Exosomes are ubiquitous in all types of body fluids, exhibiting a high degree of abundance and diversity. Given their distinctive structure and function, exosomes are involved in a range of life activities, including intercellular communication, material transport, and immune regulation. An increasing number of studies have identified exosomes as a source of diagnostic markers for diabetic retinopathy. Furthermore, exosomes represent a novel avenue for therapeutic intervention, with promising clinical applications. This paper examines the diagnostic and therapeutic mechanisms of exosomes in diabetic retinopathy, reviews the advancements in exosomes-based diagnostics and therapeutics for diabetic retinopathy, and aims to enhance the precision and efficiency of clinical diagnosis and treatment of diabetic retinopathy.

ObjectiveTo explore the effect of timosaponin BⅡ （TBⅡ） combined with icariin （ICA） on osteoclast （OC）-osteoblast （OB） coupling and decipher the mechanism from the cellular level. MethodsThe cell counting kit-8 （CCK-8） was used to assess the effects of different concentrations of TBⅡ and different concentrations of TBⅡ+ICA on the growth of RAW264.7 cells. Soluble receptor activator of nuclear factor-κB ligand （sRANKL） was used to induce the differentiation of RAW264.7 pre-osteoclasts into osteoclasts. The cells were allocated into sRANKL， TBⅡ （1， 5， 10 μmol·L^-1）， and TBⅡ+ICA groups. Tartrate-resistant acid phosphatase staining was performed to assess the effects of TBⅡ and TBⅡ+ICA on osteoclast differentiation. Real-time quantitative polymerase chain reaction （Real-time PCR） was conducted to examine the effects of TBⅡ+ICA on the expression of key genes involved in osteoclast differentiation and osteoclast-derived coupling factors. The osteogenic differentiation conditioned medium mixed with osteoclast supernatant was used to induce osteogenic differentiation of MC3T3-E1 cells. Alkaline phosphatase staining and alizarin red S staining were employed to determine the effect of TBⅡ+ICA on osteogenic differentiation. Real-time PCR was employed to evaluate the effects of conditioned medium on key genes involved in osteogenic differentiation. ResultsTBⅡ at 1， 5， 10 μmol·L^-1 had no significant effect on the cell survival rate. Compared with the sRANKL group， TBⅡ inhibited osteoclast differentiation in a dose-dependent manner and achieved the best effect at 10 μmol·L^-1 （P<0.01）. Compared with the sRANKL group， different concentrations of TBⅡ down-regulated the mRNA levels of osteoclast differentiation-related genes c-Fos， RANK， and RANKL （P<0.05）. None of 10 μmol·L^-1 TBⅡ， 10 μmol·L^-1 TBⅡ+10^-4 μmol·L^-1 ICA， or 10 μmol·L^-1 TBⅡ+10^-3 μmol·L^-1 ICA affected the viability of RAW264.7 cells. TBⅡ and/or ICA inhibited osteoclast differentiation （P<0.01）， and TBⅡ + ICA had the best effect （P<0.01）. Compared with the sRANKL group， TBⅡ and/or ICA down-regulated the mRNA levels of c-Fos， RANK， and RANKL （P<0.05）. The single application of TBⅡ and ICA had no significant effect on the mRNA levels of Wnt10b， Cthrc1， and C3a， while TBⅡ+ICA exerted up-regulating effects （P<0.05）. Compared with those in the blank group， the bone differentiation and mineralization abilities of the normal osteogenic induction group and each osteogenic induction + osteoclast supernatant group were improved （P<0.01）. Compared with the blank group， the normal osteogenic induction group and the osteogenic induction + osteoclast supernatant group showed up-regulated mRNA levels of Runx2 and OCN （P<0.01）. ConclusionTBⅡ+ICA can inhibit osteoclast differentiation， maintain the normal osteoclast-osteoblast coupling， and promote osteogenic differentiation.

