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*

Hepatocellular carcinoma (HCC) expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming. Aldolase A (ALDOA) plays a prominent role in glycolysis; however, little is known about its role in HCC development. In the present study, we aim to explore how ALDOA is involved in HCC proliferation. HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout, which is consistent with ALDOA overexpression encouraging HCC proliferation. Mechanistically, ALDOA knockout partially limits the glycolytic flux in HCC cells. Meanwhile, ALDOA translocated to nuclei and directly interacted with c-Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase; ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function. A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun, and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells. In HCC patients, the expression level of ALDOA was correlated with the phosphorylation level of c-Jun (Thr93) and poor prognosis. Remarkably, hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models, and the knockdown of A ldoa strikingly decreased HCC development in vivo. Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription, opening additional avenues for anti-cancer therapies.

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 explore the efficacy of sodium valproate and haloperidol in the treatment of Tourette's syndrome in children and the effects on serum levels of insulin-like growth factor 1(IGF-1),neuron specific enolase(NSE)and S100β.Methods Children with Tourette's syndrome were divided into treatment group and control group.Control group was given oral administration of haloperidol 2 mg every time,twice or three times a day for 3 months,treatment group was given oral administration of 20 mg·kg-1·d-1 sodium valproate for every 12 hours,totally treatment for 3 months.The clinical efficacy,Yale Global Tourette Severity Scale(YGTSS),levels of serum IGF-1,NSE and S100β,neurotransmitters,cytokines,and occurrence of adverse drug reactions were compared between the two groups of patients.Results A total of 150 patients were included in this study,including 5 cases of shedding during the trial,thus 73 cases in treatment group and 72 cases in control group were finally enrolled.The total effective rates of treatment in treatment group and control group were 91.78％(67 cases/73 cases)and 79.17％(57 cases/72 cases),with significant difference(P＜0.05).The scores of motor tic of YGTSS in treatment group and control group after treatment were(9.79±1.73)and(11.05±2.18)points;the vocal tic scores were(10.52±2.06)and(11.37±2.24)points;the total scores of YGTSS were(20.31±2.57)and(22.42±2.57)points;serum levels of IGF-1 were(60.37±3.29)and(58.04±3.16)μg·L-1;levels of NSE were(95.26±10.19)and(101.81±10.54)ng·L-1,S100β levels were(83.69±10.33)and(87.05±9.76)ng·L-1;levels of 5-HT were(59.05±5.69)and(61.37±5.52)ng·mL-1;levels of GABA were(2.37±0.32)and(2.04±0.39)ng·mL-1;levels of NE were(32.85±4.63)and(29.24±4.02)ng·mL-1;levels of IL-6 in were(19.05±2.97)and(21.31±4.01)ng·mL-1,all with significant difference(all P＜0.05).The recurrence rate in treatment group and control group were 16.44％(12 cases/73 cases)and 23.61％(17 cases/72 cases),with no significant difference(P＞0.05).There was no significant difference in the incidence of adverse drug reactions between the two groups(P＞0.05).Conclusion Compared with haloperidol,sodium valproate has higher effective rate in the treatment of children with Tourette's syndrome,and it can better relieve the clinical symptoms,improve the neurological function,and help to reduce the levels of serum IGF-1,NSE,S100βand inflammatory factors.

Aim To prepare prostate cancer exosomes containing melittin and observe their uptake by prostate cancer cells. Methods Cells treated with starvation for different time were screened for exosome extraction. Exosomes from PC-3 cells were extracted by ultracentrifugation, and the extracted particles were examined by transmission electron microscopy, nanoparticle tracking analyzer(NTA), and Western blot. Melittin exosome system was prepared by repeated freeze-thaw method, incubation at room temperature as well as electroporation, and the size of encapsulation efficiency was measured by centrifugation. A high-performance liquid chromatography(HPLC)method was applied to assay the content of melittin exosomes(exo-mel). Fluorescence inverted microscopy was employed to evaluate the uptake of melittin exosomes by PC-3 cells, DU145 cells as well as LNCaP cells. Results The results of starvation treatment showed that 24 h starvation treatment was the optimal time point. TEM results showed that the exosomes were round or oval in shape with a distinct membranous structure, and the diameter was around 100 nm. The reagent protein concentration for NTA analysis of exosomes was 0.222 g·L-1. The results of Western blot for the marker proteins of exosomes showed that Alix and CD63 were positively expressed, which indicated that the exosomes could be obtained by starvation culture of PC-3 cells and ultracentrifugation. The results of entrapment efficiency showed that the entrapment efficiency of electroporation method was 17.51% ± 2.39%, that of repeated freeze-thaw method was 11.46% ± 1.02%, and that of room temperature incubation method was 3.93% ± 2.44%. The encapsulation efficiency of electroporation was the highest with significant difference(P<0.05). The uptake assay showed that PC-3 cells could efficiently take up exo-mel in a time-dependent manner, and DU145 cells and LNCaP cells also could take up exo-mel over time. Conclusions Exosomes can be accessed by starvation treatment and high-speed centrifugation, and the prostate cancer melittin exosome system prepared by electroporation method could be taken up by prostate cancer cells.

