Objective To discuss the application effect of using a stone extractor balloon catheter to assist in crossing the anastomotic stenosis in treatment of anastomotic biliary stenosis after liver transplantation using endoscopic retrograde cholangiopancreatography(ERCP).Methods Clinical data of 48 patients who developed anastomotic biliary stenosis after liver transplantation and underwent ERCP treatment were collected.Upon unsuccessful use of a dilation catheter to cross the stricture,attempts were made to cross the anastomotic biliary stenosis by using a stone extractor balloon catheter.The success rate of the procedure was recorded,intraoperative conditions were observed,treatment outcomes and complications were analyzed.Results The main presenting symptoms in the 48 patients on admission were abdominal discomfort(32 patients),fever(7 patients),pruritus(4 patients),jaundice(3 patients),and no obvious symptoms(2 patients).Preoperative magnetic resonance cholangiopancreatography(MRCP)examination revealed isolated stricture of the anastomotic site in 35 cases,and stricture associated with stones in 13 cases.Using the stone extractor balloon catheter as a guide,guidewire crossing of the anastomotic stenosis was successful in 26 cases,resulting in a success rate of 54.17%(26/48).Through statistical analysis of the successful group and the failed group,there was a significant difference in whether the distal biliary dilatation between the two groups,and the difference was statistically significant(χ2 = 8.39,P = 0.004).In the 26 successfully treated cases,alanine transaminase(ALT),aspartate transaminase(AST),γ-glutamyl transpeptidase(γ-GT),alkaline phosphatase(ALP),and total bilirubin(TBiL)levels decreased significantly 48 hours after the procedure(P<0.05),and no serious complications occurred.Conclusion The use of a stone extractor balloon catheter significantly increases the success rate of crossing anastomotic stenosis in the treatment of anastomotic biliary stenosis after liver transplantation,especially in cases with distal dilatation of the common bile duct.This approach is safe and worth promoting.

ObjectiveTo establish a managing mode for illegal and irregular acts of occupational medical examination (OME) institutions to the requirements of the new situation. Methods The OME institutions from the “Guangdong Province Key Occupational Disease Monitoring and Management Platform” were selected as the study subjects using the judgment sampling method. The clues of suspected illegal and irregular acts of OME institutions were found and submitted to the local health commission for investigation and managed according to the case information monitoring and on-site quality assessment. The OME institutions found to have illegal and irregular acts were filed and investigated according to the national law after investigation and verification. A “follow-up inspection” was conducted on five OME institutions for closed loop management. Results A total of 12 OME institutions were found to have suspected illegal and irregular acts, including seven institutions that did not meet the filing requirements for effective personnel, five institutions that conducted projects beyond the scope without filing to the provincial health authorities within 15 work days from the start of the project, and two institutions that failed to fulfill the obligation of informing and reporting to the health authorities, employers, and workers as required. After submitting relevant clues and evidence to the local health commission for investigation and management, seven institutions were not given penalty, and five institutions were given administrative penalties including two institutions were fined and warned, and three institutions were warned. No illegal or irregular acts were found in the five institutions inspected during the “follow-up inspection”. Conclusion It is beneficial to explore the managing mode of “clue discovery, clue submission, investigation and disposal, follow-up inspection” for OME institutions suspected of illegal and irregular acts, which helps urge OME institutions to work in accordance with laws and regulations and effectively protect the legitimate rights and interests of workers' occupational health.

