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 explore the effects of estrogen receptor α (ERα) encoded by protein encoding gene ESR1 on the radiation resistance of breast cancer cells and their molecular mechanisms.Methods:The ESR1 overexpression plasmid was transfected into estrogen receptor (ER)-negative breast cancer cells. Then, the shRNA-ESR1 vector was introduced into ER-positive cell to establish models with different phenotype. The ATG5 mRNA level and protein expression levels of LC3B-I, LC3B-II, P62, FIP200, ATG5, ATG7, ATG12, Beclin1, ULK1 were detected using qPCR and Western blot techniques. Cell death was measured using flow cytometry. The radiation sensitivity was determined through the colony formation assay. The mortality of breast cancer cells under the autophagy gene knockdown and overexpression or treated with estrogen receptor inhibitor (TAM) combined with ionizing radiation were detected by trypan blue staining.Results:Under the condition of 8 Gy X-ray irradiation, the knockdown of ESR1 in ER-positive ZR75 breast cancer cells promoted cell death ( t = 3.49, 3.13, P < 0.05), while the overexpression of ESR1 in ER-negative MDA-MB-231 breast cancer cells inhibited cell death ( t = 4.16, 7.48, P < 0.05). Compared to the control group, the treatment with chloroquine increased the number of formed colonies of ESR1 knockdown ZR75 cells ( t = 8.49, P < 0.05), and inhibiting autophagy could reduce the death of ZR75 cells caused by ESR1 silencing. Under the treatment with ionizing radiation, the overexpression of ESR1 in MDA-MB-231 cells promoted protective autophagy, which, however, was reduced after ESR1 knockdown in ZR75 cells. Furthermore, it was observed that the knockdown of ATG5 in ZR75 cells was associated with reduced autophagy and an increase in cell death ( t = 4.19, 6.39, P < 0.05). In contrast, the overexpression of ATG5 in ZR75 cells reversed the increase in cell death caused by ESR1 knockdown ( t = 1.70, 4.65, P < 0.05). After the treatment of ER-positive ZR75 breast cancer cells with TAM, the expressions of ATG5 and ATG12 decreased, suggesting inhibited autophagy and an increase in cell death ( t = 18.70, P < 0.05). Furthermore, these processes were promoted by ionizing radiation ( t = 16.82, P < 0.05). Conclusions:The estrogen receptor encoded by ESR1 promotes protective autophagy of ER-positive breast cancer cells by increasing ATG5, further leading to radiation resistance in ER-positive breast cancer cells. Treatment with tamoxifen combined with ionizing radiation can increase the radiation sensitivity of ER-positive breast cancer cells.

Obejective　To investigate and compare the clinical efficacy of aroma massage with traditional massage in the treatment of chronic fatigue syndrome （CFS）. MethodsSeventy-two CFS patients were randomized into the aroma massage group and the traditional massage group， with 36 patients in each group. Both groups were treated with essential oil aromatherapy and massage were performed on the head， face， and abdomen stimultaneously. The aroma massage group used antifatigue oil， while the traditional massage group used placebo essential oil. The two groups were treated for 30 minutes each time， once every other day， three times a week， for a total of 4 weeks. The fatigue scale （FS-14） score， traditional Chinese medicine （TCM） syndrome score and patient satisfaction evaluation scale score before and after the treatment of the two groups were assessed to study the improvement of fatigue and other clinical symptoms of the patients as well as the changes of the TCM symptom scores， and to evaluate the clinical efficacy of the two groups. ResultsWith three drop-outs in the traditional massage group and two drop-outs in the aroma massage group， 33 cases in the traditional massage group and 34 cases in the aroma massage group were included in the outcome analysis. The FS-14 scores and TCM syndrome scores significantly decreased after treatment in both groups （P＜0.01）； compared to those in the traditional massage group （FS-14： 4.42±2.44； TCM syndrome score： 34.12±7.67）， the FS-14 score （3.06±2.37） and TCM syndrome score （28.79±5.62） in the aroma massage group were significantly lower （P＜0.05 or P＜0.01）. There was no significant difference in the satisfaction scores of the patients in the two groups after the treatment （P＞0.05）. The total effective rate of the aroma massage group was 94.12% （32/34）， which was significantly higher than 84.85% （28/33） of the traditional massage group （P＜0.05）. ConclusionBoth aromatherapy and traditional massage can improve the clinical symptoms of fatigue in CFS patients， and aromatherapy is more effective， which is easy to operate with high patient acceptance.

