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    Frontier review
    Reflection and exploration of digital chronic disease management based on the proactive health index
    GAO Xiang, LI Xiaoguang, ZHOU Liang, WANG Hui
    2023, 43 (2):  137-142. 
    doi: 10.3969/j.issn.1674-8115.2023.02.001

    Abstract ( 232 )   HTML ( 42 )   PDF (1672KB) ( 222 )  

    The disease burden caused by chronic non-communicable diseases continues to grow, with profound implications for public health and socio-economic development. The traditional health management of chronic diseases lacks diagnostic criteria and reasonable intervention time, and the bottleneck of the lack of residents' initiative is increasingly prominent. The construction of proactive health index (PHI) is expected to be an effective means to improve the health management of chronic diseases. As the world enters a critical period of digital transformation, China's health strategy has made clear that technological innovation and information technology should play a leading role in maintaining people's health, and digital health brings strategic opportunities for the development of chronic disease health management. In the context of the development of digital chronic disease prevention and control, this study analyzes the main bottlenecks existing in China's chronic disease health management, clarifies the importance of establishing diagnostic criteria for chronic disease health management, proposes the concept of PHI, and introduces the construction of PHI to solve the key problems of chronic disease health management. The application scenarios of PHI are deployed and prospected from the government side, the family physician side and the public side, in order to provide ideas for improving residents' health management initiative and enhancing the effectiveness of chronic disease health management.

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    Basic research
    Quantitative characteristics of serum lipoprotein phenotypes for HBV patients
    YI Xiaoxuan, HU Senlin, SUN Yang, HUANG Qingxia, TANG Huiru
    2023, 43 (2):  143-151. 
    doi: 10.3969/j.issn.1674-8115.2023.02.002

    Abstract ( 185 )   HTML ( 30 )   PDF (2500KB) ( 145 )  

    Objective ·Previous studies showed that hepatitis B virus (HBV) infection caused outstanding changes in host lipoproteins. However, there are no reports on such component changes of lipoprotein subfractions. This study aimed to quantify the HBV-caused changes in the serum lipoprotein subfractions and their components. Methods ·Hepatitis B surface antigen-positive [HBsAg (+)] patients at Division of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from March to June 2017 were included (n=40), and 40 HBsAg-negative [HBsAg (-)] population were matched as controls. Serum lipoprotein subfractions and their components were quantified by using 1H-NMR. Orthogonal partial least-squares discriminant analysis (OPLS-DA), variance analysis between the two groups, logistic regression analysis and Spearman correlation analysis were conducted to reveal the lipoprotein changes in chronic HBV patients against controls. Results ·HBsAg (+) population had significantly lower levels in most lipoprotein subfractions than HBsAg (-) population. After adjustments for age, gender, hypertension, diabetes mellitus and coronary heart disease, the levels of total VLDL, VLDL1-VLDL3, IDL, HDL4, non-HDL and their components were protective factors for HBV infection (OR < 1, P < 0.01). In contrast, VLDL5-(TAG/LP) was a risk factor for HBV infection (OR > 1, P < 0.01). In addition, the severity of inflammation in the HBsAg (+) population was negatively correlated with the levels of lipids in HDL4 with correlation coefficient ranging from -0.71 to -0.51(P≤ 0.002). Six lipoprotein subfractions were obtained through feature screening, and the AUC of HBV infection diagnosis model was 0.861. Conclusion ·HBV infection causes significant changes in liver-excretion of lipoproteins and their circulation metabolism; the lipoprotein phenotypes can differentiate HBV-infected patients from controls.

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    Expression and clinical significance of PLA2G2A in kidney renal papillary cell carcinoma
    LI Fang, LI Kaiyang, WANG Jue, YAN Ruiyang, SHEN Hui, LIU Min
    2023, 43 (2):  152-161. 
    doi: 10.3969/j.issn.1674-8115.2023.02.003

    Abstract ( 209 )   HTML ( 37 )   PDF (5167KB) ( 162 )  

