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 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 effects of M1 polarization of microglia on secondary damage in the thalamus after cerebral cortical infarction.Methods A focal cortical infarct model of adult male SD rats was pre-pared using eletrocoagulation and randomized into Sham and model groups at different time points 1～4 weeks after surgery.Based on the assessment of neurofunctional changes in each group of rats,immunohistochemistry was used to observe the number and morphology of NeuN,GFAP and Iba-1 positive cells in(Ventral posterior nucleus of thalamus,VPN)of the ipsilateral thalamus after distal middle cerebral artery occlusion(dMCAO).Immunofures-cence was used to detect the number and morphology of M1 microglia marker(Iba-1+/CD68+cells)and M2 microg-lia marker(Iba-1+/CD206+cells)in VPN of the ipsilateral thalamus after dMCAO.Western blot was used to detect the expression levels of IL-1β,TNF-α,IL-10 and Arg-1 in VPN of the ipsilateral thalamus after dMCAO.Results The results of immunohistochemistry showed a significant decrease in NeuN positive cells and an increase in the density of GFAP and Iba-1 in the ipsilateral VPN of rats after dMCAO when compared with Sham group(P<0.001).Compared with sham group,the protein levels of TNF α and IL-1β were elevated in the ipsilateral VPN elevated(P<0.05).In addition,the model group rats exhibited higher Bederson scores,beam-walking test and adhesive removal test scores after dMCAO compared with Sham group(P<0.05).The numbers of M1 microglia marker(Iba-1+/CD68+cells)were significantly increased when compared with M2 microglia marker(Iba-1+/CD206+cells)in ipsilateral VPN of rats after dMCAO.Conclusion M1 polarization of microglia may play an essential role in secondary damage of thalamus after cerebral cortical infarction.

OBJECTIVE To explore the value of providing pharmaceutical service related to risdiplam in direct-to-patient （DTP） pharmacies. METHODS The follow-up data of spinal muscular atrophy （SMA） patients who purchased and used risdiplam from Shangyao Yunjiankang Yiyao Pharmacy （Shanghai） Co.， Ltd. from May 2021 to January 2023 were collected. The medication information， therapeutic efficacy and the occurrence of adverse events were retrospectively analyzed. RESULTS A total of 42 prescriptions were checked by pharmacists in the DTP pharmacies， and 7 prescriptions were found to be unreasonable （16.7%， 7/42）， which were corrected after the timely intervention. During the follow-up management， pharmacists replied to 4 patients （9.5%， 4/42） regarding medication consultation about medication requirements and adverse events. Two patients with type Ⅰ SMA experienced adverse events： one of them presented with fever and the other presented with skin dryness with darkening. Both of them were grade Ⅰ toxic reactions and generally did not require clinical treatment. Considering that the patient sustained low-grade fever for a long time， the pharmacist suggested symptomatic treatment under the guidance of the doctor. CONCLUSIONS Pharmacists in DTP pharmacies conducting follow-up management of risdiplam use for rare disease SMA patients can help promote rational， standardized medication for patients.

Gastrointestinal tumors(GT)are characterized by both high malignancy and high mortality and have become the major diseases for prevention in the elderly.GT often present detectable changes, including bleeding and abnormal mucosal morphology.However, many technical difficulties remain in accurately monitoring the tumor itself and related abnormal lesions mentioned above, which are the key factors affecting the early detection rate of gastrointestinal tumors.In recent years, with progresses in artificial intelligence(AI)applications for digestive endoscopy image analysis, biosensors, new biomarkers and other areas, AI holds promise for the detection of bleeding, morphological and structural abnormalities of the mucosa, tumors and other major disorders.Here we review the progress of AI applications in geriatric digestive diseases affecting digestive organs and the mucosa in light of morphology and function, to provide a reference for reducing the incidence of both geriatric emergencies and GT.

There are few reports on the study of extraperitoneal robotic single-port laparoscopic radical prostatectomy in China. In this study, patients with localized prostate cancer were treated with extraperitoneal robotic single-port laparoscopic radical prostatectomy extraperitoneal robot-assisted single-port laparoscopic radical prostatectomy(EpRA-spRP)from April 2019 to June 2019.All patients performed EpRA-spRP successfully without adding additional auxiliary port. The operation time and blood loss were controllable, and hospitalization time was short. It is safe and feasible to perform EpRA-spRP for medium and low-risk prostate cancer. The short-term tumor control and functional recovery are satisfactory.However, the long-term effect needs further follow-up and observation.

