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*

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 evaluate the efficacy and safety of bendamustine combined with pomalidomide and dexamethasone (BPD regimen) in the treatment of relapsed multiple myeloma (MM) with extramedullary disease. Methods: This open, single-arm, multicenter prospective cohort study included 30 relapsed MM patients with extramedullary disease diagnosed in seven hospitals including Qingdao Municipal Hospital. The patients were treated with BPD regimen from February 2021 to November 2022. This study analyzed the efficacy and adverse reactions of the BPD regimen. Results: The median age of the 30 patients was 62 (47-72) years, of which 18 (60% ) had first-time recurrence. The overall response rate (ORR) of the 18 patients with first-time recurrence was 100%, of which three (16.7% ) achieved complete remission, 10 (55.5% ) achieved very good partial remission (VGPR), and five (27.8% ) achieved partial remission (PR). The ORR of 12 patients with recurrence after second-line or above treatment was 50%, including zero patients with ≥VGPR and six patients (50% ) with PR. Three cases (25% ) had stable disease, and three cases (25% ) had disease progression. The one-year progression free survival rate of all patients was 65.2% (95% CI 37.2% -83.1% ), and the 1-year overall survival rate was 90.0% (95% CI 76.2% -95.4% ). The common grade 3-4 hematology adverse reactions included two cases (6.7% ) of neutropenia and one case (3.3% ) of thrombocytopenia. The overall adverse reactions are controllable. Conclusions: The BPD regimen has good efficacy and tolerance in relapsed MM patients with extramedullary disease.
Humans ; Middle Aged ; Aged ; Multiple Myeloma/drug therapy* ; Bendamustine Hydrochloride/therapeutic use* ; Prospective Studies ; Dexamethasone/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

Objective:To evaluate the efficacy and safety of multimodal endovascular therapy for acute ischemic stroke in elderly patients.Methods:A total of 263 elderly patients with acute ischemic stroke were enrolled as research subjects from January 2017 to December 2018.Patients were divided into two groups: the intravenous thrombolytic therapy group and the endovascular therapy group.Treatment outcomes were compared by using the National Institutes of Health Stroke Scale(NIHSS)and the modified Rankin Scale(mRS).Results:Of 263 patients, 125 were in the intravenous thrombolytic therapy group and 138 were in the intravascular therapy group.The rate of good/excellent outcomes was higher in the endovascular treatment group than in the intravenous thrombolytic therapy group(97.8% vs.91.2%, χ2=5.713, P<0.05). The NIHSS score and mRS score were lower in the endovascular treatment group than the in intravenous thrombolytic therapy group[(2.3±0.3) vs.(6.0±1.8), (1.1±0.1) vs.(2.3±0.3), t=9.067 and 16.970, P<0.05]. There was no significant difference in the incidence of adverse reactions between the two groups(8.6% vs.8.0%, χ2=0.041, P>0.05). Conclusions:Multimodal mechanical thrombus retrieval is a safe and effective treatment for intracranial large vessel occlusion in acute ischemic stroke patients and should be recommended and promoted.

BACKGROUND: Many studies have investigated heavy metal exposure could increase the occurrence of congenital heart defects (CHDs). However, there are limited data regarding the relationship between cobalt exposure and CHD occurrence in offspring. The aim of this study was to analyze the association between cobalt exposure in mothers and the risk of CHDs in offspring. MATERIALS AND METHODS: In order to explore the association between cobalt exposure and occurrence of congenital heart defect (CHD), a case-control study with 490 controls and 399 cases with CHDs in China were developed. The concentrations of cobalt in hair of pregnant woman and fetal placental tissue were measured and processed by a logistic regression analysis to explore the relationship between cobalt exposure and risk of CHDs. RESULTS: The median concentration of hair cobalt in the control and case group was 0.023 ng/mg and 0.033 ng/mg (aOR, 1.837; 95% CI, 1.468-2.299; P < 0.001), respectively. And the median (5-95% range) fetal placental cobalt concentrations were 19.350 ng/g and 42.500 ng/g (aOR, 2.924; 95% CI, 2.211-3.868; P < 0.001) in the control and case groups, respectively. Significant differences in the middle level of cobalt in hair were found in the different CHD subtypes, including septal defects, conotruncal defects, right ventricular outflow tract obstruction, and left ventricular outflow tract obstruction (P < 0.001). Dramatically, different cobalt concentrations in fetal placental tissue were found in all subtypes of cases with CHDs (P < 0.01). CONCLUSIONS The finding suggested that the occurrence of CHDs may be associated with cobalt exposure.
Adolescent ; Adult ; Case-Control Studies ; China ; Cobalt ; adverse effects ; Female ; Hair ; chemistry ; Heart Defects, Congenital ; chemically induced ; Humans ; Maternal Exposure ; adverse effects ; Placenta ; chemistry ; Pregnancy ; Prenatal Exposure Delayed Effects ; chemically induced ; Risk Factors ; Young Adult