Background::Long non-coding RNAs (lncRNAs) plays an important role in the progression of gastric cancer (GC). Their involvement ranges from genetic regulation to cancer progression. However, the mechanistic roles of RP11-789C1.1 in GC are not fully understood.Methods::We identified the expression of lncRNA RP11-789C1.1 in GC tissues and cell lines by real-time fluorescent quantitative polymerase chain reaction. A series of functional experiments revealed the effect of RP11-789C1.1 on the proliferation of GC cells. In vivo experiments verified the effect of RP11-789C1.1 on the biological behavior of a GC cell line. RNA pull-down unveiled RP11-789C1.1 interacting proteins. Western blot analysis indicated the downstream pathway changes of RP11-789C1.1, and an oxaliplatin dosing experiment disclosed the influence of RP11-789C1.1 on the drug sensitivity of oxaliplatin. Results::Our results demonstrated that RP11-789C1.1 inhibited the proliferation of GC cells and promoted the apoptosis of GC cells. Mechanistically, RP11-789C1.1 inhibited checkpoint kinase 1 (CHK1) phosphorylation by binding ataxiatelangiectasia mutated and Rad3 related (ATR), a serine/threonine-specific protein kinase, promoted GC apoptosis, and mediated oxaliplatin sensitivity.Conclusion::In general, we discovered a tumor suppressor molecule RP11-789C1.1 and confirmed its mechanism of action, providing a theoretical basis for targeted GC therapy.

Objective:To investigate the impact of short-term exposure to atmospheric pollutants on the number of acute stroke daily admissions in Taiyuan, China.Methods:The case data of patients with stroke from three large hospitals in different regions of Taiyuan, Shanxi Province from January 1, 2018 to December 31, 2019 were collected. The daily average concentrations of atmospheric pollutants and meteorological data in Taiyuan during the same period were collected. Spearman rank correlation was used to analyze the correlation between meteorological factors and atmospheric pollutants, and a generalized additive model (GAM) based on time series research and analysis was used to investigate the impact and lag effect of air pollutants on the number of stroke daily admissions. Stratified analysis was performed based on different genders and ages (≤64 years, 65-74 years, and ≥75 years).Results:Between 2018 and 2019, a total of 4 921 patients with acute stroke were collected from three large hospitals, with a daily average of 6.74 stroke admissions. Among them, 4 310 patients (87.6%) had ischemic stroke, 521 (10.6%) had cerebral hemorrhage, and 90 (1.8%) had subarachnoid hemorrhage. GAM analysis showed that there was a significant correlation between short-term exposure to PM 2.5, PM 10, and SO 2 and the number of stroke daily admissions. All three had a significant impact on the number of stroke daily admissions on the day of onset and 3 days later. The maximum effect value was reached on the day of onset, and when the average concentrations of PM 2.5, PM 10, and SO 2 increase by 10 μg/m 3, the number of stroke daily admissions increased by 1.48% (95% confidence interval [ CI] 0.46%-2.53%), 0.80% (95% CI 0.25%-1.36%), and 2.80% (95% CI 0.76%-4.88%), respectively. Stratified analysis showed that exposure to PM 2.5, PM 10, SO 2, and CO had a more significant impact on the number of stroke daily admissions in male patients, while only PM 10 showed positive results in females. Age stratified analysis showed that PM 2.5 significantly increased the number of stroke daily admissions in individuals aged ≥75 years. Conclusion:Short-term exposure to atmospheric pollutants (PM 2.5, PM 10, SO 2, and CO) will to some extent increase the number of stroke daily admissions among residents of Taiyuan, especially among males and those aged ≥75 years.

