Objective To investigate the effect of resveratrol on airway remodeling induced by ovalbumin(OVA)in asthmatic young mice based on the sphingosine-1-phosphate(S1P)/transforming growth factor-β1(TGF-β1)pathway.Methods Young mice were randomly assigned into normal group,model group,S1P group,resveratrol group,and resveratrol+S1P group,with 12 mice in each group.A mouse model of asthma induced by OVA was established.The Wright Giemsa staining was applied to detect the number of inflammatory cells in bronchoalveolar lavage fluid(BALF).ELISA was applied to detect the levels of interleukin-4(IL),IL-5,and IL-13 in BALF.The colorimetric method was applied to detect the activities of SOD and CAT and the content of MDA in lung tissue.HE staining was applied to observe pathological changes in lung tissue,and the wall area of bronchial tube(Wat)and perimeter of basement membrane(Pbm)were analyzed.Masson staining was applied to observe the area of collagen fibers in lung tissue.Immunohistochemistry was applied to detect the expression of α-SMA in lung tissue.Western blot was applied to detect the expression of E-cadherin,N-cadherin,Snail,SP1,and TGF-β1 proteins in lung tissue.Results Compared with the normal group,the number of eosinophils,lymphocytes,neutrophils,levels of IL-4,IL-5,and IL-13 in BALF,lung tissue MDA content,Wat/Pm ratio,collagen fiber area,α-SMA positive expression,the protein levels of N-cadherin,Snail,SP1,TGF-β1 increased in the model group,while the activities of SOD,CAT,and the protein level of E-cadherin in lung tissue decreased(P＜0.05).Compared to the model group,the number of eosinophils,lymphocytes,neutrophils,levels of IL-4,IL-5,and IL-13 in BALF,lung tissue MDA content,Wat/Pm ratio,collagen fiber area,α-SMA positive expression,the protein levels of N-cadherin,Snail,SP1,TGF-β1 decreased in the resveratrol group,while the activities of SOD,CAT,and the protein level of E-cadherin in lung tissue increased(P＜0.05).The S1P recombinant protein could weaken the inhibitory effect of resveratrol on airway remodeling in asthmatic young mice.Conclusion Resveratrol can inhibit oxidative stress,airway inflammation,and epithelial mesenchymal transition,thereby suppressing airway remodeling in asthmatic young mice.Its effect is related to the inhibition of the S1P/TGF-β1 signaling pathway.

This study was aimed at analyzing the epidemiological and drug resistance characteristics of tuberculosis at a desig-nated tuberculosis hospital in Hunan Province in 2024.Patients diagnosed with TB at the hospital between April and October 2024 were included in the study.Demographic data,clinical information,and drug sensitivity test results were collected from the hospital′s electronic medical record system.Descriptive statistics,the chi-square test,and logistic regression were used to analyze the epidemic characteristics,drug resistance characteristics,and factors influencing tuberculosis.Whole genome sequencing of isolates was per-formed,and lineage classification and drug resistance gene mutations were detected with TB-Profiler.The male-to-female ratio was 2.72∶1,and the median age was 56(IQR:43-66)years.Among the 391 patients,most were farmers(46.8%,183/391)and were pri-marily from Changsha(41.1%,162/391).Significant differences were observed in sex and occupation between pulmonary tuberculosis(PTB)and extrapulmonary tuberculosis(EPTB).The overall prevalence of any type of drug resistance of tuberculosis was 33.25%,and the multidrug resistance TB(MDR-TB)and poly-drug resistance(PR-TB)rates were 14.23%and 4.35%,respectively.The re-sistance rates to rifampicin(RIF),isoniazid(INH),ethambutol(EMB),and streptomycin(SM)were 17.90%,22.25%,6.39%,and 20.20%,respectively.Multivariable logistic regression analysis indicated that both diabetes(OR:2.295,95%CI:1.082-4.866)and retreatment(OR:17.822,95%CI:8.343-38.072)were risk factors for developing MDR-TB.Lineage 2(L2)strains accounted for 64.40%(136/191),whereas lineage 4(L4)accounted for 28.80%(55/191).The most common drug resistance mutations were katG Ser315Thr(62.50%,20/32)for INH,rpoB Ser450Leu(50.00%,12/24)for RIF,embB Met306Val(55.56%,5/9)for EMB,and rpsL Lys43Arg(80.95%,34/42)for SM.In conclusion,TB drug resistance was found to be a serious problem at a designated tu-berculosis hospital in Hunan in 2024.Strengthening the treatment and management of patients infected with L2 strains,those with co-morbid diabetes,and retreatment cases is crucial for preventing and controlling the emergence of drug-resistant TB.