Objective To evaluate the role of mitochondrial ATP-sensitive potassium (mito-KATP) channels in urocortin postconditioning-induced protection of rat cardiomyocytes.Methods Clean-grade healthy male Sprague-Dawley rats,aged 16-20 weeks,weighing 200-250 g,were used in this study.Cardiomyocytes of rats were isolated,cuhured and divided into 4 groups (n =28 each) using a random number table method:control group (group C),H/R group (group HR),urocortin postconditioning group (group U) and 5-hydroxydecanoate (5-HD,mito-KAw channel blocker) plus urocortin postconditioning group (group HU).In group C,the cells were continuously cultured for 150 min in an incubator filled with 95％ O2-5％ CO2 at 37 ℃.In group HR,the cells were exposed to 40-min hypoxia in an incubator filled with 95％ N2-5％ CO2 at 37 ℃,followed by 110-min reoxygenation.In group U,the cells were exposed to 40-min of hypoxia,followed by 10-min reoxygenation,and then cultured in a cuhure medium containing 10-8mmol/L urocortin for 30 min,followed by 70-min reoxygenation.In group HU,the cells were cultured for 10 min in a culture medium containing 10-4mmol/L 5-HD,and the other treatments were similar to those previously described in group U.At the end of reoxygenation,the opening of mitochondrial permeability transition pore (mPTP) and mitochondrial membrane potential (MMP) were measured by fluorescence spectrophotometry.The expression of Bax and Bcl-2 was determined by Western blot,and the cell viability was measured by CCK-8 assay.Results Compared with group C,the viability of cardiomyocytes and MMP were significantly decreased,the opening of mPTP was increased,the expression of Bcl-2 was down-regulated,and the expression of Bax was up-regulated in the other 3 groups (P＜0.05).Compared with group HR,the viability of cardiomyocytes and MMP were significantly increased,the opening of mPTP was decreased,the expression of Bcl-2 was up-regulated,and the expression of Bax was down-regulated in group U,and the opening of mPTP was decreased (P ＜ 0.05),and no significant change was found in the other parameters in group HU (P＞0.05).Compared with group U,the viability of cardiomyocytes and MMP were significantly decreased,the opening of mPTP was increased,the expression of Bcl-2 was down-regulated,and the expression of Bax was up-regulated in group HU (P＜0.05).Conclusion The mechanism by which urocortin postconditioning attenuates H/R-induced damage to rat cardiomyocytes is associated with promoting mito-KATP channel opening and inhibiting mPTP opening.

Objective To explore the value of contrast-enhanced ultrasonography ( CEUS ) breast predictive model in the optimization of BI-RADS classification of breast lesions . Methods A total of 1049 BI-RADS 4 ,5 breast lesions were obtained from 1039 patients in 8 centers . CEUS examination was performed prior to biopsy or surgery . According to the classification of the model ,class 3 ,4A ,4B and 4C were selected as biopsy thresholds ,and the ROC curve was drawn . The diagnostic sensitivity ,specificity , accuracy ,positive predictive value ,negative predictive value and Jordanian index were calculated for the biopsy threshold . The biopsy rate of breast lesions before and after angiography ,cancer detection rate , follow-up cases of malignant risk were compared . Results There were benign lesions 586 ( 55 .9％ ) , malignant lesions 463 (44 .1％ ) in the 1049 breast lesions . The area of ROC with thresholds of 3 ,4A ,4B and 4C were 0 .695 ,0 .838 ,0 .847 and 0 .757 ,respectively ( all P < 0 .01) . Ultrasonography had a certain diagnostic effect on benign and malignant breast lesions . The diagnostic sensitivity ,specificity ,accuracy , positive predictive value and negative predictive value with class 4A after CEUS set as the biopsy threshold were 93 .32％ ,75 .65％ ,82 .75％ ,75 .57％ and 93 .35％ ,respectively ,and the Jordanian index was 0 .690 . When chass 3 after CEUS was set as the biopsy threshold ,the biopsy rate was reduced from 100％ to 76 .74％ ,the detection rate was increased from 44 .23％ to 56 .77％ ,and the risk of cancer was only 0 .67％ in the follow-up cases . When class 4A was set as the biopsy threshold ,the biopsy rate was reduced from 100％ to 55 .58％ after CEUS . The detection rate of cancer increased from 44 .23％ to 74 .44％ . The risk of cancer was 2 .96％ . Conclusions The biopsy rate of breast lesions in category 4 and 5 would be reduced and cancer detection rate of them would be increased after CEUS ,however ,the risk of malignancy in the follow -up cases would be controlled as low as category 3 and 4A in previous BI-RADS . Thus ,CEUS has a good prospect of in optimizing BI-RADS and reducing biopsy rate in unnecessary lesions .

