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 observe brain function changes in insomnia disorder(ID)patients and therapeutic effect of repeated transcranial magnetic stimulation(rTMS)based on resting-state functional MRI(rs-fMRI).Methods Totally 37 patients with ID(ID group)and 20 healthy subjects(control group)were prospectively enrolled.The scores of sleep condition and psychological state scales were compared between groups,also within ID group before and after rTMS treatment.Brain regions with amplitude of low frequency fluctuations(ALFF)and regional homogeneity(ReHo)being significantly different between groups were evaluated based on brain rs-fMRI,and voxel-based resting-state functional connectivity(FC)analysis was performed in the above regions and the predefined regions of interest.Results Before treatment,Pittsburgh sleep quality index(PSQI),insomnia severity index(ISI),Epworth sleepiness score(ESS),Beck depression inventory(BDI)score and Beck anxiety inventory(BAI)score in ID group were all higher than those in control group(all P＜0.05).ALFF values and ReHo of the right median cingulate and paracingulate gyrus(Cingulum_Mid_R)were lower in ID group than those in control group(all FWE correctedP＜0.05).FC between Cingulum_Mid_R and the left anterior cingulate gyrus and cingulate gyrus(Cingulum_Ant_L)decreased,so did that between the left hippocampus(Hippocampus_L)and the right frontal gyrus(Frontal_Mid_R)(all FWE corrected P＜0.05).After rTMS,PSQI,ISI and ESS scores of ID patients decreased compared to those before treatment(all P＜0.05),but no significant change of the above neuroimaging indicators was detected(all FWE corrected P＞0.05).Conclusion ID caused synchronous decrease of Cingulum_Mid_R ALFF value and ReHo,as well as weakened FC between frontal cingulate gyrus and frontal with lobe limbic system.rTMS could improve sleep and mental state of ID patients,but its impact on neuroimaging needed further investigation.

Objective:To successfully isolate and identify patient-derived ovarian cancer stem cells(OCSC),and to investigate the expression of monocarboxylate transporter 2(MCT2)in OCSC and its effects on the stem-ness and invasiveness of OCSC.Methods:Primary ovarian cancer cells were obtained,and OCSC models were established through screening and culturing.The screened OCSC were designated as the OCSC group,while the adherent primary cells were employed as control group 1.Two MCT2 inhibition constant Ki-specific inhibitors,namely[α-cyano-4-hydroxycinnamic acid(CHC)and ARC155858],were utilized for intervention,setting up the CHC inhibition group and the ARC155858 inhibition group.The group with only the solvent DMSO added was set respectively as CHC control group 2 and ARC 155858 control group 2.Flow cytometry and qRT-PCR were used for identification of OCSC markers.The expression levels and locations of MCT2 were detected by qRT-PCR and immunofluorescence staining.The effects of MCT2 inhibitors on the stemness and invasiveness of OCSC were verified using sphere formation assays and Matrigel invasion assays.Results:A primary OCSC cell bank consis-ting of 23 clinical models was established.qRT-PCR results showed that the expression level of MCT2 in OCSC group(5.78±3.55 and 122.89±19.90)was significantly higher than that in the control group 1(1.01±0.10 and 1.55±1.45),the difference is statistically significant(P＜0.05).Fluorescent quantitative analysis confirmed that MCT2 expression in OCSC group was higher than that in the control group 1(6.79±0.67 AU vs.2.49±1.78 AU,P=0.030).Treatment with MCT2 inhibitors in OCSC resulted in a significant reduction in sphere formation in the CHC inhibition group(6.00±2.17 spheres/1000 cells)compared to the CHC control group 2(14.62±3.07 spheres/1000 cells),the difference is statistically significant(P＜0.01),and in the ARC155858 inhibition group(11.00±4.42 spheres/1000 cells)compared to the ARC155858 control group 2(23.90±4.72 spheres/1000 cells),the difference is statistically significant(P＜0.01).In Matrigel invasion assays,the invasiveness in the in-hibitor group was significantly lower than in the control group(ARC155858:inhibitor group 10.20±5.98 cells vs.control group 67.20±28.96 cells,P＜0.05).Conclusions:This study observed that MCT2 expression significantly increased in OCSC.Inhibition of MCT2 significantly reduces the stemness and invasiveness of OCSC,providing potential research directions for targeted therapy of ovarian cancer.

