This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

OBJECTIVE To study the protective effect of saikosaponin b2(SSb2)on corticosterone(CORT)induced PC12 cell injury and its mechanism.METHODS ① PC12 cells were divided into the cell control group(24 h of culture with RPMI-1640 medium),CORT group(24 h of culture with CORT 100-800 μmol·L-1)and SSb2 group(24 h of culture with SSb2 1.5625,3.125,6.25,12.5,25,50 and 100 μmol·L-1).MTT assay was used to detect the cell survival rate.②PC12 cells were divided into the cell control group(24 h of culture with RPMI 1640 medium),model group(24 h of culture with CORT 400 μmol·L-1),and model+SSb2 group(3 h pretreatment with SSb2 1.5625,3.125,6.25,12.5 and 25 μmol·L-1,removal of the supernatant before cells were co-incubated with CORT 400 μmol·L-1 and corresponding concentrations of SSb2 for 24 h).MTT assay was used to detect the cell survival rate while micro-plate assay was used to detect the lactate dehydrogenase(LDH)leakage rate of PC12 cells.③PC12 cells were divided into the cell control group,model group and model+SSb2 12.5 μmol·L-1 group.AnnexinV-FITC/PI flow cytometry assay was used to detect PC12 cell apoptosis,ultra-perfor-mance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS)cell metabonomics was used to detect metabolic profile changes and colorimetric assay was employed to detect the glutamic acid content and glutaminase activity in PC12 cells.RESULTS Compared with the cell control group,the cell viability decreased to(55±6)%(P<0.01)when the concentration of CORT was 400 μmol·L-1.When the concentration of SSb2 was higher than 50 μmol·L-1,there was significant toxicity to PC12 cells(P<0.01).②Compared with the cell control group,the cell survival rate was signif-icantly decreased(P<0.01),while the release rate of LDH was significantly increased(P<0.01)in the model group.Compared with the model group,the cell survival rate significantly increased(P<0.05,P<0.01),while the LDH release rate significantly decreased(P<0.01)in the model+SSb2 group.③ Com-pared with the cell control group,cell apoptosis was significantly increased in the model group(P<0.05).Compared with the model group,cell apoptosis was significantly decreased(P<0.05)in the model+ SSb2 group.Metabolomics results show that SSb2 significantly back-regulated nine differential metabo-lites of glutamate,creatine,N-acetylaspartate,L-tyrosine,citric acid,L-isoleucine,lactic acid,glutamine and choline.Further network analysis of the key metabolites regulated by SSb2 yielded five major metabolic pathways:D-glutamine and D-glutamate metabolism,phenylalanine,tyrosine and tryptophan biosynthesis,alanine,aspartate and glutamate metabolism,tyrosine metabolism and arginine biosynthesis.Compared with the cell control group,the content of glutamate and activity of glutaminase were significantly decreased in the model group(P<0.01).Compared with the model group,the content of glutamate(P<0.01)and activity of glutaminase(P<0.05)were significantly increased in the model+SSb2 group.CONCLUSION SSb2 has a neuroprotective effect on CORT-injured PC12 cells,and the mechanism of which is related to inhibition of apoptosis and regulation of metabolic disorders.

Background/Aims: Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. Methods: A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. Results: Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. Conclusions In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.

