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    Oral and Cranio-maxillofacial Science
    Optimizing arch expansion with clear aligners in the mixed dentition based on finite element analysis
    LÜ Qinyi, GAO Ziqi, FENG Qingchen, MEI Hongxiang, LI Juan
    2024, 44 (8):  935-943. 
    doi: 10.3969/j.issn.1674-8115.2024.08.001

    Abstract ( 191 )   HTML ( 17 )   PDF (3720KB) ( 172 )  

    Objective ·To reveal the direction, efficiency, and mechanical load of single tooth displacement with clear aligners for expansion treatment during the transitional dentition period with the aid of finite element analysis. Additionally, overcorrection and torque compensation systems were designed to address insufficient expansion efficiency and buccal inclination of posterior teeth. Methods ·One volunteer in mixed dentition period was included to construct a three dimentional cranio-maxillary complex model and an invisible orthodontic system, simulating the buccal displacement (load 1?4: 0.200, 0.275, 0.300, 0.325 mm, respectively) and root buccal torque (load 1: buccal displacement load 0.200 mm, root buccal torque 0°; load 5: buccal displacement load 0.275 mm, root buccal torque 1.0°; load 6: buccal displacement load 0.300 mm, root buccal torque 1.3° and load 7: buccal displacement load 0.325mm, root buccal torque 1.8°) on the maxillary deciduous teeth to the first permanent molar with a non bracket invisible orthodontic appliance. Through finite element analysis, the tooth displacement and equivalent stress distribution of the periodontal membrane can be calculated. Results ·Expansion treatment with clear aligners in the transitional dentition phase primarily revealed the effect of buccal expansion of teeth; different teeth achieved different levels of expansion rate. At a set expansion amount of 0.200 mm per side, expansion efficiency in the maxillary first permanent molar was 51.86%, second primary molar 68.76%, first primary molar 73.48%, and primary cuspid 84.17%. By designing over-correction (0.275, 0.300, 0.325 mm), the results showed significant enhancement in expansion effect. When overcorrection length reached 150% (0.300 mm), expansion efficiency at the maxillary first permanent molar, second primary molar, first primary molar, and primary cuspid were 75.16%, 99.96%, 107.35%, and 122.37%, respectively. The expansion efficiency of maxillary second primary molar, first primary molar, and primary cuspid was close to 100.00%. The overcorrection design exacerbated the dental effects of expansion, intensifying the tendency for teeth to tilt toward the cheek side, leading to side effects such as buccal inclination and drooping of the palatal cusps. When the overcorrection amount for expansion reached 150%, the crown-root displacement in the upper first permanent molar, second primary molar, first primary molar, and primary cuspid were -0.109, -0.134, -0.132, and -0.298 mm, respectively. Applying specific torque compensation for different tooth positions can combat the buccal inclination of posterior teeth. At an overcorrection length of 150% (0.300 mm) with an added 1.3° root buccal torque, expansion efficiency was 56.15%, 73.88%, 79.49%, and 87.80%, respectively. While the crown-root displacement differences reduced to -0.081, -0.097, -0.095, and -0.208 mm. Conclusion ·When using clear aligners for expansion treatment during a transitional dentition period, side effects such as buccal inclination of posterior teeth exist. Furthermore, various teeth realize differing levels of expansion efficiency, necessitating the design of unique adjustment strategies according to different tooth positions. Overcorrection can improve expansion efficiency but needs to be coordinated with root buccal torque for the whole tooth to move buccally.

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    Study on macroscopic anatomy and developmental model of pterygopalatine suture
    ZHANG Wenyi, CHUNG Miri, XIE Yufan, JIANG Lingyong
    2024, 44 (8):  944-950. 
    doi: 10.3969/j.issn.1674-8115.2024.08.002

    Abstract ( 128 )   HTML ( 10 )   PDF (3342KB) ( 157 )  

    Objective ·To analyze the anatomical and macroscopic characteristics of the pterygopalatine suture (PPS) in Chinese population using cone-beam computed tomography (CBCT) technology, and to preliminarily investigate its developmental pattern and its association with the correction of maxillary underdevelopment. Methods ·A total of 134 CBCT images, taken from July to August 2023 at Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, were categorized into six age groups. The PPS landmarks were utilized to determine the overall transverse position (XPPS), sagittal position (YPPS), insertion angle (IAP), insertion width of the pyramidal process (IWP), and insertion depth of the pyramidal process (IDP). The pterygomaxillary junction was identified through multiplanar observations. Regression analysis was performed to assess the correlation of these parameters with age and gender, and pairwise comparisons were made to determine the stable age range for parameter changes. Paired t-tests and paired chi-squared tests were conducted to analyze the bilateral parameter differences. Results ·Results showed that YPPS and IDP did not exhibit significant correlation with age, whereas XPPS, IAP, IWP, and the incidence of pterygomaxillary fusion were significantly positively correlated with age (P<0.01). Gender differences were only significant for XPPS, with males demonstrating greater values than females (P<0.01). Analysis of age-related trends indicated significant differences in XPPS between group 1 (6 years≤age<9 years) and group 2 (9 years≤age<12 years) (female: P=0.006, male: P=0.004); significant differences in IAP were observed between group 2 and group 3 (12 years≤age<15 years) (P=0.042), with 98.5% of samples having an IAP greater than 45 degrees; IWP differences were significant between group 1 and group 3 (P=0.016), and the pterygomaxillary fusion incidence was significantly different among group 1, 2, and 3 (group 1 vs. 2: P<0.001, group 2 vs 3: P=0.037, group 1 vs 3: P<0.001), with an incidence rate exceeding 90% in adults. No significant bilateral differences were found for all parameters. Conclusion ·No significant changes were observed in YPPS and IDP after the age of 6, indicating a trend towards fusion of the maxilla with the pterygoid process. The overall transverse position of the PPS tends to stabilize around 12 years of age, while the IAP and IWP continue to increase and reach stability around 15 years of age,with a sagittal insertion orientation of the pyramidal process into the pterygoid notch.

