BACKGROUND:Studies have shown that vision recovery with thinner grafts is faster and the risk of rejection is lower.In China,there is a lack of clinical efficacy analysis of different graftthicknesses after endothelial transplantation.Therefore,determining the optimal graftthickness is crucial for improving surgical efficacy. OBJECTIVE:To evaluate the effects of different graftthickness on vision recovery and other prognostic indexes after simple Descemet's stripping endothelial keratoplasty. METHODS:A total of 72 patients(72 eyes)with corneal endothelial decompensation who received simple Descemet's stripping endothelial keratoplasty at the General Hospital of Northern Theater Command from January 2013 to February 2023 were selected.There were 32 cases(32 eyes)in the thin graftgroup(＜100 μm)and 40 cases(40 eyes)in the thick graftgroup(≥100 μm).The best corrected visual acuity,corneal endothelial cell count,corneal graft transparency,postoperative complications and graftsurvival were observed in both groups before and 1,3,6,and 12 months after surgery. RESULTS AND CONCLUSION:The visual acuity after surgery was significantly improved in both groups,and the best corrected visual acuity 3 months after surgery in the thin graftgroup was better than that in the thick graftgroup(P＜0.05).There was no significant difference in the number of corneal endothelial cells and grafttransparency between the two groups 1 year after surgery(P＞0.05).There was no significant difference in the incidence of postoperative complications such as secondary glaucoma,graftimmune rejection and graftdisplacement between the two groups(P＞0.05).There was no significant difference in the 1-year survival rate of grafts between the two groups(93.8%vs.92.3%,P＞0.05).To conclude,simple Descemet's stripping endothelial keratoplasty is a safe and effective surgical method for corneal endothelial transplantation,and its postoperative efficacy is similar to that of traditional Descemet's stripping endothelial keratoplasty,and the graftimplantation method is simpler.Thinner grafts can provide optimal corrected vision earlier and complete corneal remodeling sooner.Therefore,in the treatment of corneal endothelial decompensation,thinner grafts are preferred to improve recovery time.

Ferroptosis is a new programmed cell death dependent on iron ions.Ferroptosis can be induced by endogenous or exogenous pathways,and cells exhibit specific cell morphological signs and are regulated by a variety of molecular mechanisms.In recent years,more and more studies have shown that ferroptosis plays an important role in the treatment of cancer.This article summarizes the mechanism of ferroptosis in bladder cancer and the regulation of cancer cells,as well as the role of ferroptosis-related factors,non-coding RNA regulation,N6-methyladenosine(m6A),amino acid metabolism and autophagy dependent ferroptosis in the growth and proliferation of bladder cancer,with a view to provide new strategies for the treatment of bladder cancer.

Objective:To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues.Methods:From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed.Results:This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI: 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI: 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI: 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI: 6.6-11.2 months), and their mOS was 15.5 months (95% CI: 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI: 3.4-5.1 months), and their mOS was 9.3 months (95% CI: 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage ( HR=1.47, 95% CI: 1.06-2.04), primary tumor site ( HR=0.64, 95% CI: 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ( HR=2.66, 95% CI: 1.53-4.65), and whether to combine radiotherapy ( HR=0.65, 95% CI: 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site ( HR=0.68, 95% CI: 0.48-0.95), ECOG score ( HR=5.82, 95% CI: 3.14-10.82), and whether to combine radiotherapy ( HR=0.58, 95% CI: 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death ( P＜0.05). Conclusion:Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.

Objective:To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues.Methods:From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed.Results:This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI: 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI: 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI: 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI: 6.6-11.2 months), and their mOS was 15.5 months (95% CI: 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI: 3.4-5.1 months), and their mOS was 9.3 months (95% CI: 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage ( HR=1.47, 95% CI: 1.06-2.04), primary tumor site ( HR=0.64, 95% CI: 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ( HR=2.66, 95% CI: 1.53-4.65), and whether to combine radiotherapy ( HR=0.65, 95% CI: 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site ( HR=0.68, 95% CI: 0.48-0.95), ECOG score ( HR=5.82, 95% CI: 3.14-10.82), and whether to combine radiotherapy ( HR=0.58, 95% CI: 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death ( P＜0.05). Conclusion:Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.

