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.

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.

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.

Intracerebral hemorrhage is a kind of nervous system disease with high mortality and disability. By analyzing the clinical variables closely associated with the functional outcome of intracerebral hemorrhage, a scoring scale that can quickly predict the outcome of intracerebral hemorrhage is established, which is helpful to guide clinicians in risk stratification and clinical diagnosis and treatment of patients with intracerebral hemorrhage. At present, more than 10 clinical outcome scoring scales have been developed. This article summarizes these scoring scales of intracerebral hemorrhage in chronological order, and reviews their constituent variables, outcome evaluation value, and follow-up verification.

Boao Lecheng International Medical Tourism Pilot Area is the only administrative area in China where the pilot application of real-world data is performed. Based on the special healthcare policy in Boao Lecheng, conducting real-world data study to provide real-world evidence for the clinical evaluations and approvals of innovated medical products has become an important field that supports the reform of China's evaluation and approval system of medical products. Trustworthy real-world evidence needs to rely on both high-quality real-world data and reasonable and rigorous study designs. Based on the real-world data research guidelines and specifications issued by relevant academic research and regulatory authorities both at home and abroad, combined with the special policy environment of Boao Lecheng and previous practice experience, this paper summarizes the study designs of real world data in Boao Lecheng and discusses the key considerations of different study design in the context of special healthcare policies in Boao Lecheng in order to provide reference for the further study of real-world data.

Objective To explore the efficacy of hematopoietic stem cell transplantation (HSCT) for 5 patients with Ph-like acute lymphoblastic leukemia (ALL).Methods Fluorescent in situ hybridization (FISH) was performed for detecting the rearrangement of susceptibility genes.Combined therapy of chemotherapy and ruxolitinib were applied,followed by HSCT.Those failing to achieve complete remission (CR) received an infusion of chimeric antigen T-cells (CAR-T),followed by HSCT once CR was achieved.Four patients accept allogenic HSCT while another auto HSCT.Results Three of them achieved CR after chemotherapy and ruxolitinib.The remaining 2 patients got CR after CAR-T.Four patients remained in CR after HSCT.Early relapse occurred in 1 patient after HSCT.Conclusions Combined therapy of chemotherapy,ruxolitinib and CAR-T are necessary for Phlike ALL patients.HSCT after an initial CR improve patient prognosis.

Objective To evaluate the clinical efficacy of arthroscopic treatment with anchor fixation for Segond fractures.Methods A total of 29 patients with Segond fractures treated with arthroscopic evaluation and anchor fixation technique between January 2011 and December 2015 were included in this retrospective case series study.There were 17 males and 12 females,with an average age of 41 years (range,27-62 years).Among the patients with Segond fractures,there were 20 patients combined with anterior cruciate ligament (ACL) rupture,three with posterior cruciate ligament (PCL) rupture,seven with medial collateral ligament (MCL) lesion,six with lateral collateral ligament (LCL) rupture,12 with meniscus lesion,and two with tibial plateau fracture.The time duration from injury to operation was 5-14 days (mean,7 days).The operation time and intraoperative blood loss volume were recorded.The postoperative pain,complications,knee joint stability,and fracture healing were observed.The pain was evaluated using numerical rating scale (NRS).Drawer test,Lachman test,lateral stress test,and Lysholm scores were performed to assess the knee function before and after operation.Results The operation time was 40-125 minutes (mean,85 minutes),and intraoperative blood loss was 10-30 ml (mean,15 ml).All patients were followed up for 12-18 months (mean,14 months).Two weeks after operation,the pain was not obvious,with NRS of 0-1.One patient had deep venous thrombosis one week after operation,and recovered after vascular intervention therapy.Other patients had no infection,deep vein thrombosis or other postoperative complications.The results of drawer test,Lachman test,and lateral stress test were negative in all patients,which indicated good knee joint stability.All patients were seen bone union,with the healing rate of 100％.The preoperative Lysholm scores were 35-62 points [(52.0 ± 4.2) points],and the scores one year after operation were 86-95 points [(91.9 ± 1.4) points] (P ＜ 0.05).Conclusion Arthroscopic treatment with anchor fixation has advantages of minor trauma,little hemorrhage,high fracture healing rate and good function recovery,and hence is an effective surgical treatment for Segond fractures.

Objective To investigate the status and analyze the influencing factors of structural empowerment and psychological empowerment of midwives in Suzhou.Methods Using convenience sampling,totally 309 midwives from fifteen hospitals in Suzhou were investigated with the Conditions of Work Effectiveness Questionnaire-Ⅱ (CWEQ-Ⅱ) and Psychological Empowerment Scale (PES).Results The scores of structural and psychological empowerment of midwives were (18.07±3.12) and (14.82±2.01).There was a significantly positive correlation between midwives' structural and psychological empowerment (r=0.396,P＜0.01).Hospital level and whether participate in midwifery standardization training had an impact on structural empowerment score(P＜0.05).Age,parental status,job title,salary,delivery room working hours,number of night shifts per month,and whether or not participate in teaching had an impact on psychological empowerment score(P＜0.05).Conclusion Midwives' structural and psychological empowerments are at a moderate level.Administrators should take targeted intervention to create an empowerment-allowing working environment for midwives,stabilize midwives work force,strengthen midwifery discipline construction and make full specialized features of midwives.

Objective To investigate the status and influencing factors of infusion-related adverse events in third-party cord blood stem cell infusion. Methods A total of 305 patients successfully underwent haploidentical stem cell transplantation combined with the third-party cord blood(CB) infusion,were recruited by convenience sampling from January 2013 to December 2015,in hematological department of a tertiary hospital in Suzhou. A self-developed questionnaire and adverse event assessment scale were used to investigate the influencing factors. Results The rate of infusion-related adverse events was 49.51%,81.82% were related to cardiovascular adverse events with the high-est rate of hypertension(76.14%). Logistic regression analysis showed that age(OR=1.030,95CI%:1.010-1.051),HLA matching between CB and receptor (OR=0.589,95%CI:0.413-0.838),thawed CB cell activity (OR=1.064,95%CI:1.015-1.115)were major influencing factors. Conclusion Nurses should pay attention to patients who are elderly,with low matching HLA and receive thawed CB product with high cell activities,and provide timely nursing care in advance.