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.

Pelvic organ prolapse (POP), whose etiology is influenced by genetic and clinical risk factors, considerably impacts women's quality of life. However, the genetic underpinnings in non-European populations and comprehensive risk models integrating genetic and clinical factors remain underexplored. This study constructed the first polygenic risk score (PRS) for POP in the Chinese population by utilizing 20 disease-associated variants from the largest existing genome-wide association study. We analyzed a discovery cohort of 576 cases and 623 controls and a validation cohort of 264 cases and 200 controls. Results showed that the case group exhibited a significantly higher PRS than the control group. Moreover, the odds ratio of the top 10% risk group was 2.6 times higher than that of the bottom 10%. A high PRS was significantly correlated with POP occurrence in women older than 50 years old and in those with one or no childbirths. As far as we know, the integrated prediction model, which combined PRS and clinical risk factors, demonstrated better predictive accuracy than other existing PRS models. This combined risk assessment model serves as a robust tool for POP risk prediction and stratification, thereby offering insights into individualized preventive measures and treatment strategies in future clinical practice.
Humans ; Female ; Pelvic Organ Prolapse/epidemiology* ; Middle Aged ; Risk Assessment/methods* ; China/epidemiology* ; Multifactorial Inheritance ; Aged ; Risk Factors ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Case-Control Studies ; Adult ; Polymorphism, Single Nucleotide ; Genetic Risk Score ; East Asian People

Objective To establishing a chromatographic analysis method for therapeutic drug monitoring of fruquintinib by high-performance liquid chromatography （HPLC）. Methods The analysis was conducted using a Welch Ultimate XB-C₁₈ （4.6 mm×150 mm, 5 μm） column with the column temperature at 35℃. The flow rate was 1.0 ml/min and the detection wavelength was at 240 nm. The mobile phase consisted of acetonitrile and 10 mmol/L potassium dihydrogen phosphate （pH 3.15）= 40∶60（V∶V）. The internal standard substance was Apatinib．All plasma samples were extracted with ethyl acetate solution. Results The linearity of Fruquintinib in plasma was good within the range of 15.63-500.00 ng/ml （r=0.999 9）. The recoveries of the method were between 95%-110% with the RSD less than 10%. The extraction rates of the method were all higher than 97%. The stability tests met the relative requirements. Conclusion A HPLC method for the determination of Fruquintinib in human plasma was established. The method had good specialty, and could be used to detect the blood concentrations of Fruquintinib in clinical practice to improve the individualized medication．

Objective To explore the value of transvaginal ultrasound five-view method for diagnosing fetal congenital heart disease(CHD)in early pregnancy of high-risk pregnancy.Methods Totally 428 singleton fetuses at 11-13+6 weeks of gestation in high-risk pregnancies were prospectively enrolled.Fetal cardiac examinations were performed using two-dimensional grey scale imaging combined with CDFI via transabdominal ultrasound method,transvaginal ultrasound five-view method(upper abdominal transverse view,four-chamber view,three-vessel and trachea[3VT]view,ventricular outflow tract view and bilateral subclavian artery view)and transvaginal ultrasound two-view method(four-chamber view and 3VT view).Taken results of pregnant metaphase or late pregnancy fetal echocardiography,post-abortion pathology or postnatal neonatal echocardiography as gold standards,the diagnostic performances of the above 3 methods for diagnosing fetal CHD in early pregnancy were compared.Results CHD was diagnosed in 120(120/428,28.04％)fetuses.Transvaginal ultrasound five-view method made 11 false positives and 19 false negatives,with sensitivity,specificity,positive predictive value and negative predictive values for diagnosing fetal CHD in the first trimester of high-risk pregnancy of 84.17％,96.43％,90.18％and 93.99％,respectively,which were all significantly higher than of transvaginal ultrasound two-view method(70.83％,91.88％,77.27％and 88.99％)and transabdominal ultrasound method(72.50％,91.23％,76.32％and 89.49％;all P＜0.05).Conclusion Transvaginal ultrasound five-view method could be used to effectively diagnose fetal CHD in the first trimester of high-risk pregnancy.

