Gallbladder cancer is the most common malignant tumor of the biliary system,characterized by insidious growth,rapid progression,and skip metastasis.The 5-year overall survival rate is only 5%.Although targeted immunotherapies have emerged in recent years,they are still in the exploratory phase for the treatment of gallbladder cancer,and radical surgical resection remains the only potentially curative treatment.The main goal of surgery is to completely remove the tumor and perform systematic lymph node dissection to reduce the risk of recurrence.Thanks to advances in surgical techniques and continuous optimization of perioperative management,postoperative complications,and hospital mortality in patients undergoing extended radical surgery for gallbladder cancer have decreased.However,the complex mechanisms of gallbladder cancer spread and metastasis make it challenging to determine the optimal scope of surgical resection.Clinical guidelines from different countries and hepatobiliary surgery centers often vary on surgical options,especially regarding the reasonable extent of liver resection,the scope of lymph node dissection and its impact on prognosis,and whether routine extrahepatic bile duct resection should be performed.There remains significant controversy in these areas.Future extensive prospective cohort studies are still needed to provide more evidence-based medical data for the surgical treatment of gallbladder cancer.When designing a surgical plan,surgeons must consider preoperative examination results,intraoperative findings,and pathological evaluation of frozen sections.A balance must be struck between radical treatment and safety and effectiveness.The most appropriate surgical method for each patient should be chosen while also emphasizing establishing a multidisciplinary collaborative system.Based on accurate tumor staging,postoperative adjuvant therapies should be integrated to continue making progress in improving patient prognosis.

Gallbladder cancer is the most common malignant tumor of the biliary system,characterized by insidious growth,rapid progression,and skip metastasis.The 5-year overall survival rate is only 5%.Although targeted immunotherapies have emerged in recent years,they are still in the exploratory phase for the treatment of gallbladder cancer,and radical surgical resection remains the only potentially curative treatment.The main goal of surgery is to completely remove the tumor and perform systematic lymph node dissection to reduce the risk of recurrence.Thanks to advances in surgical techniques and continuous optimization of perioperative management,postoperative complications,and hospital mortality in patients undergoing extended radical surgery for gallbladder cancer have decreased.However,the complex mechanisms of gallbladder cancer spread and metastasis make it challenging to determine the optimal scope of surgical resection.Clinical guidelines from different countries and hepatobiliary surgery centers often vary on surgical options,especially regarding the reasonable extent of liver resection,the scope of lymph node dissection and its impact on prognosis,and whether routine extrahepatic bile duct resection should be performed.There remains significant controversy in these areas.Future extensive prospective cohort studies are still needed to provide more evidence-based medical data for the surgical treatment of gallbladder cancer.When designing a surgical plan,surgeons must consider preoperative examination results,intraoperative findings,and pathological evaluation of frozen sections.A balance must be struck between radical treatment and safety and effectiveness.The most appropriate surgical method for each patient should be chosen while also emphasizing establishing a multidisciplinary collaborative system.Based on accurate tumor staging,postoperative adjuvant therapies should be integrated to continue making progress in improving patient prognosis.

Objective To explore the mechanism underlying the protective effect of α2-macroglobulin (A2M) against glucocorticoid-induced femoral head necrosis. Methods In a human umbilical vein endothelial cell (HUVEC) model with injuries induced by gradient concentrations of dexamethasone (DEX;10-8-10-5 mol/L), the protective effects of A2M at 0.05 and 0.1 mg/mL were assessed by examining the changes in cell viability, migration, and capacity of angiogenesis using CCK-8 assay, Transwell and scratch healing assays and angiogenesis assay. The expressions of CD31 and VEGF-A proteins in the treated cells were detected using Western blotting. In BALB/c mouse models of avascular necrosis of the femoral head induced by intramuscular injections of methylprednisolone, the effects of intervention with A2M on femoral trabecular structure, histopathological characteristics, and CD31 expression were examined with Micro-CT, HE staining and immunohistochemical staining. Results In cultured HUVECs, DEX treatment significantly reduced cell viability, migration and angiogenic ability in a concentration- and time-dependent manner (P<0.05), and these changes were obviously reversed by treatment with A2M in positive correlation with A2M concentration (P<0.05). DEX significantly reduced the expression of CD31 and VEGF-A proteins in HUVECs, while treatment with A2M restored CD31 and VEGF-A expressions in the cells (P<0.05). The mouse models of femoral head necrosis showed obvious trabecular damages in the femoral head, where a large number of empty lacunae and hypertrophic fat cells could be seen and CD31 expression was significantly decreased (P<0.05). A2M treatment of the mouse models significantly improved trabecular damages, maintained normal bone tissue structures, and increased CD31 expression in the femoral head (P<0.05). Conclusion A2M promotes proliferation, migration, and angiogenesis of DEX-treated HUVECs and alleviates methylprednisolone-induced femoral head necrosis by improving microcirculation damages and maintaining microcirculation stability in the femoral head.

