The expression mechanism of programmed cell death 1 ligand 1 and its role in immunomodulatory ability of mesenchymal stem cells / 中华创伤杂志(英文版)

Programmed cell death 1 ligand 1 (PD-L1) is an important immunosuppressive molecule, which inhibits the function of T cells and other immune cells by binding to the receptor programmed cell death-1. The PD-L1 expression disorder plays an important role in the occurrence, development, and treatment of sepsis or other inflammatory diseases, and has become an important target for the treatment of these diseases. Mesenchymal stem cells (MSCs) are a kind of pluripotent stem cells with multiple differentiation potential. In recent years, MSCs have been found to have a strong immunosuppressive ability and are used to treat various inflammatory insults caused by hyperimmune diseases. Moreover, PD-L1 is deeply involved in the immunosuppressive events of MSCs and plays an important role in the treatment of various diseases. In this review, we will summarize the main regulatory mechanism of PD-L1 expression, and discuss various biological functions of PD-L1 in the immune regulation of MSCs.

Exosome and Its Function in Central Nervous System / 生物化学与生物物理进展

Exosome is a kind of extracellular vesicles secreted by cells to the outside. Biogenesis mainly involves two invaginations of the cytoplasmic membrane, the formation of multivesicular bodies, and the release of exosomes. Exosomes have abundant and diverse inclusions—including landmark membrane proteins, soluble proteins, various RNA molecules and DNA fragments, etc. Cells can achieve intercellular signal communication by secreting and receiving exosomes. Through interaction of ligand molecules on the exosome membrane with receptors on the surface of other cytoplasmic membranes, exosomes can activate cell signal transduction or fuse with the cell membrane to release its contents into the cytoplasm to exert regulatory functions. In the central nervous system, exosomes secreted by neurons and various glial cells can mediate wired synaptic signal transmission, but mainly play a role similar to neuromodulator by way of volume transmission. In this paper, the biogenesis of exosomes and important functional components are described in detail, and the characteristics of neural exosomes in the biogenesis, content sorting and controlled release are compared with those of synaptic vesicles. We further review the research progress on the physiological functions of neural exosomes on the central nervous system and their roles in the occurrence and development of neurodegenerative diseases and major depressive disorder. We also prospect the application of exosomes in the early diagnosis and targeted therapy of nervous system diseases.

A case of corrosive digestive tract and lung injury caused by ingestion of pipeline dredging agent / 中华劳动卫生职业病杂志

Ingestion of corrosive substances can severely burn the upper digestive tract leading to bleeding or perforation, and may even be life-threatening. Less commonly, damage to the trachea and bronchi is involved. In this paper, a case of corrosive digestive tract injury and lung injury after oral administration of pipeline dredging agent (the main components are hydroxide, sodium carbonate, sodium hypochlorite, etc.) was analyzed. After active rescue treatment, the patient died of massive hemoptysis. It is suggested that serious complications may occur after ingestion of corrosive substances. Timely diagnosis and reasonable medical management are needed to improve the level of recognition and treatment of such diseases.

Diquafosol sodium combined with intense pulsed light in the treatment of meibomian gland dysfunction / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To investigate the effect of 3% diquafosol sodium eye drops combined with intense pulsed light on the treatment of meibomian gland dysfunction and the change of meibomian glands.METHODS: Prospective study. A total of 141 patients(282 eyes)who were diagnosed with meibomian gland dysfunction from January 2021 to May 2022 in our hospital were selected and they were randomly divided into the control group(73 cases, 146 eyes)and the observation group(68 cases, 136 eyes)according to random number table. The control group was given 0.3% sodium hyaluronate eye drops combined with intense pulsed light, and the observation group was treated with 3% diquafosol sodium eye drops combined with intense pulsed light. The subjective symptom score, physical sign score, non-invasive tear break-up time, tear meniscus height, lipid layer thickness, and meibomian gland density before and after the treatment were compared between the two groups at 2wk after the end of treatment.RESULTS: There were no differences in the subjective symptom score, physical sign score, non-invasive tear break-up time, tear meniscus height, lipid layer thickness, and meibomian gland density between the two groups of patients before treatment(P>0.05). After 2wk of treatment, the symptom scores and physical sign scores of patients in the two groups continued to decrease, non-invasive tear break-up time and lipid layer thickness continued to increase, and the meibomian gland density also increased. The tear meniscus height in the observation group increased, while the control group showed no significant changes. The observation group had better clinical indicators than the control group(P<0.05). No obvious complications were observed in all patients.CONCLUSION: The combination of diquafosol sodium eye drops and intense pulsed light is synergistic in the treatment of meibomian gland dysfunction, with significant therapeutic effects and improvement of meibomian gland repair, which is significantly superior to simple intense pulsed light therapy.