    Objective ·To investigate the expression and clinical significance of phospholipase A2 Group ⅡA (PLA2G2A) in kidney renal papillary cell carcinoma (KIRP), and provide new ideas for seeking KIRP targets. Methods ·The expression level of PLA2G2A in pan-cancer and its relationship with prognosis and immune infiltration were analyzed by online software SangerBox. On this basis, the expression level of PLA2G2A in KIRP was analyzed with the help of the UCSC xena database; the correlation between PLA2G2A expression and prognosis and immune infiltration of KIRP were analyzed by using the UALCAN database and the TIMER database, respectively. In addition, the LinkedOmics database was used to analyze the related genes, Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment of PLA2G2A in KIRP. Results ·PLA2G2A was significantly low expressed in 15 tumor samples from The Cancer Genome Atlas (TCGA) including KIRP. It was further validated that PLA2G2A was significantly lower expressed in KIRP with the help of Genotype-Tissue Expression (GTEx) database. The expression level of PLA2G2A was closely related to the prognosis and immune infiltration of various tumors. The higher the expression level of PLA2G2A in KIRP was, the worse the prognosis and the higher the abundance of immune infiltration were. GO analysis showed that PLA2G2A was mainly enriched in biological regulation and metabolic process in biological process (BP), cell membrane and nucleus in cell component (CC), and protein binding and ion binding in molecular function (MF). KEGG pathway enrichment analysis suggested that the pathways positively correlated with PLA2G2A were enriched in ribosome, cell cycle, proteasome, systemic lupus erythematosus and antigen processing and presentation, while the pathways negatively correlated with PLA2G2A were enriched in citrate cycle, pyruvate metabolism, and carbon metabolism. Conclusion ·PLA2G2A is significantly lower expressed in KIRP. Unexpectedly, the higher the expression level of PLA2G2A in KIRP is, the worse the prognosis and the higher the abundance of immune infiltration are. In KIRP, the PLA2G2A positively correlated pathways are mainly enriched in cell cycle and immune-related pathways (such as systemic lupus erythematosus, antigen processing and presentation), while the negatively correlated pathways are mainly concentrated in citric acid cycle and pyruvate metabolism signaling pathways. Thus, it is needed to be further explored whether PLA2G2A plays a role in the development of KIRP as a tumor suppressor or an oncogene.

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    Change of transcription factor EB activity and autophagy in hippocampus of type 2 diabetic encephalopathy mice
    CHEN Yixin, CHENG Lizhen, LIN Yijia, MIAO Ya
    2023, 43 (2):  162-170. 
    doi: 10.3969/j.issn.1674-8115.2023.02.004

    Abstract ( 158 )   HTML ( 33 )   PDF (4484KB) ( 124 )  

    Objective ·To investigate the changes of transcription factor EB (TFEB), the activity of the upstream proteins and autophagy in the hippocampus of mice with type 2 diabetic encephalopathy. Methods ·Twenty healthy 8-week-old male C57BL/6J mice were randomly divided into type 2 diabetes mellitus (T2DM) group and control (CON) group, with 10 mice in each group. The T2DM group was fed with high fat feed and injected with streptozotocin (STZ); the CON group was fed with ordinary diet and injected with equal-volume sodium citrate buffer. The random blood glucose level and the body weight were measured on the mice in both groups weekly. In the 10th week, the Morris water maze behavioral experiments were performed. Then, the intraperitoneal glucose tolerance test (IPGTT) was carried out. The blood and hippocampus samples were collected after the mice were sacrificed. The plasma insulin content was detected by the ELISA kit. The protein levels of amyloid precursor protein (APP), tau protein, phospho-tau (p-tau) protein, autophagy-lysosome-related proteins [including lysosomal-associated membrane protein 1 (LAMP1), microtubule-related protein 1A/1B-light chain 3 (LC3), and P62], TFEB, p-TFEB, mammalian target of rapamycin (mTOR), p-mTOR, and mucolipin TRP cation channel 1 (MCOLN1) in the hippocampus were detected by Western blotting. The deposition of β-peptide (Aβ) and p-tau proteins in the hippocampus was detected by immunofluorescence staining. Results ·Compared with the CON group, the body weight, the random blood glucose level, the plasma insulin level, and the IPGTT results were significantly increased in the T2DM group (P<0.05). In the water maze experiments, the escape latency of the T2DM group in the place navigation increased, and the time spent in the target quadrant and the number of times crossing the platform in the spatial probe decreased (P<0.05), indicating that the ability of learning and memory of mice was damaged in the T2DM group. The levels of Aβ, APP, tau, p-tau, P62, p-TFEB, mTOR and p-mTOR proteins, and the ratios of p-tau/tau and p-mTOR/mTOR significantly increased, while the expression of LAMP1, TFEB and MCOLN1 and the ratio of LC3-Ⅱ/LC3-Ⅰ prominently decreased in the hippocampus of mice in the T2DM group in comparison with the CON group (P<0.05). Conclusion ·Alzheimer's disease-like neuropathy is observed in the hippocampus of diabetic encephalopathy mice, along with decreased TFEB activity, down-regulated autophagy function, decreased expression of MCOLN1, and enhanced mTOR activity in the hippocampus.

