Objective To investigate whether Danshen injection (DSI) can protect human brain organoids from oxidative stress damage by regulating the Nrf2 signaling pathway and its mechanism. Methods A Nrf2 plasmid was constructed, lentivirus was packaged and transfected into human induced pluripotent stem cell (hiPSC) to form a stable cell line. Brain organoids with Nrf2 overexpression (LV-Nrf2 group) and knockdown (sh-Nrf2 group) were constructed using kit. The transfection efficiency was verified by real-time fluorescence quantitative polymerase chain reaction. An oxidative stress injury model was established by inducing hydrogen peroxide (H₂O₂). Intervention was performed either in combination or without DSI pre-treatment. Cell viability was detected by Cell Counting Kit-8 (CCK-8), and the expression levels of Nrf2, malondialdehyde (MDA), interleukin (IL)-1β, sex-determining region Y-box protein 2 (SOX2) and neuronal-specific nuclear protein (NeuN) were detected by Western blot and immunofluorescence staining. Total RNA from human brain organoids was extracted for transcriptome sequencing and analysis. Results LV-Nrf2 group and sh-Nrf2 group brain organoid models were successfully constructed. The CCK-8 results determined that the oxidative stress model was established with 32 mmol/L H₂O₂ intervention conditions. The fluorescence expression of Nrf2 in LV-Nrf2 group was higher than that in control group, and the fluorescence expressions of MDA and IL-1β were lower than those in control group; sh-Nrf2 group showed a damage phenotype of low Nrf2 expression, high MDA and IL-1β expression (all P < 0.05). Compared with H₂O₂ group, the Nrf2 signal in DSI + H₂O₂ group was stronger, and the levels of MDA and IL-1β were lower. Among them, the protective effect of LV-Nrf2 was the most significant. H₂O₂ treatment could down-regulate the protein levels of Nrf2, SOX2 and NeuN, and DSI intervention could effectively reverse the downward trend of these indicators. Sh-Nrf2 could weaken the recovery effect of DSI on SOX2 and NeuN, while LV-Nrf2 could synergistically enhance the regulatory effect of DSI. Conclusions DSI may antagonize oxidative stress damage in human brain organoids through the Nrf2 signaling pathway, and maintaining the stability of the neural cell lineage is its core therapeutic characteristic.

Objective: To examine the mediating effect of resilience on AIDS-related stress and patient-reported outcome among elderly cases with HIV/AIDS, so as to provide the basis for promoting mental health and improving health outcomes of this population. Methods: From June to July 2024, elderly cases with HIV/AIDS receiving treatment in the infectious diseases department of a tertiary-level hospital in Sichuan Province and undergoing follow-up management at 12 community health service centers in Wuhou District, Chengdu City, Sichuan Province, were selected as study participants using convenience sampling method. Data on demographic information, duration since confirmed diagnosis and the most recent CD4+T lymphocyte count were collected through questionnaire surveys. The Chinese versions of the HIV/AIDS Stress Scale, the Chinese versions of the 10-item Connor-Davidson Resilience Scale, and the Patient-Reported Outcome Scale for Elderly HIV/AIDS Patients were used to assess AIDS-related stress, resilience, and patient-reported outcome, respectively. Structural equation modeling was performed using Mplus 8.3 software to analyze the mediating effect of resilience on AIDS-related stress and patient-reported outcome. The Bootstrap method was employed to test the significance of the mediating effect. Results: A total of 424 elderly HIV/AIDS cases were included, with a mean age of (62.04±8.73) years. Among them, 315 (74.29%) were males and 109 (25.71%) were females. The median scores were 23.00 (interquartile range, 11.00) points for AIDS-related stress, 30.00 (interquartile range, 7.00) points for resilience, and 363.45 (interquartile range, 53.03) points for the total score of patient-reported outcome. Resultsof the mediation effect analysis revealed that AIDS-related stress had a direct negative effect on patient-reported outcome (β=-0.608, 95%CI: -0.742 to -0.465). It also exerted an indirect negative effect on patient-reported outcome through the mediating role of resilience (β=-0.258, 95%CI: -0.364 to -0.158), with the mediating effect accounting for 29.79% of the total effect. Conclusion AIDS-related stress among elderly cases with HIV/AIDS can directly or indirectly negatively affect patient-reported outcome through resilience.