Objective:To investigate the factors related to the prognosis of patients with metastatic renal cell carcinoma after bone metastasectomy and to provide a reference for the clinical treatment of renal cell carcinoma.Methods:The clinical data of 143 patients with metastatic renal cell carcinoma in our center from January 2008 to December 2018 were retrospectively collected. Among 143 patients, 121 were male and 22 were female, with the average age of (54.8±12.5) year-old(from 18 to 85 year-old). The KPS scores of 138 patients were no higher than 80%. According to International Metastatic RCC Database Consortium (IMDC) risk model for metastatic renal cell carcinoma, the patients were divided into intermediate risk group (92 patients) and poor risk group (51 patients). The patients who had received complete resection for both primary lesion and metastatic tumor were regarded as tumor-free (47 patients). Otherwise, the patients with unresectable primary tumor or incomplete resection of the metastatic tumor were defined as the patients surviving conversely bone metastases were the only metastatic site, and the other 57 patients also experienced concomitant metastases comparatively. Sixty-two patients only had solitary bone metastasis lesion and 81 patients had multiple bone metastases. Kaplan-Meier survival analysis was used to calculate the 1-year, 3-year and 5-year survival rate. The impacts of different variables on the prognosis were examined by log-rank test. Univariate analysis and multivariable Cox proportional hazards regression models were used to identify the independent risk factors.Results:The median follow-up time was 49.0 months. The overall survival was 1-115 months, with the median OS was 24.0 months. The 1-year, 3-year and 5-year survival rate were 79.2%, 59.4% and 31.6%, respectively. All the patients underwent bone metastasectomy and 72 of them were treated with targeted therapy. The pathology results of metastasectomy were clear cell carcinoma for 132 patients and non-clear cell carcinoma for the 11 patients. In tumor-free group, the median OS was 30.0 months and in survival with tumor group, the median OS was 19.4 months, with a significant difference between the two groups ( P=0.030). In IMDC intermediate risk group, the prognosis was improved among the patients who received post-surgical targeted therapy after metastasectomy (24.3 months vs. 16.8 months, P=0.027), whereas the difference was not significant for IMDC poor risk group ( P=0.449). Age ≥60 years and multiple bone metastases sites were proved to be the independent risk factors for the prognosis of patients with metastatic renal cell carcinoma after bone metastasectomy. Conclusions:The prognosis of RCC patients with bone metastases was generally poor. Metastasectomy could prolong the OS of the patients who had undergone primary nephrectomy and had solitary bone metastasis. Metastasectomy combined with targeted therapy could significantly improve the prognosis of the IMDC intermediate risk patients. However, the effect of targeted therapy among IMDC poor risk patients remained to be further proved.

Objective:To assess the safety and feasibility of single-port robotic radical cystectomy.Methods:During May 2019 and August 2019, nine patients (8 males, 1 female) received single-port robotic radical cystectomy by the same surgeon. The average age was 65.6(56-78)years. After a 4.5-5.5 cm trans-umbilical incision was made, Lagiport was inserted. Da Vinci Si system 1 #, 2 # arms and 30° lens were applied. Radical cystectomy and bilateral pelvic lymphadenectomy were performed without additional ports. Urinary diversion was completed outside the body. Uterus and vaginal anterior walls were also resected for female patient. Results:All 9 surgeries were successfully conducted without additional ports or conversion to laparoscopic and open surgery. The average operation time was 437.8(280-600)min. Urinary diversion methods included 2 orthotopic ileal neobladder, 5 ideal conduit and 2 cutaneous ureterostomy. Average estimated blood loss was 227.8(100-450)ml, without blood transfusion. Average intestinal recovery time was 3.1(2-4)days, drainage duration was 8.3(3-16) days, and postoperative hospital stays was 7.7(6-13) days. Pathological TNM stage: T 2aN 0M 0 6 cases, T 2bN 0M 0 1 case, T 3aN 3M 0 1 case, T isN 0M 0 1 case. All surgical margins were negative. One bowel obstruction was cured with fasting and indwelling gastric tube. During 9-12 months’ follow-up, no tumor recurrence and metastasis were observed. There was no hydronephrosis or ureterostenosis. All surgical incision healed well. Conclusions:For experienced surgeons, single-port robotic radical cystectomy is safe and feasible with small incision and fast recovery. Short-term clinical result is satisfied.

Objective To analyze the risk factors of prognosis in elderly patients with septic shock in ICU.Methods Clinical data of 113 elderly patients with septic shock admitted in the ICU of Ningbo Medical Center Lihuili Eastern Hospital from November 2015 to March 2019 were retrospectively analyzed. Among them, 40 patients died ( death group) and 73 patients survived (survival group) within 28 d after diagnosis confirmed.The general information ,underlying disease,laboratory findings and invasive operations were compared between the two groups.Multivariate Logistic regression was used to analyze the risk factors for prognosis of patients, and ROC curve was used to analyze the predictive value of risk factors for death . Results Multivariate Logistic regression analysis showed that APACHEII score ( OR ＝1.344, 95%CI 1畅187-1.520,P＜0.01) and lactic acid level at admission (OR＝1.311,95%CI 1.075-1.599,P＜0.01) were independent risk factors for prognosis ,while platelet counts (OR＝0.986,95%CI 0.976-0.996,P＜0畅01)and albumin level(OR＝0.812,95%CI 0.697-0.945,P＜0.01)were protective factors for prognosis. ROC curve analysis showed that the area under the curve of APACHEII score ,lactic acid level at admission and APACHEII score combined with lactic acid level at admission were 0.861(95%CI 0.784-0畅919,P＜0畅01),0.752(95%CI 0.662-0.828,P＜0.01) and 0.904(95%CI 0.834-0.951,P＜0.01),respectively. The predictive value of APACHEII score combined with lactic acid level at admission was better than those of APACHEII score and lactic acid level at admission ( Z ＝2.175 and 2.879, P ＜0.05 and P ＜0畅01). Conclusions Lower APACHEII score and lactic acid level ,increased platelet counts and albumin level may be associated with a favorable prognosis for elderly patients with septic shock .APACHEII score combined with lactic acid level at admission has better predictive value for prognosis .