Objective:To explore the changing trajectory of psychological distress in young and middle-aged patients during peridialysis period.Methods:Totally 122 patients in the peridialysis period were investigated with the Self-Designed General Data Questionnaire,Distress Screening Scale(DSS),Connor-Davidson Resilience Scale(CD-RISC),Social Support Revalued Scale(SSRS)and Self-Perceived Burden Scale(SPBS)at the time of diag-nosis,initial dialysis,and dialysis for 1 month,2 months and 3 months,respectively.The growth mix model was used to identify trajectory categories.Results:The time main effect of scores of DSS,CD-RISC and SPBS in peridi-alysis patients was statistically significant(Ps＜0.05),the scores of DSS and SPBS were the highest at the initial dialysis and the lowest at 3 months of dialysis.The CD-RISC scores were the lowest at the first dialysis and the highest at 3 months of dialysis.The trajectory of psychological distress was divided into 3 types,namely continuous high level(26.20％),high level decline(40.72％),and medium-low level decline(33.08％).Conclusion:The psychological distress of young and middle-aged peridialysis patients shows different trajectories from diagnosis to regular dialysis.Clinical staff should pay more attention to the psychological status of the first-time dialysis pa-tients.

Objective:To analyze the survival and prognostic factors of male patients with breast cancer after mastectomy.Methods:Male patients with invasive breast ductal cancer who underwent mastectomy from January 1, 2000 to December 31, 2018 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Survival analysis was performed by Kaplan-Meier method, and compared by log-rank test. Prognostic factors were identified by Cox proportional hazards regression analysis.Results:A total of 1231 cases were included, with an onset age of (67 ± 12) years. The proportion of stage I-II was 81.1%. The 10-year cancer-specific survival (CSS) rates for stage IA, IIA, IIB, IIIA, IIIB, and IIIC patients were 85.4%, 84.9%, 69.0%, 68.1%, 51.9%, and 48.3%, respectively (all P<0.001). For stage IA-IIB patients, the 10-year CSS rate was 79.2% in the postoperative radiotherapy group, compared to 83.0% in the non-radiotherapy group ( P=0.019). For stage IIIA-IIIC patients, the 10-year CSS rate was 61.7% in the postoperative radiotherapy group, compared to 52.9% in the non-radiotherapy group ( P=0.021). For stage IA-IIB patients, the 10-year CSS rate was 83.8% in the postoperative chemotherapy group, compared to 79.8% in the non-chemotherapy group ( P=0.342). For stage IIIA-IIIC patients, the 10-year CSS rate was 59.7% in the postoperative chemotherapy group, compared to 54.1% in the non-chemotherapy group ( P=0.052). Multivariate analysis showed that younger age, married and grade I-II differentiation were favorable prognostic factors. The earlier the tumor staging, the better the prognosis. Conclusions:Postoperative radiotherapy can improve the CSS of stage III male patients with breast cancer. Younger age, married, grade I-II differentiation are favorable prognostic factors. The earlier the tumor staging, the better the prognosis.