Objective To study the clinical efficacy and advantages of tip-flexible semirigid ureterorenoscope combined with Holmium laser lithotripsy for the treatment of impacted upper ureteral calculi.Methods We retrospectively analyzed 75 cases of impacted upper ureteral calculi treated in our hospital between September 2015 and December 2017.There were 45 males and 30 females,aged from 35 to 65 years,mean (42.5 ± 3.5)years.All patients were diagnosed by B-ultrasound and CT with impacted upper ureteral calculi.The mean stone diameter was (1.6 ± 0.3) cm.The CT value of stone was (1 025.3 ± 215.4) HU.Tip-flexible semirigid ureterorenoscope combined with Holmium laser lithotripsy were performed in all of the cases,which were under general anesthesia with lithotomy position,to observe the successful rate of lithotripsy,operation time,intraoperative and postoperative complications,postoperative hospitalization time and stone-free rate.Results All 75 cases were successfully operated.The operation time was (38.5 ± 11.2) min.Three cases had postoperative fever.No severe perioperative complications such as septic shock,ureteral perforation or avulsion occurred.The mean hospital stay of the patients was (2.7 ± 0.4) d.A follow up by non-contrast CT scan was done 4 weeks after the procedure to evaluate the result.Sixty seven cases had stone clearances at the primary operation and the stone clearance rate was 89.3％ (67/75).Eight cases undergone ESWL and physical vibration lithecbole,the CT examination showed that the stones were cleared after 1 month.Conclusions Tip-flexible semirigid ureterorenoscope combined with Holmium laser lithotripsy in the treatment of impacted upper ureteral calculi had a definite effect,safe and comfortable for doctors.

Objective To evaluate the effects of unilateral and bilateral diffusion of cement on osteoporotic vertebral compression fractures treated with percutaneous kyphoplasty (PKP). Methods A retrospective case control study was conducted on the clinical data of 127 patients with single segment osteoporosis vertebral compression fracture (OVCF) treated by unilateral puncture PKP between July 2013 and July 2015. According to whether the diffusion of bone cement crossed the median, all cases with OVCF were divided into unilateral and bilateral diffusion groups. The unilateral diffusion group (72 cases) included 29 males and 43 females, with an average age of 69.5 ± 2.6 years (range, 63-76 years). In terms of the injured segment, there were 38 cases of L1, 20 L2, 11 L3, two L4, and one L5. In the unilateral diffusion group, the preoperative visual analog score (VAS) was (7.8 ±0.9) points, the preoperative anterior vertebral height compression ratio was (32.5 ±6. 3)％, and the preoperative Cobb's angle of the injured vertebra was (9.2±1.3)°. The bilateral diffusion group (55 cases) included 22 males and 33 females, with an average age of 71.2 ±2.9 years (range, 61-80 years). In terms of the injured segment, there were 32 cases of L1, 13 L2, six L3, three L4, and one L5. In the bilateral diffusion group, the preoperative VAS was (7.6 ±0. 9)points, the preoperative anterior vertebral height compression ratio was (34.5 ±5.8)％, and the preoperative Cobb's angle of the injured vertebra (9.8± 1.5)°. The VAS, anterior vertebral height compression ratio of the injured vertebra, Cobb's angle of the injured vertebra, and injured and non-injured vertebra refracture 1 month and 1 year after operation were recorded. Results The patients were followed up for 12-16 months (mean, 14.6 ± 0.6 months) in unilateral diffusion group and for 13- 16 months (mean, 15.2 ±0.2 months) in bilateral diffusion group. The VAS score of the unilateral diffusion group was (3.0 ±0.4) points at 1 month after the operation and (2.2±0. 4) points at 1 year after the operation, respectively. The VAS score of the bilateral diffusion group was (2.1 ±0.4) points at 1 month after the operation and (1.5 ± 0.4) points at 1 year after the operation, respectively. The VAS score decreased significantly 1 year after operation compared with that before operation (P ＜0.05), and significant difference was noted between two groups (P ＜0.05). The anterior vertebral height compression ratio of the unilateral diffusion group was (15.2±3.9)％ at 1 month after the operation and (16.3 ±3.4)％ at 1 year after the operation, respectively. The anterior vertebral height compression ratio of the bilateral diffusion group was (15.6±3.5)％ at 1 month after the operation and (16.8 ±3.9)％ at 1 year after the operation, respectively. The Cobb's angle of the injured vertebra of the unilateral diffusion group was (2.9±0.7)° at 1 month after the operation and (3.0±0.6)°at 1 year after the operation, respectively. The Cobb's angle of the injured vertebra of the bilateral diffusion group was (3.0 ± 0.7) ° at 1 month after the operation and (3.2 ± 0.7) ° at 1 year after the operation, respectively. The anterior vertebral height compression ratio and Cobb's angle of the injured vertebra decreased significantly after surgery (P ＜ 0.05), but no statistically significant differences were observed between two groups (P＞0.05). The injured vertebra refracture ratio was 6.9％ in unilateral diffusion group and 0 in bilateral diffusion group. The non-injured vertebra refracture ratio was 5.6％ in unilateral diffusion group and 5.5％ in bilateral diffusion group. No nerve root injury, cerebrospinal fluid leakage, pulmonary embolism, anaphylactic shock and postoperative infection were found in the two groups. Paravertebral bone cement leakage occurred in two cases of the unilateral diffusion group and anterior vertebral bone cement leakage occurred in one case of the bilateral diffusion group. Conclusion Compared with unilateral diffusion, bilateral diffusion of bone cement has better analgesic effect and can reduce the incidence of re fracture of injured vertebra, without increasing the risk of re-fracture of the non-injured vertebrae.