Research on the mechanisms of ethanol extract of Scutellaria baicalensis Georgi in improving CFA-induced inflammatory pain rats based on 1H NMR metabolomics / 药学学报

The purpose of this study was to investigate the effects of ethanol extract of Scutellaria baicalensis Georgi (SGE) on endogenous metabolites in toes of rats with inflammatory pain induced by complete Freund's adjuvant (CFA) based on 1H NMR metabolomics, which would provide foundation for revealing the effects and mechanisms of SGE in improving inflammatory pain. This animal experiment was approved by the Committee on the Ethics of Animal Experiments of Shanxi University (SXULL2022062). The rats model of inflammatory pain was induced by subcutaneous injection of CFA (0.1 mL), and the effect of low, medium and high doses of SGE (1.5, 3, 6 g·kg-1) on inflammatory pain were explored. The effects of SGE on relieving inflammatory pain was evaluated by mechanical nociceptive thresholds (MNTs) test. Western blot was used to detect the effects of SGE on protein expression of cyclooxygenase-2 (COX-2), nuclear factor kappa-B (NF-κB) and phospho-NF-κB (p-NF-κB). 1H NMR metabolomics was used to analyze the regulatory effects of SGE on endogenous metabolites in the toes of rats with inflammatory pain. The results showed that SGE (6 g·kg-1) could significantly relieve CFA-induced inflammatory pain, and also notably inhibit the protein expression of COX-2, NF-κB and p-NF-κB. SGE could markedly reverse the changes of 8 differential metabolites, such as glycine, glutamine, succinate, phosphorylcholine, etc. The metabolites were involved in eight metabolic pathways, such as glycine, serine and threonine metabolism, alanine, aspartate and glutamate metabolism, glyoxylate and dicarboxylate metabolism, glutathione metabolism, glycerophospholipid metabolism. These results suggest that SGE may relieve inflammatory pain by regulating NF-κB signaling pathway and metabolic abnormality.

Effects of miR-144-3p on Proliferation, Cell Cycle and Apoptosis of K562 Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the effects of miR-144-3p on cell proliferation, cell cycle and apoptosis of blast phase chronic myelogenous leukemia (CML) K562 cells.@*METHODS@#K562 cells were cultured in vitro and mimics negative control, hsa-miR-144-3p mimics, inhibitor negative control and miR-144-3p inhibitor were respectively transfected into K562 cells with transfection reagents. The cells were divided into five groups including blank control, mimics negative control, miR-144-3p mimics, inhibitor negative control and miR-144-3p inhibitor. After transfection, the cell proliferation activity was detected by CCK-8 assay. The cell cycle distribution and apoptosis were detected by flow cytometry.@*RESULTS@#Compared with the blank control and mimics negative control groups, the proliferation rate of miR-144-3p mimics group was significantly decreased (P<0.05), the proportion of S phase cells was markedly increased (P<0.05), while the proportion of G1 phase cells was obviously decreased (P<0.05), and the apoptosis rate was significantly increased (P<0.05). Compared with the blank control and inhibitor negative control groups, the proliferation rate of miR-144-3p inhibitor group was obviously increased (P<0.05), the proportion of S phase cells was markedly decreased (P<0.05), while the proportion of G1 phase cells was obviously increased (P<0.05), and the apoptosis rate was significantly decreased (P<0.05).@*CONCLUSION@#miR-144-3p can inhibit the proliferation and promote apoptosis of K562 cells, affect the cell cycle, and block K562 cells in S phase, which indicates that miR-144-3p is involved in the cell cycle activity of CML during blastic phase.

Different frequency of acupoint thread-embedding for overweight/obesity of spleen deficiency and dampness retention: a randomized controlled trial / 中国针灸

OBJECTIVES@#To compare the effect of different frequency of acupoint thread-embedding on weight loss in subjects with overweight/obesity of spleen deficiency and dampness retention.@*METHODS@#A total of 126 subjects with overweight/obesity of spleen deficiency and dampness retention were randomized into a 2-week group(63 cases, 13 cases dropped out)and a 3-week group(63 cases, 11 cases dropped out, 1 case was eliminated). The two groups were treated with acupoint thread-embedding once every 2 weeks and once every 3 weeks respectively, Zhongwan(CV 12), Shuifen(CV 9), Qihai(CV 6), Guanyuan(CV 4) and bilateral Zhangmen(LR 13), Tianshu(ST 25), Liangmen(ST 21), Daheng(SP 15), Fujie(SP 14), Pishu(BL 20), Yinlingquan(SP 9)were selected. Four times were required in the two groups. Before and after treatment, follow-up after 2 months of treatment completion, the body mass index(BMI), body weight, waist circumference, hip circumference, waist-to-hip ratio, obesity degree, fat percentage(F%), skin fold thickness were observed in the two groups.@*RESULTS@#After treatment and in follow-up, the BMI, body weight, waist circumference, hip circumference, waist-to-hip ratio, obesity degree, F%, skin fold thickness in the two groups were decreased compared with those before treatment (P<0.001, P<0.01), the changes of BMI, body weight, obesity degree, F%, skin fold thickness in the 2-week group were larger than those in the 3-week group(P<0.05, P<0.01, P<0.001).@*CONCLUSIONS@#The effect of acupoint thread-embedding once every 2 weeks on weight loss in subjects with overweight/obesity of spleen deficiency and dampness retention is superior to that once every 3 weeks.