Chaigui granules(CG)are a compound composed of six herbal medicines with significant antidepressant effects.However,the antidepressant mechanism of CG remains unclear.In the present study,we attempted to elucidate the antidepressant mechanism of CG by regulating purine metabolism and purinergic signaling.First,the regulatory effect of CG on purine metabolites in the prefrontal cortex(PFC)of chronic unpredictable mild stress(CUMS)rats was analyzed by ultra high-performance liquid chro-matography tandem mass spectrometry(UHPLC-MS/MS)targeted quantitative analysis.Meanwhile,purinergic receptors(P2X7 receptor(P2X7R),A1 receptor(A1R)and A2A receptor(A2AR))and signaling pathways(nod-like receptor protein 3(NLRP3)inflammasome pathway and cyclic adenosine mono-phosphate(cAMP)-protein kinase A(PKA)pathway)associated with purine metabolism were analyzed by western blotting and enzyme-linked immunosorbent assay(ELISA).Besides,antidepressant mecha-nism of CG by modulating purine metabolites to activate purinergic receptors and related signaling pathways was dissected by exogenous supplementation of purine metabolites and antagonism of puri-nergic receptors in vitro.An in vivo study showed that the decrease in xanthine and the increase in four purine nucleosides were closely related to the antidepressant effects of CG.Additionally,purinergic re-ceptors(P2X7R,A1R and A2AR)and related signaling pathways(NLRP3 inflammasome pathway and cAMP-PKA pathway)were also significantly regulated by CG.The results of exogenous supplementation of purine metabolites and antagonism of purinergic receptors showed that excessive accumulation of xanthine led to activation of the P2X7R-NLRP3 inflammasome pathway,and the reduction of adenosine and inosine inhibited the A1R-cAMP-PKA pathway,which was significantly ameliorated by CG.Overall,CG could promote neuroprotection and ultimately play an antidepressant role by inhibiting the xanthine-P2X7R-NLRP3 inflammasome pathway and activating the adenosine/inosine-A1R-cAMP-PKA pathway.

The ideological and political construction of medical courses reveals the educational essence of "truth, goodness, and beauty" in medicine. Scientificity and humanity are the embodiment of "seeking truth" and "advocating goodness" in medicine, and the unity of their content and form reaches the highest level of "advocating beauty". Studying the ideological and political construction of medical courses plays an important role in implementing the fundamental task of fostering virtue through education, and carrying out the Healthy China initiative. In terms of teaching objectives, the goals of ideological and political education in medical courses should not only include the goals of basic literacy goals, such as political literacy, cultural literacy, legal literacy, and moral cultivation, but also include professional literacy goals, such as medical humanistic cultivation. Thus, a "five in one" model of ideological and political education in medical courses will be established. In the practical path, it is suggested to explore from five aspects that changing the educational concept and strengthening the educational awareness, establishing teaching objectives and clarifying education direction, digging deeply into the ideological and political elements and clearing teaching content, innovating teaching methods and improving teaching effectiveness, and constructing evaluation indicators and evaluating teaching effectiveness scientifically.

Objective:To investigate the clinical effect of peroneal fracture line in the treatment of posterior Pilon fracture.Methods:The data of 26 patients treated with fibular fracture line from January 2017 to July 2019 were analyzed retrospectively, including 11 males and 15 females; the age ranged from 28 to 69 years, with an average of 42.2 years. There were 10 cases of falling injury, 9 cases of falling injury and 7 cases of traffic injury; all of them were fresh closed fibular fractures;According to Yu Guangrong's classification, there were 11 cases of type I, 8 cases of type II and 7 cases of type III; AGH was divided into 10 cases of type I, 5 cases of type IIa, 2 cases of type IIb, 5 cases of type IIIa and 4 cases of type IIIb. All cases were treated by opening the fibular fracture line through the posterolateral approach, the quality of fracture reduction was evaluated by Burwell Charnley radiological evaluation standard after operation; At the last follow-up, ankle function was evaluated by American Association of Foot and Ankle surgery (AOFAS) ankle and hindfoot scores.Results:All 26 patients were followed up for 12-23 months, with an average of 14.9 months; Bone healing was achieved in all fractures. The healing time was 3-6 months, with an average of 4.0 months. The quality of fracture reduction was evaluated according to the Burwell Charnley radiology evaluation standard after operation, including anatomical reduction in 23 cases and acceptable reduction in 3 cases. The anatomical reduction rate was 88% (23/26). At the last follow-up, AOFAS ankle and hindfoot scores ranged from 80 to 100, with an average of 89.9 points, of which 17 cases were excellent and 9 cases were good, and the excellent and good rate was 100%. At the last follow-up, no patient had complications such as reduction loss, skin necrosis, infection, internal fixation loosening or ankle stiffness.Conclusion:After the treatment of Pilon fractures via peroneal fracture line, the distal tibial articular surface and posterior ankle fracture gap can be fully exposed, which can be repositioned and fixed under direct vision, with high anatomical repositioning rate and good and safe clinical results.