Objective To explore the mechanism underlying the protective effect of α2-macroglobulin (A2M) against glucocorticoid-induced femoral head necrosis. Methods In a human umbilical vein endothelial cell (HUVEC) model with injuries induced by gradient concentrations of dexamethasone (DEX;10-8-10-5 mol/L), the protective effects of A2M at 0.05 and 0.1 mg/mL were assessed by examining the changes in cell viability, migration, and capacity of angiogenesis using CCK-8 assay, Transwell and scratch healing assays and angiogenesis assay. The expressions of CD31 and VEGF-A proteins in the treated cells were detected using Western blotting. In BALB/c mouse models of avascular necrosis of the femoral head induced by intramuscular injections of methylprednisolone, the effects of intervention with A2M on femoral trabecular structure, histopathological characteristics, and CD31 expression were examined with Micro-CT, HE staining and immunohistochemical staining. Results In cultured HUVECs, DEX treatment significantly reduced cell viability, migration and angiogenic ability in a concentration- and time-dependent manner (P<0.05), and these changes were obviously reversed by treatment with A2M in positive correlation with A2M concentration (P<0.05). DEX significantly reduced the expression of CD31 and VEGF-A proteins in HUVECs, while treatment with A2M restored CD31 and VEGF-A expressions in the cells (P<0.05). The mouse models of femoral head necrosis showed obvious trabecular damages in the femoral head, where a large number of empty lacunae and hypertrophic fat cells could be seen and CD31 expression was significantly decreased (P<0.05). A2M treatment of the mouse models significantly improved trabecular damages, maintained normal bone tissue structures, and increased CD31 expression in the femoral head (P<0.05). Conclusion A2M promotes proliferation, migration, and angiogenesis of DEX-treated HUVECs and alleviates methylprednisolone-induced femoral head necrosis by improving microcirculation damages and maintaining microcirculation stability in the femoral head.

Objective:To explore the distinctions between different educational levels: stability of learning state, views on and demand for online courses, and further investigate the influencing factors.Methods:A self-designed questionnaire with good reliability and validity was conducted, and all the students in a military medical university were selected by cluster sampling method, and the data were collected by issuing a network questionnaire. SPSS 26.0 was used for data processing.Results:Undergraduates were different from graduates and doctoral students in stability of learning state, the period of home study: doctoral students (2.41±1.30) h < graduates (2.10±1.17) h and undergraduates (2.15±0.99) h; the frequency of using online courses: undergraduates (4.18±1.10) times > graduates (3.29±1.16) times and doctoral students (3.29±0.98) times. In terms of views on online courses, necessity: undergraduates (4.14± 1.01) > graduates (3.93±1.05) and doctoral students (3.78±1.03); familiarity: undergraduates (3.42 ± 0.91) > graduates (3.27±0.97); adaptability: undergraduates (3.79±0.91) > graduates (3.58±0.94) and doctoral students (3.63±0.97); likability: undergraduates (3.36±1.04) > undergraduates (3.25±0.96) and doctoral students (3.17 ± 1.01); teaching effect: undergraduates (2.80±1.04) > graduates (2.67±1.01) and doctoral students (2.61±1.03). In terms of demand for online courses, ideal number: undergraduates (2.52±1.27) > graduates (2.11±1.21) and doctoral students (2.01±1.25); class style: undergraduates (1.77±0.94) > graduates (2.00±0.92) and doctoral students (2.04±1.83). There were statistically significant differences between undergraduates and postgraduates in all dimensions ( P<0.01 or P<0.05). Conclusion:Undergraduates may be more susceptible to academic environment than graduates and doctoral students, showing that the learning stability of undergraduates is the relatively the worst. Undergraduates most recognize online courses, and different educational levels have different demands for online courses.