Objective:To study the application of step-by-step teaching combined with case workshop in teaching spinal surgery nurse residents.Methods:A total of 100 nurse residents in spinal surgery from June 2023 to June 2024 were selected as the research subjects. They were divided into a control group and an observation group based on the order of enrollment. The control group received traditional nurse residency training, while the observation group received a training method combining step-by-step teaching and case workshop. The two groups were compared in assessment scores, comprehensive abilities, self-learning abilities, and satisfaction. The t-test and χ2 test were performed using SPSS 26.0. Results:After the residency training, the observation group outperformed the control group in theoretical assessment scores [(91.65±1.27) vs. (85.71±1.33)] and operational assessment scores [(90.24±1.52) vs. (84.78±1.46)]. The observation group also scored significantly higher than the control group in leadership ability, critical care monitoring, teaching and cooperation, planning and evaluation, communication, and professional development ( P<0.05). Additionally, the observation group showed higher scores in self-motivation and belief, self-monitoring and regulation, task analysis, and self-evaluation. The satisfaction with teaching was significantly higher in the observation group than in the control group. Conclusions:The method combining step-by-step teaching and case workshop can effectively improve the assessment scores of spinal surgery nurse residents, their comprehensive ability and self-learning ability, and their satisfaction with teaching. This method holds significant potential for application in clinical nursing teaching.

BACKGROUND:Most rotator cuff injuries occur in the supraspinatus tendon.Clinical treatment of rotator cuff injuries is very limited due to the lack of blood vessels and the complex anatomical structure of the rotator cuff.The rapid development of tissue engineering technology and stem cell biology has brought new hope for improving the quality of tendon repair.OBJECTIVE:To prepare human umbilical cord mesenchymal stem cells/gelatin methacrylate composite scaffolds by bio-3D printing technology to observe the effect of this scaffold on repairing rotator cuff injury.METHODS:(1)In vitro cell assay:The gelatin microcarrier was prepared.The tissue engineered stem cells were constructed by inoculating human umbilical cord mesenchymal stem cells on the surface of gelatin microcarrier.Gelatin methacrylate hydrogel printing ink was prepared.Tissue engineered stem cells were re-suspended with gelatin methacrylate hydrogel printing ink and put into the bio-ink container of 3D printer for printing.Human umbilical cord mesenchymal stem cells/gelatin methacrylate composite scaffold was obtained after 5 minutes of blue light irradiation and curing.The activity of human umbilical cord mesenchymal stem cells in scaffolds was detected by dead/alive staining and CCK-8 assay.(2)In vivo animal experiments:A random block design method was used to randomly assign 24 SD rats to 4 groups with 6 rats in each group.No treatment was given in the normal group.The rotator cuff injury model of supratinatus tendon tear was established in the rotator cuff injury group,the simple scaffold group,and the cellular scaffold group.The gelatin methacrylate scaffold and human umbilical cord mesenchymal stem cell/gelatin methacrylatecomposite scaffold were implanted into the tendon injury after the model was made in the simple scaffold group and the cellular scaffold group,respectively.Four weeks after operation,behavioral tests and histopathological morphology observation of supraspinatus tendon of rotator cuff were performed.RESULTS AND CONCLUSION:(1)In vitro cellular assay:The dead/alive staining showed that gelatin microcarrier could reduce the damage of human umbilical cord mesenchymal stem cells caused by 3D printing process.With the extension of culture time,the survival rate of human umbilical cord mesenchymal stem cells increased in the scaffold.The results of CCK-8 assay showed that with the extension of culture time,the activity of human umbilical cord mesenchymal stem cells in the scaffold did not change significantly.