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*

To achieve the goal of"eliminating viral hepatitis as a public health hazard by 2030",extensive screening,active prevention,and antiviral therapy are currently recommended for chronic hepatitis B virus(HBV)infection;however,no consensus has been reached on whether to initiate antiviral therapy for patients in the immune-tolerant phase of chronic HBV infection.Some experts believe that patients in the immune-tolerant phase tend to have a stable liver immune microenvironment,with a low risk of disease progression and poor response to treatment,and thus it is not recommended to initiate antiviral therapy.However,various other studies have shown that patients in the immune-tolerant phase still have inflammatory damage in the liver,with a risk of disease progression and a high level of cost effectiveness,and therefore,some experts suggest that antiviral therapy should be actively initiated for patients in the immune-tolerant phase.This article performs a literature review of the definition of patients in the immune-tolerant phase of chronic HBV infection and the advantages and disadvantages of antiviral therapy and conducts a preliminary analysis based on previous studies,in order to accumulate the evidence for whether to initiate antiviral therapy in the immune-tolerant phase of chronic HBV infection and lay a foundation for standardized clinical diagnosis and treatment of patients in the immune-tolerant phase.

Objective To determine the scores of patients with a confirmed diagnosis of drug-induced liver injury(DILI)using Roussel Uclaf Causality Assessment Method(RUCAM),Maria&Victorino assessment scale,and Revised Electronic Causality Assessment Method(RECAM),to compare the accuracy of the three scales in diagnosis,and to investigate their clinical significance in the diagnosis of DILI.Methods A total of 98 patients with a confirmed diagnosis of DILI who were hospitalized in Peking University First Hospital from January 2011 to December 2022 were enrolled,with liver biopsy results supporting DILI and a clear history of medication.Clinical data were collected from all subjects,and the above causality assessment scales were used for scoring.The chi-square test was used to analyze the diagnostic accuracy of the causality assessment scales,and the weighted kappa coefficient was used to analyze the consistency between the three scales.Results For all patients with DILI enrolled,RECAM had the highest accuracy,with a significant difference compared with RUCAM(χ2=5.667,P=0.017).RUCAM and RECAM had moderate consistency in diagnosis(κw=0.469),while RECAM and Maria&Victorino scale had poor consistency(κw=0.156).For the patients with acute DILI,RECAM,RUCAM,and Maria&Victorino scales had a diagnostic inconsistency rate of 3.7%,11.1%,and 42.6%,respectively;for the patients with hepatocellular type DILI,the three scales of a diagnostic inconsistency rate of 8.9%,21.4%,and 62.5%,respectively;for the patients with cholestasis type or mixed type DILI,the three scales of a diagnostic inconsistency rate of 10.0%,22.5%,and 47.5%,respectively.Conclusion The use of RECAM and RUCAM scales in acute DILI can improve diagnostic rate,and for hepatocellular type DILI and DILI with the clinical manifestation of cholestasis(cholestasis type DILI and mixed type DILI),the use of RECAM and RUCAM scales can also improve diagnostic rate.The selection of causality assessment scales with a relatively high accuracy based on the course and clinical classification of the disease may help to further improve clinical diagnostic rate.

Gap junction proteins have a significant impact on the propagation of neuroinflammation after cerebral ischemia.Connexin 43(Cx43),the principal connexin in the central nervous system,typically assembles hexameric hemichannels in an oligomeric state that dock with hemichannels on adjacent cells to form gap junction channels.Ordinarily,the likelihood of cell surface hemichannels opening is minimal.However,during cerebral ischemia,the excessive activation of Cx43 hemichannels leads to the liberation of a substantial quantity of ions(Na+,Cl-,Ca2+,and K+),glutamate,aspartate,and adenosine triphosphate(ATP),thereby resulting in impairment of adjacent cells and aggravation of neuronal injury.Furthermore,the activation of Cx43 hemichannels triggers the release of inflammatory factors,which exhibits a strong association with the activation of NLRP3 inflammasome after cerebral ischemia.Hence,the modulation of Cx43 hemichannels presents a potential avenue for mitigating neuroinflammation and subsequently diminishing cerebral ischemic injury.This article focuses on the relationship between Cx43 hemichannels and NLRP3 inflammasome activation,as well as its role in cerebral ischemia,all of which provide novel insights and therapeutic approaches for managing cerebral ischemia.

