Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, which increases the incidence of colorectal cancer (CRC). In the pathophysiology of IBD, ubiquitination/deubiquitination plays a critical regulatory function. Josephin domain containing 2 (JOSD2), a deubiquitinating enzyme, controls cell proliferation and carcinogenesis. However, its role in IBD remains unknown. Colitis mice model developed by dextran sodium sulfate (DSS) or colon tissues from individuals with ulcerative colitis and Crohn's disease showed a significant upregulation of JOSD2 expression in the macrophages. JOSD2 deficiency exacerbated the phenotypes of DSS-induced colitis by enhancing colon inflammation. DSS-challenged mice with myeloid-specific JOSD2 deletion developed severe colitis after bone marrow transplantation. Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-κB) and inflammation in macrophages. It was also shown that JOSD2 knockout significantly exacerbated increased azoxymethane (AOM)/DSS-induced CRC, and AAV6-mediated JOSD2 overexpression in macrophages prevented the development of colitis in mice. These outcomes reveal a novel role for JOSD2 in colitis through deubiquitinating IMPDH2, suggesting that targeting JOSD2 is a potential strategy for treating IBD.

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 assess the independent and combined effects of air pollutants, meteorological factors, and greenspace exposure on new tuberculosis (TB) cases. METHODS: TB case data from Shanghai (2013-2018) were obtained from the Shanghai Center for Disease Control and Prevention. Environmental data on air pollutants, meteorological variables, and greenspace exposure were obtained from the National Tibetan Plateau Data Center. We employed a distributed-lag nonlinear model to assess the effects of these environmental factors on TB cases. RESULTS: Increased TB risk was linked to PM _2.5, PM ₁₀, and rainfall, whereas NO ₂, SO ₂, and air pressure were associated with a reduced risk. Specifically, the strongest cumulative effects occurred at various lags: PM _2.5 ( RR = 1.166, 95% CI: 1.026-1.325) at 0-19 weeks; PM ₁₀ ( RR = 1.167, 95% CI: 1.028-1.324) at 0-18 weeks; NO ₂ ( RR = 0.968, 95% CI: 0.938-0.999) at 0-1 weeks; SO ₂ ( RR = 0.945, 95% CI: 0.894-0.999) at 0-2 weeks; air pressure ( RR = 0.604, 95% CI: 0.447-0.816) at 0-8 weeks; and rainfall ( RR = 1.404, 95% CI: 1.076-1.833) at 0-22 weeks. Green space exposure did not significantly impact TB cases. Additionally, low temperatures amplified the effect of PM _2.5 on TB. CONCLUSION Exposure to PM _2.5, PM ₁₀, and rainfall increased the risk of TB, highlighting the need to address air pollutants for the prevention of TB in Shanghai.
China/epidemiology* ; Humans ; Air Pollutants/analysis* ; Tuberculosis/epidemiology* ; Incidence ; Meteorological Concepts ; Particulate Matter/adverse effects* ; Environmental Exposure ; Male ; Female ; Adult ; Air Pollution ; Middle Aged

Phosgene is a highly reactive chemical substance and a prevalent chemical warfare agent,and it is vitally important for rapid and accurate detection of phosgene to counteract terrorist threats and industrial accidents.In this work,a phosgene probe,designated as SX-Pho,which incorporated benzimidazole and hydroxyl groups as recognition motifs,was prepared through Suzuki coupling and Debus-Radziszewski methodologies to incorporate an electron-donating carbazole moiety.This probe exhibited a large Stokes shift(Approximately 130 nm).Upon exposure to triphosgene/triethylamine conditions(in situ phosgene generation),the fluorescence emission of probe at 470 nm underwent significant quenching,with a 20-fold reduction in intensity,while the fluorescence lifetime decreased from 3.30 ns to 3.06 ns.Concentration titration experiments demonstrated that SX-Pho achieved a lower detection limit of 57.8 nmol/L with high specificity and interference resistance.Preton nuclear magnetic resonance spectroscopy(1H NMR),high-resolution mass spectrometry,and density functional theory(DFT)calculations confirmed the cyclization reaction between hydroxyl groups,imines,and phosgene.The extent of overlap between the highest occupied molecular orbital(HOMO)and the lowest unoccupied molecular orbital(LUMO)was notably decreased,leading to the suppression of radiative transitions.The energy gap underwent a reduction of 0.43 eV,while the non-radiative transition was augmented,resulting in fluorescence quenching and achieving rapid detection of phosgene.Based on this,probe-loaded test strips were prepared.The color change under 365 nm illumination allowed visual discrimination of phosgene at concentrations below 20 μL/L.Furthermore,using a smartphone's built-in RGB application to measure the intensity of the blue(B)channel after the test strips were exposed to phosgene enabled both qualitative and quantitative detection.The detection range was 1.82-50 μL/L,with a limit of detection(LOD)of 1.814 μL/L.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