Inflammation-driven endothelial dysfunction is the major initiating factor in atherosclerosis, while the underlying mechanism remains elusive. Here, we report that the non-canonical stimulator of interferon genes (STING)-PKR-like ER kinase (PERK) pathway was significantly activated in both human and mice atherosclerotic arteries. Typically, STING activation leads to the activation of interferon regulatory factor 3 (IRF3) and nuclear factor-kappa B (NF-κB)/p65, thereby facilitating IFN signals and inflammation. In contrast, our study reveals the activated non-canonical STING-PERK pathway increases scaffold protein bromodomain protein 4 (BRD4) expression, which encourages the formation of super-enhancers on the proximal promoter regions of the proinflammatory cytokines, thereby enabling the transactivation of these cytokines by integrating activated IRF3 and NF-κB via a condensation process. Endothelium-specific STING and BRD4 deficiency significantly decreased the plaque area and inflammation. Mechanistically, this pathway is triggered by leaked mitochondrial DNA (mtDNA) via mitochondrial permeability transition pore (mPTP), formed by voltage-dependent anion channel 1 (VDAC1) oligomer interaction with oxidized mtDNA upon cholesterol oxidation stimulation. Especially, compared to macrophages, endothelial STING activation plays a more pronounced role in atherosclerosis. We propose a non-canonical STING-PERK pathway-dependent epigenetic paradigm in atherosclerosis that integrates IRF3, NF-κB and BRD4 in inflammatory responses, which provides emerging therapeutic modalities for vascular endothelial dysfunction.

Purpose To explore the application value of ultrasound-guided thyroid fine needle aspiration liquid-based thin layer cytopathology combined with p21 and Cyclin D1 detection in preoperative diagnosis of papillary thyroid carcinoma.Meth-ods Immunocytochemical staining was used to detect the ex-pression differences of p21 and Cyclin D1 between benign and malignant thyroid nodules,and their correlations the clinicopath-ological features.The diagnostic efficacy of US-FNAB,p21,Cyclin D1 and the three combined detection in benign and malig-nant thyroid nodules was evaluated by constructing receiver oper-ating curve.Results The expression of p21 and Cyclin D1 was up-regulated in the papillary thyroid carcinoma group,86.36%(57/66)and 93.94%(62/66),and 1.96%(1/52)and 5.77%(3/52)in the benign nodule group,respectively;the difference between the two groups was significant(P<0.05).The positive rates of p21 and Cyclin D1 in BRAF V600E wild type PTC were 88.89%(8/9).The expression of p21 and Cyc-lin D1 was correlated with the tumor size of PTC(P<0.05),but not with gender,age,number of tumor foci,lymph node metastasis,and TNM stage(P>0.05).The sensitivity,speci-ficity,positive predictive value and negative predictive value of US-FNAB,p21 and Cyclin D1 combined detection were 95.45%,98.07%,98.43%and 94.44%,respectively,which were higher than those of US-FNAB independent detection,and the sensitivity and negative predictive value were higher than those of BRAF V600E.The area under ROC curve of US-FNAB,p21 and Cyclin D1 combined detection(AUC = 0.967 7)was larger than that of US-FNAB(AUC = 0.849 9)and the difference between the two was statistically significant(P<0.05).The area under ROC curve of the combined detection of the three was greater than that of independent detection of BRAF V600E(AUC =0.931 8),and the combined detection of US-FNAB with p21(AUC = 0.946 4)or Cyclin D1(AUC = 0.944 3).It was close to that of US-FNAB combined BRAF V600E detection(AUC = 0.971 2).Conclusion US-FNAB combined with p21 and Cyclin D1 immunohistochemical detec-tion can help improve the sensitivity of preoperative diagnosis of papillary thyroid carcinoma,and it has high diagnostic value for BRAF V600E wild-type papillary carcinoma.

Tripterygium glycosides tablet(TGT),the classical commercial drug of Tripterygium wilfordii Hook.F.has been effectively used in the treatment of rheumatoid arthritis,nephrotic syndrome,leprosy,Behcet's syndrome,leprosy reaction and autoimmune hepatitis.However,due to its narrow and limited treatment window,TGT-induced organ toxicity(among which liver injury accounts for about 40％of clinical reports)has gained increasing attention.The present study aimed to clarify the cellular and molecular events underlying TGT-induced acute liver injury using single-cell RNA sequencing(scRNA-seq)technology.The TGT-induced acute liver injury mouse model was constructed through short-term TGT exposure and further verified by hematoxylin-eosin staining and liver function-related serum indicators,including alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase and total bilirubin.Using the mouse model,we identified 15 specific subtypes of cells in the liver tissue,including endothelial cells,hepatocytes,cholangiocytes,and hepatic stellate cells.Further analysis indicated that TGT caused a significant inflammatory response in liver endothelial cells at different spatial locations;led to marked inflammatory response,apoptosis and fatty acid metabolism dysfunction in hepatocytes;activated he-patic stellate cells;brought about the activation,inflammation,and phagocytosis of liver capsular macrophages cells;resulted in immune dysfunction of liver lymphocytes;disturbed the intercellular crosstalk in liver microenvironment by regulating various signaling pathways.Thus,these findings elaborate the mechanism underlying TGT-induced acute liver injury,provide new insights into the safe and rational applications in the clinic,and complement the identification of new biomarkers and ther-apeutic targets for liver protection.