Objective:To investigate the association between the cerebral microbleeds(CMBs)and CHA 2DS 2-VASc score in patients with non-valvular atrial fibrillation(NVAF), and to analyze the related risk factors for CMBs. Method:This was a retrospective case-control study.A total of 164 patients with NVAF who had performed brain magnetic resonance susceptibility weighted imaging in Zhejiang Hospital from January 2015 to December 2017 were included.Based on the presence of CMBs, all patients were divided into the CMBs group(n=43, 26.2%)and the non-CMBs group(n=121, 73.8%). We collected the data about clinical characteristics, CHA2DS2-VASc score and number of CMBs.The association between CMBs and CHA2DS2-VASc score was analyzed by Spearman linear test.The Logistic regression analyses was used to evaluate the association between CMBs and the risk factors, including age, hypertension, etc.Results:The incidence of CMBs was markedly increased with the increase of CHA 2DS 2-VASc score( P<0.05). Besides, the rate of CMBs ≥5 was also positively associated with CHA 2DS 2-VASc score( P<0.05). Patients in the CMBs group was significantly older than those in the non-CMBs group[(81.0±8.1)years vs.(75.4±11.2)years, P<0.01]. There were significantly differences in rates of hypertension(83.7% vs. 63.2%), moderate-severe leukoaraiosis(44.2% vs.33.9%), anticoagulant therapy(34.9% vs.19.0%)and median CHA 2DS 2-VASc score(4 vs.3)between the CMBs group and the non-CMBs group(all P<0.05). Logistic regression analyses showed that age and anticoagulant therapy were the independent risk factors of CMBs in NVAF patients(all P<0.05). Conclusion:CMBs is strongly associated with CHA 2DS 2-VASc score in patients with NVAF.Age and anticoagulant therapy are its independent risk factors.It is necessary to detect the possibility of CMBs in old NVAF patients with high CHA 2DS 2-VASc score before and during anticoagulant therapy.

Objective To investigate the effects of sevoflurane post-conditioning on oxidative stress and inflammatory reaction during rat cerebral ischemia-reperfusion, and to explore its cerebral protective mechanism.Methods Thirty-six health male Sprague-Dawley rats (aged 12-14 weeks, weighing 220-260 g) were randomly divided into 3 groups (n=12 each): sham control group (group Sham), cerebral ischemia-reperfusion group (group IR), sevoflurane post-conditioning group (group SPC).Cerebral ischemia-reperfusion model was established, ischemia for 30 min followed by reperfusion 24 h.Rat middle cerebral artery was not occluded in group Sham.Cerebral ischemia-reperfusion model was established in group IR.Group SPC was subjected to 2.6% sevoflurane for 15 min in the beginning of reperfusion.At the end of reperfusion, rats were cut off the head to take out the brain tissue.The expression level of Iba-1 and HO-1 proteins was measured by western blot.The levels of reactive oxygen species (ROS), malondialdehyde (MDA), TNF-α, IL-1β and the activity of superoxide dismutase (SOD) were evaluated.Results Compared with group Sham, the expression of cerebral cortex Iba-1 protein was higher than that in groups IR and SPC (P＜0.05), the expression of Iba-1 protein in group SPC was lower than that in group IR (P＜0.05).Compared with group Sham, the contents of ROS, MDA, TNF-α and IL-1β were increased in groups IR and SPC (P＜0.05), but the activity of SOD and expression of HO-1 protein were decreased (P＜0.05).And the contents of ROS, MDA, TNF-α and IL-1β in group SPC were less than those in group IR, the activity of SOD and expression of HO-1 protein in group SPC were higher than those in group IR.Conclusion Sevoflurane post-conditioning can mitigate the microglia activation, reduce cerebral oxidative stress and inflammation, thus protect rat cerebral against ischemia reperfusion injury.

Objective To investigate the relationship between red blood cell distribution width (RDW) and prognosis in patients with multiple myeloma (MM).Methods The population that studied consisted of 27 patients with multiple myeloma and 30 healthy controls.The RDW was calculated according to the results of blood routine examination and compared between patients and healthy controls.Then,compared the difference between the two groups of RDW.MM patients were treated with international standard staging (ISS),and the differences of RDW in different stages were analyzed.ISS staging was used to draw the receiver operating curve (receiver operating characteristic curve,ROC curve),then take RDW14.65 ％ as the best cut-off point,the MM patients were divided into low RDW group (RDW=14.65 ％) and high RDW group (RDW ＞14.65％).Overall survival (OS) condition were compared between the above two groups.The impacts of RDW on OS were analyzed by Kaplan-Meier and Log-rank test.Results The average RDW value in experimental and controlled were 15.60 ％ ± 2.35 ％ vs 12.72 ％ ±0.61 ％ separately (t=6.201,P＜0.001),with statistical differences.The average RDW value in low ISS(Ⅰ + Ⅱ stage) and high ISS (Ⅲ stage) were 13.99 ％ ± 1.08％ vs 16.55 ％±2.39％ separately (t=3.800,P=0.001).The median survival time of low RDW and high RDW group was 13 months and 8 months respectively,and the difference was statistically significant (x2=6.481,P =0.011).Conclusion RDW increased in patients with MM,the risk stratification higher prognosis is worse.