AIM: To identify immune-related key genes and the extent of immune cell infiltration in a oxygen-induced retinopathy(OIR)model by bioinformatics method.METHODS: Microarray data were obtained from the GEO database, differentially expressed genes(DEGs)were identified using the “limma” R package, GO function enrichment and KEGG pathway analysis were conducted, and immune cell infiltration based on the CIBERSORT algorithm was analyzed. Weighted gene co-expression network analysis(WGCNA)was used to screen DEGs in the immune-related gene module, constructing a protein-protein interaction(PPI)network using STRING online database and Cytoscape software, and further screening final target genes using the cytoHubba plug-in.RESULTS: A total of 467 DEGs were screened, including 270 up-regulated and 197 down-regulated genes. Helper T cell 2(Th2 cells), an immune cell type, exhibited significantly high expression levels(P<0.05). WGCNA analysis identified 66 differential genes in modules most closely related to immunity. After constructing the PPI network, 5 key genes were screened through plug-ins: von Willebrand factor(vWF), vascular endothelial growth factor A(VEGF-A), Serping1, apoptosis inducing factor 1(AIF1)and signal transducers and activators of transcription 3(STAT3).CONCLUSION: The findings of this study provide valuable insights into immune cell infiltration in OIR as well as key genes related to immunity through bioinformatics analysis, which can serve as a reference for further research and treatment of retinal neovascular diseases.

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.

With the continuous advancement of technology and the increasing understanding of metastatic renal cell carcinoma(mRCC),the treatment paradigm of mRCC has undergone significant transformation.Currently,in addition to surgery,mRCC is mainly treated with targeted therapy and immunotherapy,which have shown significant efficacy but also face challenges such as drug resistance and non-responsiveness persist.To address these issues,ongoing research and development of new technologies and drugs are under way.This article presents a comprehensive review of targeted therapy,immunotherapy,exploratory therapeutic options and treatment trends of mRCC.By summarizing the differences in technological principles and patient populations,it is argued that combination therapy and precision medicine will become the primary directions for future developments.Subsequent research will focus on optimizing the synergistic integration of diverse therapeutic techniques and achieving more precise patient stratification to realize more effective treatment.

Objective To analyze the characteristics of time in range(TIR)and its relationship with oxidative stress(OS)and insulin resistance status(HOMA-IR)in patients with type 2 diabetes mellitus(T2DM)and sleep apnea-hypopnea syndrome(OSAHS).Methods According to apnea-hypopnea index(AHI),165 T2DM in patients were divided into simple T2DM group(AHI<5 times/h,n=43),T2DM combine OSAHS mild group(OSAHS-G,5≤AHI<15 times/h,n=51),T2DM combined OSAHS moderate group(OSAHS-M,15≤AHI≤30 times/h,n=40)and T2DM combine OSAHS severe group(OSAHS-S,AHI>30 times/h,n=31).TIR was calculated by dynamic blood glucose monitoring.Superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and other indexes were detected and analyzed.Results Compared with simple T2DM group,the levels of HOMA-IR,8-iso-PGF2a and Ox-LDL were higher in T2DM combined OSAHS-G,OSAHS-M or OSAHS-S group,while the levels of TIR,SOD and GSH-Px were lower(P<0.05).Pearson correlation analysis showed that TIR was positively correlated with the levels of SOD and GSH-Px(P<0.05 or P<0.01),and negatively correlated with the levels of 8-iso-PGF2a,Ox-LDL,HbA1c,HOMA-IR and the severity of OSAHS(P<0.01).Logistic regression analysis showed that TIR,SOD and GSH-Px were protective factors for severe OSAHS in T2DM patients,while 8-iso-PGE2a and Ox-LDL were the risk factors for severe OSAHS.Conclusions The glucose level fluctuates greatly in patients with T2DM and OSAHS.Insulin resistance and oxidative stress are factors that affect the normalization of TIR.