ObjectiveTo establish the multi-technique characteristic profiles of Alumen by X-ray diffraction（XRD）， Fourier-transform infrared spectroscopy（FTIR） and thermogravimetric-differential thermal analysis（TG-DTA）， and to explore the spectral characteristics for rapid identification of Alumen and its potential adulterant， Ammonium alum. MethodsA total of 27 batches of Alumen samples from 8 production regions were collected for preliminary identification based on visual characteristics. The PDF standard cards of XRD were used to differentiate Alumen from A. alum， and the XRD characteristic profiles of Alumen were established， and then the common peaks were screened. Based on hierarchical clustering analysis（HCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）， the characteristic information that could be used for identification of Alumen was selected with variable importance in the projection（VIP） value>1. FTIR characteristic profiles of Alumen were established， and key wavenumbers for identification were screened by HCA and OPLS-DA with VIP value>1. Meanwhile， the thermogravimetric differences between Alumen and A. alum were analyzed by TG-DTA， and the thermogravimetric traits that could be used for identification were screened. ResultsAlumen and A. alum could not be effectively distinguished by traits alone. However， by comparing the PDF standard cards of XRD， 15 batches of Alumen and 12 batches of A. alum could be distinguished. In the XRD profiles， 10 characteristic peaks were confirmed， corresponding to diffraction angles of 14.560°， 24.316°， 12.620°， 32.122°， 17.898°， 34.642°， 27.496°， 46.048°， 40.697° and 21.973°. In the FTIR profiles， 4 wavenumber ranges（399.193-403.050， 1 186.010-1 471.420， 1 801.190-2 620.790， 3 612.020-3 997.710 cm^-1） and 12 characteristic wavenumbers（1 428.994， 1 430.922， 1 432.851， 1 434.779， 1 436.708， 1 438.636， 1 440.565， 1 442.493， 1 444.422， 1 446.350， 1 448.279， 1 450.207 cm^-1） were identified. In the TG-DTA profiles， there were characteristic decomposition peaks of ammonium ion and mass reduction features near 555.34 ℃ for A. alum. These characteristics could serve as important criteria for distinguishing the authenticity of Alumen. ConclusionXRD， FTIR and TG-DTA can be used to rapidly detect Alumen and A. alum， and combined with the discriminant features selected through chemometrics， the rapid and accurate identification of Alumen and A. alum can be achieved. The research findings provide new approaches for the rapid identification of Alumen.

ObjectiveTo investigate the processing technology of calcined Haematitum based on the concept of quality by design（QbD） and to assess its health risk. MethodsTaking whole iron content， Fe²⁺ dissolution content and looseness as critical quality attributes（CQAs）， and calcination temperature， calcination time， spreading thickness and particle size as critical process parameters（CPPs） determined by the failure mode and effect analysis（FMEA）， the processing technology of calcined Haematitum was optimized by orthogonal test combined with analytic hierarchy process-criteria importance through intercriteria correlation（AHP-CRITIC） hybrid weighting method. The contents of heavy metals and harmful elements were determined by inductively coupled plasma mass spectrometry， and the health risk assessment was carried out by daily exposure（EXP）， target hazard quotient（THQ） and lifetime cancer risk（LCR）， and the theoretical value of the maximum limit was deduced. ResultsThe optimal processing technology for calcined Haematitum was calcination at 650 ℃， calcination time of 1 h， particle size of 0.2-0.5 cm， spreading thickness of 1 cm， and vinegar quenching for 1 time［Haematitum-vinegar（10：3）］. The contents of 5 heavy metals and harmful elements in 13 batches of calcined Haematitum were all decreased with reductions of up to 5-fold. The cumulative THQ of 2 batches of samples was>1， while the cumulative THQ of all batches of Haematitum was>1. The LCR of As in 1 batches of Haematitum was 1×10^-6-1×10^-4， and the LCR of the rest was<1×10^-6， and the LCRs of calcined Haematitum were all<1×10^-6， indicating that the carcinogenic risk of calcined Haematitum was low， but special attention should still be paid to Haematitum medicinal materials. Preliminary theoretical values of the maximum limits of Cu， As， Cd， Pb and Hg were formulated as 1 014， 25， 17， 27， 7 mg·kg^-1. ConclusionThe optimized processing technology of calcined Haematitum is stable and feasible， and the contents of heavy metals and harmful elements are reduced after processing. Preliminary theoretical values of the maximum limits of Cu， As， Cd， Pb and Hg are formulated to provide a scientific basis for the formulation of standards for the limits of harmful elements in Haematitum.

