OBJECTIVE To assess the cost-effectiveness of durvalumab combined with chemotherapy as a first-line treatment for advanced biliary tract cancer from the perspective of the Chinese healthcare system. METHODS Using data from the TOPAZ-1 clinical trial， a three-state Markov model comprising progression-free survival （PFS）， progressive disease （PD） and death was developed， with a cycle length of 21 days and a 10-year time horizon. Patients in the observation group received durvalumab in combination with gemcitabine and cisplatin， whereas those in the control group received placebo plus the same chemotherapy regimen. The evaluation indexes were quality-adjusted life year （QALY） and the incremental cost-effectiveness ratio （ICER）. The willingness-to-pay （WTP） threshold was set at three times the 2024 Chinese per capita gross domestic product （GDP） （287 247 yuan/QALY）. The sensitivity analyses， along with scenario analyses， were performed. RESULTS In the base-case analysis， the ICER of observation group compared to control group was 1 166 344.46 yuan/QALY， far exceeding the WTP threshold， indicating that the regimen was not cost-effective. One-way sensitivity analysis identified the PD state utility， discount rate， cost of durvalumab， and PFS state utility as the main drivers of ICER variation. Probabilistic sensitivity analysis showed that， at the above WTP threshold， the probability of the acceeptance of this regimen was 0， further supporting the robustness of the base-case findings. In the scenario analysis， inclusion of a patient assistance program reduced the ICER to 235 885.16 yuan/ QALY， below the above WTP threshold， suggesting cost-effectiveness under this assistance program. However， when applying a regional WTP threshold set at three times the per capita GDP （158 475 yuan/QALY） of Gansu Province （the province with the lowest GDP in China in 2024）， the ICER remained above the threshold， indicating that the regimen was not cost-effective at the regional level. CONCLUSIONS At current pricing， durvalumab plus chemotherapy as a first-line treatment for advanced biliary tract cancer is not cost-effective in China. Although the introduction of a patient assistance program can substantially reduce the ICER and achieve cost-effectiveness at a WTP threshold set at three times the 2024 per capita GDP of China， due to limited affordability in low-income areas， the program remains not cost-effective.

Objective To explore the risk factors of complicating urogenic sepsis after percutaneous nephrolithotripsy(PCNL)and construct a nomogram prediction model.Methods The data of 291 patients with stage 1 PCNL in 940 Hospital of Joint Logistics Support Force from October 2016 to October 2021 were retrospectively analyzed.The patients were divided into the sepsis group and non-sepsis group according to whether complicating urogenic sepsis after operation.The general data,stone-related data,operation-related data and laboratory detection related data were included.The independent risk factors were screened by the univariate and multivariate logistic regression analysis,and the nomogram prediction model was constructed.Results The results of univariate and multivariate logistic regression analysis showed that age≥60 years old(OR=6.438,95％CI:1.548-26.769),urinary leukocyte 3+(OR=5.651,95％CI:1.614-31.766),urinary nitrite positive(OR=7.117,95％CI:1.190-42.561),operation time≥90 min(OR=4.626,95％CI:1.137-18.817)and perfusion volume 30 L(OR=3.312,95％CI:1.090-10.061)were the independent risk factors of postoperative complicating urogenic sepsis.C-index of the constructed nomogram prediction model in the modeling samples was 0.937,the calibrated C-index was 0.914,and the model predictive efficien-cy was good.Conclusion Age ≥60 years old,urinary leukocyte 3+,urinary nitrite positive,operation time 90 min and perfusion volume ≥30 L are the independent risk factors for complicating urogenic sepsis after PCNL;the constructed nomogram prediction model has a good predictive efficiency for the occurrence of post-operative urogenic sepsis.