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    Improvement of alveolarization arrest in newborn rats with bronchopulmonary dysplasia via inhibiting alveolar epithelial cell pyroptosis
    ZHENG Xiaoyan, WANG Xingyun, ZHANG Yongjun
    2023, 43 (2):  171-179. 
    doi: 10.3969/j.issn.1674-8115.2023.02.005

    Abstract ( 154 )   HTML ( 25 )   PDF (5037KB) ( 151 )  

    Objective ·To study the effect of gasdermin D (GSDMD) inhibitor necrosulfonamide (NSA) on alveolarization arrest in lipopolysaccharide (LPS)-induced bronchopulmonary dysplasia (BPD) newborn rats via inhibiting alveolar epithelial cell pyroptosis. Methods ·Pregnant SD rats were randomly assigned to four groups as follows: control, BPD, BPD with NSA and NSA group, and then were prepared to receive intra-amniotic injection of LPS. Lung tissues of newborn rats on the first, third and seventh day after birth were stained by hematoxylin-eosin (H-E) to observe lung development. The expressions of GSDMD-N-terminal in lungs of newborn rats in each group were detected by immunofluorescence. The mRNA levels of interleukin-1β (IL-1β) of newborn rats' lungs was detected by real-time PCR. In vitro, the mouse alveolar epithelial cell line MLE-12 was cultured and treated with LPS/adenosine triphosphate (ATP) and NSA. The cell viability of MLE-12 cells was detected by CCK-8 method, the pyroptosis was detected by Hoechst 33342 and propidium iodide (PI) staining, and the expressions of surfactant protein C (SFTPC) and GSDMD-N protein in MLE-12 cells were detected by immunofluorescence. Results ·In vivo, intra-amniotic injection of LPS hindered lung development, resulting in the pathological hallmarks of BPD. The GSDMD-N expression of alveolar epithelial cells increased in the BPD rat model established by intra-amniotic injection of LPS, while NSA treatment significantly improved the lung development of BPD rats and inhibited the IL-1β mRNA expression (both P<0.05). In vitro, the study confirmed that LPS/ATP treatment decreased the viability of alveolar epithelial cells MLE-12 and induced pyroptosis, while NSA treatment increased alveolar epithelial cell viability and inhibited pyroptosis (both P<0.05). In addition, NSA treatment upregulated the SFTPC expression and inhibited the GSDMD-N expression in LPS/ATP-stimulated alveolar epithelial cells (both P<0.05). Conclusion ·Inhibiting the alveolar epithelial cell pyroptosis can improve the alveolar development in BPD newborn rats.

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    Clinical research
    Preliminary application of improved 3D printed pathological section box to assisting stitching pathological images of bone tumor
    WU Bing, LI Xiaomin, LIU Siyu, ZHAO Lulu, WU Wen, HAO Yongqiang, AI Songtao
    2023, 43 (2):  180-187. 
    doi: 10.3969/j.issn.1674-8115.2023.02.006

    Abstract ( 132 )   HTML ( 23 )   PDF (3997KB) ( 58 )  

    Objective ·To explore the feasibility of applying improved pathological section boxes based on image post-processing and 3D printing technology to assisting artificial intelligence (AI) in stitching pathological images of bone tumors. Methods ·Bone tumor patients who underwent tumor resection surgery between February 2022 and August 2022 were enrolled. Patients and their postoperative tumor specimens were examined by CT and MRI. The skeletal anatomical landmarks of bone tumors were used to register the preoperative CT, and MRI and the postoperative CT images. The personalized pathological slice box was improved and 3D printed to guide the cutting direction of bone tumor specimens. The large pathological slices were grid-like segmented and performed with hematoxylin-eosin staining. After AI stitching the pathological images, the pathological tumor boundaries were compared with the preoperative radiological boundaries. Results ·Four patients with bone tumors (2 bone metastatic neoplasm, 1 osteosarcoma, and 1 chondrosarcoma; 3 males and 1 female) were collected to design the pathological section box with an average age of (40.25±25.70) years. The lesions included 3 cases of femur and 1 case of ilium. The mean maximum tumor diameter was (12.10±4.02) cm. The modified 3D printed pathological section box could fit the surface of bone tumor individually,and overcame the problems of difficult cutting or inaccurate cutting location caused by excessive movement of bone tumor specimens in the primary pathological section box. The pathological boundaries could be completely obtained and compared with the preoperative MRI boundaries for colocalization. The outline features of the section boxes could help AI to restore the permutation of pathological fragments, and the image stitching time decreased from the previous seventy hours to one hour while the boundary coincidence rates increased to 90%. Conclusion ·The improved pathological section box of 3D printing can accurately assist AI in stitching pathological images, greatly improve the efficiency of pathological image stitching and achieve the colocalization between preoperative MRI and pathological images of bone tumor specimens.