ObjectiveTo establish the multi-technique characteristic profiles of Alumen by X-ray diffraction（XRD）， Fourier-transform infrared spectroscopy（FTIR） and thermogravimetric-differential thermal analysis（TG-DTA）， and to explore the spectral characteristics for rapid identification of Alumen and its potential adulterant， Ammonium alum. MethodsA total of 27 batches of Alumen samples from 8 production regions were collected for preliminary identification based on visual characteristics. The PDF standard cards of XRD were used to differentiate Alumen from A. alum， and the XRD characteristic profiles of Alumen were established， and then the common peaks were screened. Based on hierarchical clustering analysis（HCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）， the characteristic information that could be used for identification of Alumen was selected with variable importance in the projection（VIP） value>1. FTIR characteristic profiles of Alumen were established， and key wavenumbers for identification were screened by HCA and OPLS-DA with VIP value>1. Meanwhile， the thermogravimetric differences between Alumen and A. alum were analyzed by TG-DTA， and the thermogravimetric traits that could be used for identification were screened. ResultsAlumen and A. alum could not be effectively distinguished by traits alone. However， by comparing the PDF standard cards of XRD， 15 batches of Alumen and 12 batches of A. alum could be distinguished. In the XRD profiles， 10 characteristic peaks were confirmed， corresponding to diffraction angles of 14.560°， 24.316°， 12.620°， 32.122°， 17.898°， 34.642°， 27.496°， 46.048°， 40.697° and 21.973°. In the FTIR profiles， 4 wavenumber ranges（399.193-403.050， 1 186.010-1 471.420， 1 801.190-2 620.790， 3 612.020-3 997.710 cm^-1） and 12 characteristic wavenumbers（1 428.994， 1 430.922， 1 432.851， 1 434.779， 1 436.708， 1 438.636， 1 440.565， 1 442.493， 1 444.422， 1 446.350， 1 448.279， 1 450.207 cm^-1） were identified. In the TG-DTA profiles， there were characteristic decomposition peaks of ammonium ion and mass reduction features near 555.34 ℃ for A. alum. These characteristics could serve as important criteria for distinguishing the authenticity of Alumen. ConclusionXRD， FTIR and TG-DTA can be used to rapidly detect Alumen and A. alum， and combined with the discriminant features selected through chemometrics， the rapid and accurate identification of Alumen and A. alum can be achieved. The research findings provide new approaches for the rapid identification of Alumen.