Objective To analyze the core genes of lung ischemia-reperfusion injury and construct a competitive endogenous RNA (ceRNA) network. Methods Original data of GSE145989 were downloaded from the Gene Expression Omnibus (GEO) database as the training set, and the GSE172222 and GSE9634 datasets were used as the validation sets, and the differentially-expressed genes (DEG) were identified. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed. Protein-protein interaction (PPI) network was constructed, and the core genes were screened, and the diagnostic values of these core genes and the immune infiltration levels of immune cells were evaluated. The ceRNA network was constructed and validated. The targeted drugs based on ceRNA network were assessed. Results A total of 179 DEG were identified, including 61 down-regulated and 118 up-regulated genes. GO analysis showed that DEGs were associated with multiple biological processes, such as cell migration, differentiation and regulation, etc. They were correlated with cell components, such as vesicle membrane, serosa and membrane raft, etc. They were also associated with multiple molecular functions, such as chemokine receptor, G protein-coupled receptor, immune receptor activity and antigen binding, etc. KEGG pathway enrichment analysis revealed that DEG were involved in tumor necrosis factor (TNF), Wnt, interleukin (IL)-17 and nuclear factor (NF)-κB signaling pathways, etc. PPI network suggested that CD8A, IL2RG, STAT1, CD3G and SYK were the core genes of lung ischemia-reperfusion injury. The ceRNA network prompted that miR-146a-3p, miR-28-5p and miR-593-3p were related to the expression level of CD3G. The miR-149-3p, miR-342-5p, miR-873-5p and miR-491-5p were correlated with the expression level of IL-2RG. The miR-194-3p, miR-512-3p, miR-377-3p and miR-590-3p were associated with the expression level of SYK. The miR-590-3p and miR-875-3p were related to the expression level of CD8A. The miR-143-5p, miR-1231, miR-590-3p and miR-875-3p were associated with the expression level of STAT1. There were 13 targeted drugs for CD3G, 4 targeted drugs for IL-2RG, 28 targeted drugs for SYK and 3 targeted drugs for lncRNA MUC2. No targeted drugs were identified for CD8A, STAT1 and other ceRNA network genes. Conclusions CD8A, IL2RG, STAT1, CD3G and SYK are the core genes of lung ischemia-reperfusion injury. The research and analysis of these core genes probably contribute to the diagnosis of lung ischemia-reperfusion injury and providing novel research ideas and therapeutic targets.

[摘 要] 目的：探讨四个半LIM结构域2（FHL2）蛋白对胶质瘤细胞增殖的影响及其分子机制。方法：利用TCGA和CGGA数据库分析胶质瘤组织中FHL2 mRNA表达水平与患者预后的关系。通过WB法检测人胶质瘤组织标本及人胶质瘤细胞U87、T98G、U251、SNB19、GSC23、A172、LN229、G267和星形胶质细胞NHA中的FHL2蛋白表达水平。利用慢病毒载体构建稳定敲低FHL2的U87细胞和过表达FHL2的SNB19细胞，即U87-shGFP、U87-shFHL2-1#、U87-shFHL2-4#和SNB19-3flag、SNB19-3flag-FHL2组。通过CCK-8法、克隆形成实验检测敲低和过表达FHL2对细胞增殖的影响，免疫共沉淀（Co-IP）和液相色谱-串联质谱（LC/MS）法筛选FHL2在胶质瘤细胞中的相互作用蛋白，并用Co-IP和免疫荧光法验证它们的结合作用和共定位情况。使用酶标仪检测敲低和过表达FHL2细胞内乳酸产量和乳酸脱氢酶（LDH）活性的变化，WB法分析FHL2、LDHA及p-LDHA在正常脑组织和胶质瘤组织中的蛋白表达差异及其相互关系。在过表达 FHL2的SNB19细胞中使用LDHA的小分子抑制剂AT-101，通过CCK-8实验和酶标仪比色法验证FHL2在胶质瘤乳酸代谢中的作用，验证AT-101在胶质瘤中潜在的治疗效果。结果：Co-IP和LC/MS检测发现，FHL2与LDHA在胶质瘤细胞中存在相互作用。FHL2过表达可提高LDHA活性和乳酸生成（均P < 0.001），进而促进胶质瘤细胞增殖（P < 0.001）。相反，敲低FHL2会降低LDHA活性和乳酸产量（P < 0.001或P < 0.05）并抑制细胞增殖（P < 0.001）。AT101能抑制LDHA活性，并显著抑制FHL2促进胶质瘤细胞的增殖，同时恢复磷酸化LDHA（Y10）水平（P<0.01或P < 0.001）。结论：FHL2与LDHA蛋白相互作用，FHL2通过激活p-LDHA（Y10）的表达促进LDHA活性和乳酸产生，进而促进胶质瘤细胞的增殖，靶向这种相互作用可能成为治疗胶质瘤的潜在策略。