Objective:To further optimize the nutritional support program for elderly neurocritical patients, analyze the changes and influencing factors of serum albumin levels in elderly neurocritical patients after surgery, and explore the impact on prognosis.Methods:A retrospective cohort study was conducted to investigate the medical records of neurosurgical intensive patients in Shanghai Tenth People's Hospital from May 2015 to September 2019. All the patients were treated for at least 5 days after operation. Patients with severe liver and kidney dysfunction, mental illness and incomplete medical records were not included in the study. Patients aged ≥65 years were included as the experimental group and patients aged <65 years served as the control group. Generalized estimating equation and other models were used to analyze the difference in the trend of albumin level and its influencing factors between the two groups. Automated machine learning was used to explore the influence of factors such as albumin level, nutrition mode, age, sex, diagnosis, preoperative consciousness level on the prognosis of patients.Results:A total of 284 patients were included in the study, including 85 in the experimental group and 199 in the control group. There were no significant differences in baseline data such as sex, age, and proportion of nutritional patterns between the two groups. Generalized estimating equation and generalized mixed additive equation showed that albumin level in both groups reached the minimum on the 3rd day after operation, and the average level in the experimental group was significantly lower than that in the control group ( P=0.03). Cerebral hemorrhage, emergency surgery, and low preoperative albumin were risk factors ( P<0.05); intravenous supplementation of human albumin might have an adverse effect on the experimental group ( P = 0.047). Machine learning models suggested that the higher the serum albumin level at discharge, the better the prognosis at 1 month after surgery. The area under ROC curve was 0.906, the specificity was 93.7%, and the sensitivity was 67.0%. Conclusions:The changes of albumin level in elderly patients with neurological critical illness after surgery are basically the same as those in young patients, with the lowest albumin level on the 3rd day after surgery, and the albumin levels even lower on the 3rd day after surgery in patients with cerebral hemorrhage, emergency surgery and preoperative low albumin. The higher the albumin level at discharge, the better the prognosis of patients may be.

