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*

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.

Objective To observe the effects of repeated intravitreal injections of ranibizumab and aflibercept on cor-neal morphology of patients with neovascular age-related macular degeneration(nAMD),diabetic macular edema(DME)or retinal vein obstruction(RVO).Methods In this prospective study,64 patients(64 eyes)who underwent therapy in the injection center of the Ophthalmology Department of our hospital from June 2021 to June 2022 were enrolled,including 19 nAMD patients,20 DME patients and 25 RVO patients.Among these patients,29 were treated with aflibercept(40 g·L-1)and 35 were treated with ranibizumab(10 g·L-1).Monocular injections were adopted for all patients,and 3+pro re nata(PRN)therapy was used.Confocal microscope was used for corneal nerve examination,and corneal endo-thelial microscope was used to measure corneal thickness(CT)and corneal endothelial cells.The CT,corneal endothelial cell density(ECD),coefficient of variation(CV),average cell size(ACS),proportion of hexagonal cells(Hex％),cor-neal nerve fiber length(CNFL),corneal nerve fiber density(CNFD)of patients with nAMD,DME and RVO after repeated intravitreal injections of anti-vascular endothelial growth factor(VEGF)drugs were compared,and those parameters at 1 month after injection of different anti-VEGF drugs were compared with the baseline.Results Before injection,ECD in the DME group was lower than that in the nAMD and RVO groups,and the ACS in the DME group was higher than that in the nAMD and RVO groups(all P＜0.05).There was no significant difference in the other indexes among the three groups(all P＞0.05).After 3 injections of anti-VEGF drugs,the ECD in the DME group was lower than that in the nAMD and RVO groups,the ACS in the DME group was higher than that in the nAMD and RVO groups,and the CNFL in the DME group was lower than that in the nAMD and RVO groups(all P＜0.05).The ECD decreased compared with that before injection from the 2nd injection of aflibercept in the nAMD group(all P＜0.05).Hex％decreased significantly after each injection compared with the baseline(all P＜0.05).Other indexes have no significant differences from the baseline(all P＞0.05).In the RVO group,ECD decreased from the 2nd ranibizumab injection compared with the baseline(all P＜0.05).Conclu-sion Repeated intravitreal injections of anti-VEGF drugs can reduce the Hex％and ECD to a certain extent.After injec-tions,CNFL in the DME group is significantly lower than that in the nAMD and RVO groups.

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.

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.

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 explore the influence of pancreatic stents of different lengths on the incidence of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP).Methods:Data of 299 patients with biliary tract diseases who received endoscopic retrograde cholangiopancreatography (ERCP) and 5 Fr prophylactic pancreatic stents placement at the First Affiliated Hospital of Air Force Medical University from January 2013 to January 2022 were retrospectively analyzed. Patients were divided into the short-stent group (<5 cm, n=163) and the long-stent group (>5 cm, n=136). Baseline data, intraoperative procedures, and postoperative outcomes were compared between the two groups and propensity score matching (PSM) was used for complementary analysis. The primary endpoint was the incidence of PEP. The risk factors for PEP in patients with prophylactic pancreatic stents placement was explored by logistic regression analysis . Results:The overall PEP incidence was 11.0% (33/299). There was no significant difference in the PEP incidence [11.7% (19/163) VS 10.3% (14/136), χ 2=0.140, P=0.708], moderate-to-severe PEP incidence [1.8% (3/163) VS 2.2% (3/136), χ 2=0.000, P=1.000], or spontaneous stent dislodgement rate within two weeks [81.7% (103/126) VS 78.4% (87/111), χ 2=0.421, P=0.516] between the two groups. After PSM, 123 patients were included in each group, and the overall PEP incidence was 8.9% (22/246). There was no significant difference in PEP incidence [8.9% (11/123) VS 8.9% (11/123), χ 2=0.000, P=1.000], moderate-to-severe PEP incidence [0.8% (1/123) VS 1.6% (2/123), χ 2=0.000, P=1.000], or spontaneous stent dislodgement rate within two weeks [80.6% (75/93) VS 78.6% (77/98), χ 2=0.126, P=0.722] between the two groups. Logistic regression analysis showed that normal liver function ( OR=2.36, 95% CI:1.01-5.51, P=0.046) and failed bile duct cannulation ( OR=7.51, 95% CI:2.18-25.96, P=0.001) were independent risk factors for PEP in patients with biliary tract diseases who received prophylactic pancreatic stents placement. Conclusion:Longer 5 Fr pancreatic stents (>5 cm) do not further reduce the overall risk of PEP or moderate-to-severe PEP compared with 5Fr-5 cm stent. Normal liver function and failure of bile duct intubation were independent risk factors for PEP after prophylactic pancreatic stent placement in patients with biliary diseases.

