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*

Developing and identifying effective medications and targets for treating hepatic fibrosis is an urgent priority. Our previous research demonstrated the efficacy of artesunate (ART) in alleviating liver fibrosis by eliminating activated hepatic stellate cells (HSCs). However, the underlying mechanism remains unclear despite these findings. Notably, endocytic adaptor protein (NUMB) has significant implications for treating hepatic diseases, but current research primarily focuses on liver regeneration and hepatocellular carcinoma. The precise function of NUMB in liver fibrosis, particularly its ability to regulate HSCs, requires further investigation. This study aims to elucidate the role of NUMB in the anti-hepatic fibrosis action of ART in HSCs. We observed that the expression level of NUMB significantly decreased in activated HSCs compared to quiescent HSCs, exhibiting a negative correlation with the progression of liver fibrosis. Additionally, ART induced senescence in activated HSCs through the NUMB/P53 tumor suppressor (P53) axis. We identified NUMB as a crucial regulator of senescence in activated HSCs and as a mediator of ART in determining cell fate. This research examines the specific target of ART in eliminating activated HSCs, providing both theoretical and experimental evidence for the treatment of liver fibrosis.
Hepatic Stellate Cells/cytology* ; Liver Cirrhosis/genetics* ; Artesunate/pharmacology* ; Cellular Senescence/drug effects* ; Membrane Proteins/genetics* ; Animals ; Humans ; Nerve Tissue Proteins/genetics* ; Tumor Suppressor Protein p53/genetics* ; Male ; Mice

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 efficacy and safety of percutaneous lauromacrogol injection (PLI) in treatment of cystic or predominantly cystic thyroid nodules. Methods: A total of 114 cystic thyroid nodules and 61 predominantly cystic thyroid nodules with pain or uncomfort or aesthetic complaints were offered PLI. Therapeutic success rates and side effects were evaluated. From October 2012 to December 2015,114 patients with cystic thyroid nodules and 61 with predominantly cystic thyroid nodules with pain or uncomfortable or aesthetic complaints at the outpatient clinic of the First Affiliated Hospital of Wenzhou Medical University were offered percutaneous lauromacrogol sclerotherapy. Cytological results were benign. This study was a prospective trial. Ultrasonography sound examination was performed in all patients before treatment. The baseline data of all the patients and the data of the patients examined at the follow-up of 1, 3, 6 and 12 months were analyzed. Therapeutic success rate (nodule volume reduction >50%) and safety were observed. The data of nodule volume reduction ratio and the function of thyroid were normal distribution and analyzed by Mann-Whitney test and t test. The data of nodule volume, symptoms score and cosmetic score were skewed distribution, which were indicated with median and analyzed by nonparamentic test. Results: The mean volume of the cystic thyroid nodules was reduced from 12.5 cm³ before PLI to 0.2 cm³ at 12 months after PLI (χ²=266.175, P<0.001), with a therapeutic success rate of 100%, and the mean volume of the predominantly cystic thyroid nodules was reduced from 10.5 cm³ before PLI to 2.0 cm³ at 12 months after PLI (χ²=203.122, P<0.001) with a therapeutic success rate of 93.4%(57/61). Pressure symptom score and cosmetic grade were significantly improved at 12 months after PLI in patients with cystic or predominantly cystic thyroid nodules. Pressure symptom score and cosmetic grade in patients with cystic thyroid nodules were Z=-6.126 and Z=-13.735, respectively; pressure symptom score and cosmetic grade in patients with predominantly cystic thyroid nodules were Z=-3.126 and Z=-7.212, respectively (all P<0.001) . There no significant difference in the thyroid functions before and after PLI in two groups of patients (all P>0.05) . The side effects of PLI were mild. Conclusion PLI is a safe and effective alternative to treat benign cystic or predominantly cystic thyroid nodules.

Objective To compare the safety and efficacy of insulin degludec (IDeg) with those of insulin glargine (IGlar) in insulin-naive subjects with type 2 diabetes (T2DM).Methods This was a 26-week,randomized,open-label,parallel-group,treat-to-target trial in 560 Chinese subjects with T2DM (men/women:274/263,mean age 56 years,mean diabetes duration 7 years) inadequately controlled on oral antidiabetic drugs (OADs).Subjects were randomized 2:1 to once-daily IDeg (373 subjects) or IGlar(187 subjects),both in combination with metformin.The primary endpoint was changes from baseline in glycosylated hemoglobin(HbA1c) after 26 weeks.Results Mean HbA1c decreased from 8.2％ in both groups to 6.9％ in IDeg and 7.0％ in IGlar,respectively.Estimated treatment difference (ETD) of IDegIGlar in change from baseline was-0.10％ points (95％ CI-0.25-0.05).The proportion of subjects achieving HbA1c ＜ 7.0％ was 56.3％ and 49.7％ with IDeg and IGlar,respectively [estimated odds ratio of IDeg/IGlar:1.26 (95 ％ CI 0.88-1.82)].Numerically lower rateof overall confirmed hypoglycaemia and statistically significantly lower nocturnal confirmed hypoglycemia were associated with IDeg compared with IGlar,respectively [estimated rateratio of IDeg/IGlar 0.69 (95％ CI 0.46-1.03),and 0.43 (95％ CI 0.19-0.97)].No differences in other safety parameters were found between the two groups.Conclusions IDeg was non-inferior to IGlar in terms of glycaemic control,and was associated with a statistically significantly lower rate of nocturnal confirmed hypoglycaemia.IDeg is considered to be suitable for initiating insulin therapy in Chinese T2DM patients on OADs requiring intensified treatment.Clinical trail registration Clinicaltrials.gov,NCT01849289.