Objective To observe brain function changes in insomnia disorder(ID)patients and therapeutic effect of repeated transcranial magnetic stimulation(rTMS)based on resting-state functional MRI(rs-fMRI).Methods Totally 37 patients with ID(ID group)and 20 healthy subjects(control group)were prospectively enrolled.The scores of sleep condition and psychological state scales were compared between groups,also within ID group before and after rTMS treatment.Brain regions with amplitude of low frequency fluctuations(ALFF)and regional homogeneity(ReHo)being significantly different between groups were evaluated based on brain rs-fMRI,and voxel-based resting-state functional connectivity(FC)analysis was performed in the above regions and the predefined regions of interest.Results Before treatment,Pittsburgh sleep quality index(PSQI),insomnia severity index(ISI),Epworth sleepiness score(ESS),Beck depression inventory(BDI)score and Beck anxiety inventory(BAI)score in ID group were all higher than those in control group(all P＜0.05).ALFF values and ReHo of the right median cingulate and paracingulate gyrus(Cingulum_Mid_R)were lower in ID group than those in control group(all FWE correctedP＜0.05).FC between Cingulum_Mid_R and the left anterior cingulate gyrus and cingulate gyrus(Cingulum_Ant_L)decreased,so did that between the left hippocampus(Hippocampus_L)and the right frontal gyrus(Frontal_Mid_R)(all FWE corrected P＜0.05).After rTMS,PSQI,ISI and ESS scores of ID patients decreased compared to those before treatment(all P＜0.05),but no significant change of the above neuroimaging indicators was detected(all FWE corrected P＞0.05).Conclusion ID caused synchronous decrease of Cingulum_Mid_R ALFF value and ReHo,as well as weakened FC between frontal cingulate gyrus and frontal with lobe limbic system.rTMS could improve sleep and mental state of ID patients,but its impact on neuroimaging needed further investigation.

Objective:To successfully isolate and identify patient-derived ovarian cancer stem cells(OCSC),and to investigate the expression of monocarboxylate transporter 2(MCT2)in OCSC and its effects on the stem-ness and invasiveness of OCSC.Methods:Primary ovarian cancer cells were obtained,and OCSC models were established through screening and culturing.The screened OCSC were designated as the OCSC group,while the adherent primary cells were employed as control group 1.Two MCT2 inhibition constant Ki-specific inhibitors,namely[α-cyano-4-hydroxycinnamic acid(CHC)and ARC155858],were utilized for intervention,setting up the CHC inhibition group and the ARC155858 inhibition group.The group with only the solvent DMSO added was set respectively as CHC control group 2 and ARC 155858 control group 2.Flow cytometry and qRT-PCR were used for identification of OCSC markers.The expression levels and locations of MCT2 were detected by qRT-PCR and immunofluorescence staining.The effects of MCT2 inhibitors on the stemness and invasiveness of OCSC were verified using sphere formation assays and Matrigel invasion assays.Results:A primary OCSC cell bank consis-ting of 23 clinical models was established.qRT-PCR results showed that the expression level of MCT2 in OCSC group(5.78±3.55 and 122.89±19.90)was significantly higher than that in the control group 1(1.01±0.10 and 1.55±1.45),the difference is statistically significant(P＜0.05).Fluorescent quantitative analysis confirmed that MCT2 expression in OCSC group was higher than that in the control group 1(6.79±0.67 AU vs.2.49±1.78 AU,P=0.030).Treatment with MCT2 inhibitors in OCSC resulted in a significant reduction in sphere formation in the CHC inhibition group(6.00±2.17 spheres/1000 cells)compared to the CHC control group 2(14.62±3.07 spheres/1000 cells),the difference is statistically significant(P＜0.01),and in the ARC155858 inhibition group(11.00±4.42 spheres/1000 cells)compared to the ARC155858 control group 2(23.90±4.72 spheres/1000 cells),the difference is statistically significant(P＜0.01).In Matrigel invasion assays,the invasiveness in the in-hibitor group was significantly lower than in the control group(ARC155858:inhibitor group 10.20±5.98 cells vs.control group 67.20±28.96 cells,P＜0.05).Conclusions:This study observed that MCT2 expression significantly increased in OCSC.Inhibition of MCT2 significantly reduces the stemness and invasiveness of OCSC,providing potential research directions for targeted therapy of ovarian cancer.