Correlation analysis between body mass index and clinical characteristics of rheumatoid arthritis / 北京大学学报(医学版)

OBJECTIVE@#To analyze the clinical features of overweight and obese rheumatoid arthritis (RA)patients, and the relationship between body mass index (BMI) and disease characteristics.@*METHODS@#The demographic data, extra-articular manifestations, comorbidities, and disease activity of RA patients admitted to the Rheumatology and Immunology Department of Peking University Third Hospital from January 2015 to December 2020 were collected, and the above characteristics of overweight and obese RA patients were retrospectively analyzed. According to the WHO, BMI≥30 kg/m2 referred to obese individuals, 25≤BMI < 30 kg/m2 referred to overweight individuals, 18.5≤BMI < 25 kg/m2 referred to normal individuals, BMI < 18.5 kg/m2 referred to reduced body mass individuals. t test was used for the quantitative data in accordance with normal distribution. Wilcoxon rank sum test was used for the quantitative data of non-normal distribution. The qualitative data were analyzed by chi square test. But while 1≤theoretical frequency < 5, Chi square test of corrected four grid table was used. And Fisher exact probability method was used when theoretical frequency < 1. Analyzing whether overweight or obesity was associated with comorbidities using Logistic regression adjusted confounding factors.@*RESULTS@#A total of 481 RA patients were included in this study, with an average BMI value of (23.28±3.75) kg/m2.Of the patients, 31 cases (6.5%) were with BMI < 18.5 kg/m2, 309 cases (64.2%) with 18.5≤ BMI < 25 kg/m2, amounting to 340 cases (70.7%). There were 119 overweight individuals (25≤ BMI < 30 kg/m2, 24.7%) and 22 obese individuals (BMI≥30 kg/m2, 4.6%), totaling 141 (29.3%).The proportion of the overweight and obese RA patients suffering from hypertension (57.4% vs. 39.1%, P < 0.001), diabetes (25.5% vs. 15.0%, P=0.006), hyperlipidemia (22.7% vs. 10.9%, P=0.001), fatty liver (28.4% vs. 7.4%, P < 0.001), osteoarthritis (39.0% vs. 29.4%, P=0.040) was significantly higher, and the proportion of the patients with osteoporosis(59.6% vs. 70.9%, P=0.016) and anemia (36.2% vs. 55.6%, P < 0.001) was significantly lower. However, there was no difference between the two groups in coronary heart disease (5.7% vs. 7.6%, P=0.442), cerebrovascular disease (6.4% vs. 8.8%, P=0.372) and peripheral atherosclerosis (9.2% vs. 7.6%, P=0.565).The median C-reactive protein (CRP, 1.52 mg/dL vs. 2.35 mg/dL, P=0.008), median erythrocyte sedimentation rate (ESR, 34.0 mm/h vs. 50.0 mm/h, P=0.003), pain visual simulation score (VAS) (3.66±3.08 vs. 4.40±2.85, P=0.011), and 28 joint disease activity scores (DAS-28, 5.05±1.60 vs. 5.45±1.52, P=0.010) in the overweight and obese RA group were all lower than those in the normal and reduced weight groups. Multivariate regression analysis showed that overweight and obesity was an independent risk factor for hypertension, diabetes, hyperlipidemia and fatty liver, and had protective effects on osteoporosis and anemia.@*CONCLUSION@#In RA patients, RA disease activity is lower in overweight and obesity patients. Overweight and obesity is associated with hypertension, diabetes and hyperlipidemia, but not with cardiovascular and cerebrovascular diseases.

Comparison of clinical and immunological characteristics between primary Sjögren's syndrome patients with positive and negative anti-SSB antibody / 北京大学学报(医学版)

