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 investigate the effect of Th17 cell-specific Stat3 knockout on anxiety-and depressive-like behaviors.Methods·Mice with specific Stat3 knockout in Th17 cells(Stat3fl/fl;Il17a-CreERT2),named Stat3△Il17a,and wild-type mice(Stat3fl/fl,WT)were generated through the Cre/LoxP system,and Stat3 knockout was induced by intraperitoneal injection of tamoxifen.CD4+T cells were isolated using magnetic-activated cell sorting and induced to differentiate into Th17 cells.Reverse transcription polymerase chain reaction and Western blotting were used to verify Stat3 knockout efficiency.Mice were assigned into 4 groups:WT-C group,Stat3△Il17a-C group,WT-P group,and Stat3△Il17a-P group.The periodontitis model was established in the WT-P group and the Stat3△Il17a-P group by injection of Porphyromonas gingivalis-lipopolysaccharide(P.gingivalis-LPS)into the gingival sulcus.Behavioral tests,including the open field test,elevated zero maze,and forced swimming test,were conducted to evaluate changes in anxiety-and depressive-like behaviors.Micro-computed tomography was used to observe destruction of alveolar bone.Neuronal injury was observed by H-E staining,and the level of brain-derived neurotrophic factor(BDNF)was detected by enzyme-linked immunosorbent assay.Results·mRNA expression and protein levels of Stat3 in Stat3△Il17a mice were inhibited compared to WT mice(P<0.05).Experimental periodontitis model was successfully established in the WT-P group and the Stat3△Il17a-P group.The degree of alveolar bone destruction was reduced in the Stat3△Il17a-P group compared to the WT-P group.In the WT-P group,decreased residence time in the central area and in the open area was observed in the open field test and elevated zero maze respectively,and increased immortal time was recorded in the forced swimming test(P<0.05).Moreover,neuronal injury was detected and significantly decreased expression levels of BDNF in the brain were measured in the WT-P group compared with the WT-C group(P<0.05).The degree of abnormal behaviors and neuronal injury was reduced in the Stat3△Il17a-P group compared to the WT-P group(P<0.05).Moreover,the level of BDNF in the Stat3△Il17a-P was higher than that in the WT-P group(P<0.05).Conclusion·Periodontitis may contribute to anxiety-and depressive-like behaviors and neuronal damage in mice,while Th17-specific conditional knockout of Stat3 could significantly alleviate pathological behaviors and neuronal damage.Stat3-mediated-Th17 cell immune responses may play a crucial role in the correlation between periodontitis and anxiety and depression.

Objective·To investigate the effect of Th17 cell-specific Stat3 knockout on anxiety-and depressive-like behaviors.Methods·Mice with specific Stat3 knockout in Th17 cells(Stat3fl/fl;Il17a-CreERT2),named Stat3△Il17a,and wild-type mice(Stat3fl/fl,WT)were generated through the Cre/LoxP system,and Stat3 knockout was induced by intraperitoneal injection of tamoxifen.CD4+T cells were isolated using magnetic-activated cell sorting and induced to differentiate into Th17 cells.Reverse transcription polymerase chain reaction and Western blotting were used to verify Stat3 knockout efficiency.Mice were assigned into 4 groups:WT-C group,Stat3△Il17a-C group,WT-P group,and Stat3△Il17a-P group.The periodontitis model was established in the WT-P group and the Stat3△Il17a-P group by injection of Porphyromonas gingivalis-lipopolysaccharide(P.gingivalis-LPS)into the gingival sulcus.Behavioral tests,including the open field test,elevated zero maze,and forced swimming test,were conducted to evaluate changes in anxiety-and depressive-like behaviors.Micro-computed tomography was used to observe destruction of alveolar bone.Neuronal injury was observed by H-E staining,and the level of brain-derived neurotrophic factor(BDNF)was detected by enzyme-linked immunosorbent assay.Results·mRNA expression and protein levels of Stat3 in Stat3△Il17a mice were inhibited compared to WT mice(P<0.05).Experimental periodontitis model was successfully established in the WT-P group and the Stat3△Il17a-P group.The degree of alveolar bone destruction was reduced in the Stat3△Il17a-P group compared to the WT-P group.In the WT-P group,decreased residence time in the central area and in the open area was observed in the open field test and elevated zero maze respectively,and increased immortal time was recorded in the forced swimming test(P<0.05).Moreover,neuronal injury was detected and significantly decreased expression levels of BDNF in the brain were measured in the WT-P group compared with the WT-C group(P<0.05).The degree of abnormal behaviors and neuronal injury was reduced in the Stat3△Il17a-P group compared to the WT-P group(P<0.05).Moreover,the level of BDNF in the Stat3△Il17a-P was higher than that in the WT-P group(P<0.05).Conclusion·Periodontitis may contribute to anxiety-and depressive-like behaviors and neuronal damage in mice,while Th17-specific conditional knockout of Stat3 could significantly alleviate pathological behaviors and neuronal damage.Stat3-mediated-Th17 cell immune responses may play a crucial role in the correlation between periodontitis and anxiety and depression.