Objective:To evaluate the reliability and validity of the Chinese version of HEMO-FISS-QoL(HF-QoL) questionnaire (HF-QoL-C) in the Chinese population with hemorrhoids.Methods:From November 2021 to November 2022, a self-constructed general information questionnaire, HF-QoL-C, and the 36-item short form health survey (SF-36), Goligher classification, and Giordano severity of hemorrhoid symptom questionnaire (GSQ) were used to conduct a questionnaire survey on 760 hemorrhoid patients in the anorectal department of six hospitals. The data was analyzed for reliability and validity using SPSS 21.0 and AMOS 26.0 software.Results:The Cronbach's α coefficient of HF-QoL-C and its dimension ranged from 0.831 to 0.960, and the split coefficient was 0.832-0.915. Four common factors were extracted through principal component exploratory factor analysis. Confirmatory factor analysis indicated acceptable structural validity( χ2/ df=8.152, RSMEA=0.097, CFI=0.881, IFI=0.881, NFI=0.867). HF-QoL-C was correlated with SF36 and GSQ( r=-0.694, 0.501, both P<0.01). There were differences in the total score and dimensional scores of HF-QoL-C between surgical and drug treated patients, different grades of Goligher classification for hemorrhoidal disease, and different ranges of hemorrhoid prolapse (all P<0.001). No ceiling effect was found in the total score and the scores of each dimension(0.3%-2.0%). There was a floor effect in both psychological function and sexual activity dimensions (16.7%, 35.1%). Conclusion:HF-QoL-C has good reliability and validity, which can be used to measure the quality of life of Chinese hemorrhoid patients.

Objective:To explore the effectiveness of 1+N+N team model with family physician as the core for rehabilitation of community-dwelling stroke patients.Methods:Convalescent stroke patients in Fenglin Community of Shanghai Xuhui District, who were followed up and registered from January 2019 to October 2021, were continuously enrolled in this intervention study. The 1+N+N care team consisted of a family doctor as the core (“1”) with the professional and technical team of the community health service center (“N”) and specialists in second or third hospitals (“N”). Patients were randomly divided into 1+N+N intervention group and control group. The control group was treated with traditional stroke management scheme, while the intervention group was treated by the 1+N+N team model. The activities of daily living (ADL), motor function and psychological status scores were evaluated at baseline and 12 months after intervention. Multivariate linear regression model was used to analyze the association of intervention methods with the improvement of ADL score, motor function score and psychological status score of patients.Results:A total of 120 patients were enrolled (60 in each group), including 59 males and 61 females with a mean age of (71.5±6.8) years. Compared with the control group, the age of patients in the intervention group was younger ( P=0.013), and the proportion of patients with coronary heart disease was lower ( P=0.003). There was no significant differences in other variables between the two groups ( P>0.05). After 12 months of intervention, the scores of ADL, motor function and psychological status were significantly improved compared with those before intervention in both groups ( P<0.01). There was no significant difference in motor function scores between the intervention group and the control group before intervention ( P>0.05), but the scores of ADL and psychological status in the intervention group were higher than those in the control group ( P<0.001). After intervention, the above scores in the intervention group were higher than those in the control group ( P<0.01). After adjusting for confounding factors, multivariate linear regression showed that the 1+N+N team model had no significant correlation with ADL score ( t=0.27, P=0.799), but had a positive correlation with motor function score ( t=15.64, P<0.01) and psychological status score ( t=13.70, P<0.01). Conclusion:The 1+N+N team model can effectively improve the daily living ability, motor function and psychological status of stroke patients in the convalescent period, and the intervention effect on the latter two is better than that of the traditional rehabilitation mode.