Objective The study aimed to construct and validate a predictive model for pulmonary nodules(PN)nature based on clinicopa-thological features,imaging,and serum biomarkers,so as to provide scientificdecision-making for early diagnosis and treatment of lung cancer.Methods A retrospective was performed on 816 PN patients with definited pathological diagnosis who received surgical resection analysisor lung biopsy in the Department of Thoracic Surgery and Oncology of Shenzhen Traditional Chinese Medicine Hospital from January 2019 to February 2023.Among them,113 cases that did not meet the inclusion criteria were excluded,and the remaining 703 cases were included in the study.The study based on the clinicopathologic features(age,gender,smoking history,smoking cessation history and family history of cancer),chest imaging(maximum diameter of nodule,location of lesion,clear border,Lobulation,spiculation,vascular convergence sign,vacuole,calcification,air bronchial sign,emphysema,nodule type and pleural indentation,nodule number)and serum carcinoembryonic antigen(CEA),cytokeratin 19 fragment(CYFRA21-1),squamous cell carcinoma antigen(SCCA)in patients with PN.These cases were randomly divided into a modeling group(n=552,237 benign,315 malignant)and a validation group(n=151,85 benign,66 malignant).First,univariate analysis was performed to screen for statistically significant predictors of nodules nature.Then,multivariate regression analysis was performed to screen for independent predictors of nodules nature.Finally,the prediction model of PN nature was constructed by logistic regression analysis.Subsequently,the validation group data were entered into the proposed model and Mayo clinic(Mayo)model,veterans affairs(VA)model,Brock University(Brock)model,Peking University(PKU)model and Guangzhou Medical University(GZMU)model,respectively.PN malignancy probability was calculated.The receiver operating characteristic(ROC)curves were plotted.The diagnostic efficiency of each model was compared according to the area under the curve(AUC).Results There were statistically significant variables including age,family history of cancer,maximum nodule diameter,nodule type,upper lobe of lung,calcification,vascular convergence sign,lobulation,clear border,spiculation,and serum CEA,SCCA,CYFRA21-1 using univariate analysis.Multiple regression analysis showed that age,CEA,clear border,CYFRA21-1,SCCA,upper lobe of lung,maximum nodule diameter,family history of cancer,spiculation and nodule type were independent predictors of PN nature.The prediction model equation constructed in this study is as follows:f(x)= ex/(1+ex),X=(-6.318 8+0.020 8×Age+0.527 4×CEA-0.928 4×clear border+0.294 6×Cyfra21-1+0.294×maximum nodule diameter+1.220 1×family history of cancer +0.573 2×upper lobe of lung +0.064 8×SCCA +1.461 5×Spiculation +1.497 6×nodule type).The AUC(0.799 vs 0.659,0.650)of the proposed model was significantly higher compared with Mayo model and VA model,and there were statistically significant differences(Z=3.029,2.638,P=0.003,0.008).However,compared with Brock model,PKU model and GZMU model,the differences of AUC(0.799 vs 0.762,0.773,0.769)were not statistically significant(Z=1.063,0.686,0.757,P=0.288,0.493,0.449).Conclusion The prediction model for PN nature established in this study is accurate and reliable,which can help clinics with early diagnosis and early intervention,and this prediction model deserves to be popularized.