A combined radiation-wound injury refers to a radiation injury combined with a traumatic wound, with the characteristics of repeated ulceration and a long and difficult healing process, which is a focus in the field of research on difficult-to-heal wounds. To research combined radiation-wound injuries, the establishment of animal models is a key part, and appropriate animal models are a guarantee of reliable experimental results. This review summarizes the current research progress on various animal models of combined radiation-wound injuries in terms of radiation types, animal species, and injury types and location, aiming to provide a scientific basis for establishing standardized animal models, studying injury mechanisms, and evaluating prevention and treatment efficacy for combined radiation-wound injuries.

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.

Bone homeostasis is a relative balance between bone formation and resorption. Signal transducer and activator of transcription 3 (STAT3), which is closely related to bone homeostasis, takes part in multiple intracellular and extracellular signal pathways. STAT3 participates in the process of osteoblast differentiation regulated by several factors. It can also maintain bone homeostasis by regulating the recruitment, differentiation and activation of osteoclasts. In addition, STAT3 is involved in the interaction between osteoblasts and osteoclasts. Patients with STAT3 mutations can have several inherited bone metabolism diseases. Furthermore, STAT3 plays a critical role in load-driven bone remodeling. Mechanical stimulation promotes osteoblast differentiation and bone formation through activating or enhancing STAT3 expression during bone remodeling process. This review summarizes the participation of STAT3 in maintaining bone homeostasis together with its possible mechanisms and discusses the connection between STAT3 and mechanical stimulation in bone remodeling, so as to provide a potential pharmacological target for the treatment of bone diseases.

Objective:To investigate the prevalence, risk factors and outcomes of diastasis recti abdominis (DRA) in multiparas after the second delivery.Methods:From June 2017 to September 2019, 300 multiparas with an average age of (31.7±4.0) years (26 to 43 years) after the second delivery were recruited at 6 weeks postpartum from two hospitals in Wenzhou. There were 171 multiparas with two natural births,36 multiparas with one natural birth and one caesarean delivery, and 93 multiparas with two caesarean deliveries. The interrectus distance (IRD) was measured with palpation at 6 weeks, 6 months and 12 months after delivery. Data on age, height, weight before pregnancy and delivery, baby′s birth weight, abdominal circumference before pregnancy and delivery, fetus number, delivery mode and occupation type were collected. Strength and endurance of abdominal muscle was assessed using manual muscle testing and curl-ups, low back pain was assessed using Oswestry disability index(ODI), urinary incontinence was assessed with International Consultation on Incontinence guestionnaire-incontinentia urinae (ICIQ-UI) short form (ICIQ-SF), and quality of life was assessed using 36-item short form health survey (SF-36).Results:Prevalence of DRA was 51.7%(155/300), 39.3%(116/295) and 27.7%(80/289) 6 weeks, 6 months and 12 months after delivery, respectively. Logistic regression analysis indicated that age ( OR=1.39, 95 %CI:1.02-1.91, P=0.38), abdominal circumference ratio ( OR=2.31, 95 %CI:1.23-4.33, P=0.01), twins ( OR=11.41, 95 %CI:2.15-60.76, P<0.01), and cesarean section ( OR=1.44, 95 %CI:1.06-1.95, P=0.02) were the risk factors of DRA at 12 months after delivery. At 12 months after delivery, the multiparas with DRA had weaker strength and endurance of abdominal muscle ( Z=-3.62, P<0.01; Z=-8.91, P<0.01), more serious low back pain ( Z=-2.10, P=0.04), and lower quality of life on physical health ( t=-3.34, P<0.01) than the multiparas without DRA. No difference in prevalence and severity of urinary incontinence and quality of life on psychological health was found when comparing multiparas with and without DRA (χ 2=0.66, P=0.42; Z=-1.18, P=0.24; t=0.91, P=0.36). Conclusion:Multipara after the second delivery has great likelihood for DRA.Age, abdominal circumference ratio, twins, and cesarean section are the risk factors of DRA. DRA is related to abdominal muscle dysfunction, low back pain, and quality of life.

