BACKGROUND:Small diameter artificial vessels are urgently needed to treat coronary artery and peripheral artery diseases in clinical practice.At present,vascular tissue engineering has become the main method for preparing small diameter artificial vessels.Selecting suitable biomaterials and cell sources is the key factor for successful construction of small diameter tissue engineered vessels. OBJECTIVE:To observe the effect of four kinds of electrospinning membrane materials on proliferation,adhesion and differentiation of bone marrow mesenchymal stem cells into vascular smooth muscle cells. METHODS:Bone marrow mesenchymal stem cells were isolated and extracted from SD rats.The bone marrow mesenchymal stem cells were inoculated separately on polycaprolactone(PCL),polycaprolactone-hyaluronic acid(PCL-HA),polycaprolactone-silk-filament proteins(PCL-SF),and polycaprolactone-gelatin(PCL-GEL)electrospinning membrane materials.After 1,3,and 7 days of culture,the cell arrangement on the material was observed under scanning electron microscope.The proliferation and adhesion of the material were observed by phalloidin staining.The mRNA expressions of CD90,Meflin,and transforming growth factor β were detected by qRT-PCR.After 7 days of induced differentiation into vascular smooth muscle cells,the mRNA expression ofɑ-smooth muscle actin on the material was detected by qRT-PCR. RESULTS AND CONCLUSION:(1)Bone marrow mesenchymal stem cells were arranged along the fibers of the four kinds of electrospinning membranes under scanning electron microscopy.(2)Phalloidin staining showed the regular distribution of bone marrow mesenchymal stem cells on the four kinds of electrospinning membranes and parallel distribution along the fiber direction.Moreover,PCL-HA,PCL-SF,and PCL-GEL electrospinning membranes were more conducive to the proliferation and adhesion of bone marrow mesenchymal stem cells than PCL electrospinning membranes.Compared with PCL-HA and PCL-GEL electrospinning membranes,PCL-SF electrospinning membranes were more conducive to the proliferation and adhesion of bone marrow mesenchymal stem cells.(3)qRT-PCR showed that the four kinds of electrospun membrane materials could maintain the mRNA expression of CD90 and Meflin in bone marrow mesenchymal stem cells,but there was no significant difference between groups(P>0.05).The mRNA expression of transforming growth factor β in PCL-HA,PCL-SF,and PCL-GEL groups was higher than that in PCL group on days 1 and 7(P<0.05),and the mRNA expression of transforming growth factor β in PCL-SF group was higher than that in the other three groups on days 3 and 7(P<0.05).The mRNA expression of transforming growth factor β in PCL-HA group was higher than that in PCL-GEL group on day 7(P<0.05).(4)qRT-PCR showed that the mRNA expression of ɑ-smooth muscle actin in PCL-SF group was higher than that in the other three groups(P<0.05),and that in PCL-HA group was higher than that in PCL group(P<0.05).(5)The results indicate that compared with PCL,PCL-HA and PCL-GEL electrospinning membranes,PCL-SF electrospinning membranes combined with bone marrow mesenchymal stem cells are more suitable for the preparation of small diameter tissue engineered vessels.

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.

Background The Qingcaosha Reservoir is facing issues of algal blooms and eutrophication, and the resulting increase in the level of chlorination disinfection by-products in the water has been a major concern. Objective To evaluate the impact of "Algae Monitoring and Control Program in Qingcaosha Reservoir" (hereinafter referred to as the program) on the control of trihalomethanes (THMs) in conventional finished water. Methods From 2011 to 2019, water samples were collected from the Lujiazui Water Plant once per season, one sample each time, and the concentrations of four THMs (trichloromethane, dichlorobromomethane, monochlorodibromomethane, and tribromomethane) were measured in the samples. Using 2014 when the program was implemented as a cut-off point, the entire study period was divided into two phases: pre-implementation (2011–2013) and post-implementation(2014–2019). Segmented linear regression with interrupted time series analysis was applied to assess the concentrations and trends of THMs in the finished water before and after the program launch. Results The concentration of total THMs in finished water increased by 1.561 µg·L⁻¹ (P=0.010) for each season of time extension before launching the program. The change in the concentration of total THMs in finished water was not statistically significant after the program launch, but the THMs concentration showed a decreasing trend as the slope was −0.626 (P=0.001). From 2017 until the end of 2019, the average concentration of THMs in finished water of Lujiazui Water Plant dropped to 10 μg·L⁻¹ or less. Conclusions The algae and eutrophication control measures in Qingcaosha Reservoir have achieved good results, controlling THMs in finished water at a low level, and the trend of THMs has changed from a yearly increase pattern before the program to a yearly decrease pattern after the program.

