ObjectiveTo investigate the association between sarcopenia and short-term prognosis in patients with acute-on-chronic liver failure （ACLF）， to assess the value of Model for End-Stage Liver Disease （MELD）， MELD combined with serum sodium concentration （MELD-Na）， MELD 3.0， and Chinese Group on the Study of Severe Hepatitis B （COSSH）-ACLF Ⅱ score in predicting the 90-day prognosis of ACLF patients， and to analyze the predictive gain of sarcopenia over traditional prognostic scoring models. MethodsA retrospective study was conducted among 219 patients with ACLF who were hospitalized in The Affiliated Hospital of Inner Mongolia Medical University， No. 2 Hospital of Hohhot， Hohhot First Hospital， and Inner Mongolia People’s Hospital from July 2018 to July 2024. L3 skeletal muscle index （L3-SMI） was measured and calculated based on abdominal computed tomography images， and sarcopenia was diagnosed based on L3-SMI. According to 90-day prognosis， the patients with ACLF were divided into survival group with 124 patients and death group with 95 patients. The chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups； the independent samples t-test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. The multivariate Cox regression analysis （stepwise backward approach） was used to identify independent risk factors for 90-day mortality in ACLF patients. The Kaplan-Meier method was used for survival analysis， and the Log-rank test was used for comparison between groups. The receiver operating characteristic curve was plotted to evaluate the predictive performance of each model， and the DeLong test， bootstrap internal validation， net reclassification improvement （NRI）， and integrated discrimination improvement （IDI） were used to assess the predictive gain of sarcopenia. ResultsThe multivariate Cox regression analysis showed that presence of sarcopenia （hazard ratio ［HR］=3.385， 95% confidence interval ［CI］： 1.722 — 6.657， P<0.05）， older age （HR=1.036， 95%CI： 1.017 — 1.056， P<0.05）， elevated alkaline phosphatase （HR=1.006， 95%CI： 1.004 — 1.009， P<0.05）， elevated total bilirubin （HR=1.003， 95%CI： 1.001 — 1.005， P<0.05）， elevated potassium （HR=1.581， 95%CI： 1.160 — 2.155， P<0.05）， elevated serum creatinine （HR=1.015， 95%CI： 1.007 — 1.024， P<0.05）， and prolonged prothrombin time （HR=1.035， 95%CI： 1.015 — 1.055， P<0.05） were independent risk factors for 90-day mortality in ACLF patients， while elevated albumin （HR=0.885， 95%CI： 0.837 — 0.935， P<0.05） was an independent protective factor against 90-day mortality. MELD， MELD-Na， MELD 3.0， and COSSH-ACLF Ⅱ scores had an area under the ROC curve （AUC） of 0.569， 0.570， 0.632， and 0.659， respectively， for predicting the 90-day prognosis of ACLF patients， suggesting that these scores had unsatisfactory performance； after they were respectively combined with sarcopenia， the AUC was increased to 0.702， 0.687， 0.723， and 0.728， respectively. The DeLong test， NRI， and IDI analyses showed the combined models had significantly better predictive performance （all P<0.05）. ConclusionSarcopenia is an independent risk factor for 90-day mortality in patients with ACLF. Traditional scoring models have limited predictive performance for 90-day prognosis in ACLF patients， and the combination with sarcopenia significantly improves predictive value， suggesting that sarcopenia can be used as an important supplementary indicator for prognostic evaluation of ACLF in clinical practice.