Objective To investigate the frequency of JAK2 V617F mutation and JAK2 V617F mutation allele burden in patients with essential thrombocythemia (ET), and explore the relationship between mutation and hematological parameters and coagulation function. Methods The clinical and laboratory parameters of 90 ET patients were analyzed. JAK2 V617F mutation was detected by AS-PCR and the mutation allele burden of JAK2 V617F was detected by qPCR. The correlation between mutation frequency and mutation burden of JAK2 V617F and blood laboratory parameters were investigated in ET. Results JAK2 V617F mutation was found in 50 patients (55.6 %). RBC [(4.67±0.89)×109/L vs (4.04±0.99)×109/L, P =0.003], WBC (11.64±5.20)×109/L vs (9.11±4.11)×109/L, P = 0.014], HCT (0.41±0.07) vs (0.36±0.07), P =0.005) in the JAK2 V617F mutated group were higher than those in the wild-type group. PT in mutated patients was longer than that in wild-type group [(13.18±1.63) s vs (12.02±1.24) s, P = 0.000]. The JAK2 V617F mutation allele burden was (29.91 ±18.63) %. No significant correlation was found between JAK2 V617F mutation allele burden and hematological parameters such as WBC, RBC and Plt (all P>0.05), but the JAK2 V617F mutation allele burden had a significant correlation with FDP (r = 0.456, P = 0.001). Conclusions JAK2 V617F mutation occurs in significant percentage patients with ET. Detection of JAK2 V617F mutation allele burden at diagnosis may play an important role in the early prevention of vascular events.

Objective To investigate the role of AKT/GSK3β/mTOR signaling molecule in myocardial protection of sevoflurane postconditioning.Methods Thirty-nine male Sprague-Dawley rats,weighing 200-250 g,installed in vivo myocardial ischemia-reperfusion model by left anterior de-scending coronary occlusion for 30 min.Rat hearts were randomly divided into 3 groups (n = 13 ):sham control group (group Sham),purely ischemia-reperfusion group (group IR),sevoflurane post-conditioning group (group SPC).With the exception of group Sham,each group was subjected to oc-clusion for 30 min followed by 2 h reperfusion.Group SPC was subjected to sevoflurane postcondi-tioning:2.4% sevoflurane was inhaled for 1 5 min starting from the end of ischemia until 1 5 min after beginning of reperfusion,while 33% oxygen was inhaled in the other groups.At the end of 2 h reper-fusion,cardiac function was evaluated by two-dimensional echocardiography,myocardial infarction size was measured by using 1% 2,3,5-triphenyltetrazolium chloride triazole (TTC),myocardial ultra-structural alterations was detected by transmission electron microscopy (TEM),cardiomyocytes ap-optosis was examined by terminal deoxynucleotidyl nickend labeling (TUNEL),the expressions of p-AKT/t-AKT, p-GSK3β/t-GSK3β, p-mTOR/t-mTOR,Bcl-2 and Bax proteins was measured by Western blot.Results Compared with group Sham,cardiac function was deteriorated,myocardial in-farct size was increased,cardiomyocyte mitochondrial damage was increased,positive apoptotic car-diomyocyte was increased,the expression of Bcl-2 was down-regluated,and the expressions of p-AKT/t-AKT,p-GSK3β/t-GSK3β,p-mTOR/t-mTOR and Bax were up-regluated in group IR (P <0.05).Compared with group IR,cardiac function was improved,myocardial infarct size was de-creased,cardiomyocyte mitochondrial damage was decreased,positive apoptotic cardiomyocyte was decreased,the expression of Bax was down-regluated,and the expressions of p-AKT/t-AKT,p-GSK3β/t-GSK3β,p-mTOR/t-mTOR and Bcl-2 were up-regluated in group SPC (P < 0.05 ). Conclusion Sevoflurane postconditioning can mitigate ischemia-reperfusion injury to in vivo rat hearts,decreased cardiomyocyte mitochondrial damage,inhibited cardiomyocyte apoptosis,and its mechanism was related to the activation of AKT/GSK3β/mTOR signaling molecule.

Aim To detect the effect of Bio on impro-ving insulin resistance and explore its molecular mech-anism. Methods The HepG2 liver cells were derivat-ed by high concentration insulin to establish the insulin resistance cell model, and the cells were intervened by Bio. The glucose consumption was measured by glu-cose oxidase and peroxidase ( GOD-POD) assay. The expression of PPARγmRNA was detected by RT-PCR. The expression of PPARγ protein was detected by Western blot method. Results The glucose consump-tion was significantly decreased in the insulin resist-ance cells after incubated with 1 . 72 × 10 -5 mol · L-1 insulin ( P<0. 05 ) . 10 -5 ,10 -6 ,10 -7 mol · L-1 Bio increased the glucose consumption 135%,62%,39%separately in the insulin resistance cells. RT-PCR a-nalysis of PPARγ showed that Bio raised the PPARγmRNA. Western blot analysis displayed that the pro-tein of PPARγ with Bio was increased. Conclusion Bio can improve the insulin resistance of the HepG2 cells, and the molecular mechanism may be relevant with raising PPARγ expression.