ObjectiveTo observe the efficacy and safety of Uyghur medicine Yangxin Dawayimixike Honey Paste （养心达瓦依米西克蜜膏， YDMHP） in the treatment of stable angina pectoris （SAP） of qi stagnation and blood stasis syndrome. MethodsA randomized ， double-blind， positive-controlled，multi-center clinical trial was conducted， in which 370 patients with SAP of qi stagnation and blood stasis syndrome were randomly divided into treatment group（279 cases）and control group（91cases）at a ratio of 3∶1. The treatment group was orally administered with YDMHP， 3 g each time， and placebo of Xuefu Zhuyu Capsule （血府逐瘀胶囊）， 2.4 g each time， while the control group was treated with Xuefu Zhuyu Capsule， 2.4 g each time， and placebo of YDMHP， 3 g each time， both twice a day for a course of 12 weeks. The primary outcome was the effect of angina pectoris symptom. The secondary outcomes include single angina symptom scores such as number of attacks， duration of attacks， pain intensity and usae of nitroglycerin scores， the total angina symptom score before and after the treatment， the usage of nitroglycerin， the exercise duration in treadmill exercise test （TET） and the Duck treadmill score among patients，the scores of Seattle Angina Questionnaire （SAQ） on five dimensions including physical limitations， anginal stability， anginal frequency， treatment satisfaction， and disease perception， and efficacy of TCM syndrome and of each single TCM symptom after treatment. The safety were evaluated by examine blood routine， urine routine， liver and kidney function， fasting blood sugar， electrocardiogram， adverse events. ResultsThe total effective rate of angina symptom in the treatment group was 71.69% （200/279）， significantly higher than 51.64% （47/91） in the control group （P＜0.01）. The curative and markedly effective rate of TCM syndrome in the treatment group was 53.05% （148/279）， which was significantly higher than 25.27% （23/91） in the control group （P＜0.01）. After treatment， scores of the number as well as duration of angina attacks and pain severity， the total score of angina symptoms， and the usage of nitroglycerin significantly decreased in both groups， and more changes were seen in the treatment group than in the control group； the scores of physical limitations， anginal stability， anginal frequency， treatment satisfaction， and disease perception in both groups significantly increased， and more improvement were shown in the experimental group regarding the anginal stability， anginal frequency and treatment satisfaction （P＜0.05 or P＜0.01）. The effects of chest pain， chest tightness， palpitation， shortness of breath and fatigue in experimental group were significantly higher than those in control group （P＜0.05 or P＜0.01）. There was no significant difference in the exercise duration of treadmill test and Duke score among patients between the two groups either before or after treatment （P＞0.05）. Adverse events occurred in 66 cases （23.66%） of the experimental group and 16 cases （17.58%） of the control group， with no statistical significance between the two groups （P＞0.05）. ConclusionThe Uyghur medicine YDMHP can effectively improve symptoms of angina pectoris， reduce the number， duration， and intensity of attacks， decrease the dosage of nitrogly-cerin and improve the individual TCM symptoms and has good safety in the treatment of SAP patients of qi stagnation and blood stasis.

After kidney transplantation,the recipients have been under long-term immunosuppression due to the use of immunosuppressive drugs,and they are high-risk population of Pneumocystis jirovecii pneumonia(PJP).The risk of PJP is the highest within 6 months after kidney transplantation and after intensified anti-rejection therapy.Fever,dry cough,progressive dyspnea and hypoxemia are common clinical manifestations of PJP after kidney transplantation.Trimethoprim-sulfamethoxazole(TMP-SMX)can effectively prevent and treat PJP,and significantly reduce the incidence rate and fatality of PJP.To standardize the diagnosis,treatment and prevention of PJP after kidney transplantation,Branch of Organ Transplantation of Chinese Medical Association organized relevant Chinese experts to formulate the"Guidelines for Clinical Diagnosis and Treatment of Pneumocystis Jirovecii Pneumonia After Kidney Transplantation in China"based on clinical concerns,aiming to provide guidance for the prevention and comprehensive clinical treatment of PJP after kidney transplantation.