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    Progress in the regulatory mechanisms of mandibular condylar development and deformity
    LIU Jingyi, XU Hongyuan, DAI Qinggang, JIANG Lingyong
    2024, 44 (8):  951-958. 
    doi: 10.3969/j.issn.1674-8115.2024.08.003

    Abstract ( 212 )   HTML ( 20 )   PDF (2155KB) ( 406 )  

    The temporomandibular joint is the only joint structure within the craniofacial skeletal system, responsible for performing functions related to opening and closing mouth movements, such as chewing, speaking, and facial expression in daily life. The condyle of the mandible, as a vital component of the temporomandibular joint, originates from the mandibular process formed by the first gill arch and is the key growth center at the end of the mandibular ramus. Condyle is composed of a layer of cartilage as its surface and subchondral bone below, exhibiting unique biological processes during its growth and development. In the articular fossa, the functional movement of the condyle depends on its normal physiological and anatomical structure, which plays a crucial role in establishing occlusion and shaping facial features. Abnormal growth and development can lead to the occurrence of condylar deformities, which affect the vertical height of the patient's maxillofacial region and ultimately lead to secondary skeletal class Ⅱ or Ⅲ craniofacial deformities. During the process of growth and development, the condyle is subject to complex signal regulation. In recent years, with in-depth research on the temporomandibular joint, researchers have begun to discuss the regulatory mechanisms of condyle growth and development from the perspectives of gene expression and molecular level, in order to explain the causes of temporomandibular joint diseases and condylar deformities. This article provides a review on the growth process and structure of condyle, classification and pathological manifestations of condylar deformities, and related regulatory mechanisms of the growth and development of condyle, as well as pathogenesis of condylar deformities. The aim of this article is to provide research ideas for temporomandibular joint diseases and craniofacial malformations caused by abnormal development of the mandibular condyle in clinical practice.

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    Clinical nursing
    Mediating effect of rehabilitation self-efficacy on perceived social support and rehabilitation exercise adherence in hospitalized patients after hip/knee arthroplasty
    XU Jiale, FU Liqin, WU Hong, ZAN Jiaojiao, WU Jing
    2024, 44 (8):  959-967. 
    doi: 10.3969/j.issn.1674-8115.2024.08.004

    Abstract ( 146 )   HTML ( 15 )   PDF (1736KB) ( 135 )  

    Objective ·To explore the correlation among perceived social support, rehabilitation self-efficacy and rehabilitation exercise adherence of in-patients after hip/knee arthroplasty, and examine the mediating role of rehabilitation self-efficacy in the correlation between perceived social support and rehabilitation exercise adherence. Methods ·A convenience sampling method was used, and 141 post-total hip/knee arthroplasty inpatients in the bone and joint ward of the First Affiliated Hospital of Naval Medical University (Shanghai Changhai Hospital) from October 2021 to February 2023 were selected as the study subjects. The general demographic data, such as age and gender, and the information of disease and operation were assessed by using General Data Questionnaire. The adherence to rehabilitation exercise in patients after hip/knee arthroplasty was assessed by using the Rehabilitation Exercise Adherence Scale (REAS); the self-efficacy of rehabilitation exercise was assessed by using the Self-Efficacy for Rehabilitation Outcome Scale (SER); the social support level of individual subjective feelings of the patients was assessed by using the Perceived Social Support Scale (PSSS). Pearson's correlation analysis was used to test the correlation between the variables, and Bootstrap method was used to investigate the mediating role of rehabilitation self-efficacy in the correlation between perceived social support and rehabilitation exercise adherence. Results ·A total of 167 questionnaires were distributed and 141 valid questionnaires were recovered, with a valid recovery rate of 84.4%. The age range of the 141 patients after hip/knee arthroplasty was 26?84 years old, and the average age was (64.75±10.74) years old. The total score of SER of the patients after hip/knee arthroplasty was (100.45±21.71), the total score of PSSS was (68.29±10.89), and the total score of REAS was (11.93±2.29). Pearson's correlation analysis results showed that there was a significant correlation between SER score and PSSS score, SER score and REAS score, and PSSS score and REAS score in patients after hip/knee arthroplasty. The mediation effect analysis showed that the indirect effect of perceived social support on rehabilitation exercise adherence was significant (effect value 0.033, 95%CI 0.017?0.058, P<0.05), and the direct effect of perceived social support on rehabilitation exercise adherence was not significant (effect value 0.027, 95%CI -0.008?0.065, P>0.05). Conclusion ·Perceived social support positively predicts rehabilitation exercise adherence, and rehabilitation self-efficacy fully mediates the correlation. Direct intervention in rehabilitation self-efficacy is superior to moderating the level of perceived social support.