Objective To explore the safety and efficacy of laparoscopic left renal vein stent implantation combined with microsurgical varicocelectomy in the treatment of nutcracker syndrome complicated with varicocele.Methods A retrospective analysis was conducted on the data of 50 patients with nutcracker syndrome complicated with varicocele admitted to our hospital during Nov.2018 and Jul.2023.All patients underwent laparoscopic left renal vein stent implantation combined with microsurgical varicocelectomy.Results Altogether 47 patients were followed up after operation,with a mean age of(21.45±3.84)years.All operations were successful,and gross hematuria,proteinuria,abdominal pain and other symptoms relieved within 3-7 days after surgery.Postoperative follow-up showed that no patients had serious complications or recurrence of clinical symptoms.Left renal vein ultrasound and CT showed that the blood flow of the left renal vein was restored,and the stent position was stable.Compared with those before surgery,the angle between the abdominal aorta and the superior mesenteric artery[(44.91±6.59)° vs.(22.58±6.61)°]and the diameter of the left renal vein at the angle[(6.03±0.99)mm vs.(1.87±0.46)mm]were significantly increased,and the blood flow velocity of the left renal vein at the angle[(48.77±14.79)cm/s vs.(102.53±41.15)cm/s]was significantly decreased,with statistically significant differences(P＜0.001).Scrotal ultrasound confirmed that there was no recurrence of varicocele 6 months after surgery,and the diameter of the spermatic vein was significantly reduced,with statistically significant differences(P＜0.001).Semen analysis showed that the sperm concentration[(60.27±48.45)×106/mL vs.(36.57±36.67)×106/mL,P=0.032]and percentage of rapid forward movement of sperm were significantly increased[(22.54±10.70)vs.(15.01±10.77),P=0.005],with statistically significant differences.The increase value of semen concentration[(23.7±41.48)×106/mL vs.(6.12±4.97)×106/mL,P=0.016)]increased after combined operation compared with left renal venous stenting alone,and there was no significant difference in the diameter of spermatic vein,inner diameter of renal vein and flow rate between the two surgical methods(P＞0.05).Conclusion Laparoscopic left renal vein stent implantation combined with microsurgical varicocelectomy is a minimally invasive,safe and effective method for the treatment of nutcracker syndrome complicated with varicocele.

Sarcomatoid carcinoma of the renal pelvis accounts for a very low percentage of malignant tumors in the renal pelvis and has a poor prognosis. This article reported a patient with sarcomatoid carcinoma of the renal pelvis. The patient presented with macroscopic hematuria as the first symptom, and CT suggested left renal occupancy, unilateral nephrectomy was performed, and pathology suggested sarcomatoid carcinoma of the renal pelvis. Three weeks after surgery, a follow-up CT showed tumor recurrence. Programmed death 1(PD-1)inhibitor was given once every 3 weeks. Repeated CT examination after 24 weeks of continuous treatment suggested that the recurrent tumor disappeared. The patients was followed-up for 42 months without tumor recurrence or metastasis.

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.