Objective:To assess the efficacy and safety of 100 units of botulinum toxin A (BTX-A) intradetrusor injection in patients with overactive bladder.Methods:From April 2016 to December 2018, 17 tertiary hospitals were selected to participate in this prospective, multicenter, randomized, double-blind, placebo-controlled study. Two phases of study were conducted: the primary phase and the extended phase. This study enrolled patients aged 18 to 75 years who had been inadequately managed by anticholinergic therapy (insufficient efficacy or intolerable side effects) and had spontaneous voiding with overactive bladder. Exclusion criteria included patients with severe cardiac, renal and hepatic disorders, patients with previous botulinum toxin treatment for 6 months or allergic to BTX-A, patients with urinary tract infections, patients with urinary stones, urinary tract tumors, diabetes mellitus, and bleeding tendency. Eligible patients were randomly assigned to BTX-A group and placebo control group in a ratio of 2∶1. Two groups of patients received 20 intradetrusor injections of BTX-A 100U or placebo at the depth of the submucosal muscle layer respectively under cystoscope, including 5 injections at the base of the bladder, 3 injections to the bladder triangle, 5 injections each to the left and right walls and 2 injections to the top, sparing the bladder neck. As a placebo control group, patients received same volume of placebo containing no BTX-A and only adjuvant freeze-dried preparations for injection with the same method. A combination of gelatin, sucrose, and dextran served as adjuvants. Average micturition times per 24 hours, urinary incontinence (UI) episodes per day, average micturition volume per day, OAB symptom score(OABSS), and quality of life (QOL) score were recorded at baseline and the 2nd, 6th and 12th week after treatment. The primary efficacy endpoint was the change from baseline in the average micturition times per 24 hours at the 6th week after treatment. The secondary efficacy endpoints included the change from baseline in the average micturition times per 24 hours at 2nd and 12th week, as well as the change from baseline in the OABSS, QOL score, average frequency of urgency and UI episodes per day, urgency score, average micturition volume per day at 2nd, 6th and 12th week after treatment. Patients were followed for 12 weeks to assess adverse events (AEs). After assessed at week 12, if the micturition times has decreased less than 50% compared to baseline and the patient is willing to receive retreatment, then patients could enter the extended trial phase. In that phase, patients in both groups were injected with 100 units BTX-A from 12th week onwards and then followed up the same indicators for 12 weeks.Results:216 patients were enrolled in this trial (144 cases in the BTX-A group and 72 cases in the placebo control group). Baseline characteristics such as age (47.75±14.20 in the BTX-A group and 46.39±15.55 in the control group), sex (25 male/117 female in the BTX-A group and 10/61 in the control group), and disease duration (0.51 years in the BTX-A group and 0.60 years in the control group) were balanced between the two groups( P>0.05). A marked reduction from baseline in average micturition times per 24 hours was observed in all treatment groups at the 6th week and the reduction of the two groups was statistically different ( P<0.001 and P=0.008 respectively). Compared with the baseline, the average micturition times per 24 hours at the 6th week decreased from baseline by 2.40(0.70, 4.60)times for the BTX-A group and 0.70(-1.00, 3.30) times for the placebo control group respectively, and the difference between the two groups was considered to be statistically significant ( P=0.003). The change rates of average micturition times per 24 hours from baseline at the 6th week of the two groups were (16±22)% and (8±25)% respectively, and the difference between the two groups was statistically significant ( P=0.014). Compared with the baseline, the average micturition times per 24 hours at 2nd and 12th week decreased by 2.00(0.00, 4.00)and 3.30(0.60, 5.03)for the BTX-A group, 1.00(-1.00, 3.00)and 1.70(-1.45, 3.85)for the placebo control group respectively. The difference between two groups was considered to be statistically significant ( P=0.038 and P=0.012); the changes of average urgency times per day for the BTX-A group and the control group at the 2nd, 6th and 12th week were 2.00(0.00, 4.30)and 2.40(0.30, 5.00), 3.00(0.30, 5.70)and 0.70(-1.30, 2.70), 0.70(-1.30, 3.00) and 1.35(-1.15, 3.50), respectively. There were significant differences between two groups at the 2nd, 6th and 12th week, ( P=0.010, P=0.003 and P=0.025, respectively). The OABSS of the BTX-A group and the control group at the 6th week decreased by 1.00(0.00, 4.00)and 0.50(-1.00, 2.00) compared with the baseline, and the difference between the two groups was statistically significant ( P=0.003). 47 cases of BTX-A group and 34 cases of placebo control group entered the extended trial phase, and 40 and 28 cases completed the extended trial phase, respectively. The average micturition volume per 24 hours changed by -16.60(-41.60, -0.60)ml and -6.40(-22.40, 13.30)ml, (-35.67±54.41)ml and(-1.76±48.69)ml, (-36.14±41.51)ml and (-9.28±44.59)ml, (-35.85±43.35)ml and(-10.41±40.29)ml for two groups at the 12th, 14th, 18th and 24th week, and the difference between two groups was statistically significant at each follow-up time ( P=0.01, 0.006, 0.012 and 0.016, respectively). There was no significant difference in other parameters( P>0.05). However, adverse reactions after intradetrusor injection included increased residual urine volume (27 in the BTX-A group and 3 in the control group), dysuria (21 in the BTX-A group and 6 in the control group), urinary infection (19 in the BTX-A group and 6 in the control group), bladder neck obstruction (3 in the BTX-A group and 0 in the control group), hematuria (3 in the BTX-A group and 1 in the control group), elevated alanine aminotransferase (3 in the BTX-A group and 0 in the control group), etc. During the follow-up period, there was no significant difference in the other adverse events between two groups except the increase of residual urine volume( P<0.05). In the primary trial phase, among the 27 cases with increased residual urine volume in BTA group, only 1 case (3.70%) with PVR more than 300 ml; the PVR of 3 patients in the placebo group was less than 100 ml. The increase of residual urine volume caused by the injection could be improved or disappeared with the passage of time. Conclusions:Intradetrusor injection of Chinese BTX-A improved the average micturition times per 24 hours, the average daily urgent micturition times, OABSS, and average micturition volume per time, and reduced the adverse effects in patients with overactive bladder.Chinese BTX-A at dose of 100U demonstrated durable efficacy and safety in the management of overactive bladder.