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    Correlation study of pregnancy stress, pre-pregnancy health care behavior and coping style of pregnant women
    LI Jingling, XU Xiaoyan, LI Jing, ZHOU Qian, GAO Yi, ZHOU Xuan, SHUAI Ying, LIU Hanmei
    2024, 44 (8):  968-974. 
    doi: 10.3969/j.issn.1674-8115.2024.08.005

    Abstract ( 125 )   HTML ( 10 )   PDF (1427KB) ( 145 )  

    Objective ·To assess the levels of pregnancy-related stress, pre-pregnancy health care behaviors, and coping styles among pregnant women,analyze the influencing factors of pregnancy stress and provide insights for the management of pregnancy health in expectant mothers. Methods ·A total of 265 pregnant women receiving treatment at the Obstetrics Clinic of the Affiliated Hospital of Zunyi Medical University from April to August 2022 were included as participants. General information questionnaires, pre-pregnancy health care behavior questionnaires, pregnancy stress scales and simple coping style questionnaires were utilized for data collection. After obtaining the consent of the patients, assessments on pregnancy stress levels, pre-pregnancy health care behaviors, and coping styles were conducted. Results ·The overall average score for pregnancy stress among pregnant women was 1.05±0.41. Multiple linear regression analysis revealed that age, number of pregnancies, history of threatened abortion, fetal gender expectations, attending prenatal education classes or reviewing relevant manuals significantly influenced pregnancy-related stresses (P<0.05). The score of pre-pregnancy health care behavior was 10.09±2.63 with proportions indicating high-level, medium-level, and low-level adherence at 17.36%, 54.34%,and 28.30%. In pregnant women, the total score for coping styles was 27.22±9.68, with a positive coping dimension score of 17.79±9.84 and a negative coping dimension score of 9.42±7.39. Pearson correlation analyses demonstrated a negative association between pregnancy-related stresses and pre-pregnancy health care behaviors (r=-0.313, P<0.01), and a negative correlation between pregnancy-related stresses and coping styles (r=-0.163, P<0.01), while a positive relationship existed between pre-pregnancy health care behaviors and coping styles (r=0.220, P<0.01). Conclusion ·Pregnant women experience moderate levels of pressure during their pregnancies and have suboptimal engagement in preconceptional healthcare practices. Nursing staff should intensify efforts towards disseminating knowledge on preconceptional healthcare practices, thereby empowering women of childbearing age to actively acquire pertinent reproductive-health knowledge prior to conception so that minimizing adverse maternal-infant outcomes, optimizing maternal-infant healthcare strategies, and enhancing overall well-being can be achieved through these measures.

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    Clinical effect of oral motor training combined with pediatric tui-na on feeding intolerance in preterm infants
    CUI Fangming, WANG Jingna, ZHANG Yuxia
    2024, 44 (8):  975-980. 
    doi: 10.3969/j.issn.1674-8115.2024.08.006

    Abstract ( 97 )   HTML ( 14 )   PDF (1306KB) ( 133 )  

    Objective ·To investigate the intervention effect of oral motor training combined with pediatric tui-na on feeding intolerance in preterm infants to provide new treatment options and improve the quality of care. Methods ·By using a non-simultaneous controlled clinical trial method, 75 eligible preterm infants from the neonatal unit of a tertiary care hospital in Jinan were selected as the experimental group to implement oral training combined with pediatric massage therapy. Another 60 preterm infants admitted in 2020 were selected as the control group, who had already received oral motor training but had not received pediatric massage. The experimental group was treated for 7 d and the efficacy of the two groups was compared. Comparisons between the two groups included signs of feeding intolerance such as vomiting, gastric remnants and other outcome indicators such as first oral feeding time, gastric tube retention time, increased milk volume at day 3 and increased milk volume at day 7, feeding initiation time, increased weight at day 3 and increased weight at day 7, recovery time of birth weight, and days of hospitalization in both groups. Results ·The differences in gender, age, birth weight, and Apgar score between the two groups before treatment were not statistically significant (P>0.05) indicating comparability. After treatment, preterm infants in the experimental group showed significant improvement in feeding performance, first oral feeding time, gastric tube retention time, increased milk volume at day 3 and increased milk volume at day 7, increased weight at day 3 and increased weight at day 7,hospitalization days and other observed indexes compared with the control group, and the differences were statistically significant (P<0.05). There was no significant difference in the feeding initiation time and recovery time of birth weight between the two groups (P>0.05). Conclusion ·The combined application of oral motor training and pediatric tui-na is significantly more effective than single oral motor training in the short-term treatment of feeding intolerance in preterm infants. This combination therapy helps preterm infants to increase milk intake and accelerate weight gain, helps the children to recover intestinal function, establishes early nutritional support, promotes growth and development, and reduces the risk of long-term complications. This treatment is simple, safe and efficient, and has the value of popularization.