(2)In vivo animal experiments:Behavioral test results showed that compared with rotator cuff injury group and simple scaffold group,cellular scaffold group significantly improved limb motor function.The results of hematoxylin-eosin and Masson staining of rotator cuff supraspinatus tendon showed that compared with rotator cuff injury group and simple scaffold group,the muscle fiber arrangement in the cellular scaffold group was more regular;there was no obvious inflammatory cell infiltration,and the percentage of collagen volume decreased.The results of immunofluorescence staining showed that the expression levels of interleukin 6 and tumor necrosis factor α in the rotator cuff supraspinatus tendon were significantly decreased in the cellular scaffold group compared with the rotator cuff injury group and the simple scaffold group.(3)The results showed that bio-3D-printed cell scaffolds encapsulating human umbilical cord mesenchymal stem cells/gelatin methacrylate could promote tissue repair and regeneration of rotator cuff injuries.

Objective To investigate the correlation between spread through air space (STAS) of sub-centimeter non-small cell lung cancer and clinical characteristics and radiological features, constructing a nomogram risk prediction model for STAS to provide a reference for the preoperative planning of sub-centimeter non-small cell lung cancer patients. Methods The data of patients with sub-centimeter non-small cell lung cancer who underwent surgical treatment in Nanjing Drum Tower Hospital from January 2022 to October 2023 were retrospectively collected. According to the pathological diagnosis of whether the tumor was accompanied with STAS, they were divided into a STAS positive group and a STAS negative group. The clinical and radiological data of the two groups were collected for univariate logistic regression analysis, and the variables with statistical differences were included in the multivariate analysis. Finally, independent risk factors for STAS were screened out and a nomogram model was constructed. The sensitivity and specificity were calculated based on the Youden index, and area under the curve (AUC), calibration plots and decision curve analysis (DCA) were used to evaluate the performance of the model. Results A total of 112 patients were collected, which included 17 patients in the STAS positive group, consisting of 11 males and 6 females, with a mean age of (59.0±10.3) years. The STAS negative group included 95 patients, with 30 males and 65 females, and a mean age of (56.8±10.3) years. Univariate logistic regression analysis showed that male, anti-GAGE7 antibody positive, mean CT value and spiculation were associated with the occurrence of STAS (P＜0.05). Multivariate regression analysis showed that associations between STAS and male (OR=5.974, 95%CI 1.495 to 23.872), anti-GAGE7 antibody positive (OR=11.760, 95%CI 1.619 to 85.408) and mean CT value (OR=1.008, 95%CI 1.004 to 1.013) were still significant (P＜0.05), while the association between STAS and spiculation was not significant anymore (P=0.438). Based on the above three independent predictors, a nomogram model of STAS in sub-centimeter non-small cell lung cancer was constructed. The AUC value of the model was 0.890, the sensitivity was 76.5%, and the specificity was 91.6%. The calibration curve was well fitted, suggesting that the model had a good prediction efficiency for STAS. The DCA plot showed that the model had a good clinically utility. Conclusion Male, anti-GAGE7 antibody positive and mean CT value are independent predictors of STAS positivity of sub-centimeter non-small cell lung cancer, and the nomogram model established in this study has a good predictive value and provides reference for preoperative planning of patients.