Recent research has highlighted structural and functional abnormalities in the cerebral cortex of patients with premature ejaculation (PE). These anomalies could play a pivotal role in the physiological mechanisms underlying PE. This study leveraged functional magnetic resonance imaging (fMRI), a noninvasive technique, to explore these neural mechanisms. We conducted resting-state fMRI scans on 36 PE patients and 22 healthy controls (HC), and collected data on Premature Ejaculation Diagnostic Tool (PEDT) scores and intravaginal ejaculation latency time (IELT). Employing a surface-based regional homogeneity (ReHo) approach, we analyzed local neural synchronous spontaneous activity, diverging from previous studies that utilized a volume-based ReHo method. Areas with significant ReHo differences between PE and HC groups underwent surface-based functional connectivity (FC) analysis. Significant discrepancies in ReHo and FC across the cortical surface were observed in the PE cohort. Notably, PE patients exhibited decreased ReHo in the left triangular inferior frontal gyrus and enhanced ReHo in the right middle frontal gyrus. The latter showed heightened connectivity with the left lingual gyrus and the right orbital superior frontal gyrus. Furthermore, a correlation between ReHo and FC values with PEDT scores and IELT was found in the PE group. Our findings, derived from surface-based fMRI data, underscore specific brain regions linked to the neurobiological underpinnings of PE.
Male ; Humans ; Premature Ejaculation ; Brain Mapping/methods* ; Brain ; Cerebral Cortex ; Magnetic Resonance Imaging/methods*

Humans ; RNA, Long Noncoding/genetics* ; MicroRNAs/genetics* ; Cell Line, Tumor ; Inflammation/genetics* ; Apolipoproteins E ; Apoptosis

AIM: To explore the etiology classification and clinical characteristics of infants with moderate-severe visual impairment aged 0-2 years old, and preliminarily formulate a set of process for grass-roots health-care institutions to carry out the screening and management of children visual impairment.METHODS: There were 245 cases of children aged 0-2 years with moderate-severe visual impairment who were admitted to the Children Eye Care Specialist Clinic in Nanjing Maternal and Child Health Hospital from January 2009 to December 2020 were retrospectively analyzed. A complete profile of visual development was established, including age, sex, medical history, vision, eye position and movement, anterior segment examination, fundus examination, refractive examination under cycloplegia with 1% atropine ophthalmic gel, if necessary, some special eye examinations such as fundus photography, eye A/B ultrasound and visual electrophysiology were received.RESULTS: The average visit age of 245 cases of infants was 1.82±0.79 years, including refraction error of 128 cases(52.2%), among them, 100 cases(40.8%)were high refraction error; 79 cases(32.2%)were eye diseases, most of which were congenital cataract(33 cases); and 38 cases(15.5%)were cerebral visual impairment(CVI)(15.5%).CONCLUSION: It is necessary to proceed classified managements according to the etiology and clinical characteristics of infant visual impairment to find early and diagnose and treat multidisciplinary,including drawing up screening plans for remediable eye diseases, carrying out necessary refractive correction and training children to use residual visual function.

Objective: To compare the effects between second toe tibial dorsal artery flap (2-TDAF) and second toe tibial plantar proper artery flap (2-TPPAF) in repairing finger skin and soft tissue defects. Methods: A retrospective cohort study was conducted. From January 2019 to June 2020, 27 patients with skin and soft tissue defects at the fingertips with area of 1.5 cm×1.2 cm-2.6 cm×1.8 cm after debridement who met the inclusion criteria were admitted to Suzhou Ruihua Orthopaedic Hospital, including 21 males and 6 females, aged 19-59 (37±10) years. According to flap repair methods used in the defective fingers, the patients were divided into 2-TDAF group (12 cases) and 2-TPPAF group (15 cases). The area of 2-TDAF ranged from 1.5 cm×1.2 cm to 2.5 cm×1.6 cm, and the area of 2-TPPAF ranged from 1.7 cm×1.3 cm to 2.6 cm×1.8 cm. Full-thickness skin grafts from the medial side of the ipsilateral leg were grafted to the wounds in donor sites, and the wounds in donor sites of skin grafts were directly sutured. Flap arterial diameter, flap excision time, flap survival situation of patients in 2 weeks after operation, and follow-up time were recorded. At the last follow-up, the two-point discrimination distance of flap graft site, total action motion (TAM) of the finger joints, and wound healing of the flap donor site were recorded; the Vancouver scar scale (VSS) was used to score the scar in donor area of the second toe and the recipient area of fingers; the appearance and self-satisfaction subscales of the Michigan hand outcomes questionnaire (MHQ) were used to evaluate the affected finger. Data were statistically analyzed with independent sample t test or Fisher's exact probability test. Results: The flap artery diameter of patients in 2-TDAF group was 0.35-0.80 (0.56±0.14) mm and the flap cutting time was (14.0±2.7) min, which were significantly shorter than 0.80-1.35 (1.02±0.16) mm and (19.7±3.4) min in 2-TPPAF group (with t values of 7.81 and 4.79, respectively, P<0.01). The flaps of patients in the 2 groups in recipient areas survived well in 2 weeks after operation, and the wounds in donor areas of flaps of patients in the 2 groups healed well at the last follow-up. There was no statistically significant difference in the postoperative follow-up time, and two-point discrimination distance of flap graft site, TAM of the finger joints, VSS score of scar in the second toe donor site and the finger recipient site, and the appearance and self-satisfaction of MHQ scores of the affected finger at the last follow-up (P>0.05). Conclusions: Compared with 2-TPPAF, 2-TDAF has a shallower anatomical layer and shorter time for surgical flap removal, which can preserve the proper arteries and nerves at the base of the toes and reduce the damage to the donor site.
Male ; Female ; Humans ; Soft Tissue Injuries/surgery* ; Finger Injuries/surgery* ; Cicatrix/surgery* ; Plastic Surgery Procedures ; Retrospective Studies ; Treatment Outcome ; Surgical Flaps ; Skin Transplantation ; Toes/surgery* ; Arteries ; Perforator Flap