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    Clinical analysis of insulin resistance in liver cirrhosis patients
    SHI Cuicui, ZHANG Jie, HUANG Heming, SANG Yuer, LI Guangming
    2023, 43 (2):  188-193. 
    doi: 10.3969/j.issn.1674-8115.2023.02.007

    Abstract ( 160 )   HTML ( 35 )   PDF (1364KB) ( 91 )  

    Objective ·To investigate the insulin resistance in liver cirrhosis patients. Methods ·Patients with liver cirrhosis from Xinhua Hospital,Shanghai Jiao Tong University School of Medicine in 2013?2017 were retrospectively assessed. Biochemical indexes, including fasting blood glucose (FBG), glycosylated hemoglobin A1c (HbA1c), fasting insulin and homeostatic model assessment-insulin resistance (HOMA-IR), were collected. The complications of liver cirrhosis were recorded, including esophagogastric varices bleeding (EVB), ascites and hepatic encephalopathy (HE). According to HOMA-IR value, the liver cirrhosis patients were divided into non-insulin resistance group (IR≤1.64) and insulin resistance group (IR>1.64). Various indicators were compared between the two groups. Results ·A total of 376 patients with liver cirrhosis were included in this study. The proportions of Child-Pugh A, Child-Pugh B and Child-Pugh C were 162 (43.09%), 148 (39.36%), and 66 (17.55%), respectively. The main cause of liver cirrhosis was hepatitis B virus infection 163 (43.35%). Fasting insulin levels were measured in 208 of 376 liver cirrhosis patients. Among them, 117 patients (56.25%) had no insulin resistance and 91 patients (43.75%) had insulin resistance. The body mass index (BMI) of liver cirrhosis patients in the insulin resistance group was significantly higher than that in the non-insulin resistance group (P=0.000), and the prevalence of type 2 diabetes in the former was also higher (P=0.001). The scores of Child-Pugh in patients with liver cirrhosis in the insulin resistance group were lower than those in the non-insulin resistance group, and the difference in Child-Pugh score was statistically significant (6.93±1.99 vs 7.63±2.20, P=0.020). The proportion of Child-Pugh C grade in the insulin resistance group was significantly lower than that in the patients without insulin resistance (P=0.028). The prevalence of ascites in cirrhotic patients with insulin resistance was significantly lower than that in cirrhotic patients without insulin resistance (36.26% vs 66.67%, P=0.000). There was no significant difference in the prevalence of EVB and HE between the two groups (P>0.05). Conclusion ·Nearly half of patients with liver cirrhosis are associated with insulin resistance. Compared with no-insulin resistance patients, cirrhotic patients with insulin resistance have a higher BMI, lower percentage of Child-Pugh C, and fewer ascites prevalence.

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    Effect of intraoperative use of low-dose dexmedetomidine on the prognosis of patients undergoing breast cancer surgery
    YANG Xiaoxuan, ZHU Shan, QIAN Cheng, CHU Xiaoying
    2023, 43 (2):  194-200. 
    doi: 10.3969/j.issn.1674-8115.2023.02.008

    Abstract ( 137 )   HTML ( 28 )   PDF (1581KB) ( 101 )  

    Objective ·To investigate the influence of intraoperative dexmedetomidine infusion on the recurrence-free survival (RFS) and overall survival (OS) rate of patients undergoing breast cancer surgery. Methods ·A retrospective analysis was performed on patients who underwent breast cancer surgery at the Breast Disease Diagnosis and Treatment Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from July 2013 to June 2014. Patients were divided into dexmedetomidine group and control group according to whether dexmedetomidine was injected intraoperatively at 0.7?0.8 ìg/kg. After correcting the confounding factors between the two groups by using the propensity score matching method, the factors affecting the prognosis and survival of patients undertaking breast cancer surgery were investigated by univariate and multivariate analysis, and the Kaplan-Meier survival curve was further used to analyze the effect of intraoperative dexmedetomidine on RFS and OS after five years of breast cancer surgery. Results ·There were significant differences in age, progesterone receptor (PR) positive ratio, proliferating cell nuclear antigen (Ki67) expression score, American Society of Anesthesiologists (ASA) grade, and anesthesia duration between the two groups before propensity score matching. After propensity score matching, a total of 239 pairs were successfully matched, and there was no significant difference in baseline data and perioperative data between the two groups (P>0.05). Univariate analysis showed that age (P=0.032), postoperative radiotherapy (P=0.041), Ki67 score (P=0.021), and tumor TMN stage (P=0.029) were significantly correlated with postoperative five-year OS. The results of multivariate analysis showed that postoperative radiotherapy, Ki67 score, and tumor TMN stage were significantly correlated with postoperative five-year OS (P<0.05). Intraoperative low-dose dexmedetomidine infusion was not a risk factor for postoperative five-year OS (P>0.05). Compared with the control group, the five-year postoperative RFS and OS in dexmedetomidine group did not decrease significantly (P>0.05). Conclusion ·Intraoperative use of low dosage of dexmedetomidine (0.7?0.8 μg/kg) has no significant effect on RFS and OS in patients undergoing breast cancer surgery at five years postoperatively, providing theoretical reference for the rational selection of anesthetics for tumor patients. The effect of higher dosage of dexmedetomidine needs to be further confirmed by prospective multicenter randomized controlled studies.