Objective:To investigate the changes and clinical significance of blood coagulation function and von Willebrand factor antigen (vWF:Ag) in patients with HELLP syndrome (hemolysis, elevated liver function, low platelet count).Methods:The clotting data of patients with severe preeclampsia and HELLP syndrome (observation group) admitted to the department of critical care medicine of the Fifth Center Hospital in Tianjin from May 2015 to December 2019 were retrospectively analyzed, and normal late pregnancy women with the same period were enrolled as the control group. The coagulation indexes such as prothrombin time (PT), activated partial thrombin time (APTT), antithrombin (AT), fibrinogen (Fib), D-dimer and plasma vWF:Ag level were compared between the two groups, and among patients with HELLP syndrome with different disease degree.Results:① Sixty-five patients with HELLP syndrome and 65 normal pregnant women with third trimester were included. Both groups were women of childbearing age, and there were no significant difference in the baseline data. ② The levels of Fib, D-dimer in both groups increased, but they were significantly higher in the observation group than those in the control group [Fib (g/L): 4.94 (4.76, 5.85) vs. 3.58 (2.97, 4.14), D-dimer (mg/L): 3.34 (2.55, 4.32) vs. 1.72 (1.29, 2.08), both P < 0.05], the AT was obviously reduced [62.00 (49.00, 73.00)% vs. 97.50 (90.75, 107.00)%, P < 0.01], and both PT and APTT were in the normal reference range in the two groups. In addition, the plasma vWF:Ag level in the observation group was significantly higher than that in the control group [516.50 (467.20, 563.00)% vs. 246.45 (189.95, 274.10)%, P < 0.01]. ③ According to thrombocytopenia, among the 65 patients with HELLP syndrome, 26 cases were mild [platelet count (PLT) > 100×10 9/L], 22 cases were moderate [PLT (50-100)×10 9/L], and 17 cases were severe (PLT < 50×10 9/L). With the aggravation of the disease, the D-dimer, Fib, vWF:Ag levels in the mild, moderate, severe patients significantly increased, while the AT level significantly decreased, and there was statistically significant difference between the two groups [D-dimer (mg/L): 2.63 (2.60, 2.73), 3.15 (2.55, 3.73), 3.84 (3.52, 4.23); Fib (g/L): 4.23 (4.06, 4.47), 4.72 (4.34, 5.04), 5.43 (5.14, 5.76); vWF:Ag: 465.20 (437.20, 495.40)%, 500.10 (472.40, 534.50)%, 543.50 (521.30, 563.00)%; AT: 67.50 (61.60, 78.00)%, 63.70 (53.30, 70.40)%, 54.40 (44.00, 61.20)%; all P < 0.05]. Conclusion:Patients with HELLP syndrome may show hypercoagulability and excessive expression of peripheral blood vWF:Ag level, which can induce platelet aggregation, leading to thrombocytopenia and thrombotic microangiopathy, and the clinicians should pay attention to that.