OBJECTIVE@#To analyze the differences of clinical manifestations and laboratory features between primary Sjögren's syndrome (pSS) patients with positive and negative anti-Sjögren's syndrome type B (SSB) antibody.@*METHODS@#The clinical data of pSS patients hospitalized in Department of Rheumato-logy and Immunology, Peking University Third Hospital were retrospectively analyzed to investigate the differences of clinical and laboratory features between anti-SSB positive and negative groups. The t test, Mann-Whitney U test, Chi-square test and Fisher's exact probability were used for analysis.@*RESULTS@#A total of 142 pSS patients were enrolled in this study, including 137 females and 5 males with a mean age of (54.8±13.3) years. The anti-SSB positive group included 44 patients accounting for 31.0% of the pSS patients. The anti-SSB positive pSS patients were younger at disease onset and at visit [age at visit: (50.9±14.5) years vs. (56.5±12.4) years; age at onset: (42.2±14.8) years vs. (49.5±15.3) years, P < 0.05]. The patients with anti-SSB positive more frequently presented with rash (29.5% vs. 14.3%, P < 0.05), enlargement of parotid glands (27.3% vs. 8.2%, P < 0.05), renal tubular acidosis (15.9% vs. 4.2%, P < 0.05), immune thrombocytopenia (9.1% vs. 1.0%, P < 0.05), rheumatoid factor (RF) positive (85.0% vs. 49.4%, P < 0.05), higher RF and antinuclear antibody (ANA) titers (median: 89.8 IU/mL vs. 20.5 IU/mL; median: 320 vs. 160, P < 0.05), anti-Sjögren's syndrome type A (SSA) antibody positive (97.7% vs. 64.3%, P < 0.05), elevation of γ globulin (71.4% vs. 38.5%, P < 0.05), higher levels of IgG (median: 21.0 g/L vs. 15.6 g/L, P < 0.05), higher proportions of CD3-CD19+ cells [(21.0±11.9)% vs. (13.7±9.6)%, P < 0.05] and lower proportions of CD3+ cells [(67.2±14.4)% vs. (76.6%±13.1)%, P < 0.05] than those negative. However, the anti-SSB positive group was less likely to show anti-mitochondrial antibodies (AMA)-M2 positivity (10.5% vs. 35.6%, P < 0.05). Glucocorticoids (90.9% vs. 73.5%, P < 0.05) and immunosuppressants (54.5% vs. 36.7%, P < 0.05) were more frequently used in anti-SSB positive pSS patients than those negative.@*CONCLUSION@#The anti-SSB positive pSS patients were younger at disease onset while more frequently presenting with various symptoms, higher levels of other antibodies and activation of B cells than those negative. Glucocorticoids and immunosuppressants were more frequently used, indicating that anti-SSB positive group presented with a more severe clinal phenotype.

Medical visit status and clinical features in patients with IgG4 related disease / 北京大学学报(医学版)

OBJECTIVE@#To understand the medical treatment and clinical characteristics of patients with IgG4-related disease (IgG4-RD) with complex clinical manifestations and easy to be misdiagnosed and missed, and to improve the recognition of this disease among doctors from relevant medical departments.@*METHODS@#A retrospective analysis was conducted on the medical records of patients diagnosed with IgG4-RD who were hospitalized and discharged from Peking University Third Hospital from January 1, 2012 to December 31, 2022. The patient' s medical visit status, clinical manifestations, laboratory examinations, diagnosis, and treatment information were summarized.@*RESULTS@#A total of 116 patients diagnosed with IgG4-RD were included in this study, with a male to female ratio of 2. 52∶ 1 and an average age of (61.83±10.80) years. The departments for initial visits were gastroenterology, general surgery, and ophthalmology. While the departments responsible for definitive diagnosis were gastroenterology, rheumatology and immunology, and respiratory medicine. Twenty-one patients (18. 10%) required consultation and treatment from three or more departments before receiving a definitive diagnosis. The median time from symptom onset to the initial clinic visit was 2 (1, 7) months, and the median time from symptom onset to diagnosis was 1 (1, 12) month. Twenty-four patients (20.69%) underwent surgical resection of the affected sites before diagnosis. According to the classification criteria of IgG4-RD, sixty-eight (58.62%) cases were diagnosed definitively, eight (6.9%) cases were likely to be diagnosed, and 40 (34.48%) cases were suspected to be diagnosed. In the 68 definitively diagnosed patients, the most commonly affected organs were submandibular gland, the pancreas, biliary tract, parotid in sequence. The median serum IgG4 (IgG4, immunoglobulin G4) level was 6.16 (3. 61, 12. 30) g/L. Fifty-seven patients (83.82%) were treated with glucocorticoids, and 14 patients (20.59%) were treated with immunosuppressants. The use of immunosuppressants was mainly in the rheumatology and immunology department (78. 57%).@*CONCLUSION@#IgG4-RD is more common in elderly males, with submandibular gland, the pancreas, biliary tract, and parotid being most commonly affected. The distribution of initial visit departments in patients is wide. The proportion of definitive diagnosis based on pathology is relatively low. In terms of treatment, the main approach is steroid treatment, while the use of immunosuppres-sants is not widespread.

Mechanism of HES1 regulating herceptin resistance in gastric cancer cells by ferroptosis / 药学学报

Drug resistance of cancer cells is the main causes of chemotherapy failure, and gene mutation or function loss is key factor to induce drug resistance. Previous studies have shown that hairy and enhancer of split 1 (HES1) is up-regulated in herceptin-resistant gastric cancer cells, and inhibition of its activity can reverse its resistance while the potential mechanism has not yet been elucidated. In this study, we employed CRISPR/Cas9 to establish HES1 knock-out cell line (△HES1/NCI N87R) to investigate the functions of HES1 in herceptin resistance of NCI N87R cells and its potential mechanisms. We investigated proteomics profiling of △HES1/NCI N87R cells based on quantitative proteomics. Gene ontology analysis was conducted by GeneSet Enrichment Analysis (GSEA) and Metascape database, and pathway enrichment analysis was done using GeneAnalytics database. The selected molecules were quantified by Western blot and some pathways were verified by using inhibitors. The results showed that the resistance to herceptin of △HES1/NCI N87R cells decreased compared to NCI N87R cells. Proteomic data demonstrated that the expression of 1 263 genes changed significantly in △HES1/NCI N87R cells, among which 761 genes were up-regulated while 502 ones down-regulated comparing with NCI N87R cells. Pathway analysis showed that ferroptosis, fatty acid β-oxidation, autophagy and glutathione metabolism, etc. exhibited notable changes in △HES1/NCI N87R cells. The functional studies showed that the levels of iron ion and malondialdehyde increased, and glutathione decreased in △HES1/NCI N87R cells. It was further found that Fer-1, a ferroptosis inhibitor, could reverse the expression of pTP53, solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) in △HES1/NCI N87R cell, and reduce the sensitivity of △HES1/NCI N87R cells to herceptin. It is suggested that HES1 regulated the resistance of NCI N87R cells to herceptin through TP53/SLC7A11/GPX4 signaling pathway, and targeting TP53/SLC7A11/GPX4 signal axis mediated by HES1 is a potential strategy to reverse herceptin resistance in gastric cancer.