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.

Objective:To investigate the clinical features of patients with local recurrence and secondary operation after partial nephrectomy for renal cancer.Methods:The clinical data of 14 patients who underwent secondary operation for local recurrence of renal cancer after partial nephrectomy in the First Affiliated Hospital and the Second Affiliated Hospital of Naval Medical University from January 2000 to January 2022 were retrospectively analyzed. There were 12 males and 2 females. Nine patients had a body mass index ≥24 kg/m 2. At first diagnosis of renal cancer, nine patients’ R. E.N.A.L. score of renal mass were at least 7. Partial nephrectomy was performed in the first operation of each patient, including 4 cases of open surgery, 6 cases of laparoscopic surgery, and 4 cases of robot-assisted laparoscopic surgery. The pathological stage of nine patients was pT 1aN 0M 0 and that of five patients was pT 1bN 0M 0. Twelve cases were clear cell carcinoma, 1 case was sarcomatoid carcinoma and 1 case was chromophobe cell carcinoma. The mean time from the first operation to local recurrence was (29.3±16.8) months. All recurrence lesions were found by abdominal CT or MRI. Thirteen patients had no clinical symptom at the time of tumor recurrence. The location of recurrence was clear. No sign of invasion of peripheral organs and tissues was observed. There was no other suspicious lesion. The tumor was considered to be completely resectable in all patients. All 14 cases underwent secondary operation. Ten patients underwent radical nephrectomy [tumor size was (2.8±0.9) cm]. Partial nephrectomy was performed in 4 cases [tumor size was (1.8±0.9) cm]after full evaluation by surgeons, including 2 cases of anatomic solitary kidney, and 2 cases of recurrent tumor less than 2 cm with clear tumor margin. Results:Eleven of the 14 cases underwent minimally invasive surgery, and no cases were converted to open surgery. The other 3 cases underwent open surgery. Seven patients had severe adhesions in the operation area. The blood loss in the partial nephrectomy group and the radical nephrectomy group was (100.0±70.7) ml and (143.0±81.2) ml, respectively. According to the Clavien-Dindo classification of surgical complications, Grade Ⅰ and Grade Ⅱ complication occurred in 1 patient respectively, and no patient had Grade Ⅲ or above complication. No tumor cell was found at the surgical margin. The pathological type and nuclear grade were the same as those in the first operation. There were 10 cases of pT 1aN 0M 0 stage, 3 cases of pT 3aN 0M 0 stage and 1 case of pT 3aN 1M 0stage. The follow-up time of 13 patients with complete follow-up data was (21.4±14.9) months after local recurrence resection. The tumor recurred in 3 patients and metastasized in 2 patients. The disease-free survival time of the above 5 patients was (13.2±8.8) months. Of the 4 patients who underwent partial nephrectomy, 3 had recurrence or metastasis. Among the 9 patients who underwent radical nephrectomy, 2 had postoperative recurrence or metastasis, and 7 patients survived without tumor until the last follow-up. Conclusions:For patients with local recurrence after partial nephrectomy who are in good condition and the recurrent lesions can be completely resected, the second operation is safe, feasible and effective. Patients with secondary radical nephrectomy have better prognosis. If the patient has a solitary kidney, the recurrent tumor is small and the margin is clear, partial nephrectomy can also be selected for the second operation. But the postoperative follow-up should be emphasized, and the adjuvant drug therapy should be given if necessary.

Objective:To evaluate the efficacy and safety of endoscopic retrograde cholangiopancreatography (ERCP) after pancreaticoduodenectomy and endoscopic selection strategies.Methods:Clinical data of 34 patients treated with ERCP after pancreaticoduodenectomy at the Endoscopic Center of the First Affiliated Hospital of Air Force Medical University from January 2013 to December 2021 were retrospectively analyzed. The success rates of endoscopic insertion, diagnosis, treatment and ERCP, and the incidence of adverse events were analyzed.Results:Fifty ERCP treatments were performed in 34 patients. The success rates of endoscopic insertion, diagnosis, treatment, and ERCP after pancreaticoduodenectomy were 92.0% (46/50), 93.5% (43/46), 88.4% (38/43) and 76.0% (38/50), respectively. The success rates of ERCP assisted with colonoscope and balloon-assisted enterosocpe were 76.0% (19/25) and 75.0% (18/24), respectively. There were 3 adverse events, including 1 case of anastomotic mucosa tear during surgery, 1 case of cardiopulmonary arrest and 1 case of postoperative cholangitis.Conclusion:ERCP is effective and safe after pancreaticoduodenectomy in general. ERCP assisted with colonoscope and balloon-assisted colonoscope shows similar success rate after pancreaticoduodenectomy.