Objective To discuss the genotype and phenotype features of 187 patients with spinocerebellar ataxia type 3 (SCA3) and analyze their genotype-phenotype relationship.Methods A total of 187 patients genetically diagnosed as having SCA3 from 160 families were enrolled from our hospital from 2005 to 2015.Detailed medical histories were collected.SPSS 22.0 was conducted to statistically analyze the genotypes and pathogenic CAG expansions of A TXN3 gene in the patients.Results One hundred males and 87 females suffered SCA3.Mean age at onset was 35.43±11.17 years.The ranges of pathogenic CAG expansion were 65-86 repeats,with mean pathogenic CAG expansion of 74.11±3.56 repeats.A negative correlation was found between number of CAG repeats and age of onset (r=-0.815,P=0.000).Frequencies of the patients with tendon hyporeflexia were 28.9％ and 6.0％,respectively,in the smaller pathogenic CAG expansion group (≤74) and larger pathogenic CAG expansion group (＞74),with significant difference (P＜0.05).Frequencies of patients with rigidity were 27.8％ and 49.4％,respectively,in the smaller pathogenic CAG expansion group and larger pathogenic CAG expansion group,with significant difference (P＜0.05).Conclusions SCA3 is neurodegenerative disorder with high clinical and genetical heterogeneity.There are distinct correlations between number of pathogenic CAG expansion and age of onset,frequency ofhyporeflexia and rigidity.

Objective To investigate the effect of gastrointestinal lipase inhibitor combined with biguanides on serum estrogens in the treatment of polycystic ovary syndrome with infertility in patients.Methods 72 cases with polycystic ovary syndrome with infertility from Huangyan Hospital Affiliated to Wenzhou Medical University were selected and randomly divided into 2 groups, 36 cases of each group.The control group received conventional therapy, and the treatment group received more with orlistat, serological indicators, clinical symptoms, signs, pregnancy rate and ovulation rate were compared after the treatment.Results Compared with control group, levels of blood glucose and blood lipid index decreased in treatment group after treatment (P<0.05), the levels of luteinizing hormone (LH), follicles estrogen (FSH), estradiol (E2) and testosterone (T) decrease(P<0.05), levels of visfatin (VF) and leptin (LEP) decreased(P<0.05), adiponectin (APN) increased(P<0.05), and levels of BMI, WHR, hirsutism score and ovarian volume decreased (P<0.05).Compared with the control group(69.44%, 55.56%), the ovulation rate and pregnancy rate in the treatment (91.67%, 80.56%) were higher(P<0.05).Conclusion Gastrointestinal lipase inhibitor combined with biguanides could improve the pregnancy rate and ovulation rate in patients with polycystic ovary syndrome with infertility, reduce the levels of estrogens.

Objective To investigate the kidney function changes and the risk factors in elderly patients aged 80 years and over.Methods A total of 1054 hospitalized patients aged ≥80 years in our hospital were selected.Serum levels of creatinine,urea,uric acid and urinate were tested.Cockcroft-Gault equation was used to estimate glomerular filtrate rate (GFR).Results The renal function in 87.1 ％ of the patients was reduced.The percentage of patients with 30≤eGFR ＜60 ml · min-1 · 1.73 m-2 was 66.2％.The percentage of patients with 15≤eGFR ＜30 ml · min-1 · 1.73 · m-2had a gender difference (P＜0.05).Serum creatinine level was not an ideal indicator for early renal dysfunction in the elderly,especially in emaciated elderly people.Multivariate logistic regression analysis showed that gender,hypertension,coronary heart disease and hyperuricemia were independent risk factors for the decline of renal function (OR=1.937,1.602,1.842,7.020,respectively,all P＜0.05).Conclusions The rate of renal dysfunction is high in very old people.Many risk factors affect renal dysfunction.

Objective To explore the hospitalization costs of patients with diabetic foot ulcer and analyze key influencing factors.Methods A total of 570 diabetic foot inpatients were recruited from January 2008 to March 2012 for analysis of the relationship between their hospitalization costs and clinical symptoms.The multifactor regression analysis model was used to identify main influencing factors for their hospitalization costs.Results The medical costs of such inpatients amounted to 1 9 825.6 yuan (12 476.6~32 745.9)yuan,while average hospitalization costs of the 3 401 diabetic patients admitted over the same period were but 9 757.1 yuan (6 282.1 ~ 1 5 723.7 )yuan,a difference of statistic significance.The single-factor analysis found statistical differences from the differences of hospitalization among various age,occupation,dorsal artery of foot,B ultrasound of lower extremity arteries,wagner classification,amputation,transfer,leucocyte,hemoglobin,serum albumin,serum creatinine and high density lipoprotein.Multifactor analysis found that the significant factors influencing the medical costs of inpatients were days of stay,albumin,wagner classification,dorsal artery of foot,leucocyte and age. Conclusion Hypoalbuminemia,high stage of wagner classification,weak or absent pulsation of foot dorsal artery,severe infection and aging were significant factors contributing to higher medical costs of hospitalization for patients with diabetic foot ulcer.