Effect of high-intensity training on bone mineral density in basketball players / Efeito do treinamento de alta intensidade na densidade mineral óssea em jogadores de basquete / Efecto del entrenamiento de alta intensidad sobre la densidad mineral ósea en jugadores de baloncesto

ABSTRACT Introduction Increasing the bone mineral density of athletes can provide better basic physical conditions for basketball players, prevent fractures caused by osteopenia and reduce the occurrence of serious sports injuries. Objective Explore the effect of high-intensity training on bone mineral density in basketball players. Methods In this experiment, 30 subjects were divided into male and female groups, and high-intensity exercise training was performed for 60 minutes, three times a week, for eight weeks. The relevant indices were measured before and after training, and their data were classified and analyzed. Results High-intensity training can significantly improve the bone mineral density of basketball players, and the increase of bone mineral density of female basketball players is slightly lower than that of male players. In addition, the increase in bone mineral density can comprehensively improve athletes' muscular strength and physical fitness. Conclusion High-intensity training can improve basketball players' bone mineral density and sports skills, requiring promoting studies for its popularization in colleges and universities. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução Aumentar o nível de densidade mineral óssea dos atletas pode proporcionar melhores condições físicas básicas para jogadores de basquetebol, prevenir fraturas causadas pela osteopenia e reduzir a ocorrência de lesões esportivas graves. Objetivo Explorar o efeito do treinamento de alta intensidade na densidade mineral óssea de jogadores de basquetebol. Métodos Neste experimento, 30 indivíduos foram divididos em grupo masculino e feminino, o treinamento de exercícios de alta intensidade foi realizado por 60 minutos, três vezes por semana durante um total de 8 semanas. Os índices relevantes foram medidos antes e após o treinamento, seus dados foram classificados e analisados. Resultados O treinamento de alta intensidade pode melhorar significativamente a densidade mineral óssea dos jogadores de basquetebol, e o aumento da densidade mineral óssea das jogadoras de basquetebol feminino é ligeiramente menor do que o dos jogadores masculinos. Além disso, o aumento da densidade mineral óssea pode melhorar de forma abrangente a força muscular e a aptidão física dos atletas. Conclusão O treinamento de alta intensidade pode promover a melhoria da densidade mineral óssea e habilidades esportivas dos jogadores de basquetebol, necessitando de estudos promotores para sua popularização em Faculdades e Universidades. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción Aumentar el nivel de densidad mineral ósea de los deportistas puede proporcionar mejores condiciones físicas básicas a los jugadores de baloncesto, prevenir las fracturas causadas por la osteopenia y reducir la aparición de lesiones deportivas graves. Objetivo Explorar el efecto del entrenamiento de alta intensidad sobre la densidad mineral ósea en jugadores de baloncesto. Métodos En este experimento, 30 sujetos se dividieron en el grupo de hombres y mujeres, se realizó un entrenamiento de ejercicios de alta intensidad durante 60 minutos, tres veces por semana durante un total de 8 semanas. Se midieron los índices relevantes antes y después del entrenamiento, se clasificaron sus datos y se analizaron. Resultados El entrenamiento de alta intensidad puede mejorar significativamente la densidad mineral ósea de los jugadores de baloncesto, y el aumento de la densidad mineral ósea de las jugadoras de baloncesto es ligeramente inferior al de los jugadores. Además, el aumento de la densidad mineral ósea puede mejorar ampliamente la fuerza muscular y la forma física de los deportistas. Conclusión El entrenamiento de alta intensidad puede promover la mejora de la densidad mineral ósea y de las habilidades deportivas en los jugadores de baloncesto, siendo necesario promover estudios para su popularización en Colegios y Universidades. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

New discovery and short-term effect analysis of tensor tympani muscle tenotomy for Meniere's disease under otoscope / 中华耳鼻咽喉头颈外科杂志