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    Basic research
    Effect of high-fat diet on adipose tissues structure and inflammatory characteristics during pregnancy in mice
    LU Xingyu, XU Yidan, LIU Yiqin, ZHANG Qianren, DONG Yan
    2024, 44 (8):  981-990. 
    doi: 10.3969/j.issn.1674-8115.2024.08.007

    Abstract ( 160 )   HTML ( 22 )   PDF (4045KB) ( 78 )  

    Objective ·To investigate the changes of adipose tissues in mice after high-fat diet before and during pregnancy and the potential effects on adipose tissues in their offspring. Methods ·C57BL/6J female mice were randomly assigned to the normal diet (CON group, n=12) or the high-fat diet (HFD group, n=12) for 5 weeks. The two groups were further subdivided according to pregnancy: a normal diet non-pregnancy group (CON-UN group), a normal diet pregnancy group (CON-P group), a high-fat diet non-pregnancy group (HFD-UN group), and a high-fat diet pregnancy group (HFD-P group). The original diet was maintained during pregnancy and lactation. White adipose tissues (WAT) and brown adipose tissues (BAT) were collected from visceral and scapula of mice after 5 weeks of feeding or E18.5d. Offspring from both dietary groups were placed on a normal diet after weaning, and their adipose tissues were collected at the 11th week. H-E staining was used to observe the changes of adipocytes. Flow cytometry was employed to detect the proportions of CD4+T cells, CD8+T cells, total T cells, CD4+T/CD8+T and NK cells in WAT. RT-PCR was used to assess the expression of IL-6 and IL-1β mRNA in WAT. Results ·After 5 weeks on a high-fat diet, the body weight of female mice in the HFD group was higher than that in the CON group (P<0.05). Both WAT and BAT weights were markedly increased in the HFD groups before and during pregnancy (both P<0.05). In the WAT from HFD-UN and HFD-P groups, the number of cells within the same visual field decreased, the size of adipose cells varied, the proportion of fat droplets increased and the cell volume expanded. The proportion of lipid drop area to total visual field in the HFD-UN group and HFD-P group was compared with the CON-UN group and CON-P group, respectively, and the difference was statistically significant (all P<0.05). BAT in the HFD-UN and HFD-P groups showed a relatively chaotic arrangement and varying adipocyte sizes, although cell volume remained unchanged. The proportions of CD8+T cells and total T cells in adipose tissues were elevated in the HFD-UN and HFD-P groups, accompanied by increased mRNA levels of IL-6 and IL-1β, respectively, compared with the CON-UN and CON-P groups, and the differences were statistically significant (all P<0.05). NK cells proportions decreased at reproductive age (HFD-UN group) but increased significantly during pregnancy (HFD-P group), showing a divergent trend. Despite a return to a normal diet after weaning, offspring from the high-fat diet group had significantly higher weight of body, WAT and BAT, compared to those of normal diet (all P<0.05), and the volume of WAT was significantly enlarged. Conclusion ·A high-fat diet can induce the changes of adipocyte structure and immune cell ratio, and elevate inflammation levels in adipose tissues before and during pregnancy, which also impacts the adipose structure in offspring. Adipose tissue may be a new vector mediating the intergenerational transmission of obesity.

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    Effects of sennoside A on atherosclerotic plaque formation and expression of 5-hydroxytryptamine signal moleculars in mice with diabetes mellitus type 2
    LIU Meizhi, WANG Ziyang, JIANG Yaning, MI Meng, SUN Yongning
    2024, 44 (8):  991-998. 
    doi: 10.3969/j.issn.1674-8115.2024.08.008

    Abstract ( 144 )   HTML ( 21 )   PDF (3158KB) ( 64 )  

    Objective ·To investigate the effects of sennoside A (SA) on the formation of atherosclerotic plaque and the expression of 5-hydroxytryptamine (5-HT) and its receptor in mice with diabetes mellitus type 2 (T2DM). Methods ·Twelve mice with knocked-out apolipoprotein E gene were randomly divided into two groups, namely the model group and the model+SA group, with six mice in each group. Six C57BL/6J mice with the same genetic background were used as the control group. The control group was fed with normal diet, and the model group and the model+SA group were given intraperitoneal injection of streptozotocin (30 mg/kg) daily on the basis of high-fat diet to establish a model of T2DM. The model+SA group was given SA daily by gavage for 8 weeks, and the control group and the model group were given equal volume of distillation-distillation H2O by gavage. The body weight, fasting blood glucose (FBG) and 2-h postprandial blood glucose of mice were compared before and after modeling and treatment. The area of aortic plaque was observed by oil red O staining and hematoxylin-eosin (H-E) staining, and the level of 5-HT in serum and thoracic aorta was measured by ELISA kit. Western blotting was used to detect the expression of 5-hydroxytryptamine receptor 2B (HTR2B) and serotonin transporter (SERT) in thoracic aorta of mice. Results ·Compared with the control group, the body weight, FBG and 2-h postprandial blood glucose in the model group increased, and glucose metabolism was disordered. The expression of HTR2B and SERT protein in thoracic aorta increased, while the concentration of 5-HT in thoracic aorta decreased. The serum 5-HT concentration increased (all P<0.05). After treatment with SA, compared with the model group, the body weight of the model+SA group decreased, and FBG and 2-h postprandial blood glucose were significantly improved. The area of aortic plaque and the expression of HTR2B and SERT protein in thoracic aorta significantly decreased, while the concentration of 5-HT increased. The serum 5-HT concentration decreased (all P<0.05). Conclusion ·SA can reduce atherosclerotic plaque area in T2DM mice, which may be related to lowering blood glucose and inhibiting the expression of 5-HT and its receptor.