OBJECTIVE: To investigate the association of various polycyclic aromatic hydrocarbon (PAH) metabolites with diverse subtypes of cardiovascular disease (CVD) risk. METHODS: A novel predicting risk of cardiovascular disease EVENTs PREVENT equation was used to estimate the 10-year diverse subtypes of CVD risk, and their associations with PAH metabolites were analyzed using multiple logistic regression models, the weighted quantile sum (WQS) model, the quantile g-computation (qgcomp) model, and a stratified analysis of subgroups. RESULTS: For this study, six thousand seven hundred and forty-five participants were selected, and significant positive associations were observed between PAHs, naphthalene (NAP), and fluorene (FLU), and the risks of total CVD, atherosclerotic cardiovascular disease (ASCVD), and heart failure (HF). NAP and FLU were the primary contributors to the effects of PAH mixtures, and their associations with total CVD, ASCVD, and HF risk were significant in younger participants (30 ≤ age < 50 years); however, the associations of phenanthrene (PHEN) with ASCVD, HF, coronary heart disease (CHD), and stroke were dominant in aging participants (age ≥ 50 years). Notably, pyrene (PYR) was negatively associated with the risk of ASCVD, HF, CHD, and stroke. Similarly, negative associations of PYR with the four CVD subtypes were noticeable in aging participants. CONCLUSION Different PAHs metabolites had different impacts on each CVD subtype among different age groups. Notably, the protective effects of PYR on ASCVD, HF, CHD, and stroke were noticeable in aging individuals.
Humans ; Cardiovascular Diseases/chemically induced* ; Middle Aged ; Polycyclic Aromatic Hydrocarbons/metabolism* ; Male ; Female ; Adult ; Aged ; Risk Factors ; China/epidemiology*

Objective To investigate the mechanism of autophagy induced by House dust mites(HDM)on airway epithelial tight junction through β-catenin-Snail signaling pathway.Methods Human bronchial epithelial cells(16HBE)were stimulated with HDM at different time points(0,3,6,12,24,48 h)and different concen-trations(0,40,100,200 μg/mL)to screen the appropriate stimulation concentration and stimulation time.16HBE cells were treated with oxidative stress inhibitor N-acetylcysteine(NAC),autophagy inhibitor 3-methylad-enine(3-MA),HDM,and their combinations.Cells were transfected with mCherry-EGFP-LC3B,Beclin-1-siRNA,and ATG14-siRNA lentivirus and then stimulated with NAC and HDM.Immunofluorescence was used to detect the expression levels of autophagy-related protein LC3B,tight junction-related proteins Occludin,and ZO-1 in airway epithelial cells.The level of reactive oxygen species(ROS)was detected by using DCFH-DA in each group.The protein expression levels of Occludin,ZO-1,LC3B,Beclin-1,ATG5,ATG14,P62,Snail,β-catenin and p-β-catenin were detected by Western blot method.Results Immunofluorescence results showed that compared with the control group,200 μg/mL HDM stimulation induced cellular autophagy,increased the expression level of LC3B protein,and promoted the level of ROS,all with statistical significances(all P<0.05).Compared with the HDM group,the HDM+3-MA,HDM+ATG14-si,and HDM+Beclin-1-si groupsall showed significantincreases in the expression levels of tight junction-related proteins Occludin and ZO-1(P<0.05).The HDM+NAC group demonstrated significant decreases both in the level of ROS andin the expression level of LC3B protein.Western blot results revealed that compared with HDM,3-MA and autophagy protein low-expression beads(Beclin-1-si,ATG14-si)attenuated HDM-induced cellular autophagy(P<0.05),inhibited HDM-induced upregulation of Snail and p-β-catenin expression,and improved HDM-induced decreases in Occludin and ZO-1(P<0.05).Moreover,compared with the HDM group,the NAC+HDM group exhibited significant decreases both in the conversion of LC3BⅠ to LC3BⅡ(P<0.001)in the protein levels of Snail,p-β-catenin,Beclin-1 and ATG14(P<0.01),but significant increases in the protein levels of Occludin and ZO-1(P<0.05).Conclusion HDM affects the tight connections between airway epithelial cells by inducing autophagy,which may be attributed to the β-catenin-Snail signaling pathway.