Objective: To explore the feasibility and short-term effect of tensor tympani muscle Tenotomy in the treatment of Meniere's disease under otoscope. The possible pathogenesis was discussed and our views were put forward. Methods: The clinical data of 9 cases of Meniere's disease treated by otoscopic Tenotomy were analyzed retrospectively, including 2 males, 7 females, 5 right ones, 2 left ones and 2 bilateral ones. The average age was (56.33± 10.56) years, ranging from 38 to 75 years. We evaluated intraoperative findings and short-term postoperative efficacy, respectively evaluated postoperative aural fullness, tinnitus and hearing recovery, and evaluated postoperative vertigo attack in a short time. Results: Nine patients were completed the operation under general anaesthesia and otoscopy, and no serious complications occurred. We found new pathological changes in tympanic cavity in some cases during operation. There were rupture of round window membrane in 1 case, severe fibrous hyperplasia near the round window membrane and vestibular window and adhesion with ossicular chain in 1 case, fibrous cord and membranous hyperplasia near vestibular window and round window membrane in 1 case, fibrous hyperplasia and adhesion near the round window membrane in 2 cases, membranous hyperplasia and adhesion around vestibular window in 1 case. No fibrous hyperplasia was found in 3 cases in the tympanic cavity. The round window membrane can be exposed in 4 cases and failed in 5 cases. After 3 months of follow-up, we found that we found that 5/5 cases of aural fullness disappeared, 2/2 cases of earache disappeared, 3/8 cases of tinnitus improved, 5/8 cases presented with improvement and no aggravation, 3/3 cases of hearing allergy improved, 4/9 cases of hearing improved, and 5/9 cases showed no improvement or decrease. 9 patients were followed up for 3 months, of whom 8 patients had no vertigo, one patient suffered from vertigo twice within 3 months after operation, and the patient suffered from rupture of round window membrane. Conclusions: Endoscopic Tenotomy for Meniere's disease has obvious curative effect and quick recovery after operation. During the operation, we find that most of Meniere's patients have fibrous cord hyperplasia near the inner ear window membrane, which may be the pathological manifestation after repeated rupture and repair of the inner ear window membrane. The vertigo of Meniere's disease may be related to the destruction and repair of inner ear membrane structure caused by improper contraction or spasm of tympanic tensor muscle.

RUNX3 regulates trastuzumab resistance of gastric cancer cells: a metabolomic analysis based on UPLC-Q Exactive Focus Orbitrap mass spectrometry / 南方医科大学学报

OBJECTIVE@#To explore the role of Runt-related transcription factor 3 (RUNX3) in metabolic regulation of trastuzumab-resistant gastric cancer cells and investigate the mechanism of RUNX3 knockdown-mediated reversal of trastuzumab resistance.@*METHODS@#We performed a metabolomic analysis of trastuzumab-resistant gastric cancer cells (NCI N87R) and RUNX3 knockdown cells (NCI N87R/RUNX3) using ultra performance liquid chromatography (UPLC) coupled with Q Exactive Focus Orbitrap mass spectrometry (MS). Multivariate combined with univariate analyses and MS/MS ion spectrums were used to screen the differential variables. MetaboAnalyst 5.0 database was employed for pathway enrichment analysis. Differential metabolites-genes regulatory relationships were constructed based on OmicsNet database. The changes in GSH/GSSG and NADPH/NADP ratios in NCI N87R/RUNX3 cells were measured using detection kits.@*RESULTS@#The metabolic profile of NCI N87R cells was significantly altered after RUNX3 knockdown, with 81 differential metabolites identified to contribute significantly to the classification, among which 43 metabolites were increased and 38 were decreased (P < 0.01). In NCI N87R cells, RUNX3 knockdown resulted in noticeable alterations in 8 pathways involving glutamine metabolism, glycolysis, glycerophospholipid, nicotinate-nicotinamide and glutathione metabolism, causing also significant reduction of intracellular GSH/GSSG and NADPH/NADP ratios (P < 0.01). The differential metabolites-genes network revealed a regulatory relationship between the metabolic molecules and genes.@*CONCLUSION@#RUNX3 reverses trastuzumab resistance in gastric cancer cells by regulating energy metabolism and oxidation-reduction homeostasis and may serve as a potential therapeutic target for trastuzumab-resistant gastric cancer.