OBJECTIVE: To investigate possible associations between physical function assessment scales, such as Short Physical Performance Battery (SPPB) and Berg Balance Scale (BBS), with all-cause mortality in acute decompensated heart failure (ADHF) patients. METHODS: A total of 108 ADHF patients were analyzed from October 2020 to October 2022, and followed up to May 2023. The association between baseline clinical characteristics and all-cause mortality was analyzed by univariate Cox regression analysis, while for SPPB and BBS, univariate Cox regression analysis was followed by receiver operating characteristic curves, in which the area under the curve represented their predictive accuracy for all-cause mortality. Incremental predictive values for both physical function assessments were measured by calculating net reclassification index and integrated discrimination improvement scores. Optimal cut-off value for BBS was then identified using restricted cubic spline plots, and survival differences below and above that cut-off were compared using Kaplan-Meier survival curves and the log-rank test. The clinical utility of BBS was measured using decision curve analysis. RESULTS: For baseline characteristics, age, female, blood urea nitrogen, as well as statins, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, or angiotensin receptor-neprilysin inhibitors, were predictive for all-cause mortality for ADHF patients. With respect to SPPB and BBS, higher scores were associated with lower all-cause mortality rates for both assessments; similar area under the curves were measured for both (0.774 for SPPB and 0.776 for BBS). Furthermore, BBS ≤ 36.5 was associated with significantly higher mortality, which was still applicable even adjusting for confounding factors; BBS was also found to have great clinical utility under decision curve analysis. CONCLUSIONS BBS or SPPB could be used as tools to assess physical function in ageing ADHF patients, as well as prognosticate on all-cause mortality. Moreover, prioritizing the improvement of balance capabilities of ADHF patients in cardiac rehabilitation regimens could aid in lowering mortality risk.

Objective To compare the differences of endoscopic ultrasound (EUS)-guided non-invasive measurement of portal venous pressure and EUS-guided portal pressure gradient(EUS-PPG) in measurement of portal venous pressure on animals and their correlation. Methods Twenty-four miniature pigs were selected and fed with carbon tetrachloride and phenobarbital sodium combined with high-fat,low-protein and low-choline diet for 16 weeks to establish a liver cirrhotic portal hypertension model. The changes of biochemical indexes of liver function and liver pathology in the experimental pigs were observed to evaluate whether the model was successful. After the model was successfully established,the hemodynamic parameters of the portal venous trunk were measured non-invasively under EUS guidance,including portal venous blood flow and splenic artery pulsatility index,thereby calculating portal venous pressure. Then,taking EUS-PPG,the portal vein,hepatic vein,and inferior vena cava were punctured with an 18G puncture needle under general anesthesia guided by the translinear endoscopic ultrasound,and the PPG was calculated through the central venous pressure monitoring system.The Pearson correlation analysis,Kappa test,ICC intraclass correlation coefficient and Bland-Altman plot were used for consistency analysis. Results All the 24 pigs survived 16 weeks after modeling.The serum levels of alanine transaminase (ALT),aspartate transaminase (AST),albumin (ALB),globulin (GLB),total bilirubin (TBIL) and indirect bilirubin (IBIL)after modeling were higher than those before modeling(P<0.05). HE staining and Sirius red staining showed abnormal liver morphology and increased collagen fibers after modeling,suggesting that the experimental pig model of liver cirrhotic portal hypertension was successfully established. The results of EUS-guided non-invasive measurement of portal venous pressure showed that the mean splenic artery pulsatility index was (2.03±0.68),the mean portal vein flow was (17.27±4.31)cm/s,and the mean portal venous pressure was (15.97±3.65)mmHg. The measurement results of the mean portal venous pressure,hepatic venous pres-sure and PPG of EUS-PPG were (20.68±4.71)mmHg,(4.07±2.14)mmHg and (16.38±4.28)mmHg respectively. Pearson correlation analysis showed that there was a significant positive correlation between the portal venous pressures measured by the two methods (r=0.902,P<0.001);the consistency tests of Kappa test and ICC intraclass correlation coefficient showed that the measurement results of the two methods were highly consistent (Kappa=0.699,P<0.001;ICC=0.945);Bland-Altman plot analysis showed that most of the points fell within 95％ limits of agreement. Conclusion EUS-guided non-invasive measurement of portal venous pressure has a high correlation and consistency with the measurement results by EUS-PPG,which has high success rate,and accurate reflection of portal venous pressure,with low cost and good safety.