Objective To evaluate the effect of Kaixin San(KXS)combined with fluoxetine on hippocampal neural stem cells in mice with chronic stress stress and depression.Methods A mouse model of depression was constructed using the method of chronic unpredictable stress stress,and the highest dose of KXS water extract and fluoxetine for clinical application was given for 28 days,and behavioral tests were carried out.Nissl staining was used to detect the pathological status of hippocampal tissues in mice.The expression of TUNEL and Nestin in mouse hippocampus was determined by immunofluorescence.Western blotting was used to detect the expressions of apoptotic proteins cleaved caspase-3 and caspase-3,pyroptosis proteins GSDMD and cleaved caspase-1,as well as the expression of neural stem cell marker Nestin in the hippocampus,and the expression of Wnt/β-catenin signaling pathway-related proteins in the hippocampus.Results The combination of KXS extract and fluoxetine can significantly improve the depression-like behavior of model mice,and the effect is better than fluoxetine alone.The combination inhibited the activation of apoptosis and pyroptosis signaling pathways in the hippocampus when used alone with high-dose fluoxetine,significantly upregulated the expression of Nestin,and regulated the expression of Wnt/β-catenin signaling pathway protein.Conclusion The combination of KXS and high-dose fluoxetine can improve apoptosis and pyroptosis in the hippocampus of stress stress and depression model mice,and upregulate the expression of neural stem cell marker Nestin by regulating the Wnt/β-catenin signaling pathway,which may be a key link to improve the antidepressant effect of the combination drug.

Objective:To identify the gene mutation types of 4 suspected β-thalassemia patients in Yunnan Province,and to analyze the genotypes and hematological phenotypes.Methods:Whole genome sequencing was performed on the samples of 4 suspected β-thalassemia patients from the Dai ethnic group in a thalassemia endemic area of Yunnan Province,whose hematological phenotypes were not consistent with the results of common thalassemia gene mutations.The mutations of β-globin gene clusters were confirmed by polymerase chain reaction(PCR)and Sanger DNA sequencing technology.Results:The 3.5 kb deletion in β-globin gene cluster(NC_000011.10:g.5224302-5227791 del3490bp)was detected in 4 patients'samples,of which 1 case was also detected with HbE mutation and 1 case with CD17 mutation.These 2 patients displayed moderate anemia phenotype,while the two patients with only the 3.5 kb deletion presented with other mild anemia phenotype.Conclusion:Heterozygous carriers with rare 3.5 kb deletion of the β-globin gene cluster may develop mild anemia,compound mutations of the 3.5 kb deletion with other mutations may led to intermediate thalasemia with moderate to sever anemia.In areas with a high incidence of thalassemia,suspected patients should undergo genetic testing to avoid missing or misdiagnosing rare mutations.

Objective:To investigate the incidence and high-risk pathogenic factors of cardiovascular disease（CVD）in patients with rheumatic and autoimmune diseases，and to construct and validate a predictive model for the risk of CVD occurrence in these patients.Methods:A retrospective analysis was conducted on 239 patients with rheumatic and autoimmune diseases who underwent treatment and echocardiography at the Affiliated Hospital of Inner Mongolia Medical University between June 2020 and June 2023. General patient data，laboratory test results，and echocardiographic findings were collected. Follow-up was performed via electronic medical records or telephone surveys until December 2024 to determine the incidence of CVD，starting from the date of the first echocardiographic examination. Predictive factors were screened using univariate analysis and Lasso regression，and a Logistic regression model was constructed. Internal validation was performed using the Bootstrap method. The model's accuracy and clinical utility were assessed using the Hosmer-Lemeshow test，calibration curve，and decision curve analysis.Results:Among the 239 patients，111 developed CVD. Logistic regression analysis identified age，diastolic blood pressure，use of immunosuppressants，lymphocyte count（LYM），α-hydroxybutyrate dehydrogenase（α-HBDH）level，serum cystatin C（CysC），and right ventricular fractional area change（RVFAC）as independent predictive factors for CVD in these patients（all P<0.05）. The area under the ROC curve（AUC）for the prediction model was 0.895（95% CI = 0.856 - 0.935），and after Bootstrap validation，it was 0.894（95% CI = 0.861-0.925）. The Hosmer-Lemeshow test，calibration curve，and decision curve analysis all indicated that the model had good accuracy and clinical utility. Conclusions:Age，diastolic blood pressure，use of immunosuppressants，LYM，α-HBDH，CysC，and RVFAC may serve as independent risk factors for CVD in patients with rheumatic and autoimmune diseases. The prediction model based on echocardiography combined with laboratory indicators can，to some extent，predict the risk of CVD occurrence in these patients.