Differences in Protective Effect of Five Formulas for Promoting Blood Circulation and Removing Blood Stasis on Endothelial Cells of New Zealand Rabbits with Heart Blood Stasis Syndrome Through JNK Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the differences in the protective effects of five formulas for promoting blood circulation and removing blood stasis on the aortic endothelial cells of New Zealand rabbits with heart blood stasis syndrome. MethodEighty New Zealand rabbits were randomly divided into a normal group （n=10） and an experimental group （n=70）. The heart blood stasis syndrome model was induced by starvation combined with a high-fat diet and adrenaline in the rabbits of the experimental group. Subsequently， the model rabbits were randomly divided into a model group， a Xuefu Zhuyutang group （3.55 g·kg-1·d-1）， a Taohong Siwutang group （2.66 g·kg-1·d-1）， a Danshenyin group （1.962 g·kg-1·d-1）， a Huoluo Xiaolingdan group （2.80 g·kg-1·d-1）， a Shixiaosan group （0.56 g·kg-1·d-1）， and a c-Jun N-terminal kinase （JNK） inhibitor （SP600125， 5 μg·kg-1）group. The normal group and the model group received the same amount of distilled water. The rabbits in five Chinese medicine groups were treated correspondingly by gavage， and those in the SP600125 group were injected with 0.5 mL of SP600125-dimethyl sulfoxide diluent. After the treatment， the aorta was collected， and terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） assay was used to detect the apoptosis of aortic endothelial cells. The enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6）. Western blot was used to detect the protein expression of JNK， phosphorylated JNK （p-JNK）， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cysteinyl aspartate-specific protease-9 （Caspase-9）， and cysteinyl aspartate-specific protease-3 （Caspase-3） in aortic tissues. Real-time fluorescence-based quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA levels of JNK， Bcl-2， Bax， Caspase-9， and Caspase-3 in aortic tissues. ResultFive formulas could improve the apoptosis of aortic endothelial cells to varying degrees. To be specific， Xuefu Zhuyutang and Taohong Siwutang were optimal in efficacy， followed by Huoluo Xiaolingdan， Shixiaosan， and Danshenyin， and SP600125 was the worst （P<0.05， P<0.01）. Five formulas could reduce the content of TNF-α and IL-6 （P<0.05， P<0.01）， down-regulate the protein expression levels of JNK， p-JNK， Bax， Caspase-9， and Caspase-3 （P<0.05， P<0.01）， decrease the mRNA expression levels of JNK， Bax， Caspase-9， and Caspase-3 （P<0.05， P<0.01）， and up-regulate the protein and mRNA expression levels of Bcl-2 （P<0.05， P<0.01）. ConclusionFive formulas can all reduce the apoptosis of aortic endothelial cells in New Zealand rabbits with heart blood stasis syndrome with different efficacies. It may be related to the different effects of five formulas on the JNK signaling pathway.

Effect of Pien Tze Huang against EV71 / 中国中药杂志

This study aims to investigate the inhibitory effect of Pien Tze Huang(PZH) on enterovirus 71(EV71). To be speci-fic, chemiluminescence method was adopted to evaluate the toxicity of PZH to African green monkey kidney(Vero) cells and human rhabdomyosarcoma(RD) cells, and cytopathic effect(CPE) method to assess the inhibition on EV71-GFP reporter virus and EV71 C4 wild-type virus. The results showed that PZH had low cytotoxicity to Vero cells and RD cells, with the half-maximal cytotoxic concentration(CC_(50)) of about 0.691 3-0.879 2 mg·mL~(-1) for the two. In addition, PZH can effectively inhibit the replication of EV71 within the non-cytotoxic concentration range, and dose-dependently alleviate the cytopathic changes caused by virus infection, with the half-maximal effective concentration(EC_(50)) of 0.009 2-0.106 3 mg·mL~(-1). On the basis of the above results, the green fluorescent protein(GFP), indirect immunofluorescence assay(IFA), and median tissue culture infective dose(TCID_(50)) were employed to assess and verify the anti-EV71-GFP and anti-EV71 C4 activity of PZH. The results demonstrated that PZH can dose-dependently lower the expression of GFP by EV71-GFP and structural protein VP-1 by EV71 C4 and decrease the production of progeny infectious viruses. The EC_(50) of PZH for EV71-GFP and EV71 C4 was about 0.006 0-0.006 2 mg·mL~(-1) and 0.006 6-0.025 6 mg·mL~(-1), respectively. This study suggested that PZH may exert antiviral activity by acting on EV71 and interfering with the expression of VP-1. At the moment, there is still a lack of specific anti-EV71 drugs. This study proposed a new idea for the symptomatic treatment of EV71 infections such as hand-foot-mouth disease and verified an effective drug for the treatment of EV71 infections.

Effect of Jianpi Huogu Formula on function damage of vascular endothelial cells induced by glucocorticoid / 中国中药杂志

This study aimed to observe the intervention effect of Jianpi Huogu Formula(JPHGF) on the functional damage of vascular endothelial cells caused by glucocorticoid, and explore its action mechanism from the PI3 K/Akt and mitogen activated protein kinase(MAPK) signaling pathways. The extracted thoracic aorta ring of normal SD rats were intervened first with vascularendothelial growth factor(VEGF, 20 μg·L-1) and/or sodium succinate(MPS, 0. 04 g·L-1) in vitro and then with JPHGF(8, 16, and 32 μg·L-1) for five mcontinuous ethylpdays, rednisolofollowed nebythe statistics of the number, length, and area of microvessels budding fromvascular rings. In addition, the human umbilical vein endothelial cells(HUVECs) induced by VEGF(20 μg·L-1) were added with MPS(0. 04 g·L-1) and then with JPHGF(8, 16, and 32 μg·L-1) for observing the migration, invasion, and luminal formation abilities of HUVECs in the migration, invasion and luminal formation experiments. The protein expression levels of PI3 K, p-Akt, p-JN K, and p-ERK in HUVECs were assayed by Western blot. The results showed that JPHGF dose-dependently improved the num-ber,length, and area of microvessels in MPS-induced rat thoracic aortic ring, reversed the migration, invasion and lumen formation abiliti es of HUVECs reduced by MPS, and up-regulated the protein expression levels of PI3 K, p-Akt, and p-JNK in HUVECs. All thesehave suggested that JPHGF exerts the protective effect against hormone-induced damage to the angiogenesis of vascular endothelial cells by activating the PI3 K/Akt and MAPK signaling pathways, which has provided reference for exploring the mechanism of JPHGF in treating s teroid-induced avascular necrosis of femoral head(SANFH) and also the experimental evidence for enriching the scientific connotationof spleen-invigorating and blood-activating therapy.