OBJECTIVES: Farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily of ligand activated transcription factors and belongs to bile acid receptor. Studies have shown that the expression of FXR in renal tissue can reduce renal injury via regulation of glucose and lipid metabolism, inhibition of inflammatory response, reduction of oxidative stress and renal fibrosis. However, it is unclear whether FXR is involved in autophagy in renal diseases. This study aims to investigate the role of FXR in cisplatin-induced acute renal injury and whether its mechanism is related to autophagy regulation. METHODS: Twelve male WT or FXR-KO mice at 12 weeks were randomly divided into a WT group, a WT+cisplatin group, a FXR-KO group, and a FXR-KO+cisplatin group, with 6 mice in each group. The WT+cisplatin group and the FXR-KO+cisplatin group were intraperitoneally injected with cisplatin (20 mg/kg), and the WT group and the FXR-KO group were intraperitoneally injected with equal volume of cisplatin solvent. Seventy-two hours later, the mice were killed and blood and renal tissue samples were collected. The levels of SCr and BUN were detected by immunoturbidimetry. After the staining, the pathological changes of renal tissue were observed under optical microscope. The protein levels of LC3 and p62 were detected by Western blotting and immunohistochemistry. The clearance of damaged mitochondria and the accumulation of lysosomal substrate were observed under electron microscope. The apoptosis of renal tubular epithelial cells was detected by TUNEL. RESULTS: Compared with the WT group or the FXR-KO group, both SCr and BUN levels in the WT+cisplatin group or the FXR-KO+cisplatin group were significantly increased (P<0.01 or P<0.001), and SCr and BUN levels in the FXR-KO+cisplatin group were significantly higher than those in the WT+cisplatin group (both P<0.05). Under the light microscope, there were no obvious pathological changes in the renal tissue of mice in the WT group and the FXR-KO group. Both the WT+cisplatin group and the FXR-KO+cisplatin group had vacuolar or granular degeneration of renal tubular epithelial cells, flat cells, lumen expansion, brush edge falling off, and even exposed basement membrane and tubular formation. The scores of renal tubular injury in the WT+cisplatin group and the FXR-KO+cisplatin group were significantly higher than those in the WT group and the FXR-KO group, respectively (both P<0.001), and the score in the FXR-KO+cisplatin group was significantly higher than that in the WT+cisplatin group (P<0.05). Under the transmission electron microscope, the mitochondria of mouse tubular epithelial cell in the WT+cisplatin group and the FXR-KO+cisplatin group was swollen, round, vacuolated, cristae broken or disappeared; the lysosome was uneven and high-density clumps, and the change was more obvious in the FXR-KO+cisplatin group. Western blotting showed that the ratio of LC3-II to LC3-I was decreased and the expression of p62 was increased in the WT+cisplatin group compared with the WT group and the FXR-KO+cisplatin group compared with FXR-KO group (P<0.05 or P<0.01); compared with the FXR-KO group, the ratio of LC3-II to LC3-I was decreased and the expression of p62 was increased significantly in the FXR-KO+cisplatin group (both P<0.05). Immunohistochemistry results showed that the expression of total LC3 and p62 in renal cortex of the WT+cisplatin group and the FXR-KO+cisplatin group was increased significantly, especially in the FXR-KO+cisplatin group. TUNEL results showed that the mice in the WT group and the FXR-KO group had negative staining or only a few apoptotic tubular epithelial cells, and the number of apoptotic cells in the WT+cisplatin group and the FXR-KO+cisplatin group were increased. The apoptosis rates of renal tubular epithelial cells in the WT+cisplatin group and the FXR-KO+cisplatin group were significantly higher than those in the WT group and the FXR-KO group, respectively (both P<0.001), and the apoptosis rate in the FXR-KO+cisplatin group was significantly higher than that in the WT+cisplatin group (P<0.05). CONCLUSIONS Knockout of FXR gene aggravates cisplatin induced acute renal injury, and its mechanism may be related to inhibiting autophagy and promoting apoptosis.
Acute Kidney Injury/pathology* ; Animals ; Apoptosis/physiology* ; Cisplatin/adverse effects* ; Female ; Humans ; Kidney/pathology* ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout

