double somatic variants (EC-dspv). The three subtypes of EC have different pathogenesis and clinical characteristics. Therefore, they must be distinguished according to clinical and immunological characteristics in order to adopt precise treatments. This article mainly introduces the classification of MMRd-related endometrial carcinoma, and compares the three subtypes with the mismatch repair proficiency (MMRp) of EC in terms of clinical and immune features. Finally, this review introduces recent researches and clinical trials related to the treatment and prognosis of MMR.

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    Research progress of the relationship between high-fat diet and colorectal cancer and its prevention and treatment countermeasures
    Wen-hui XU, Jing BIAN, Lei-zhen ZHENG
    2021, 41 (11):  1514-1517. 
    doi: 10.3969/j.issn.1674-8115.2021.11.017

    Abstract ( 104 )   HTML ( 5 )   PDF (803KB) ( 46 )  

    Colorectal cancer (CRC) is one of the five malignant tumors in the world, with the second incidence rate and the third mortality of malignancy, which seriously threatens human life and health. Epidemiological studies show that the incidence rate of CRC in the economically developed countries is significantly higher than that in the underdeveloped countries, and that in city is higher than that in rural areas. The difference of CRC incidence populations in different geographical environments indicates that dietary factors can significantly affect incidence rate and prognosis of CRC. There is evidence that the western diet structure represented by high-fat diet is closely related to the occurrence and development of CRC, and exploring the related mechanism of high-fat diet in the process of CRC is very important to prevent the occurrence of CRC and improve the prognosis of the patients. This paper summarizes the relevant mechanism between high-fat diet and the occurrence and development of CRC at home and abroad in recent years, and puts forward the corresponding prevention strategies, so as to provide theoretical reference for the diet structure-related research and the prevention, diagnosis and treatment of CRC from the perspective of precision medicine.

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    Review of clinical application of peripheral neuropathy scales
    Qun-feng WANG, Li CAO, Xing-hua LUAN
    2021, 41 (11):  1518-1523. 
    doi: 10.3969/j.issn.1674-8115.2021.11.018

    Abstract ( 157 )   HTML ( 15 )   PDF (867KB) ( 69 )  

    Peripheral neuropathy (PN) refers to a group of diseases caused by the dysfunction and structural changes of peripheral motor, sensory and autonomic nerves. Scales for screening and assessing PN are continuously being used in clinical practice. This article summarizes PN score scales for four kinds of PN, including chronic inflammatory demyelinating polyradiculoneuropathy, Charcot-Marie-Tooth disease, diabetic PN and neuropathic pain, aiming to improve medical staff's understanding and application ability of the PN assessment scale.

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    Methods and timing of removing cesarean scar pregnancy after uterine artery embolization
    Li-ping YU, Zhuo-wei XUE, Yin-cheng TENG
    2021, 41 (11):  1524-1528. 
    doi: 10.3969/j.issn.1674-8115.2021.11.019

    Abstract ( 82 )   HTML ( 4 )   PDF (847KB) ( 23 )  

    Cesarean scar pregnancy (CSP) is a special type of ectopic pregnancy that seriously threatens the life safety of women of childbearing age and leads to the loss of reproductive function. Uterine artery embolization (UAE) is an auxiliary method for the treatment of CSP, which can quickly block the blood supply to the lesion and reduce bleeding. Clinically, the combined scheme of UAE is often used to treat CSP, such as combined drug treatment (methotrexate, etc.), and surgical treatment (curettage, hysteroscopy, transabdominal, laparoscopic, transvaginal and other ways) to remove pregnancy. At present, for different types of CSP, how to choose the combination treatment scheme of UAE and the time to remove pregnancy while taking into account the cure rate and safety is a problem faced by clinicians. And there are no clear guidelines and unified standards for the treatment of CSP at home and abroad. This paper reviews the literature at home and abroad in recent years, and summarizes the effect of UAE combined with different treatment methods and the timing of removing pregnancy, in order to provide reference for follow-up research.

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    Research progress of chaperone-mediated autophagy in Alzheimer's disease
    Jun-hui CHEN, You-quan GU, Li-he YAO, Wei ZHANG, Huai-xiang WANG
    2021, 41 (11):  1529-1534. 
    doi: 10.3969/j.issn.1674-8115.2021.11.020

    Abstract ( 131 )   HTML ( 13 )   PDF (902KB) ( 54 )  

    Alzheimer's disease (AD) is a common neurodegenerative disease. Its main pathological change is senile plaque (SP) formed by massive accumulation of amyloid β-protein (Aβ) and neurofibrillary tangles (NFTs) formed by excessive phosphorylation and accumulation of Tau protein in cells. Chaperone-mediated autophagy (CMA) selectively transfers proteins with CMA motifs to lysosomes for degradation. When the autophagy process is impaired, Aβ and abnormal phosphorylated Tau protein will accumulate in neurons, which can destroy the normal function of cells and accelerate their death. Relevant studies have shown that CMA is an important pathway for abnormal protein degradation in early AD, and the inactivation of this pathway may play an important role in the progression of AD. This paper reviews the concept, and physiological role of CMA and the pathological relationship between CMA and AD, and elaborates the role of inactivation of CMA pathway in AD diseases, in order to provide new ideas for the research and treatment of AD pathogenesis.

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    Review of non-invasive brain stimulation for the treatment of somatic symptoms in major depressive disorder
    Lin-jie SHEN, Yu-xin HUANG, Yong WANG, Hua JIN
    2021, 41 (11):  1535-1539. 
    doi: 10.3969/j.issn.1674-8115.2021.11.021

    Abstract ( 110 )   HTML ( 6 )   PDF (885KB) ( 36 )  

    The somatic symptoms of major depressive disorder are related to the course of disease, remission rate and severity of clinical symptoms. At present, the first-line treatment is drug therapy, but the adverse effects of drugs often overlap with somatic symptoms. The studies have shown that non-invasive brain stimulation has application values in the treatment of somatic symptoms in major depressive disorder. This paper reviews the current status of repetitive transcranial magnetic stimulation and transcranial direct current stimulation in the treatment of somatic symptoms of major depressive disorder. It also discusses the efficacy of these two types of non-invasive brain stimulation techniques in the treatment of pain and insomnia in the patients with major depressive disorder, as well as the shortcomings of the existing research, and proposes the developing direction of future research.

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    A review of tools for risk assessment of necrotizing enterocolitis
    Yan JIANG, Qiao-ling FAN, Cheng CAI, Jia-yu QIU, Yan LI, Kai ZHANG
    2021, 41 (11):  1540-1544. 
    doi: 10.3969/j.issn.1674-8115.2021.11.022

    Abstract ( 80 )   HTML ( 10 )   PDF (802KB) ( 27 )  

    The risk assessment tools for neonatal necrotizing enterocolitis were reviewed, and the clinical applicability, and content and methods of using the assessment tools were described. The deficiencies of the tools were analyzed, so as to provide reference for healthcare worker in early identification of high-risk neonates, judgment of disease progression and timing of surgery.

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