Objective:To compare the effect of interlocking intramedullary nail and locking plate in the treatment of varus proximal humeral fractures in the elderly.Method:A retrospective case-control study was conducted to analyze the clinical data of 46 elderly patients with varus proximal humeral fractures treated in Central Theater General Hospital of PLA from June 2016 to January 2019, including 27 males and 19 females, at age of 60-84 years［（71.9±5.7）years］. All fractures were fresh. Overall 25 patients were treated with interlocking intramedullary nail（intramedullary nail group）, and 21 patients were treated with locking plate（bone plate group）. The incision length, operation time, intraoperative bleeding and fracture healing time were compared between the two groups. Visual analogue scale（VAS）was used to evaluate the degree of pain relief at 1 week and 1 month after operation, and Constant-Murley score was used to evaluate the recovery of shoulder function at 1 month, 3 months and 1 year after operation. The cervical trunk angle was recorded at 2 days and 1 year after operation to judge whether there was a loss of cervical trunk angle. Postoperative complications were observed.Results:All patients were followed up for 12-32 months［（19.7±6.6）months］. The incision length［（7.1±0.6）cm］, operation time［（60.8±5.2）minutes］, intraoperative bleeding［（64.4±8.4）ml］and fracture healing time［（10.0±1.0）weeks］in intramedullary nail group were significantly less than those in bone plate group［（13.6±0.9）cm,（80.2±8.1）minutes,（151.0±15.2）ml,（11.0±1.5）weeks］（ P<0.05）. In both groups, the VAS decreased significantly over time, and markedly increased Constant-Murley score was detected as well（ P<0.05）. The VAS in intramedullary nail group［（2.8±0.2）points,（1.1±0.2）points］was significantly lower than that in bone plate group［（4.0±0.2）points,（1.5±0.1）points］at 1 week and 1 month after operation（ P<0.05）. The Constant-Murley score in intramedullary nail group［（59.9±6.9）points,（79.1±6.8）points］was higher than that in bone plate group［（50.1±8.5）points,（73.6±8.4）points］at 1 month and 3 months after operation（ P<0.05）, but the score showed no significant difference between intramedullary nail group［（89.1±5.3）points］and bone plate group［（86.4±6.4）points］at 1 year after operation（ P>0.05）. According to Constant-Murley score, 10 patients were evaluated as excellent and 15 patients as good in intramedullary nail group at 1 year after operation, with the excellent and good rate of 100%, while 8 patients were evaluated as excellent, 11 patients as good and 2 patients as fair in bone plate group at 1 year after operation, with the excellent and good rate of 91%（ P>0.05）. The cervical trunk angle in intramedullary nail group［（140.2±2.9）°,（139.6±2.3）°］had significant difference from that in bone plate group［（139.6±3.2）°,（138.8±3.3）°］at 2 days and 1 year after operation（ P<0.05）. In both groups, the cervical trunk angle had slight lost at 1 year after operation compared with that at 2 days after operation, but the difference was not statistically significant（ P>0.05）. In intramedullary nail group, 1 patient had subacromial impact. In bone plate group, 1 patient had screw cutting, 2 patients subacromial impact, and 2 patients delayed fracture healing. The incidence of complications in intramedullary nail group was 4%（1/25）, lower than 24%（5/21）in bone plate group（ P<0.05）. Conclusion:Compared with locking nail plate, interlocking intramedullary nail in the treatment of senile varus proximal humeral fracture has the advantages of small trauma, early fracture healing, less pain, early function recovery and less complications.

Objective To explore the clinical efficacy of early combined application of parenteral nutrition and enteral nutrition among patients in neurosurgical intensive care unit(NICU).Methods Two hundred fifty-five patients with severe neurological diseases were admitted to NICU of Shanghai Tenth People's Hospital from January 1 to August 31 in 2018.The patients were divided into two groups:traditional enteral nutrition group (control group,n=170),who were treated with enteral nutrition management at the early stage,and early combined application of parenteral and enteral nutrition group (experimental group,n=85),who were at first treated with parenteral nutrition since admission and then enteral nutrition management 72 hours later.The differences of Glasgow outcome scale (GOS),incidence of individual adverse reactions,daily average enteral nutrition,human albumin supplement,daily average fluid supplement,pulmonary infection rate,infection time and albumin level during hospitalization between the two groups were compared.The relationship among the course of enteral nutrition,nutrient content,pulmonary infection and serum albumin level in the experimental group were also discussed.The GOS was predicted by decision tree,random forests,nearest neighbor algorithm,adaboost and bagging.Results There was no significant difference between baseline scores after 1∶2 propensity score matching.The dominance ratio of GOS between the two groups was 1.853 (95％CI:1.018-3.385) (P=0.043).The change of albumin level was not related to the choice of nutritional regimen,but was related to the level of consciousness after admission and the level of basic albumin before admission.The level of consciousness in the experimental group was higher than that of the control group,and the fluid infusion volume was decreased while the daily average enteral nutrition and albumin supplementation were increased,the types of adverse reactions occurred more and earlier (P＜0.05).The misjudgment rate of GOS prediction models ranged from 0.482 to 0.606.Conclusions Compared with traditional early enteral nutrition therapy,early combined parenteral nutrition and enteral nutition can improve the prognosis of patients with severe neurological diseases.