BACKGROUND:Most rotator cuff injuries occur in the supraspinatus tendon.Clinical treatment of rotator cuff injuries is very limited due to the lack of blood vessels and the complex anatomical structure of the rotator cuff.The rapid development of tissue engineering technology and stem cell biology has brought new hope for improving the quality of tendon repair.OBJECTIVE:To prepare human umbilical cord mesenchymal stem cells/gelatin methacrylate composite scaffolds by bio-3D printing technology to observe the effect of this scaffold on repairing rotator cuff injury.METHODS:(1)In vitro cell assay:The gelatin microcarrier was prepared.The tissue engineered stem cells were constructed by inoculating human umbilical cord mesenchymal stem cells on the surface of gelatin microcarrier.Gelatin methacrylate hydrogel printing ink was prepared.Tissue engineered stem cells were re-suspended with gelatin methacrylate hydrogel printing ink and put into the bio-ink container of 3D printer for printing.Human umbilical cord mesenchymal stem cells/gelatin methacrylate composite scaffold was obtained after 5 minutes of blue light irradiation and curing.The activity of human umbilical cord mesenchymal stem cells in scaffolds was detected by dead/alive staining and CCK-8 assay.(2)In vivo animal experiments:A random block design method was used to randomly assign 24 SD rats to 4 groups with 6 rats in each group.No treatment was given in the normal group.The rotator cuff injury model of supratinatus tendon tear was established in the rotator cuff injury group,the simple scaffold group,and the cellular scaffold group.The gelatin methacrylate scaffold and human umbilical cord mesenchymal stem cell/gelatin methacrylatecomposite scaffold were implanted into the tendon injury after the model was made in the simple scaffold group and the cellular scaffold group,respectively.Four weeks after operation,behavioral tests and histopathological morphology observation of supraspinatus tendon of rotator cuff were performed.RESULTS AND CONCLUSION:(1)In vitro cellular assay:The dead/alive staining showed that gelatin microcarrier could reduce the damage of human umbilical cord mesenchymal stem cells caused by 3D printing process.With the extension of culture time,the survival rate of human umbilical cord mesenchymal stem cells increased in the scaffold.The results of CCK-8 assay showed that with the extension of culture time,the activity of human umbilical cord mesenchymal stem cells in the scaffold did not change significantly.(2)In vivo animal experiments:Behavioral test results showed that compared with rotator cuff injury group and simple scaffold group,cellular scaffold group significantly improved limb motor function.The results of hematoxylin-eosin and Masson staining of rotator cuff supraspinatus tendon showed that compared with rotator cuff injury group and simple scaffold group,the muscle fiber arrangement in the cellular scaffold group was more regular;there was no obvious inflammatory cell infiltration,and the percentage of collagen volume decreased.The results of immunofluorescence staining showed that the expression levels of interleukin 6 and tumor necrosis factor α in the rotator cuff supraspinatus tendon were significantly decreased in the cellular scaffold group compared with the rotator cuff injury group and the simple scaffold group.(3)The results showed that bio-3D-printed cell scaffolds encapsulating human umbilical cord mesenchymal stem cells/gelatin methacrylate could promote tissue repair and regeneration of rotator cuff injuries.