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    PRMT6 promotes the proliferation and migration of breast cancer cells
    HAN Yishan, XU Ziqi, TAO Mengyu, FAN Guangjian, YU Bo
    2024, 44 (8):  999-1010. 
    doi: 10.3969/j.issn.1674-8115.2024.08.009

    Abstract ( 144 )   HTML ( 27 )   PDF (4763KB) ( 117 )  

    Objective ·To examine the expression level of protein arginine methyltransferase 6 (PRMT6) in breast carcinoma tissues and to assess its impact on the proliferative and migratory behaviors of breast cancer cells. Methods ·The PRMT6 transcriptome sequencing data between 33 tumor tissues and normal tissues from The Cancer Genome Atlas (TCGA) database was analyzed through the R language. The gene expression profile interactive analysis (GEPIA2) online database was used to analyze the difference of PRMT6 expression in normal breast tissues and breast cancer tissues. By using the immunohistochemistry (IHC) data of human normal breast tissues and breast cancer tissues from Human Protein Atlas (HPA) database to analyze the protein expression of PRMT6. IHC was used to detect the expression of PRMT6 in breast cancer tissues and paired para-tumor tissues from 27 clinical samples. After PRMT6 was knocked down with small interfering RNA (siRNA) in MDA-MB-231 and MCF-7 cells, the expression of PRMT6 was detected by qRT-PCR and Western blotting. The proliferation ability of breast cancer cells was measured with cell counting kit-8 (CCK-8) assay and colony formation assay. The effect of PRMT6 on the migration ability of breast cancer cells was detected by wound healing assay and Transwell assay. By using the RNA-sequence data from GSE210948 of Gene Expression Omnibus (GEO) database, differentially expressed genes were analyzed in control and low expression groups of PRMT6. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed to reveal the signaling pathways associated with PRMT6. Cell cycle analysis was detected by flow cytometry. The expressions of cyclin D1 and EMT-related proteins (E-cadherin, N-cadherin and Vimentin) were detected by Western blotting after knocking down PRMT6. Results ·Bioinformatics analysis and IHC results showed that PRMT6 was highly expressed in breast cancer tissues compared with normal tissues (P=0.000) and para-tumor tissues (P=0.001). qRT-PCR and Western blotting results verified that the siRNA significantly reduced the expression level of PRMT6 in MDA-MB-231 and MCF-7 cell lines compared with the control group (mRNA: P=0.006, P=0.004; P=0.001, P=0.043. Protein: P=0.035, P=0.001; P=0.003, P=0.002). After knocking down PRMT6, the proliferation (P=0.014, P=0.000; P=0.003, P=0.003) and migration (P=0.000, P=0.000; P=0.000, P=0.002) ability of breast cancer cells were inhibited significantly. The KEGG pathway enrichment analysis showed that the expression of PRMT6 affected the cell cycle pathway. After knocking down PRMT6, the expression of cyclin D1 decreased in protein level (P=0.021, P=0.000; P=0.034, P=0.014) and transcription level (P=0.036, P=0.001; P=0.044, P=0.000). Knock down of PRMT6 increased the number of cells in G0/G1 phase (P=0.000; P=0.003) and decreased the number of cells in G2/M phase of the cell cycle. The expression level of E-cadherin increased (P=0.002, P=0.012; P=0.043, P=0.003), while the expression levels of N-cadherin (P=0.004, P=0.041; P=0.032, P=0.034) and Vimentin (P=0.028, P=0.005; P=0.024, P=0.001) decreased in PRMT6 knockdown cells. Conclusion ·PRMT6 is highly expressed in breast cancer, which can promote the proliferation and migration of breast cancer cells.