Objective To compare the perioperative parameters and renal function in patients,whose aged was 65 year-old or above,with clinical T1-2 renal tumors undergoing partial nephrectomy (PN) or radical nephrectomy (RN).Methods A retrospective review of 469 patients,who underwent RN and PN in our center,was conducted from January 2012 to November 2018,icluding 247 in the RN group and 222 in the PN group.The RN group consisted of 170 male and 77 female patients,with the mean age of (70.96 ± 5.21) year-old.126 cases were found that the tumor located on the fight side,with the median diameter of (4.93 ± 2.03) cm.The median BMI,median R.E.N.A.L.score and pre-operation eGFR of the RN group were (24.4 ± 3.1) kg/m2,8.39 ± 1.45) and (80.23 ± 15.14) ml/(min · 1.73 m2),respectively.The PN group consisted of 150 male and 72 female patients,with the mean age of (70.23 ± 4.62) years old.108 patients had tumors on the left side while 114 on the right side,with the median diameter of (3.17 ± 1.41) cm.The median BMI,median R.E.N.A.L score and pre-operation eGFR of the PN group were (23.5 ± 3.2) kg/m2,(6.69 ± 1.81) and (82.83 ± 14.36) ml/(min · 1.73m2),respectively.No statistical difference was noticed in the age,gender,tumor location and BMI between RN group and PN group(P ＞ 0.05).The PN group had smaller tumors and lower R.E.N.A.L.scores than the RN group (P ＜ 0.05).Various parameters were compared between the PN and RN groups,including operative duration,surgical procedure,intraoperative blood loss,perioperative blood transfusion,drainage tube removal time,postoperative duration of hospitalization,pathological results,the renal function immediately after surgery and at 1 month,1 year,2 years,3 years,4 years,5 years after surgery,and the incidence of chronic renal dysfunction.Results Significant differences were found in multiple variables between the two cohorts,such as operative duration [(115.70 ± 39.69) min in RN vs.(132.26 ± 49.02) min in PN],estimated intraoperative blood loss [(45.85 ± 55.93) days in RN vs.(66.60 ± 61.55) ml in PN],drainage tube removal time [(4.38 ± 1.71) days in RN vs.(4.86 ± 1.61) days in PN],duration of postoperative hospitalization [(5.14 ± 1.65) days in RN vs.(5.52 ± 1.32) days in PN] (P ＜ 0.05).Furthermore,higher proportion of RCC was detected in the RN cohort (93.5％ in RN vs.86.5 ％ in PN,P ＜ 0.05).There was no significant difference in perioperative blood transfusion rate between the two cohorts (10.93％ vs.9.01％,P ＞ 0.05).Compared with the RN cohort,the PN cohort had higher eGFR immediately after surgery [(74.08 ± 18.31) ml/(min · 1.73m2) vs.(52.58 ± 14.21) ml/(min · 1.73m2)],1 month after surgery [(76.11 ± 18.34) ml/(min · 1.73m2) vs.(53.78 ± 15.03)ml/(min · 1.73m2)] and at the last follow-up [(73.92 ± 18.59) ml/(min · 1.73m2) vs.(52.35 ± 16.13) ml/(min · 1.73m2)] (P ＜ 0.001).Compared with those of the RN cohort,the incidences of eGFR ＜ 45 ml/(min · 1.73m2) of the PN cohort were lower immediately after surgery [9.01％ (20/222) vs.31.9％ (79/247)],1 month after surgery [7.87％ (14/178) vs.27.31％ (62/227)],1 year after surgery [8.96％ (13/145) vs.38.75％ (62/16 0)],2 years after surgery [9.89％ (9/91) vs.31.57％ (42/133)],3 years after surgery [13.21％ (7/53) vs.30.61％ (30/98)],4 years after surgery [16.21％ (6/37) vs.30.26％ (23/76)] and 5 years after surgery [18.18％ (4/22) vs.31.11％ (14/45)] (P ＜ 0.001).Conclusion The perioperative risk of PN in the treatment of elderly patients aged 65 and above with clinical cT1-2 renal tumor is controllable.PN could better retain renal function for those patients and reduce the risk of postoperative chronic renal insufficiency.