Objective To analyze the problems found in the on-site quality assessment of occupational medical examination (OME) institutions in Guangdong Province. Methods A total of 150 OME institutions were selected as the research subjects from Guangdong Province in 2023 using a random number table method. The on-site quality assessment was conducted by listening to reports, meeting discussion, on-site inspection, data review and human-machine assessment. The relevant assessment results were analyzed. Results Occupational disease prevention and treatment institutes (institutes, centers) and disease control and prevention centers (hereinafter referred to as "occupational prevention institutions"), public hospitals, and private institutions accounted for 8.7%, 51.3%, and 40.0% respectively. The top three categories of registered inspections were physical factors, chemical factors and dust, accounted for 98.0%, 96.7% and 96.0%, respectively, among the 150 OME institutions. A total of 1 063 rectification items were identified, and the average number of rectification items identified per occupational prevention institutions, public hospitals and private institutions was four, six and nine, respectively. The rectification rates of the four modules of quality assessment from high to low were OME work quality control, quality management system, organizational structure, and OME information reporting, accounted for 53.2%, 23.3%, 13.7% and 9.7%, respectively. The coincidence rate from high to low of occupational reporting of noise-exposure, dust-exposure, and other hazard-exposure was 92.5%, 91.1%, and 93.4%, respectively. The on-site failure rate of quality control director, technical director, chief physician, pneumoconiosis film reader, audiometry reader and pulmonary function examination operator accounted for 15.3%, 12.7%, 8.0%, 6.7%, 6.0% and 2.7%, respectively. Institutions capable of conducting registered and partially registered OME accounted for 90.7% and 6.0%, respectively. The five institutions that were unable to conduct registered OME were private institutions. A total of five private institutions were found to be suspected of illegal and irregular activities. Conclusion The problems of OME in the on-site quality assessment of OME institutions in Guangdong Province were mainly quality control. Private institutions had more prominent problems in various aspects. It is necessary to strengthen the training of key personnel such as technical directors, quality control directors, and chief physicians.

Purpose: This study aims to evaluate the efficacy and safety of a new combination treatment of vinorelbine and pyrotinib in human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC) and provide higher level evidence for clinical practice. Materials and Methods: This was a prospective, single-arm, phase 2 trial conducted at three institutions in China. Patients with HER2-positive MBC, who had previously been treated with trastuzumab plus a taxane or trastuzumab plus pertuzumab combined with a chemotherapeutic agent, were enrolled between March 2020 and December 2021. All patients received pyrotinib 400 mg orally once daily plus vinorelbine 25 mg/m2 intravenously or 60-80 mg/m2 orally on day 1 and day 8 of 21-day cycle. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival, and safety. Results: A total of 39 patients were enrolled. All patients had been pretreated with trastuzumab and 23.1% (n=9) of them had accepted trastuzumab plus pertuzumab. The median follow-up time was 16.3 months (95% confidence interval [CI], 5.3 to 27.2), and the median PFS was 6.4 months (95% CI, 4.0 to 8.8). The ORR was 43.6% (95% CI, 27.8% to 60.4%) and the DCR was 84.6% (95% CI, 69.5% to 94.1%). The median PFS of patients with versus without prior pertuzumab treatment was 4.6 and 8.3 months (p=0.017). The most common grade 3/4 adverse events were diarrhea (28.2%), neutrophil count decreased (15.4%), white blood cell count decreased (7.7%), vomiting (5.1%), and anemia (2.6%). Conclusion Pyrotinib plus vinorelbine showed promising efficacy and tolerable toxicity as second-line treatment in patients with HER2-positive MBC.

Objective To evaluate the application efficacy of SpyGlass endoscopic direct visualization system in management of complex biliary complications after orthotopic liver transplantation. Methods Clinical data of 369 adult patients with biliary complications after orthotopic liver transplantation who received endoscopic retrograde cholangiopancreatography (ERCP) for the first time were retrospectively analyzed. Preoperative conditions, intraoperative manifestations, treatment outcomes and complications of patients treated with SpyGlass system were analyzed. Results Fifty-six patients were treated with SpyGlass system. The main preoperative symptoms included abdominal discomfort in 38 cases, fever in 8 cases, jaundice in 6 cases and skin itching in 4 cases. Ultrasound examination in 18 patients indicated common bile duct stenosis and significant intrahepatic bile duct dilatation. Preoperative magnetic resonance cholangiopancreatography (MRCP) of 56 patients revealed that 36 cases were diagnosed with common bile duct stenosis complicated with stones, 16 cases of common bile duct stenosis alone and 4 cases of suspected tumors. All patients had definite indications for SpyGlass system treatment. Among 56 patients treated with SpyGlass system, 34 cases were diagnosed with anastomotic stricture complicated with stones, 12 cases of anastomotic stricture alone, 1 case of biliary stone and 4 cases of tumors. Among 48 cases who were successfully treated, the levels of alanine aminotransferase, aspartate aminotransferase, γ-glutamyltransferase, alkaline phosphatase and total bilirubin at postoperative 48 h were all significantly lower than preoperative levels (all P<0.05). No severe complications occurred in 56 patients treated with SpyGlass system. Conclusions Use of SpyGlass system may significantly increase success rate and guarantee surgical safety in the treatment of complex biliary complications after liver transplantation, which is worthy of promotion and application.