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    Targeting folate cycle enhances effects of cancer immunotherapy by modulating myeloid-derived suppressor cells
    HE Rui, YAN Kepeng, WANG Jing
    2024, 44 (8):  1011-1022. 
    doi: 10.3969/j.issn.1674-8115.2024.08.010

    Abstract ( 215 )   HTML ( 17 )   PDF (2897KB) ( 172 )  

    Objective ·To explore the regulatory mechanism of folate cycle metabolism in the immunosuppressive effect of myeloid derived suppressor cells (MDSCs). Methods ·Bone marrow cells were isolated from C57BL/6 mice and cultured in RPMI 1640 medium supplemented with GM-CSF, G-CSF, and IL-6 to induce MDSCs in vitro. PD-L1 expression level and ROS production level of induced MDSCs were detected by flow cytometry. CD8+ T cells were enriched from the spleen by MACS with anti-CD8a-conjugated microbeads, labeled with Celltrace violet, and then co-cultured with MDSCs. After 72 h, proliferation was assessed by flow cytometry. Folate cycle-related metabolic enzymes in MDSCs were detected by real-time quantitative PCR. MDSCs were treated with folate cycle metabolic enzyme MTHFD2 inhibitor DS18561882 (DS18) and folic acid antagonist Pemetrexed. ROS and mitoROS production in MDSCs were assessed by flow cytometry. CD8+ T cells were enriched from the spleen by MACS with anti-CD8a-conjugated microbeads, labeled with Celltrace violet, and then co-cultured with Pemetrexed or DS18-treated MDSCs. After 72 h, proliferation was assessed by flow cytometry. Transcript levels of folate cycle-related metabolic enzymes in pemetrexed or DS18-treated MDSCs were detected by RNAseq. A subcutaneous tumor mouse model of colon cancer was established. From the tenth day post-implantation, tumor-bearing mice were intraperitoneally injected with Pemetrexed (200 mg/kg) and tumor size was recorded for tumor growth curve. On the fourteenth day, mice were sacrificed, and tumors were harvested. MC38 tumor-bearing mice were treated with isotype antibody, anti-CD8 monoclonal antibody (1 mg/kg, deplete CD8+ T cells), Pemetrexed (200 mg/kg), and combination of Pemetrexed with anti-CD8 antibody. MC38 tumor-bearing mice were treated with isotype antibody, anti-Gr1 monoclonal antibody (1.25 mg/kg, clearing MDSCs), combination of Pemetrexed with anti-Gr1 antibody. On the tenth day after implantation, tumor-bearing mice were treated with Pemetrexed (50 mg/kg), anti-PD-1 monoclonal antibody (250 μg/kg), Pemetrexed, and combination of Pemetrexed with anti-PD-1 antibody. Results ·Flow cytometry data showed that PD-L1 level and ROS production were increased in induced MDSCs, and CD8+ T cell proliferation was also suppressed significantly. qPCR data revealed the expression of folate cycle-related metabolic enzymes MTHFD2 and others was increased in MDSCs. The accumulation of MDSCs was affected by DS18 or Pemetrexed, ROS production in MDSCs was reduced, and the immunosuppression of CD8+ T cells was relieved. RNA-seq results showed that genes related to MDSCs differentiation, such as S100 calc-binding protein A8, and genes related to MDSCs inhibition, such as cytochrome b-245β chain, which is related to ROS production, were also down-regulated after treatment with two folic acid cycling inhibitors. Tumor growth was suppressed by Pemetrexed. Tumor progression was promoted by combination of Pemetrexed with anti-CD8 antibody, compared with Pemetrexed monotherapy. However, tumor growth delay was inhibited by combination of Pemetrexed and anti-CD8, compared with anti-CD8 monotherapy. Tumor growth delay was caused by MDSCs depletion. But tumor growth was promoted by combination of pemetrexed and anti-Gr1, compared with pemetrexed monotherapy. Tumor growth was restricted by combination of pemetrexed and anti-PD-1 antibody, compared with anti-PD-1 monotherapy. Conclusion ·Pemetrexed relies on CD8+ T cells for anti-tumor effects and further retards tumor growth by reprogramming MDSCs to an anti-tumor phenotype. Modulating MDSCs by targeting folate cycle could impair their immunosuppressive ability and enhance the efficacy of immune checkpoint blockade in cancer treatment.

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    Clinical research
    Efficacy and safety of compound amino acid capsules in the treatment of malnutrition and calcium and phosphorus metabolism disorders in maintenance hemodialysis patients
    WU Wangshu, WANG Minzhou, SONG Ahui, ZHAO Bingru, LU Jiayue, HONG Wenkai, GU Leyi, XIE Kewei, LU Renhua
    2024, 44 (8):  1023-1029. 
    doi: 10.3969/j.issn.1674-8115.2024.08.011

    Abstract ( 152 )   HTML ( 11 )   PDF (1823KB) ( 104 )  