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    Cone-beam CT analysis of anatomical structure of maxillary sinus arteries
    WU Jiongrui, GAO Yiming
    2023, 43 (2):  201-207. 
    doi: 10.3969/j.issn.1674-8115.2023.02.009

    Abstract ( 113 )   HTML ( 19 )   PDF (3160KB) ( 60 )  

    Objective ·To analyze the anatomical structural characteristics of maxillary sinus artery (MSA) by cone-beam CT (CBCT) measurement. Methods ·The MSAs in the bilateral maxillary sinuses were observed in 1 021 patients who went to Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, for implant surgery due to dentition defect or loss. In the CBCT bone window view, the position between the MSA foramen and the bone wall at the midline of the second premolar (P2), the first molar (M1), and the second molar (M2) was measured, and the intrasinus (the artery was located below the mucosa of maxillary sinus), intraosseous (the artery was completely located in the lateral wall of maxillary sinus), and superficial (the artery was located below the periost of the lateral wall of maxillary sinus) types of their location were classified. The distance between the upper and lower edges of the MSA foramen was measured as the diameter of the artery (DMSA). The distance between the lower margin of the vessel and the sinus floor (DVSF) was measured. The lateral wall thickness of maxillary sinus and the width of maxillary sinus at 5 mm above the maxillary sinus floor at the middle line of the M1 tooth position were measured, and the angle formed by the internal and external side walls of maxillary sinus at 10 mm above the lowest point of maxillary sinus floor was measured. The differences of variability of MSA position, MSA shape type, DMSA and DVSF in patients of different genders and ages were statistically analyzed. At the same time, the correlation between DMSA and DVSF of MSA and the lateral wall thickness, width and angle of maxillary sinus were statistically analyzed. Results ·① Variability of MSA position: In the 1 021 patients, 42 patients (4.1%) had MSA located at the lateral wall of the maxillary sinus and close to the maxillary sinus floor, of which 14 patients (33.3%) had bilateral MSA, and 28 patients (66.7%) had unilateral MSA. Seven patients (0.7%) had MSA located in the alveolar bone below the maxillary sinus floor, of which 1 case (14.3%) had MSA located in the alveolar bone bilaterally, and 6 cases (85.7%) had MSA located in the alveolar bone unilaterally. ② MSA shape type: The intrasinus type accounted for 36.5%, the intraosseous type accounted for 60.4%, and the superficial type accounted for 3.1%. The proportion of intraosseous type in middle-aged patients (63.0%) was higher than that in young and elderly patients (P=0.005). ③ DMSA: DMSA was the largest in M1 tooth position, which was (1.42±0.44) mm. The DMSAs of males in P2, M1 and M2 tooth position were bigger than those of females. There was a weak positive correlation between the lateral wall thickness of maxillary sinus and DMSA in P2 and M1 tooth position (r =0.2, r =0.2). In M1 tooth position, the width and angle of maxillary sinus were weakly negatively correlated with DMSA (r =-0.1, r =-0.2). ④DVSF: DVSF decreased gradually from M2 to P2. The DVSFs of males in P2 and M2 tooth position were larger than those of females. There was a weak negative correlation between the lateral wall thickness of maxillary sinus and DVSF in M1 tooth position (r =-0.3). There was a weak negative correlation between the width of maxillary sinus and DVSF in M1 position (r =-0.1). Conclusion ·The position of MSA may vary in the alveolar bone at the maxillary sinus floor and at the alveolar bone. With the increasing of age, the shape type of MSA changes from intrasinus type to intraosseous type.Male patients have greater DMSA and greater risk of arterial bleeding than women. The larger DMSA can be observed in the thicker lateral wall of maxillary sinus, while the DMSA is smaller when the width and angle of maxillary sinus is larger. The DVSF in men is larger than that in women, and the DVSF is smaller in the thicker lateral wall of maxillary sinus or when the width of maxillary sinus is larger.