Objective:To provide clues for exploring the molecule mechanisms underlying ruptured intracranial aneurysms(IAs)by constructing a competitive endogenous RNA(ceRNA)network.Methods:Gene expression data sets of 21 ruptured IAs(RIAs)and 21 unruptured IAs samples were downloaded from the Gene Expression Omnibus(GEO)database.First, mRNAs and long non-coding RNAs(lncRNAs)related to ruptured IAs were identified by integrated analysis of weighted gene co-expression network analysis(WGCNA)and differential gene expression analysis with DESeq2, respectively.Then, mRNA-miRNA associations were obtained based on miRWalk 2.0; miRNA-lncRNA associations were predicted based on miRcode and data from the literature.Lastly, a ceRNA network including mRNAs, miRNAs, and lncRNAs was constructed via combining lncRNA-miRNA associations and lncRNA-miRNA associations.Results:A total of 470 mRNAs and 78 lncRNAs related to ruptured IAs were obtained through WGCNA and differential gene expression analysis.Based on the databases, 49 miRNAs were predicted to be able to bind to the above mRNAs and lncRNAs, and in combination with data from the literature, 13 miRNAs, 7 lncRNAs and 73 mRNAs were screened to construct a ceRNA network.Conclusions:A new ruptured IA-related ceRNA network including 13 miRNAs, 7 lncRNAs and 73 mRNAs has been constructed and may provide some clues for exploring the mechanisms underlying ruptured IAs.

Objective To investigate the distribution of chronic disease and geriatric syndrome in hospitalized elderly patients with multimorbidity by chronic disease investigation and comprehensive geriatric assessment.Methods A total of 176 patients aged ≥60 years admitted into the geriatric department in our hospital were selected,and demographic factors were collected.Their chronic diseases and geriatric syndrome were recorded.The comprehensive geriatric assessment was consummated,and the biochemical indicators for chronic disease and geriatric syndrome were detected.Results All patients suffered from two or more kinds of chronic diseases.The top three most common diseases were hypertension (112 cases),diabetes (94 cases),and respiratory diseases (73cases).The sum of chronic diseases kinds were ≥3 in 137 patients,≥4 in 78 patients,≥5 in 40 patients.The amount of chronic diseases showed an increased tendency along with ageing.Totally 175 patients had more than one geriatric syndrome,the top three most common types were frailty and prefrailty(133 cases),visual impairment (117 cases),impaired daily activities (107 cases).There were significant differences in the number of geriatric syndrome among different age groups(x2 =16.989,P ＜ 0.001).Spearman analysis showed that the number of patients with geriatric syndrome were positively correlated with age(r =0.307,P＜0.001).Conclusions The prevalence of chronic disease and geriatric syndrome is high in hospitalized elderly patients with multimorbidity,which is increased with aging.We should pay attention to the screening of chronic disease and geriatric syndrome in multimorbid elderly patients

OBJECTIVE： To provide references for improving the standard operating procedures of drug management in clinical trials and drug management in clinical trials. METHODS： According to Good Clinical Practice （GCP）， Data On-site Verification Points of Drugs Clinical Trial， Qualification Examination Rules of Drug Clinical Trial Institution， based on the quality control project carried out in our hospital since July 2016， the matters needing attention in the non-standard operation and key process of drug management in clinical trial were summarized， and the improvement measures were discussed. RESULTS & CONCLUSIONS： Non-standard drug management is a high-incidence link of non-standard operation in the trial process. Among them， the acceptance， distribution and use of drugs are the three links with the highest incidence of non-standard operation of drug management in the trial process. Therefore， when formulating the relevant management system， each institution should pay attention to it according to its own situation； such as， when accepting drugs in clinical trials， attention should be paid to checking the intact degree of drug packaging； drugs transported in cold chain should also be checked for temperature records and rejected in case of over-temperature； the copies of the waybill should be kept in file with the original to avoid fading of the thermosensitive paper； whether the relevant characteristics of the control drugs and placebos meet the requirements. Institutions can standardize the key links of drug management in the trial process， the time of project establishment， project start-up， quality control and supervision， formulate and constantly improve the relevant drug management system and standard operating procedures （SOP）. For example， when starting a project， attention should be paid to the participation of drug administrators in the training and signature of start-up meeting， whether the design of the form is complete， standardized and operable. It is necessary for clinical trial institutions to pay attention to the standardization and precision of drug management and the key links in clinical trials.