Objective To explore the pathogenesis of steroid-induced osteonecrosis of the femoral head(SONFH)and the mechanism of Traditional Chinese Medicine(TCM)-based prescription for"Bringing Blood Downward"targeting SONFH through the OPG/RANKL/RANK signaling pathway.Methods Fifty male SD rats were randomly divided into model group and control group.The rats in the model group were treated with LPS and methylprednisolone to build a SONFH model.After 6 weeks,two rats were randomly selected respectively from the two groups,and the SONFH model was confirmed by histomorphological examination under light microscopy.The rats in a low,medium and high dose treatment groups(group L,M,and H)were intragastrically administrated with the Prescription for"Bringing Blood Downward"at concentrations of 2.5/5/10 g/kg.While the rats in the model group and control group were intragastrically administrated with normal saline at a concentration of 5 g/(kg·d).The pathological changes and expression levels of OPG,TRAF-6,and RANKL in each group were examined 4 weeks later.Results Compared with the model group,chondrocytes and cell matrix of groups L,M and H were less reduced,osteoclastic absorption and trabecular structure were less destroyed and the cells were less adipose.The adipocyte density in the control group and each treatment group was significantly lower than that in the model group(P<0.01).In the control group,the bone marrow cavity area was smaller than that in the model group(P<0.05),but there was no significant difference between each dose treatment groups and the model group(P>0.05).The expression levels of OPG,RANKL,TRAF-6 and OPG/RANKL ratio in the control group and groups L,M and H were significantly lower than those in the control group(P<0.01).Conclusion The TCM-based prescription for"Bringing Blood Downward"works to treat SONFH byregulating the activity of osteoclasts and osteogenic differen-tiation process of osteoblasts,improving the microcirculation environment of the femoral head,and inducing the formation of trabecular bone through the OPG/RANKL/RANK signaling pathway.It functions with its multitargetsin diverse methods.

Objective:To evaluate the clinical efficacy of PTCD and ERCP combined with T tube in the perioperative period of biliary anastomosis in patients with moderate to severe obstructive jaundice.Methods:The data of 93 patients with moderate obstructive jaundice who met the inclusion criteria and planned to undergo cholangiojejunostomy (including reconstruction after pancreaticoduodenectomy) in Shuguang Hospital Affiliated to Shanghai University of traditional Chinese medicine from March 2015 to December 2021 were collected. According to the perioperative drainage strategy, 54 cases were divided into PTCD group and 39 cases were divided into ERCP combined with intraoperative T-tube drainage group. Retrospective cohort method was used to analyze the bile duct diameter, postoperative hospital stay, operation cost, time of jaundice reduction, degree of jaundice reduction, average postoperative bile loss, postoperative bile leakage, abdominal infection of the two groups. The measurement data were expressed as mean ± standard deviation( ± s), and t test was used for comparison between groups. The data of skewed distribution were represented by M( Q1, Q3), and nonparametric rank sum test was used. Chi-square test was used for counting data. Results:The preoperative yellowing reduction time, operation cost, mean bile loss 7 days after operation, time to remove biliary drainage tube, and postoperative hospital stay in PTCD group were (5.9±3.1) d, (59 846.3±9 129.7) yuan, 210.0(170.0, 325.0) mL/d, (18.4±5.6) d, and(10.7±4.4) d, respectively, while those in ERCP group were (9.5±4.4) d, (77 833.1±12 164.5) yuan, 285.0(225.0, 370.0) mL/d, (41.4±17.2) d and(15.3±5.6) d, respectively. The difference between the two groups was statistically significant ( P<0.05). There was no significant difference between the two groups in general condition before drainage, cholangitis and hemorrhage after drainage, degree of jaundice reduction, bile leakage after surgery, abdominal infection, etc. Conclusions:When performing biliary enterostomy in patients with moderate or above obstructive jaundice, PTCD and ERCP combined with intraoperative T-tube drainage are effective means to improve the safety of perioperative period. PTCD has some advantages in reducing jaundice efficiency, operation cost and rapid postoperative rehabilitation.