Objective:To explore the feasibility of 400 mL Sprite Zero ? in gastric preparation for magnetically controlled capsule endoscopy (MCE) . Methods:A randomized controlled trial at the Department of Gastroenterology of Changhai Hospital, Naval Medical University from December 16th, 2019 to January 15th, 2020 was conducted. The patients and healthy volunteers who intended to receive MCE were randomly divided into the Sprite Zero ? (S) group and the water (W) group at 1∶1. For subjects in the W group, 800 mL water was taken 10 minutes before swallowing the capsule. And for subjects in the S group, 400 mL Sprite Zero ? was taken. The primary endpoint was gastric filling score and the secondary endpoint included the fullness score, gastric transit time (GTT), small bowel transit time (SBTT), completion rate (CR) for small bowel examination and the diagnostic yield. Results:A total of 102 subjects were enrolled, 52 subjects in the S group and 50 subjects in the W group. The median score of gastric filling was 4 at 0-5 min, >5-10 min and >10-15 min after taking the capsule in both groups, with less median liquid consumption in the S group than the W group (500 mL VS 950 mL, P<0.001). The S group showed lower median fullness score (7.0 scores VS 7.5 scores, P=0.030) and higher proportion of patients with GTT less than 30 minutes [69.57% (16/52) VS 27.59% (8/29), P=0.030] compared with the W group. The CR of small bowel examination in the S group was 100.00%, higher than that of the W group (89.66%, P=0.245). Conclusion:Compared with 800 mL water, 400 mL Sprite Zero ? can fully fill the stomach with more comfort. It has the potential to accelerate gastric emptying and improve the CR of small bowel examination, which is feasible for the gastric preparation.

Rehabilitation medicine is one of the most important specialties in community health institutions. This article introduces the 12 year′s development of rehabilitation medicine in Fenglin Community Health Service Center, focusing on the talent allocation, service capabilities, resource expansion, basic facilities, personnel recruiting, department operating, service scope, and its achievements and influence, to provide reference for planning and construction of featured specialty in community health service centers.

Community health institutions have entered a new development stage of featured specialty construction. After 12 years of development, rehabilitation medicine now is the featured specialty of Fenglin Community Health Service Center. This article presents the train of thought and key points of specialty construction in primary care institutions based on the Fenglin′s experience. The positioning of featured specialty should be based on the community. The construction process should include 7 elements, namely, the standard operation procedure(SOP)of service system construction, the detailed publicity and implementation of the collaboration of specialists, prevention and control knowledge promotion for general practitioners, prevention and control knowledge education for community residents, service list, clinical efficacy evaluation, and clinical database. In the later iterations, the head of the department should always focus on the service system construction SOP and clinical database construction, and the rest parts can be assigned to the relevant team members.

The construction of featured specialties is the current development strategy of community health service institutions to improve the service scope and to meet the health needs of residents. The rehabilitation medicine has undergone 12 years of development and become a relatively mature featured specialty in Fenglin Community Health Service Center. Based on the Fenglin′s experience, this article discusses the development status and restriction bottlenecks of general practice, and the development status and trend of rehabilitation medicine in the community; and also explores the integrated development model of community-featured specialty with general practice.

Background: Gastroesophageal reflux disease (GERD) is strongly associated with sleep disturbances. Proton pump inhibitors (PPIs) are the main treatment to improve the reflux symptoms in GERD patients. Aims: To investigate the efficacy of PPIs on nighttime reflux symptoms and associated sleep disturbances in general GERD population in North China. Methods: In this multicenter, prospective observational study, adult GERD patients with nighttime heartburn or regurgitation were recruited from 11 tertiary hospitals in North China during July 2017 to March 2018. All the patients received oral PPIs treatment. Data on nighttime reflux symptoms and associated sleep disturbances were obtained by patient diary and self-report questionnaire, the quality of sleep was defined by the Pittsburgh Sleep Quality Index (PSQI). The efficacy of PPIs was estimated by the relief rate after 4-week treatment. Results: Of the 750 GERD patients analyzed, 585 (78.0%) reported nighttime reflux-associated sleep disturbances, and 427 (56.9%) were defined as poor sleepers with a PSQI score >5. After 4-week PPIs treatment, 51.3% of the patients achieved a relief of nighttime reflux symptoms. The complete relief rates for nighttime reflux symptoms and associated sleep disturbances were 32.5% and 51.5%, respectively. PSQI score was significantly improved from 6.82 ± 3.38 at baseline to 4.56±2.50 after 4-week PPIs treatment (P<0.05). Conclusions: PPIs treatment provides an effective relief of nighttime reflux symptoms and associated sleep disturbances and improving the sleep quality in general GERD population in North China.