"State-target medicine" is a traditional Chinese medicine （TCM） diagnosis and treatment theoretical system proposed by Academician Tong Xiaolin based on the current development of modern medicine. The active stage of gastric ulcer， as a precancerous state of gastric cancer， has a great impact on people's health. Prof. ZHOU Xuewen， a master of TCM， innovatively put forward the theory of "toxicity-heat" etiology for the active stage of gastric ulcer， which plays an important guiding role in clinical diagnosis and treatment. The article took the theoretical system of "state-target medicine" as the framework to explain the rationale， method， formula， and medicine of Prof. ZHOU Xuewen， who applied the Xiaoyong Kuidekang based on the "toxicity-heat" theory to treat the gastric ulcer in the active stage. The Chinese medical name of gastric ulcer， "gastric carbuncle"， was established， and it was believed that gastric ulcer is born due to "toxicity" and is based on "toxicity and heat". In the course of the disease， "toxicity"， "heat"， "deficiency"， and "stasis" coexisted， and its pathogenesis was divided into three phases， namely， toxicity-heat accumulation phase， toxicity-heat affecting the health phase， and weakened body resistance and strengthened toxicity phase. According to the positioning of gastric ulcer as an "internal carbuncle"， Prof. ZHOU Xuewen proposed the treatment of gastric ulcer in the active stage with "carbuncle theory" and introduced the surgical methods of "elimination"， "support"， and "tonifying" into the treatment of gastric ulcer in the active stage. Prof. ZHOU Xuewen took "clearing heat and removing toxins， eliminating carbuncle and generating muscle" as the basic treatment of the disease. For different stages of the disease， Prof. ZHOU Xuewen emphasized the use of the methods of clearing heat and removing toxins， supporting rot and muscle growth， and strengthening the spleen and harmonizing the stomach and created the representative formula for the treatment of gastric ulcer in the active stage with "carbuncle theory"， namely "Xiaoyong Kuidekang"， which could regulate state and targets.

Objective:To explore the mechanism of peritoneal dialysis solution (PDS)-induced peritoneal microinflammation through activation of ceramide (CER) in peritoneal dialysis model mice.Methods:Thirty 5-week-old male C57BL/6 mice weighing about 22 g were used to set up peritoneal dialysis models, and then were randomly divided into 4 groups: sham operation group (1.5 ml sterilized water, n=7), high glucose-PDS group (1.5 ml 4.25% PDS, n=8), high glucose-PDS+ acid sphingomyelinase (ASMase) inhibitor desipramine (DES) group (1.5 ml sterilized water+10 mg/kg DES, n=8), high glucose-PDS+Src kinase inhibitor PP2 group (1.5 ml sterilized water +1 mg/kg PP2, n=7), with intraperitoneal injection once a day. After 28 days, the mice were sacrificed to retain peritoneal tissues. HE staining and Masson staining were used to observe the histological changes of peritoneum. Immunohistochemistry was used to detect the Toll-like receptor 4 (TLR4) and macrophages. High performance liquid chromatography, liquid chromatography/mass spectrometry and immunofluorescence were used to detect the expression of ASMase and CER. Real-time quantitative PCR was used to detect the mRNA levels of c-Src, p-Src, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Western blotting was used to detect the protein levels of c-Src, and p-Src. Enzyme-linked immunosorbent assay was used to detect the serum C reactive protein (CRP), IL-6 and TNF-α. Results:(1) High glucose-PDS led to peritoneal hyperplasia, collagen deposition and fibrosis in the peritoneal dialysis mice, indicating successful modeling. Compared with high glucose-PDS group, peritoneal hyperplasia, collagen deposition and fibrosis of mice treated with DES and PP2 were significantly improved (all P<0.05). (2) Compared with sham operation group, ASMase activation and CER level of peritoneal tissues were significantly higher in high glucose-PDS group, and DES could significantly inhibit activated ASMase and increased CER expression caused by high glucose-PDS (both P<0.05). PP2 had no significant effect on ASMase activation and CER level (both P>0.05). (3) Compared with sham operation group, there were more TLR4 and macrophage positive staining cells in peritoneal tissues in high glucose-PDS group, and the mRNA expression levels of IL-6 and TNF-α in peritoneal tissues and serum CRP, IL-6 and TNF-α were higher (all P<0.05). DES and PP2 could significantly inhibit the increased TLR4, macrophages and related inflammatory factors induced by high glucose-PDS (all P<0.05). (4) Compared with sham operation group, c-Src and p-Src mRNA and protein expression levels of peritoneal tissues in high glucose-PDS group were significantly higher (all P<0.05). PP2 significantly inhibited the increased p-Src mRNA and protein levels caused by high glucose-PDS (both P<0.05), but had no significant effect on the mRNA and protein expression levels of c-Src (both P>0.05). DES had no significant effect on the mRNA and protein expression levels of c-Src and p-Src (all P>0.05). Conclusions:High glucose-PDS may enhance the expression of CER through stimulating the activity of ASMase, phosphorylate Src, activate TLR4 and induce inflammatory damage of peritoneum in peritoneal dialysis model mice.