    Objective ·To explore the efficacy and safety of compound amino acid capsules in the treatment of malnutrition and calcium and phosphorus metabolism disorders in maintenance hemodialysis patients. Methods ·In this prospective, randomized, controlled, single-center study, forty maintenance hemodialysis patients from Renji Hospital, Shanghai Jiao Tong University School of Medicine were randomly divided into two groups, the treatment group (n=21) and the control group (n=19). The treatment group was given oral compound amino acid capsules on the basis of regular hemodialysis treatment, while the control group received no special nutritional intervention. Serum albumin, prealbumin, hemoglobin, ferritin, calcium, phosphorus, 1,25-(OH)2-D3 and intact parathyroid hormone levels were analyzed every 3 months, and the incidence of adverse events including death, cardio-cerebrovascular accidents and vascular access failure was recorded. The total follow-up period was 9 months. Results ·Serum albumin and prealbumin in the treatment group at 6-month and 9-month were significantly higher than the baseline parameters (albumin, t=3.574, 5.599, both P<0.05; prealbumin, t/Z=-2.485, 2.921, both P<0.05). Albumin in the control group increased at 9-month with a lower amplification compared to the treatment group (t=3.877, P=0.001), while the difference of prealbumin showed no statistical significance during follow-up. Hemoglobin and serum ferritin in the treatment group started to increase at 3-month (hemoglobin, t=2.192; ferritin, t=2.994; both P<0.05). Phosphorus in treatment group decreased at 3-month and 9-month (t/Z=-2.743, -2.103, both P<0.05), while phosphorus in the control group remained relatively stable during the first 6 months and increased at 9-month (Z=-2.178, P=0.029). Calcium and 1,25-(OH)2-D3 in the treatment group at 3-month and 6-month were significantly higher than the baseline parameters (calcium, t=4.581, 4.922, both P=0.000; 1,25-(OH)2-D3t/Z=4.504, -2.374, both P<0.05), while the increase in blood calcium in the control group was significantly smaller than that in the treatment group during the same period. 1,25-(OH)2-D3 in the control group showed no significant improvement. There was no significant difference in intact parathyroid hormone level, incidence of adverse events and other laboratory examination results between the two groups. Conclusion ·Compound amino acid capsules can ameliorate the nutrition status and regulate calcium and phosphorus metabolism effectively and safely in maintenance hemodialysis patients.

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    Clinical validation and application value exploration of multi-modal pulmonary nodule diagnosis model
    XU Wanxing, WANG Lin, GUO Qiaomei, WANG Xueqing, LOU Jiatao
    2024, 44 (8):  1030-1036. 
    doi: 10.3969/j.issn.1674-8115.2024.08.012

    Abstract ( 198 )   HTML ( 19 )   PDF (1853KB) ( 219 )  

    Objective ·To verify the performance and explore the clinical application value of a multi-modal pulmonary nodule diagnosis model combined with metabolic fingerprints, protein biomarker CEA and Image-AI via random forest (MPI-RF). Methods ·This study enrolled 289 patients with pulmonary nodules who were admitted to the Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine and were detected by low-dose helical computed tomography (LDCT). The patients were divided into malignant nodule group ( n=197) and benign nodule group ( n=92) based on postoperative pathological results, and the basic information of the two groups was collected and compared. Electrochemiluminescence was used to detect the preoperative serum CEA levels of the patients in the two groups, matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) was used to detect the serum metabolic fingerprints, and the CT image artificial intelligence model Image-AI was used to calculate the image scores. CEA data, serum metabolic fingerprints data and image scores were integrated and input into MPI-RF to calculate the malignant probability score of each patient. The receiver operator characteristic curve (ROC curve) and area under the curve (AUC) were used to evaluate the performance of different models, and the DeLong test was used for comparative analysis, including the diagnostic performance of MPI-RF in different types (solid nodule, pure ground-glass nodule and part-solid nodule) and sizes (diameter<8 mm and diameter≥8 mm) of pulmonary nodules, the diagnostic performance comparison of MPI-RF with Mayo Clinic model, veterans administration (VA) model and Brock model, and the diagnostic performance comparison of MPI-RF with lung imaging reporting and data system (Lung-RADS) in benign and malignant nodules. Results ·MPI-RF had good diagnostic performance in the differentiation of benign and malignant pulmonary nodules (AUC=0.887, 95% CI 0.848?0.925, sensitivity 81.22%, specificity 83.70%). Among them, the AUC of MPI-RF for solid nodules was 0.877 (95% CI 0.820?0.934), for part-solid nodules was 0.858 (95% CI 0.771?0.946), and for pure ground-glass nodules was 0.978 (95% CI 0.923?1.000). The AUC of MPI-RF was 0.840 (95% CI 0.716?0.963) for nodules within 8 mm diameter and 0.891 (95% CI 0.849?0.933) for nodules larger than 8 mm diameter. Compared with the existing models, the diagnostic performance of MPI-RF was better than that of Mayo Clinic model, VA model and Brock model (all P=0.000). Compared with Lung-RADS, MPI-RF had better diagnostic performance in the total samples and different types of nodules (all P=0.000). Conclusion ·MPI-RF is a model for the differential diagnosis of benign and malignant pulmonary nodules with excellent performance, and has potential clinical application value.