ObjectiveTo investigate the processing technology of calcined Haematitum based on the concept of quality by design（QbD） and to assess its health risk. MethodsTaking whole iron content， Fe²⁺ dissolution content and looseness as critical quality attributes（CQAs）， and calcination temperature， calcination time， spreading thickness and particle size as critical process parameters（CPPs） determined by the failure mode and effect analysis（FMEA）， the processing technology of calcined Haematitum was optimized by orthogonal test combined with analytic hierarchy process-criteria importance through intercriteria correlation（AHP-CRITIC） hybrid weighting method. The contents of heavy metals and harmful elements were determined by inductively coupled plasma mass spectrometry， and the health risk assessment was carried out by daily exposure（EXP）， target hazard quotient（THQ） and lifetime cancer risk（LCR）， and the theoretical value of the maximum limit was deduced. ResultsThe optimal processing technology for calcined Haematitum was calcination at 650 ℃， calcination time of 1 h， particle size of 0.2-0.5 cm， spreading thickness of 1 cm， and vinegar quenching for 1 time［Haematitum-vinegar（10：3）］. The contents of 5 heavy metals and harmful elements in 13 batches of calcined Haematitum were all decreased with reductions of up to 5-fold. The cumulative THQ of 2 batches of samples was>1， while the cumulative THQ of all batches of Haematitum was>1. The LCR of As in 1 batches of Haematitum was 1×10^-6-1×10^-4， and the LCR of the rest was<1×10^-6， and the LCRs of calcined Haematitum were all<1×10^-6， indicating that the carcinogenic risk of calcined Haematitum was low， but special attention should still be paid to Haematitum medicinal materials. Preliminary theoretical values of the maximum limits of Cu， As， Cd， Pb and Hg were formulated as 1 014， 25， 17， 27， 7 mg·kg^-1. ConclusionThe optimized processing technology of calcined Haematitum is stable and feasible， and the contents of heavy metals and harmful elements are reduced after processing. Preliminary theoretical values of the maximum limits of Cu， As， Cd， Pb and Hg are formulated to provide a scientific basis for the formulation of standards for the limits of harmful elements in Haematitum.

Objective To analyze the clinical characteristics and high risk factors of prognosis in patients with chronic heart failure and renal insufficiency. Methods A total of 499 patients with chronic heart failure and renal insufficiency from September 2022 to September 2024 were selected. The clinical data of patients were collected, and the clinical characteristics were analyzed. After 3 months of follow-up, the patients were divided into survival group and death group according to the prognosis status. Univariate analysis, and multivariate logistic regression analysis were adopted to analyze the risk factors affecting the prognosis of patients. Results According to different ejection fraction values, patients were classified into HFrEF group (n=164), HFmrEF group (n=103) and HFpEF group (n=232). The age in HFpEF group was the lowest (P<0.05). The cardiac function grading was the highest in HFrEF group, and the systolic blood pressure was lower while the diastolic blood pressure was higher than that in the other two groups (P<0.05), and there were no differences in cardiac function, systolic blood pressure and diastolic blood pressure between HFmrEF group and HFpEF group (P>0.05). The levels of Hb and ALB in HFpEF group were higher than those in HFrEF group (P<0.05), and no differences were observed between HFmrEF group and the other two groups (P>0.05). HFrEF group had the lowest total cholesterol and Scr, and the highest serum uric acid, eGFR, BNP and cTnI (P<0.05). The level of hs-CRP in HFmrEF group was the lowest. The LVEDD was lower in HFpEF group than that in the other two groups (P<0.05). The levels of serum uric acid, Scr and hs-CRP in death group were higher while the eGFR was lower compared to survival group (P<0.05). After logistic analysis, it was found that elevated levels of serum uric acid and hs-CRP and decreased eGFR were risk factors for poor prognosis (P<0.05). Conclusion Patients with chronic heart failure and renal insufficiency are mainly HFpEF. Elevated serum uric acid and hs-CRP and decreased eGFR are the high risk factors for poor prognosis.

Obstructive sleep apnea(OSA)is a dis-order characterized by chronic intermittent hypoxia and sleep fragmentation,usually manifested by ob-struction of the upper respiratory tract,resulting in sleep fragmentation,intermittent hypoxia,and hy-percapnia.OSA and significant comorbidities are as-sociated with perioperative complications.Opioids,as the most commonly used pain relievers,may fur-ther affect perioperative pain management in OSA and comorbidities.Studies have shown that OSA patients are more susceptible to the respiratory de-pressant effects of opioids.OSA also increases the risk of opioid-induced respiratory depression.There-fore,understanding the effects and mechanisms of opioids on OSA has important clinical significance for optimizing drug use,improving prognosis,and reducing respiratory adverse events.This article aims to review the effects of opioids on OSA and their relationship.