Application of metagenomics in the diagnosis of ophthalmic diseases / 国际眼科杂志(Guoji Yanke Zazhi)

@#In recent years, metagenomics(MGS)is the fastest growing fields in microbiology, and has been broadly applied in the detection of pathogenic microorganisms. Comparing with the traditional poly merase chain reaction(PCR)-based detecting technology which relies on microbial culture, MGS can directly detect the sequences of the total microbial DNA from uncultured samples with the high-throughput sequencing platform. It can help the doctors identify the involved pathogens more quickly and provide better medication guidance. Among the known ophthalmic diseases, a lot of them are caused by the infection of pathogens and have many difficulties in clinical diagnosis and treatment. The development of metagenomics provides us a more effective and reliable way for detecting the pathogens of ophthalmic diseases. This article was aimed to review the development of MGS, applications and in the field of ophthalmology, as well as its current deficiencies and the possible development directions in the future.

Effects of Bilateral Arm Transcutaneous Electrical Acupoint Stimulation on Upper Limb Function for Subacute Stroke Hemiplegic Patients / 中国康复理论与实践

Objective:To explore the effects of bilateral arm transcutaneous electrical acupoint stimulation (TEAS) based on mirror therapy (MT) on upper limb function of subacute stroke hemiplegic patients. Methods:From September, 2017 to October, 2019, 48 subacute stroke hemiplegic patients were randomly divided into control group (n = 24) and experimental group (n = 24). All the patients accepted routine rehabilitation and MT, while the experimental group received bilateral arm TEAS and the control group received sham TEAS, for four weeks. They were assessed with Fugl-Meyer Assessment-Upper Extremity (FMA-UE), Action Research Arm Test (ARAT), Wolf Motor Function Test (WMFT) and modified Barthel Index (MBI) before and after treatment. Results:All the scores of FMA-UE, ARAT, WMFT and MBI improved in both groups after treatment (|t| > 11.870, P < 0.001), and improved more in the experimental group than in the control group (|t| > 2.678, P < 0.05). Conclusion:Bilateral arm TEAS based on MT can promote the upper limb function of subacute stroke hemiplegic patients.

Effect of Panlongqi Tablet on Cervical Spondylosis of Vertebral Artery Type in Rats / 中国实验方剂学杂志

Objective:To establish a model of cervical spondylosis of vertebral artery type （CSA） in rats by mixed modeling method， and observe the intervention effect of Panlongqi tablet （PLQT） on CSA rats. Method:SD rats were divided into a normal control group， a model group， low- （0.16 g·kg^-1）， medium- （0.32 g·kg^-1）， and high-dose （0.64 g·kg^-1） PLQT groups， and a Jingfukang granule （JFK， 1.35 g·kg^-1） group. The rats were treated correspondingly 24 hours after modeling for eight weeks， and those in the normal control group received an equal volume of normal saline by gavage. The limb movement was tested by the inclined plate assay， vertebral artery flow volume by multi-mode high-frequency sound wave for small animals， and microcirculatory blood flow in the pia mater by the laser Doppler. The imaging of the cervical spine was recorded and scored by X-ray micro-computed tomography （Micro CT）. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of endothelin-1 （ET-1）， nitric oxide （NO）， tissue plasminogen activator （t-PA）， and plasminogen activator inhibitor （PAI）. Result:Compared with the normal control group， the model group showed decreased limb movement， vertebral artery flow volume， and microcirculatory blood flow in the pia mater， and increased imaging of the cervical spine and score （<italic>P</italic><0.05，<italic>P</italic><0.01）. PLQT could dose-dependently improve the motor function， increase the vertebral artery flow volume and microcirculatory blood flow in the pia mater， and reduce the degree and score of imaging of the cervical spine in CSA rats（<italic>P</italic><0.05，<italic>P</italic><0.01）. The serum levels of NO and t-PA were decreased and those of ET-1 and PAI were increased in the model group as compared with those in the normal control group， while such changes were reversed by PLQT treatment（<italic>P</italic><0.05，<italic>P</italic><0.01）. Conclusion:PLQT can enhance the limb movement， promote the vertebral artery flow volume and microcirculatory blood flow in the pia mater， improve the degree of imaging of the cervical spine， regulate the vasomotor function， and improve the coagulation and fibrinolysis system of CSA rats， which shows good potential for the treatment of CSA.