Objective To investigate and compare the epidemiological characteristics of common respiratory viruses among influenza-like illness(ILI)and severe acute respiratory infection(SARI)cases in Huzhou,Zhejiang Province before and after the COVID-19 pandemic,so as to provide a basis for formulating and adjusting the prevention and control strategies for viral respiratory infectious diseases.Methods ILI and SARI cases at two influenza surveillance sentinel hospitals in Huzhou and had throat swab samples collected during Nov 2017 to Feb 2020(pre-COVID-19 pandemic period)and Dec 2022 to Apr 2024(post-COVID-19 mitigation phase)were selected as the participants.Seven common viral respiratory pathogens were tested,including influenza A virus(H1N1 and H3N2 subtypes),influenza B virus(Victoria lineage,FluB),respiratory syncytial virus(RSV),rhinovirus(HRV),adenovirus(ADV),and severe acute respiratory syndrome coronavirus-2(SARS-CoV-2).The positive rates of respiratory pathogens before and after the COVID-19 pandemic were compared across different age groups and different time.Results A total of 7 948 ILI samples and 2 294 SARI samples were included.The overall positive rate of ILI samples increased from 33.6%to 47.1%,primarily due to the increase in influenza and COVID-19 infections;the overall positive rate of SARI samples decreased from 31.4%to 24.8%,mainly due to the reduction in HRV and ADV infections.During the post-COVID-19 mitigation phase,SARS-CoV-2(22.1%),H3N2(12.7%),and FluB(6.0%)were the primary pathogens in ILI samples,while RSV(7.1%),H3N2(5.3%),and HRV(4.5%)dominated in SARI samples.During the post-COVID-19 mitigation phase,the influenza virus circulation period was shortened.Before the COVID-19 pandemic,RSV was mainly detected in autumn and winter,while during the post-COVID-19 mitigation phase,out-of-season RSV epidemics were observed in spring and summer.Co-infection rate in ILI cases increased significantly in the post-COVID-19 mitigation phase,predominantly consisting of co-infections of COVID-19 and influenza A virus,while co-infection rate in SARI cases showed a decline.Conclusion We found important epidemiological changes in respiratory viruses in Huzhou during the post-COVID-19 mitigation phase compared to pre-COVID-19 period,including increased positive rates of influenza and COVID-19,and disruptions to the seasonal patterns of influenza and RSV.The prevention and control strategies should be adjusted in a timely manner based on the monitoring data.