BACKGROUND: Pulmonary microvascular endothelial cells (PMVECs) were not complex, and the endothelial barrier was destroyed in the pathogenesis progress of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Previous studies have demonstrated that hepatocyte growth factor (HGF), which was secreted by bone marrow mesenchymal stem cells, could decrease endothelial apoptosis. We investigated whether mTOR/STAT3 signaling acted in HGF protective effects against oxidative stress and mitochondria-dependent apoptosis in lipopolysaccharide (LPS)-induced endothelial barrier dysfunction and ALI mice. METHODS: In our current study, we introduced LPS-induced PMEVCs with HGF treatment. To investigate the effects of mammalian target of rapamycin (mTOR)/signal transducer and activator of transcription 3 (STAT3) pathway in endothelial oxidative stress and mitochondria-dependent apoptosis, mTOR inhibitor rapamycin and STAT3 inhibitor S3I-201 were, respectively, used to inhibit mTOR/STAT3 signaling. Moreover, lentivirus vector-mediated mTORC1 (Raptor) and mTORC2 (Rictor) gene knockdown modifications were introduced to evaluate mTORC1 and mTORC1 pathways. Calcium measurement, reactive oxygen species (ROS) production, mitochondrial membrane potential and protein, cell proliferation, apoptosis, and endothelial junction protein were detected to evaluate HGF effects. Moreover, we used the ALI mouse model to observe the mitochondria pathological changes with an electron microscope in vivo. RESULTS: Our study demonstrated that HGF protected the endothelium via the suppression of ROS production and intracellular calcium uptake, which lead to increased mitochondrial membrane potential (JC-1 and mitochondria tracker green detection) and specific proteins (complex I), raised anti-apoptosis Messenger Ribonucleic Acid level (B-cell lymphoma 2 and Bcl-xL), and increased endothelial junction proteins (VE-cadherin and occludin). Reversely, mTOR inhibitor rapamycin and STAT3 inhibitor S3I-201 could raise oxidative stress and mitochondria-dependent apoptosis even with HGF treatment in LPS-induced endothelial cells. Similarly, mTORC1 as well as mTORC2 have the same protective effects in mitochondria damage and apoptosis. In in vivo experiments of ALI mouse, HGF also increased mitochondria structural integrity via the mTOR/STAT3 pathway. CONCLUSION In all, these reveal that mTOR/STAT3 signaling mediates the HGF suppression effects to oxidative level, mitochondria-dependent apoptosis, and endothelial junction protein in ARDS, contributing to the pulmonary endothelial survival and barrier integrity.
Animals ; Apoptosis ; Calcium/metabolism* ; Endothelial Cells/metabolism* ; Endothelium/metabolism* ; Hepatocyte Growth Factor/metabolism* ; Lipopolysaccharides/pharmacology* ; Mammals/metabolism* ; Mechanistic Target of Rapamycin Complex 1/metabolism* ; Mechanistic Target of Rapamycin Complex 2/metabolism* ; Mice ; Mitochondria/metabolism* ; Oxidative Stress ; Reactive Oxygen Species/metabolism* ; Respiratory Distress Syndrome ; Sirolimus/pharmacology* ; TOR Serine-Threonine Kinases/metabolism*