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    Review
    Progress in cumulative risk assessment of human health from combined exposure to environmental pollutants
    CHENG Xiaomeng, ZHANG Yan, GAO Yu, TIAN Ying
    2024, 44 (8):  1037-1043. 
    doi: 10.3969/j.issn.1674-8115.2024.08.013

    Abstract ( 225 )   HTML ( 26 )   PDF (1516KB) ( 283 )  

    The combined exposure to environmental pollutants can result in unanticipated adverse effects on human health, and how to compare and assess these effects has always been a matter of great concern for the international community. Currently, several prevalent methods for assessing combined exposure risks in the field of human health risk assessment primarily encompass the hazard index (HI) method, the point of departure index (PODI) method, the margin of exposure (MOE) method, and the relative potency factor (RPF) method. The review summarizes the application of these methods to the cumulative risk assessment of combined exposure to the same class of chemicals with the same toxic mechanism, primarily focusing on pesticides such as organophosphorus pesticides, pyrethroids, carbamates, and neonicotinoids, as well as typical compounds intimately related to human production and life, including organophosphorus flame retardants, per- and poly-fluoroalkyl substances, and bisphenols. Furthermore, progress in the application of physiologically based pharmacokinetics models to human health risk assessment has been introduced, which might provide more options for risk assessment of combined exposure to multiple chemicals, and help to provide insights for further exploration and establishment of more systematic and scientific approaches to human health risk assessment.

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    Research progress in late-onset group B Streptococcus infection in infants and its prevention
    LI Yibai, CUI Ruiji, GAO Shan, HU Jiajin, GUO Xiaoying
    2024, 44 (8):  1044-1049. 
    doi: 10.3969/j.issn.1674-8115.2024.08.014

    Abstract ( 132 )   HTML ( 15 )   PDF (1254KB) ( 112 )  

    Group B Streptococcus (GBS) is a major member of the Gram-positive Streptococcus family, which occupies a dominant position in the infection spectrum of newborns and young infants. GBS infections occurring 0?6 days after birth are called GBS early-onset disease (GBS-EOD), and those occurring 7?89 days are called GBS late-onset disease (GBS-LOD). With the use of intrapartum antibiotic prophylaxis, the incidence of neonatal GBS-EOD has declined without a notable impact on GBS-LOD, which brings great pressure and challenge to clinical diagnosis and nursing work. However, the specific mechanisms by which GBS transmission triggers illness in newborns and young infants are not fully elucidated. Some factors, such as maternal GBS colonization, maternal characteristics (age, weight and ethnicity), preterm birth, GBS infection in multiple births, and exposure to human immunodeficiency virus, have been identified as risk factors for GBS-LOD. To prevent maternal and infant GBS infection, some measures, such as vaccination of pregnant women, gut microbiota regulation and lactoferrin supplementation, are developing. In addition, strengthening maternal health care and health education, along with some other conventional infection control strategies (including enhancing hand hygiene awareness among caregivers and making good disinfection of the environment and equipment) is also effective in the prevention of GBS-LOD. This review elaborates the prevalence, transmission, risk factors and prevention of GBS-LOD in infants, aiming to improve the understanding and clinical practice ability of the medical staff.

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    Advances in dietary interventions for the treatment of depression-related symptoms
    CHEN Shentse, CHEN Yiming, WANG Fan, ZHANG Mengke, YANG Weichieh, LÜ Dongbin, HONG Wu
    2024, 44 (8):  1050-1055. 
    doi: 10.3969/j.issn.1674-8115.2024.08.015

    Abstract ( 160 )   HTML ( 22 )   PDF (1270KB) ( 228 )  

    Major depressive disorder (MDD) is a common mental illness. Currently, nearly 16% of the global population is affected by depression-related symptoms, while the diagnosis and treatment rate of MDD patients in China is only 9.5%. MDD is characterised by high morbidity and low recovery rate, and how to effectively improve its therapeutic effect has been a hot research topic in recent years. Antidepressants, as the main treatment for MDD, have the disadvantages of many adverse effects and slow onset of action, prompting people to pay attention to the non-pharmacological treatments of MDD. Dietary intervention is a kind of non-pharmacological treatment by changing dietary structures and rhythms; the current application of dietary intervention to psychiatry is very extensive, and it has been proved to be effective in the treatment of depression. Recent research suggests that dietary interventions can treat and ameliorate depressive symptoms by influencing brain-gut axis-related eating mechanisms. This article reviews the multidimensional exploration of dietary interventions in the treatment of depression: dietary structure interventions, dietary rhythm interventions, and the role of intestinal flora. It details the modalities of dietary interventions and the related mechanisms involved, and provides reference for dietary interventions in the treatment of depression-related symptoms.

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    Case report
    A case report of dissociative conversion disorder primarily manifesting as intermittent fainting accompanied by myoclonic seizures
    TANG Peiyuan, WANG Chongze, HONG Wu, FEI Hui, YI Zhenghui, LÜ Qinyu
    2024, 44 (8):  1056-1060. 
    doi: 10.3969/j.issn.1674-8115.2024.08.016

    Abstract ( 117 )   HTML ( 14 )   PDF (1909KB) ( 120 )  

    The characteristic features of dissociative conversion disorder entail a partial or complete loss of normal integration in memory, identity awareness, immediate sensation, and motor control. This article documents a case of the disorder presenting with an onset of depressive mood, diminished interest, and facial tics, subsequently accompanied by intermittent fainting spells with limb convulsions. Despite multiple consultations in both general hospitals and psychiatric settings, and despite treatment with various antidepressants and antiepileptic medications, the patient's symptoms showed no significant improvement. The report of this case deepens the understanding of a complex and commonly misdiagnosed condition, offering valuable insights for the diagnosis and treatment of patients exhibiting similar symptoms.

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