The transgender children and adolescents(TCAs)face serious social dilemmas in the process of gender identity and expression,which hinders this group from seeking reasonable and equal rights to survival and development.From the perspective of equal rights and the theoretical framework of social dilemma,by interviewing TCAs who seek help from medical social workers in a hospital's multi-disciplinary transgender clinic,this paper revealed that under the traditional system of"binary gender",TCAs lacked social inclusiveness and infrastructure,which led to the two major social dilemmas of"social traps"and"social barriers"encountered by this group in the process of gender expression and gender identity.Specifically,the social gender selection of TCAs often leads to collective irrational reactions and gender punishment,preventing their legal and effective medical services.To this end,the research team used critical methodology to construct a joint disciplinary diagnosis and treatment path for TCAs with the participation of medical social workers,as well as verified that the path has significant intervention effects in rationalizing the needs of TCAs and their families,alleviating their psychological pressure and social adaptation problems in the process of gender identity,fostering a diverse dialogue environment in their families,as well as enhancing their self-efficacy and social participation,to provide assistahce to the TCAs groups in social difficulties,assisting their rights and interests be included in the child-friendly indicator system,and improving the whole society's tolerance and understanding for TCAs group.

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.

Objective To investigate the characteristics of peroperative blood pressure and heart rate in patients with normotensive incidental pheochromocytomas in order to provide the basis for peroperative treatment. Methods This retrospective study collected the data of 104 patients with a pathological diagnosis of unilateral pheochromocytoma at PLA General Hospital during January 2011 to December 2016. They were divided into normotensive incidental pheochromocytomas(NIP) group (n＝50) if the patients were normotensive and HIP group ( n＝54) if the patients were with hypertension. The clinical features, imaging features and peroperative hemodynamics were analyzed. Results ( 1) The age, urinary norepinephrine, daily dosage and duration of phenoxybenzamine in NIP group were less than those of HIP group (all P<0.05). (2) Preinduction blood pressure, maximum blood pressure, and total fluid intake in NIP group were lower than those in HIP group(all P<0.05). The blood pressure range, heart rate range, increased blood pressure, minimum mean arterial pressure, vasoactive medication were without statistical significance between these two groups. ( 3) The times and rate of intraoperative systolic blood pressure more than 30% baseline, 200 mmHg (1 mmHg＝0.133 kPa), 180 mmHg, 160 mmHg, intraoperative tachycardia, bradycardia, intraoperative hypotension and postoperative hypotension were without statistical significance between these two groups. (4) Stratified analysis of age (50 years), phenoxybenzamine (40 mg/d), tumor diameter (50 mm) and preinduction blood pressure (130/80 mmHg) showed that intraoperative blood pressure and heart rate were without statistical significance between these two groups. ( 5) There was no correlation between phenoxybenzamine ( daily dosage or duration ) and peroperative hypotension. Applying phenoxybenzamine or vasoactive medication was not correlated with peroperative hypotension in NIP group. Conclusion The peroperative blood pressure and heart rate of patients with NIP are similar to those of patients with HIP. Adequate peroperative treatment should be applied to NIP to avoid hemodynamic instability.

Objective To characterize the baseline status of Chinese diabetic patients based on data derived from Chinese cohort from SOLVETM study.Methods Patients with type 2 diabetes initiating basal insulin detemir at the decision of the physician were eligible for the study.Data on demographics,medical history,glycemic profile and treatment regimen at baseline were collected by physicians.Results A total of 3272 patients [female 42％,male 58％,mean age (56.2 ± 10.8) years] were included in the study.Their BMI was (25.3 ± 3.3) kg/m2.The duration of diabetes was 4.0 (0.1-27.0) years,and the duration of treatment with oral antidiabetic drugs (OADs) was 3.0(0.0-20.2) years.The proportions of subjects with diabetic macro-and micro-vascular complications were 15.8％ (515 cases) and 27.1％ (866 cases),respectively.The hemoglobin Al c (HbAl c) at baseline was (8.33 ± 1.70) ％,and the fasting blood glucose (FPG) was (9.5 ± 2.6) mmol/L.Conclusions A large proportion of patients with type 2 diabetes remain in poor glycemic control,and the prevalence of diabetic complications is high,which requires optimal therapeutic strategy for the patients with suboptimal glycemic control.