Objective:To evaluate the cost effectiveness of primary prophylaxis (PP) with pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF), PP with recombinant human granulocyte colony stimulating factor (rhG-CSF) and no prophylaxis in women with early-stage breast cancer in China.Methods:Two phase Markov models were constructed for a hypothetical cohort of patients aged 45 with stage Ⅱ breast cancer. The first phase modelled costs and outcomes of 4 cycles docetaxel combined with cyclophosphamide [TC×4, febrile neutropenia (FN) risk>20%] chemotherapy, which assumptions based on literature reviews, including FN rates [base-case (deterministic sensitivity analysis range), 0.29 (0.24-0.35)] and related events [FN case-fatality, 3.4 (2.7-4.1)]. Second phase modelled the long term survival which was link with the relative dose intensity (RDI) [mortality hazard ratio ( HR) of RDI < 85% vs ≥85%, 1.45 (1.00-2.32)]. Clinical effectiveness, therapeutic costs, and economic utilities were estimated from peer-reviewed publications and expert opinions in case of unavailability of published evidences. Results:Compared to rhG-CSF PP and no prophylaxis, the cost of PEG-rhG-CSF PP increased to 5 208.19 RMB and 5 222.73 RMB, respectively. The quality-adjusted life-years (QALYs) enhanced to 0.066 and 0.297, respectively. Accordingly, the incremental cost effectiveness ratios (ICERs) are 79 146.3 RMB and 17 558.77 RMB per QALY, which were both below the willingness to pay (WTP) threshold of three times GDP per capita (18, 000 RMB) recommended by the WHO. Sensitivity analysis suggested that the more clinically effective the primary prophylaxis with PEG-rhG-CSF is, the more cost-effective primary prophylaxis with PEG-rhG-CSF will be. And the lower the mortality HR of RDI<85% vs ≥85% is, the more cost-effective primary prophylaxis with PEG-rhG-CSF will be. Conclusion:Although the cost of PP PEG-rhG-CSF is higher, considering the additional benefits, the administrating of PP PEG-rhG-CSF is likely to be a cost-effective alternative to PP rhG-CSF and no prophylaxis in patients with early stage breast cancer whose FN risks are more than 20% in China.

Objective:To evaluate the cost effectiveness of primary prophylaxis (PP) with pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF), PP with recombinant human granulocyte colony stimulating factor (rhG-CSF) and no prophylaxis in women with early-stage breast cancer in China.Methods:Two phase Markov models were constructed for a hypothetical cohort of patients aged 45 with stage Ⅱ breast cancer. The first phase modelled costs and outcomes of 4 cycles docetaxel combined with cyclophosphamide [TC×4, febrile neutropenia (FN) risk>20%] chemotherapy, which assumptions based on literature reviews, including FN rates [base-case (deterministic sensitivity analysis range), 0.29 (0.24-0.35)] and related events [FN case-fatality, 3.4 (2.7-4.1)]. Second phase modelled the long term survival which was link with the relative dose intensity (RDI) [mortality hazard ratio ( HR) of RDI < 85% vs ≥85%, 1.45 (1.00-2.32)]. Clinical effectiveness, therapeutic costs, and economic utilities were estimated from peer-reviewed publications and expert opinions in case of unavailability of published evidences. Results:Compared to rhG-CSF PP and no prophylaxis, the cost of PEG-rhG-CSF PP increased to 5 208.19 RMB and 5 222.73 RMB, respectively. The quality-adjusted life-years (QALYs) enhanced to 0.066 and 0.297, respectively. Accordingly, the incremental cost effectiveness ratios (ICERs) are 79 146.3 RMB and 17 558.77 RMB per QALY, which were both below the willingness to pay (WTP) threshold of three times GDP per capita (18, 000 RMB) recommended by the WHO. Sensitivity analysis suggested that the more clinically effective the primary prophylaxis with PEG-rhG-CSF is, the more cost-effective primary prophylaxis with PEG-rhG-CSF will be. And the lower the mortality HR of RDI<85% vs ≥85% is, the more cost-effective primary prophylaxis with PEG-rhG-CSF will be. Conclusion:Although the cost of PP PEG-rhG-CSF is higher, considering the additional benefits, the administrating of PP PEG-rhG-CSF is likely to be a cost-effective alternative to PP rhG-CSF and no prophylaxis in patients with early stage breast cancer whose FN risks are more than 20% in China.