Objective To investigate the effect of resveratrol on airway remodeling induced by ovalbumin(OVA)in asthmatic young mice based on the sphingosine-1-phosphate(S1P)/transforming growth factor-β1(TGF-β1)pathway.Methods Young mice were randomly assigned into normal group,model group,S1P group,resveratrol group,and resveratrol+S1P group,with 12 mice in each group.A mouse model of asthma induced by OVA was established.The Wright Giemsa staining was applied to detect the number of inflammatory cells in bronchoalveolar lavage fluid(BALF).ELISA was applied to detect the levels of interleukin-4(IL),IL-5,and IL-13 in BALF.The colorimetric method was applied to detect the activities of SOD and CAT and the content of MDA in lung tissue.HE staining was applied to observe pathological changes in lung tissue,and the wall area of bronchial tube(Wat)and perimeter of basement membrane(Pbm)were analyzed.Masson staining was applied to observe the area of collagen fibers in lung tissue.Immunohistochemistry was applied to detect the expression of α-SMA in lung tissue.Western blot was applied to detect the expression of E-cadherin,N-cadherin,Snail,SP1,and TGF-β1 proteins in lung tissue.Results Compared with the normal group,the number of eosinophils,lymphocytes,neutrophils,levels of IL-4,IL-5,and IL-13 in BALF,lung tissue MDA content,Wat/Pm ratio,collagen fiber area,α-SMA positive expression,the protein levels of N-cadherin,Snail,SP1,TGF-β1 increased in the model group,while the activities of SOD,CAT,and the protein level of E-cadherin in lung tissue decreased(P＜0.05).Compared to the model group,the number of eosinophils,lymphocytes,neutrophils,levels of IL-4,IL-5,and IL-13 in BALF,lung tissue MDA content,Wat/Pm ratio,collagen fiber area,α-SMA positive expression,the protein levels of N-cadherin,Snail,SP1,TGF-β1 decreased in the resveratrol group,while the activities of SOD,CAT,and the protein level of E-cadherin in lung tissue increased(P＜0.05).The S1P recombinant protein could weaken the inhibitory effect of resveratrol on airway remodeling in asthmatic young mice.Conclusion Resveratrol can inhibit oxidative stress,airway inflammation,and epithelial mesenchymal transition,thereby suppressing airway remodeling in asthmatic young mice.Its effect is related to the inhibition of the S1P/TGF-β1 signaling pathway.

The glucagon receptor (GCGR) is a critical target for the treatment of metabolic disorders such as Type 2 Diabetes Mellitus (T2DM) and obesity. Activation of GCGR enhances systemic insulin sensitivity through paracrine stimulation of insulin secretion, presenting a promising avenue for treatment. However, the discovery of effective GCGR agonists remains a challenging and resource-intensive process, often requiring time-consuming wet-lab experiments to synthesize and screen potential compounds. Recent advances in artificial intelligence technologies have demonstrated great potential in accelerating drug discovery by streamlining screening and efficiently predicting bioactivity. In the present work, we propose DeepGCGR, a two-layer deep learning model that leverages graph convolutional networks (GCN) integrated with a multiple attention mechanism to expedite the identification of GCGR agonists. In the first layer, the model predicts the bioactivity of various compounds against GCGR, efficiently filtering large chemical libraries to identify promising candidates. In the second layer, DeepGCGR classifies high bioactive compounds based on their functional effects on GCGR signaling, identifying those with potential agonistic or antagonistic effects. Moreover, DeepGCGR was specifically applied to identify novel GCGR-regulating compounds for the treatment of T2DM from natural products derived from traditional Chinese medicine (TCM). The proposed method will not only offer an effective strategy for discovering GCGR-targeting compounds with functional activation properties but also provide new insights into the development of T2DM therapeutics.
Deep Learning ; Drug Discovery/methods* ; Humans ; Diabetes Mellitus, Type 2/metabolism* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/pharmacology*

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Although enteric glial cell (EGC) abnormal activation is reported to be involved in the pathogenesis of Parkinson's disease (PD), and inhibition of EGC gliosis alleviated gut and dopaminergic neuronal dysfunction was verified in our previous study, the potential role of gut microbiota on EGC function in PD still need to be addressed. In the present study, fecal microbiota transplantation revealed that EGC function was regulated by gut microbiota. By employing 16S rRNA and metabolomic analysis, we identified that 3-indolepropionic acid (IPA) was the most affected differential microbial metabolite that regulated EGC gliosis. The protective effects of IPA on PD were validated in rotenone-stimulated EGCs and rotenone (30 mg/kg i.g. for 4 weeks)-induced PD mice, as indicated by decreased inflammation, improved intestinal and brain barrier as well as dopaminergic neuronal function. Mechanistic study showed that IPA targeted pregnane X receptor (PXR) in EGCs, and inhibition of IL-13Rα1 involved cytokine-cytokine receptor interaction pathway, leading to inactivation of downstream JAK1-STAT6 pathway. Our data not only provided evidence that EGC gliosis was critical in spreading intestinal damage to brain, but also highlighted the potential role of microbial metabolite IPA in alleviating PD pathological damages through gut-brain axis.