Objective To investigate the impacts of epidural anesthesia with ropivacaine combined with dezocine on lower limb motor nerve block and maternal and infant outcomes in primipara undergoing painless delivery.Methods A total of 159 primiparas who delivered in Nanjing Jiangbei Hospital were selected as the research objects,and divided into the blank group(53 cases),the ropivacaine group(53 cases)and the combined group(53 cases)by the random number table method.Parturients in the blank group were given natural delivery mode,parturients in the ropivacaine group were given ropivacaine epidural anesthesia,and parturients in the combined group were given dezocine anesthesia on the basis of ropivacaine.Analgesic effect at different time points,time of the first,second and third stage of labor,pressing times of analgesic pump,lower limbs motor nerve block,maternal and infant outcomes,and adverse reactions of parturients were compared among the three groups.Results At 10 minutes after analgesia,60 minutes after analgesia,when the cervix was fully dilated and when the fetus was delivered,the VAS scores of the parturients in the ropivacaine group and the combined group were lower than those in the blank group(P<0.05),and the VAS scores of the parturients in the combined group were significantly lower than those in the ropivacaine group(P<0.05).There was no significant difference in the time of the first,second or third stage of labor of parturients among the three groups(P>0.05);The pressing times of analgesic pump of parturients in the combined group was significantly less than that in the ropivacaine group(P<0.05).There was no statistically significant difference in terms of low limb motor nerve block after painless labor of parturients among the three groups(P>0.05).There were no statistically significant differences in the perineal incision rate or the Apgar scores of newborns at 1 minute and 5 minutes after birth among the three groups(P>0.05).The usage rate of forceps and the rate of conversion to cesarean section in the combined group were significantly lower than those in the ropivacaine group and the blank group(P<0.05).There was no statistically significant difference in the incidence of total adverse reactions among the blank group,the ropivacaine group and the combined group(P>0.05).Conclusion The combination of ropivacaine and dezocine for epidural anesthesia has a better analgesic effect on primiparas with painless delivery,has a smaller impact on lower limb motor nerve block in parturients,and can achieve better maternal and infant outcomes.

Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca²⁺ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca²⁺ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.

Acute respiratory distress syndrome(ARDS)is a common respiratory emergency,but current clinical treatment remains at the level of symptomatic support and there is a lack of effective targeted treatment measures.Our previous study confirmed that inhalation of hydrogen gas can reduce the acute lung injury of ARDS,but the application of hydrogen has flammable and explosive safety concerns.Drinking hydrogen-rich liquid or inhaling hydrogen gas has been shown to play an important role in scavenging reactive oxygen species and maintaining mitochondrial quality control balance,thus improving ARDS in patients and animal models.Coral calcium hydrogenation(CCH)is a new solid molecular hydrogen carrier prepared from coral calcium(CC).Whether and how CCH affects acute lung injury in ARDS re-mains unstudied.In this study,we observed the therapeutic effect of CCH on lipopolysaccharide(LPS)induced acute lung injury in ARDS mice.The survival rate of mice treated with CCH and hydrogen inhalation was found to be comparable,demonstrating a significant improvement compared to the untreated ARDS model group.CCH treatment significantly reduced pulmonary hemorrhage and edema,and improved pulmonary function and local microcirculation in ARDS mice.CCH promoted mitochon-drial peripheral division in the early course of ARDS by activating mitochondrial thioredoxin 2(Trx2),improved lung mitochondrial dysfunction induced by LPS,and reduced oxidative stress damage.The results indicate that CCH is a highly efficient hydrogen-rich agent that can attenuate acute lung injury of ARDS by improving the mitochondrial function through Trx2 activation.

Objective To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application.Methods and Results Recommendations were formulated based on literature review and expert group discussion,and consensus was reached following expert consultation.The consensus recommendations are comprehensive,covering the entire treatment procedures from preoperative assessment and preparation,surgical operation process,postoperative management and traditional Chinese medicine treatment to individualized treatment planning.The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain,reduced the use of opioid drugs,and significantly improved the quality of life and enhanced immune function of the patients.Postoperative follow-up suggested good treatment tolerance among the patients without serious complications.Conclusion The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy.The combined treatment has a high clinical value with a good safety profile for management of cancer pain.