Objective:To evaluate the clinical effects of transperitoneal and retroperitoneal laparoscopic decortication in the treatment of simple renal cysts.Methods:PubMed, EMBASE, Cochrane Library, CNKI, VIP and WanFang databases were searched, All studies about comparing transperitoneal and retroperitoneal laparoscopic decortication for simple renal cysts were included. The evaluation indicators included operative time, intraoperative blood loss, postoperative drainage time, postoperative hospital stay, and complication rate. Statistical analysis of the data using RevMan 5.3 software.Results:A total of 14 control studies were included, 409 cases in the transperitoneal group and 452 cases in the retroperitoneal group. Meta-analysis demonstrated that compared with the transperitoneal group, the retroperitoneal group had shorter operation time ( MD=8.81, 95% CI: 3.79-13.82, P<0.01), less intraoperative blood loss ( MD=4.89, 95% CI: 1.40-8.38, P<0.01), and shorter postoperative hospital stay ( MD=0.60, 95% CI: 0.24-0.96, P<0.01). However, there were not significant differences between the two approaches in postoperative drainage time ( MD=-0.12, 95% CI: -0.26-0.03, P=0.13) and complication rate ( OR=1.47, 95% CI: 0.48-4.47, P=0.05). Conclusions:Compared with the transperitoneal, the retroperitoneal laparoscopic decortication has the advantages of short operation time, less intraoperative blood loss and short postoperative hospital stay. Therefore, retroperitoneal laparoscopic decortication is expected to be the first choice for the treatment of simple renal cysts.

Objective: To explore the psychological and behavioral characteristics of problematic social networks usage. Methods: Totally 11 problematic social networks users were selected from 269 Beijing college students who often used social networks, and they were also deeply interviewed. The Interpretative Phenomenological Analysis (IPA) was used to analyze transcriptional texts. Results: Problematic social networks usage was classified into the following 6 aspects, deviant behaviors, poor attention state, impaired social function, bad moods, abstinence reaction (withdrawal) and tolerance. Conclusion: The present study generalizes the psychological and behavioral characteristics of problematic social networks usage and offers the basis of exploring its measurement tools.

Objective Recent studies have indicated that early brain injury is the leading cause of death in patients with subarachnoid hemorrhage ( SAH) .Our study investigated the role of aminoguanidine ( AG) in early brain injury after SAH . Methods Sixty-eight male SD rats were equally randomized into four groups of equal number :control, sham, SAH, and AG.The animals in the sham group were injected with isotonic saline solution , while those of the latter two groups with femoral artery blood ( FAB) and FAB+AG, respectively, into the pre-chiasmatic cistern to induce SAH. At 24 hours after modeling , all the rats were killed for HE staining , obtainment of behavioral neurological assessment ( BNA ) scores by Garcia, measurement of the apoptosis of neurons by TUNEL , and de-termination of the expressions of the iNOS and NSE proteins by West-ern blot. Results The results of HE staining showed the presence of more red blood cells in the subarachnoid cavity of the rats in the SAH group, with a significantly decreased BNA score ( 14.47 ± 0.62) as compared with those in the control (17.94 ±0.24), sham (17.59 ±0.51), and AG group (15.71 ±0.47) (P<0.05). The rate of positive cells was remarkably higher in the SAH group ([42.38 ±2.38]%) than in the control ([6.35 ±0.94]%), sham ([6.85 ±0.69]%), and AG group ([30.48 ±2.89]%) ( P<0.01), with significant differences among the latter three groups (P<0.05).The expressions of iNOS and NSE were markedly higher in the SAH group ([3.86 ±0.07] and [1.59 ±0.06]) than in the control (0 and[0.35 ±0.09]), sham ([2.96 ±0.34] and [0.38 ±0.08]), and AG group ([3.41 ±0.04] and [0.70 ±0.12]) ( P<0.05).Both the expression levels of iNOS and NSE were positively correlated with the rate of positive cells (r=0 .879 and 0.935, P<0.01). Conclusion AG can alleviate early brain injury after SAH in SD rats by improving the neuro-ethologic function , suppressing the apoptosis of neurons , and reducing the expressions of iNOS and NSE .