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    Evidence-based medicine
    Effectiveness of vitamin E on oral mucositis caused by radiotherapy and chemotherapy: a meta-analysis
    LIANG Yanjing, HUANG Chuxian, LI Hongyan, HOU Lili
    2023, 43 (2):  208-214. 
    doi: 10.3969/j.issn.1674-8115.2023.02.010

    Abstract ( 167 )   HTML ( 25 )   PDF (2731KB) ( 88 )  

    Objective ·To examine, using a systematic review and meta-analysis, the effectiveness of vitamin E on treating oral mucositis caused by radiotherapy and chemotherapy. Methods ·A systematic literature search was performed by using PubMed, Embase, Cochrane Library, Web of Science, CINAHL, OpenGrey, Chinese biomedical literature database (CBM), Chinese national knowledge infrastructure (CNKI), Wanfang Data, and China Science and Technology Journal Database (VIP). The retrieval time was up to March 2022. The risk of bias was assessed by using the Cochrane Risk-of-Bias tool, version 2.0. RevMan 5.4 was used for meta-analysis. Results ·A total of 563 literatures were retrieved. A total of 7 randomized controlled trials were included. The results of meta-analysis revealed that vitamin E supplementation did not significantly affect oral mucositis caused by chemoradiotherapy (RR=0.44, 95%CI 0.15?1.25, Z=1.54, P=0.120). However, vitamin E may have some effect on severe oral mucositis (RR=0.22, 95%CI 0.11?0.43, Z=4.33, P=0.000). Conclusion ·It cannot be explained that vitamin E can effectively treat oral mucositis caused by radiotherapy and chemotherapy, but vitamin E may be effective for severe oral mucositis.

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    Techniques and methods
    Observation on the therapeutic effect of intraorbital injection of compound betamethasone on the treatment of IgG4-related ophthalmic disease
    LIU Xiaohong, WANG Yanuo, JIAO Qin, CHENG Yu
    2023, 43 (2):  215-221. 
    doi: 10.3969/j.issn.1674-8115.2023.02.011

    Abstract ( 155 )   HTML ( 21 )   PDF (2616KB) ( 75 )  

    Objective ·To investigate the effect of intraorbital injection of compound betamethasone on IgG4-related ophthalmic disease (IgG4-ROD). Methods ·Patients with IgG4-ROD who received intraorbital injection of compound betamethasone in the Department of Ophthalmology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from September 2016 to August 2021 were included. The enrolled patients met the 2019 American College of Rheumatology/European League Against Rheumatism classification criteria for IgG4-related disease (IgG4-RD) and all had lacrimal gland involvement. The intraorbital administration regimen was 0.5 mL compound betamethasone (containing betamethasone propionate 5 mg/mL, and betamethasone sodium phosphate 2 mg/mL) into the affected orbit once a week for 6 weeks, and then once a month for 3 months. The drug was injected into the lacrimal gland and its surrounding superficial orbital tissue. For patients with extraocular muscle and optic nerve involvement, periocular injection was added. Before and after treatment, the IgG4-RD responder index (IgG4-RD RI) was recorded according to the clinical manifestations, serum IgG4 level and imaging findings. If recurrence was determined according to the IgG4-RD RI, maintenance treatment was adopted. Maintenance treatment regimen was once a month for 6 months, and then changed to bimonthly according to the doctor's judgment. Results ·According to the IgG4-RD RI before and after treatment, all patients achieved complete remission after initial treatment with remission periods of 4, 4, 6, and 5 months in case 1, 2, 3 and 4, respectively, but relapse occurred. Despite recurrence, case 1, 3, and 4 remained in remission with maintenance therapy in the follow-up of 50, 45, and 27 months, respectively. Due to the low total dosage of glucocorticoid, no obvious systemic and local side effects occurred during treatment. Also no serious injection-related side effects occurred. Case 2 refused maintenance therapy and the lacrimal gland returned to its original size after discontinuation, but did not aggravate further in the 47 months follow-up. Conclusion ·Intraorbital injection of compound betamethasone may be a useful treatment option for IgG4-ROD. However, patients require repeat injections due to relapse.