The transcription factor nuclear factor kappa B (NF-B) is activated in hepatocytes in the pathogenesis of hepatic steatosis. However, the action mechanism of NF-B remains to be established in the hepatic steatosis. In this study, the subunit of NF-B was found to promote the hepatic steatosis through regulation of histone deacetylase 1 (HDAC1) in hepatocytes. The activity was supported by the phenotypes of knockout (-KO) mice and knockout (-KO) mice. Hepatic steatosis was reduced in the -KO mice, but not in the -KO mice. The reduction was a result of inhibition of HDAC1 activity in the -KO cells. Knockdown of gene led to suppression of hepatocyte steatosis in HepG2 cells. A decrease in sterol-regulatory element binding protein 1c (SREBP1c) protein was observed in the liver of -KO mice and in cell with knockdown. The decrease was associated with an increase in succinylation of SREBP1c protein. The study suggests that stabilizes HDAC1 to support the SREBP1c activity in hepatic steatosis in the pathophysiological condition. Interruption of this novel pathway in the -KO, but not the -KO mice, may account for the difference in hepatic phenotypes in the two lines of transgenic mice.

Objective To study the effects of high volume hemofiltration (HVHF) according to pulse-indicated continuous cardiac output (PiCCO) on patients with acute respiratory distress syndrome (ARDS).Methods A prospective randomly controlled trial was conducted.163 patients with ARDS admitted to Taizhou People's Hospital,Medical College,Nantong University,between February 2011 and January 2014,were enrolled.The patients were randomly divided into conventional therapy group (n＝ 50),HVHF group (n =55),and PiCCO + HVHF group (n＝58) by random number table.The patients in conventional therapy group received routine treatment including mechanical ventilation and drug treatment according to ARDS treatment guideline.The patients in the HVHF group received HVHF treatment of 18 hours per day on 1,3,5,7 days on the basis of conventional therapy.Patients in the PiCCO + HVHF group received HVHF treatment according to PiCCO.The indexes of lung function and PiCCO monitoring were recorded at intensive care unit (ICU) admission (before) and 4 days and 7 days after treatment.The serum levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were determined by enzyme linked immunosorbent assay (ELISA),and the prognosis of patients was recorded.Results In three groups,oxygenation index (PaO2/FiO2),static lung compliance (Cs) were gradually increased,and respiratory rate (RR),lactic acid (Lac) were gradually decreased.The indicators in HVHF and PiCCO + HVHF groups were significantly improved compared with conventional therapy group.The indexes in PiCCO + HVHF group were significantly increased or decreased compared with those in HVHF group,and the statistical differences were found on the 7th day after treatment [PaO2/FiO2 (mmHg,1 mmHg=0.133 kPa):189.3 ± 36.8 vs.166.3 ± 36.1,Cs (mL/cmH2O):76.7 ± 18.9 vs.67.0 ± 18.2,RR (times/min):16.4 ±5.2 vs.19.2 ± 5.4,Lac (mmol/L):1.20 ±0.41 vs.1.41 ±0.43,all P＜0.01].In PiCCO +HVHF group,cardiac index (CI) was gradually increased,and extra vascular lung water index (EVLWI) and intra thoracic blood volume index (ITBVI) were gradually decreased.There were significant differences in the indexes 4 days and 7 days after treatment compared with those before treatment [CI (L·min-1·m-2):4.62 ± 1.13,4.83 ± 1.10 vs.4.01 ± 1.02,EVLWI (mL/kg):7.6 ± 2.7,6.5 ± 2.6 vs.12.4 ± 2.9,ITBVI (mL/m2):801.3 ± 120.9,785.4 ± 118.7 vs.980.1 ± 168.6,all P＜0.01].After treatment,the serum levels of TNF-α and IL-1β in three groups were gradually decreased.Compared with the conventional therapy group,the serum levels of TNF-α and IL-1β on 4 days and 7 days in the HVHF and PiCCO + HVHF groups were significantly decreased,and the statistical differences were found on 7 days [TNF-α (ng/L):68.35 ± 12.63,67.54 ± 12.90 vs.85.35 ± 13.70; IL-1β (ng/L):424.6 ± 142.9,412.2 ± 140.2 vs.895.2 ± 187.7,all P＜0.01].Compared with the HVHF group,the serum levels of TNF-α and IL-1β in the PiCCO + HVHF group were slightly decreased without statistical differences.Compared with the conventional therapy group,the number of organ failure,duration of mechanical ventilation,the length of stay in ICU and hospital mortality in HVHF group and PiCCO + HVHF group were lowered,and the statistical differences were found in PiCCO + HVHF group compared with HVHF group [number of organ failure:2.41 ± 0.79 vs.2.72 ± 0.80,duration of mechanical ventilation (days):4.8 ± 2.0 vs.5.7 ± 2.1,the length of stay in ICU (days):11.5 ± 3.4 vs.13.1 ± 3.6,hospital mortality:31.0％ (18/58) vs.41.8％ (23/55),all P＜0.05].Conclusions Levels of inflammatory factors in patients with ARDS could be reduced by HVHF.The oxygenation and compliance of lung can be improved,the number of organ failure can be lowered,the duration of mechanical ventilation and the length of stay in ICU can be shortened,and the hospital mortality could be declined by PiCCO guided HVHF.