Objective:To analyze any effect of combining hyperbaric oxygen with qingkailing on the metabolic biomarkers of consciousness disorder (CD) caused by brain trauma using metabolomics technology. Also, to screen out diagnostic markers for clinical treatment and prognosis.Methods:Thirty-six patients with a CD caused by brain trauma formed the observation group, while 40 healthy gender-, age- and ethnicity-matched individuals were the control group. Both groups were given routine supportive treatment, while the observation group additionally received hyperbaric oxygen and oral qingkailing medication. Before and after 14 days consciousness disturbance was evaluated using the Glasgow Coma Scale (GCS). Venous blood was collected for metabolomic analysis using liquid chromatography linked to a mass spectrometer to screen out specific metabolic biomarkers. Metabolic markers associated with the disease and of diagnostic significance were thus identified.Results:After the treatment the average GCS score of the observation group had improved significantly and the degree of coma was significantly relieved. Twenty-one metabolic markers were found to be significant, with creatine, proline, uric acid, acetyl-L-carnitine, histidine, proline leucine, tryptophan and 9E-octagenoic acid potentially of high diagnostic value. After the treatment, all of those markers came close to the levels observed in the healthy control group.Conclusions:Proline, leucine, 9E-octagenoleic acid, uric acid and acetyl-L-carnitine could be used for diagnosis and evaluating efficacy with such patients. Hyperbaric oxygen supplemented with qingkailing can relieve coma, correct metabolic disorders and accelerate patients′ awakening. Metabolomics provides a new method for identifying endogenous metabolic abnormalities in patients with post-traumatic consciousness disorders. It can be useful in prognosis and clinical treatment.

Objective:To investigate the feasibility of oblique overlap anastomosis plus single flap valvuloplasty (OSF) for reconstruction after laparoscopic proximal gastrectomy.Methods:The C-shaped seromuscular flap (2.5 × 3.5 cm), which was 2 cm from the top of the remnant stomach, was extracorporeally created on the anterior wall of the remnant stomach. The stomach was opened approximately 1.0 cm above the lower edge of the mucosal flap. Four supporting stitches were sutured around the hole and the right wall of the esophageal stump was incised with a support suture to prevent the linear stapler from entering the submucosa. Liner stapler was inclined to the left side of the esophagus at an angle of about 30 degrees to the longitudinal axis of the esophagus for oblique anastomosis between the dorsal side of the esophagus and the anterior stomach and then esophagogastrostomy was performed with the length of anastomosis was 4 cm. Entry hole was suture with 3 stitches and then the linear stapler was used for closing the entry hole. Finally, the seromuscular flap was closed using barbed sutures.Results:Clinical data of 11 patients with Siewert type II esophagogastric junction adenocarcinoma who underwent radical gastrectomy and reconstruction by OSF between January 2022 and May 2023 were retrospectively collected. There were 7 males and 4 females. The average age was (69.9±7.8) years, the BMI was (21.7±7.2) kg/m 2 and the tumor size was (2.1±0.6) cm. OSF reconstruction was successfully completed in all 11 patients. The median operative time was 275 (270-428) minutes, the time for OSF reconstruction was 112 (80-140) minutes, and the blood loss was 50 (20-400) ml. The pathological stage was 0-I in 7 cases and II-III in 4 cases. The patients were fed on the 4th day (4-7 days) and discharged from hospital on the 7th day (6-9 days) after surgery. No patient had gastroesophageal reflux symptoms of grade B and above, and no patient took anti-reflux medicine. Conclusions:OSF is a safe and feasible treatment for Siewert type II esophagogastric junction adenocarcinoma.