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    Research progress in the roles of Notch signaling pathway during fracture healing
    GUO Liqiang, ZHAO Shitian, SHU Bing
    2023, 43 (2):  222-229. 
    doi: 10.3969/j.issn.1674-8115.2023.02.012

    Abstract ( 154 )   HTML ( 46 )   PDF (1584KB) ( 125 )  

    Fracture is the most common large-organ injury in humans. It takes several months or even longer from the onset to the completion of bone reconstruction. In severe cases, delayed healing or even bone discontinuity can occur. The current treatment of fractures mainly pursues the completion of clinical healing and bone healing, and the healing process is divided into three stages: early, intermediate and late. Various factors affect the speed of the healing process, among which signaling pathways and cytokines play an important role in fracture healing, so understanding the important role of signaling pathways and cytokines is important for treating fractures and promoting fracture healing. Recent studies have shown that the Notch signaling pathway can affect cell proliferation and differentiation, inflammatory response, bone reconstruction, angiogenesis and nerve regeneration during fracture healing, and its changes are also closely related to mechanical stimulation and other factors. Therefore, this paper reviews the research progress in the role of Notch signaling pathway in various aspects of fracture healing from the perspectives of cell proliferation and differentiation, inflammatory response, bone reconstruction, angiogenesis, nerve regeneration and mechanical stimulation, and provides new research directions and therapeutic strategies for fracture healing treatment.

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    Research progress of subcellular structure-targeted therapy in spinal cord injury
    LIU Tiexin, LIN Junqing, ZHENG Xianyou
    2023, 43 (2):  230-236. 
    doi: 10.3969/j.issn.1674-8115.2023.02.013

    Abstract ( 130 )   HTML ( 27 )   PDF (1579KB) ( 124 )  

    Spinal cord injury is a serious disease that greatly affects the sensory function, motor function and autonomic nervous function of patients. It not only brings serious physical and mental harm to patients but also causes huge economic burden to the society. With the development of medical technology, the research on the internal mechanism of spinal cord injury is also deepening, and the treatment methods of spinal cord injury emerge in endlessly. However, the therapeutic effect is not satisfactory, so it is urgent to further explore new therapeutic strategies and expand new therapeutic ideas for spinal cord injury. Many studies have shown that various subcellular structures are closely related to nerve regeneration and functional recovery after spinal cord injury. Therefore, targeting subcellular structures to treat spinal cord injury plays an important role in promoting nerve regeneration and repair after spinal cord injury. This targeted therapy mainly refers to targeting a variety of subcellular structures such as mitochondria, lysosomes/autophagosomes, endoplasmic reticulum, intracellular bodies and proteasomes. A variety of therapeutic strategies targeting subcellular structures have significant therapeutic effects on spinal cord injury. Among them, mitochondrial targeting or endoplasmic reticulum targeting mainly focuses on maintaining mitochondrial energy metabolism at the injury site, while endoplasmic reticulum targeting mainly focuses on inhibiting endoplasmic reticulum stress. This article reviews the research progress of subcellular structure-targeted therapy in spinal cord injury, which is expected to be a new targeted therapy strategy for spinal cord injury and provide a new idea for the treatment of spinal cord injury.

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    Crosstalk between epigenetic modification and circRNA in colorectal cancer: recent advances
    PENG Tian, XU Leiming
    2023, 43 (2):  237-243. 
    doi: 10.3969/j.issn.1674-8115.2023.02.014

    Abstract ( 139 )   HTML ( 30 )   PDF (1286KB) ( 91 )  

    Colorectal cancer (CRC) is generally regarded as the third frequent malignancy worldwide, while current diagnosis and treatment of the disease are limited. The previous studies of CRC revealed that epigenetic modification plays a crucial role in the progression of CRC. Epigenetic modification is identified as heritable changes in gene functions that occur without changing the DNA sequence, resulting in cells with similar DNA eventually developing into different types with different functions, which encompasses DNA/RNA methylation, histone modification, and non-coding RNA regulation. Circular RNA (circRNA), a kind of non-coding RNA that forms a covalently closed loop, is widely present in various cells which drive initiation and progression of cancers through multiple pathways. The emerging data show that epigenetic modification may affect the biological functions of circRNA, while circRNA can also participate in the progression of CRC by targeting molecules related to epigenetic modification. N6-methyladenosine (m6A) has been found to directly promote production, translation, and functions of circRNA on the one hand, and interact with circRNA on the other hand, thereby altering onset, progression, and metastasis of the disease. DNA methylation and histone modification have also been observed to have potential interaction with circRNA. This review provides a brief overview about the association between current epigenetic modifications and circRNA, and the significant role they may play in the progression of CRC, and also outlines the potential applications to diagnosis and treatment, and the research direction in the future.