Objective To investigate and compare the epidemiological characteristics of common respiratory viruses among influenza-like illness(ILI)and severe acute respiratory infection(SARI)cases in Huzhou,Zhejiang Province before and after the COVID-19 pandemic,so as to provide a basis for formulating and adjusting the prevention and control strategies for viral respiratory infectious diseases.Methods ILI and SARI cases at two influenza surveillance sentinel hospitals in Huzhou and had throat swab samples collected during Nov 2017 to Feb 2020(pre-COVID-19 pandemic period)and Dec 2022 to Apr 2024(post-COVID-19 mitigation phase)were selected as the participants.Seven common viral respiratory pathogens were tested,including influenza A virus(H1N1 and H3N2 subtypes),influenza B virus(Victoria lineage,FluB),respiratory syncytial virus(RSV),rhinovirus(HRV),adenovirus(ADV),and severe acute respiratory syndrome coronavirus-2(SARS-CoV-2).The positive rates of respiratory pathogens before and after the COVID-19 pandemic were compared across different age groups and different time.Results A total of 7 948 ILI samples and 2 294 SARI samples were included.The overall positive rate of ILI samples increased from 33.6%to 47.1%,primarily due to the increase in influenza and COVID-19 infections;the overall positive rate of SARI samples decreased from 31.4%to 24.8%,mainly due to the reduction in HRV and ADV infections.During the post-COVID-19 mitigation phase,SARS-CoV-2(22.1%),H3N2(12.7%),and FluB(6.0%)were the primary pathogens in ILI samples,while RSV(7.1%),H3N2(5.3%),and HRV(4.5%)dominated in SARI samples.During the post-COVID-19 mitigation phase,the influenza virus circulation period was shortened.Before the COVID-19 pandemic,RSV was mainly detected in autumn and winter,while during the post-COVID-19 mitigation phase,out-of-season RSV epidemics were observed in spring and summer.Co-infection rate in ILI cases increased significantly in the post-COVID-19 mitigation phase,predominantly consisting of co-infections of COVID-19 and influenza A virus,while co-infection rate in SARI cases showed a decline.Conclusion We found important epidemiological changes in respiratory viruses in Huzhou during the post-COVID-19 mitigation phase compared to pre-COVID-19 period,including increased positive rates of influenza and COVID-19,and disruptions to the seasonal patterns of influenza and RSV.The prevention and control strategies should be adjusted in a timely manner based on the monitoring data.

Objective To compare the differences of endoscopic ultrasound (EUS)-guided non-invasive measurement of portal venous pressure and EUS-guided portal pressure gradient(EUS-PPG) in measurement of portal venous pressure on animals and their correlation. Methods Twenty-four miniature pigs were selected and fed with carbon tetrachloride and phenobarbital sodium combined with high-fat,low-protein and low-choline diet for 16 weeks to establish a liver cirrhotic portal hypertension model. The changes of biochemical indexes of liver function and liver pathology in the experimental pigs were observed to evaluate whether the model was successful. After the model was successfully established,the hemodynamic parameters of the portal venous trunk were measured non-invasively under EUS guidance,including portal venous blood flow and splenic artery pulsatility index,thereby calculating portal venous pressure. Then,taking EUS-PPG,the portal vein,hepatic vein,and inferior vena cava were punctured with an 18G puncture needle under general anesthesia guided by the translinear endoscopic ultrasound,and the PPG was calculated through the central venous pressure monitoring system.The Pearson correlation analysis,Kappa test,ICC intraclass correlation coefficient and Bland-Altman plot were used for consistency analysis. Results All the 24 pigs survived 16 weeks after modeling.The serum levels of alanine transaminase (ALT),aspartate transaminase (AST),albumin (ALB),globulin (GLB),total bilirubin (TBIL) and indirect bilirubin (IBIL)after modeling were higher than those before modeling(P<0.05). HE staining and Sirius red staining showed abnormal liver morphology and increased collagen fibers after modeling,suggesting that the experimental pig model of liver cirrhotic portal hypertension was successfully established. The results of EUS-guided non-invasive measurement of portal venous pressure showed that the mean splenic artery pulsatility index was (2.03±0.68),the mean portal vein flow was (17.27±4.31)cm/s,and the mean portal venous pressure was (15.97±3.65)mmHg. The measurement results of the mean portal venous pressure,hepatic venous pres-sure and PPG of EUS-PPG were (20.68±4.71)mmHg,(4.07±2.14)mmHg and (16.38±4.28)mmHg respectively. Pearson correlation analysis showed that there was a significant positive correlation between the portal venous pressures measured by the two methods (r=0.902,P<0.001);the consistency tests of Kappa test and ICC intraclass correlation coefficient showed that the measurement results of the two methods were highly consistent (Kappa=0.699,P<0.001;ICC=0.945);Bland-Altman plot analysis showed that most of the points fell within 95％ limits of agreement. Conclusion EUS-guided non-invasive measurement of portal venous pressure has a high correlation and consistency with the measurement results by EUS-PPG,which has high success rate,and accurate reflection of portal venous pressure,with low cost and good safety.