Objective:To compare the therapeutic effects of partial nephrectomy (PN) and cryoablation (CA) in patients with stage cT 1N 0M 0 renal cell carcinoma (RCC). Methods:A retrospective analysis was conducted on clinical data of patients with stage cT 1N 0M 0 RCC who underwent CA and PN treatment at The First Affiliated Hospital of Naval Medical University and Shanghai Ninth People's Hospital between March 2011 and December 2019. There were 50 cases in the CA group (36 from The First Affiliated Hospital of Naval Medical University and 14 from the Shanghai Ninth People's Hospital), and 1 323 cases in the PN group (all from The First Affiliated Hospital of Naval Medical University). PN included open surgery, laparoscopic surgery, or robotic surgery performed under general anesthesia through the abdominal or retroperitoneal approach. CA included laparoscopic surgery under general anesthesia and percutaneous treatment guided by CT or ultrasound under local anesthesia. Propensity score matching was performed based on baseline data of the patients to obtain balanced samples between the two groups using a 1∶2 nearest-neighbor matching method. After matching, comparisons were made between the two groups in terms of perioperative conditions, overall survival (OS), and recurrence-free survival (RFS). Results:After PSM, patient distributions were closely balanced in baseline data such as gender (male/female: 28/19 cases in CA group and 58/36 cases in PN group), age [66.0(53.0, 75.0) years vs. 59.5(50.0, 69.3) years], body mass index[ (24.1 ± 6.4) kg/m 2 vs. (24.1 ± 3.1) kg/m 2], Charlson comorbidity index [1(0, 2) vs. 1(0, 2)], history of malignant tumors [19.1% (9/47) vs. 17.0% (16/94)], preoperative estimated glomerular filtration rate (eGFR) [85.2(65.5, 97.1) ml/(min·1.73m 2) vs. 87.0(73.4, 100.4) ml/(min·1.73m 2)], and R. E.N.A.L. score [6(5, 7) vs. 7(6, 8)] between CA(n=47) and PN(n=94) group. There were significant differences in operative time [97.5(81.2, 117.5) min vs. 145.0(110.2, 185.0) min, P<0.001], estimated blood loss [85.0(50.0, 100.0) ml vs. 100.0(75.0, 200.0)ml, P=0.021], length of hospital stay [3.0(2.0, 4.0) days vs. 7.6(5.0, 9.0) days, P<0.001] between the CA and the PN group. No significant differences were observed in the incidence of postoperative complications [4.3% (2/47) vs. 5.3% (5/94), P=0.784], the eGFR within one week after surgery [83.7(65.6, 106.6) ml/(min·1.73m 2) vs. 83.2(66.7, 97.7) ml/(min·1.73m 2), P=0.645], the median follow-up time [ 93 (67, 126) months vs. 85 (68, 139) months, P=0.955], the RFS rate[81.8% vs. 96.8%, P=0.074], or the OS rate [85.7% vs. 97.8%, P=0.190] between the CA and the PN group. Conclusions:For patients with cT 1N 0M 0 stage RCC, CA and PN demonstrate comparable oncologic treatment efficacy, while CA offering the advantages of shorter surgical time, shorter hospital stay, and less blood loss.

Focal therapy for renal cell carcinoma is a precision treatment technique that directly targets and destroys cancerous lesions while preserving the maximum amount of surrounding healthy kidney tissue through localized intervention. It is primarily indicated for early-stage renal cell carcinoma in patients with tumors ≤4 cm in diameter (T 1a), particularly for those at higher surgical risk. Compared to traditional radical nephrectomy and partial nephrectomy, focal therapy offers several advantages, including lower physical demands on the patient, minimally invasive nature, reduced risk of complications, and faster recovery. The focal therapy techniques currently utilized in clinical practice include cryoablation, radiofrequency ablation, microwave ablation, irreversible electroporation, high-intensity focused ultrasound, and stereotactic body radiotherapy. This article reviews the principles of various focal therapy techniques, patient selection, and the oncological outcomes, complications, and renal function preservation associated with these focal therapies.

Objective:To investigate the clinical efficacy of triamcinolone acetonide peribulbar injection combined with vitrectomy for rhegmatogenous retinal detachment associated with choroidal detachment (RRD-CD).Methods:This study was a retrospective case series study. Nineteen cases (19 eyes) with RRD-CD who had undergone pars plana vitrectomy at the Dalian No.3 People′s Hospital were analyzed. All the cases received 20 mg triamcinolone acetonide peribulbar injection within 3 to 7 days before surgery. The severity of patient′s uveitis was assessed before and after peribulbar injection of triamcinolone acetonide. Best corrected visual acuity (BCVA) and intra ocular pressure (IOP) before and after surgery, the area of retinal detachment, the rate of retinal reattachment, the rate of recurrent retinal detachment and surgical complications were analyzed. Patients′ blood pressure and blood glucose levels were also monitored.Results:19 patients were followed up for (13.1±1.5)months. The severity of uveitis reduced to different extents compared with preoperative condition. The IOP was (8.73±3.38)mmHg before injection and (10.95±2.46)mmHg after injection, and the difference was statistically significant ( t=-7.571, P=0.027). The choroid detachment range was 4-12(9.37±2.69)sites before injection, and 0-11(4.63±4.10)sites after injection, and the difference was statistically significant ( Z=-3.834, P=0.001). Compared with the preoperative results, the BCVA increased in 12 patients, unchanged in 5 cases and decreased in 2 cases. In the final follow-up of 18 patients with retinal reattachment, 17 eyes underwent a single operation, 2 eyes had recurrent retinal detachment, and 1 eye had retinal reattachment after a second operation. There were no significant difference in blood glucose and blood pressure before and after injection (all P>0.05). There were no other complications besides temporarily elevated IOP and cataract. Conclusions:Vitrectomy combined with triamcinolone acetonide peribulbar injection is effective and safe for patients with RRD-CD.