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    Research progress in diagnosis and treatment of chylothorax after esophagectomy
    WANG Xinyu, ZHAO Xiaojing, TANG Jian
    2023, 43 (2):  244-249. 
    doi: 10.3969/j.issn.1674-8115.2023.02.015

    Abstract ( 155 )   HTML ( 29 )   PDF (1497KB) ( 96 )  

    Thoracic duct is the longest lymphatic duct in the human body and plays an important role in maintaining normal metabolism and immune function. Chylothorax is a rare complication after esophageal surgery, which is caused by the injury of the thoracic duct during esophagectomy, resulting in the accumulation of chyle in the pleural cavity. The etiology may be related to anatomical variation, patient's general condition, tumor stage, perioperative intervention and other factors. Preoperative and intraoperative preventive measures can reduce the incidence of chylothorax. Although the incidence rate is low, misdiagnosis or unsuccessful management can increase postoperative complications and lead to serious metabolic disorders and even death. Therefore, early diagnosis and intervention are of paramount importance. Diagnosis should be based on clinical manifestations, supplemented by laboratory and imaging studies. Currently, there is no standard for treatment, which mainly includes conservative treatment, interventional treatment, and surgical treatment. It is necessary to make a comprehensive judgment according to the actual situation and select the appropriate treatment method. In recent years, interventional technology could accurately localize the chylothorax, which is expected to play a more important role in the treatment of chylothorax. This article reviews the latest advances in the etiology, diagnosis, treatment, and prevention of chylothorax after esophagectomy and provides a flow chart of treatment steps to effectively manage this complication.

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    Research progress of immune checkpoint inhibitors in the treatment of metastatic colorectal cancer
    TU Juanjuan, JIN Zhiming
    2023, 43 (2):  250-255. 
    doi: 10.3969/j.issn.1674-8115.2023.02.016

    Abstract ( 142 )   HTML ( 30 )   PDF (1270KB) ( 114 )  

    Colorectal cancer (CRC) is a common malignancy with a high incidence of metastatic events in China and the world. Immunotherapy has received increasing attention as an emerging therapy in the treatment of metastatic colorectal cancer (mCRC). Immune checkpoint inhibitor (ICI) is one of the important methods, mainly represented by programmed cell death protein 1 (PD-1), programmed cell death ligand 1 (PD-L1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) antibodies. The strong potential of ICIs in the treatment of mCRC has been confirmed by completed and ongoing clinical trials. The U.S. Food and Drug Administration has approved some ICIs for the first-line treatment of microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) mCRC. ICI cannot yet replace the conventional therapy in the treatment of microsatellite stable (MSS)/mismatch repair proficient (pMMR) mCRC, but an increasing number of ICI combination programs have entered the clinical trial phase and have initially shown good clinical efficacy and application prospects. Finding new markers to identify potentially beneficial patients, validating new combination regimens, and developing new immune checkpoints are all important to the future of ICI research.

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    Progress in functional mechanisms and biomarkers of miRNA related to Kawasaki disease
    FENG Jiali, PENG Yu, DUAN Junkai
    2023, 43 (2):  256-260. 
    doi: 10.3969/j.issn.1674-8115.2023.02.017

    Abstract ( 114 )   HTML ( 27 )   PDF (1192KB) ( 68 )  

    Kawasaki disease is an acute febrile exanthema pediatric disease with systemic vasculitis as the main lesion, which is the most common cause of acquired heart disease in children. The etiology of the disease is not clear, and the pathogenesis remains to be explored. Some cases of Kawasaki disease are prone to misdiagnosis due to atypical clinical presentations, and patients who have not been effectively treated are at increased risk of coronary artery lesion. Therefore, timely diagnosis of Kawasaki disease and prediction of coronary artery lesion have great significance for early treatment and prognosis of Kawasaki disease. MiRNA plays an important role in various life processes of organisms, and dysregulation of miRNA is involved in the occurrence and development of many diseases. Current studies have shown that miRNA can assist in the diagnosis, prognosis assessment and large-scale population screening of diseases, and has potential clinical application prospects as a novel biomarker. Recent studies have found that miRNA is associated with the pathogenesis of Kawasaki disease, and expression dysregulation will lead to immune imbalance and vascular damage in patients with Kawasaki disease. Other studies have shown that circulating miRNA can be used as a potential biomarker of Kawasaki disease, mainly focusing on early diagnosis and efficacy prediction of Kawasaki disease. The current research is still at the exploratory stage, and more clinical studies are needed to verify the early diagnosis and prediction efficacy of miRNA related to Kawasaki disease. This article reviews the functional mechanism and biomarkers of miRNA in Kawasaki disease in recent years.

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