Objective To develop and validate a machine learning (ML)model based on serum Klotho protein that can accurately predict all-cause mortality in chronic kidney disease (CKD ) patients.Methods A retrospective cohort trial was conducted on all the non-dialysis adult patients diagnosed with CKD stages 1～5 in our department from February 7,2012 to October 18,2019.They were assigned into a training set and an internal validation set in a ratio of 7:3.A total of 47 clinical features,including serum Klotho protein level,were used as variables to inform these models.Based on the training set,univariate Cox regression model was employed to screen out the possible risk factors for all-cause mortality,and Lasso-Cox regression model was further applied for the screening.Then multivariate Cox stepwise regression analysis was conducted to develop a nomogram risk prediction model for all-cause mortality,and the model performance was evaluated through internal validation.Results There were totally 400 patients enrolled in this trial,and 280 of them (including 52 dead and 228 survival)were assigned into the training set and other 120 (including 21 dead and 99 survival)into the validation set.For the constructed 5-year all-cause mortality risk prediction model,the area under the curve (AUC)value was 0.760 (95％CI:0.676～0.844)in the training set and 0.788 (95％CI:0.679～0.897)in the validation set,and the overall C-index was 0.755 (95％CI:0.685～0.826)and 0.720 (95％CI:0.614～0.826),respectively in the 2 sets.Univariate Cox regression analysis showed that age,history of cardiovascular disease(CVD),cystatin C(Cys-C),alkaline phosphatase (ALP),albumin,eosinophil (EOS)count,hemoglobin (Hb),complement C3,calcium,C-reactive protein (CRP),TNF-α and serum Klotho protein may be predictive factors for all-cause mortality (P<0.05).Multivariate Cox stepwise regression analysis finally screened age,albumin,complement C3 and serum Klotho protein as independent predictors (P<0.05).Based on these 4 predictors,a risk prediction model for all-cause mortality was constructed and validated.Conclusion A Klotho-based risk ML model for predicting all-cause mortality in CKD patients is successfully developed and validated.Advanced age is a risk factor,and higher albumin,complement C3 and serum Klotho protein levels are protective factors for all-cause mortality in CKD patients.

[Objective]To explore the diagnostic value of conventional ultrasound combined with shear wave elastography (SWE) for sarcopenia in patients with chronic kidney disease (CKD).[Methods]The study included 94 CKD patients (34 with sarcopenia and 60 without). All patient underwent the Simplified Assessment Rating Questionnaire (SARC-CalF),Mini Nutritional Assessment (MNA),Short Physical Performance Battery (SPPB),grip strength test,bioelectrical impedance analysis (BIA),conventional muscle ultrasound and SWE of the thighs. We then compared the differences in indicators between the sarcopenia group and non-sarcopenia group,used Spearman correlation analysis to assess the relationship between the two examinations (conventional ultrasound and SWE) and other clinical indicators,identified the diagnostic markers for sarcopenia,created receiver operating characteristic (ROC) curves,calculated the area under the curve (AUC) and determined the diagnostic performance of conventional ultrasound,SWE and their combination. Binary logistic regression was used to analyze the influencing factors of sarcopenia in CKD patients and a combined diagnosis model was established.[Results]The sarcopenia group showed lower upper arm circumference,calf circumference,6-meter walking speed and handgrip strength than non-sarcopenia group,and the differences were statistically significant (P<0.05). The sarcopenia group exhibited lower SARC-CalF and SPBB scores,as well as more compromised nutritional status. Statistically significant differences were observed in the ultrasound parameters between the two groups,including thickness of the subcutaneous fat and rectus femoris,combined thickness of the rectus femoris and vastus intermedius,rectus femoris cross-sectional area,elastic modulus of the rectus femoris and vastus medialis (all P<0.05). The muscle mass index had a moderate positive correlation with muscle thickness and cross-sectional area of the rectus femoris (0.3

Background/Aims: The accuracy of endosonographers in diagnosing gastric subepithelial lesions (SELs) using endoscopic ultrasonography (EUS) is influenced by experience and subjectivity. Artificial intelligence (AI) has achieved remarkable development in this field. This study aimed to develop an AI-based EUS diagnostic model for the diagnosis of SELs, and evaluated its efficacy with external validation. Methods: We developed the EUS-AI model with ResNeSt50 using EUS images from two hospitals to predict the histopathology of the gastric SELs originating from muscularis propria. The diagnostic performance of the model was also validated using EUS images obtained from four other hospitals. Results: A total of 2,057 images from 367 patients (375 SELs) were chosen to build the models, and 914 images from 106 patients (108 SELs) were chosen for external validation. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the model for differentiating gastrointestinal stromal tumors (GISTs) and non-GISTs in the external validation sets by images were 82.01%, 68.22%, 86.77%, 59.86%, and 78.12%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in the external validation set by tumors were 83.75%, 71.43%, 89.33%, 60.61%, and 80.56%, respectively. The EUS-AI model showed better performance (especially specificity) than some endosonographers.The model helped improve the sensitivity, specificity, and accuracy of certain endosonographers. Conclusions We developed an EUS-AI model to classify gastric SELs originating from muscularis propria into GISTs and non-GISTs with good accuracy. The model may help improve the diagnostic performance of endosonographers. Further work is required to develop a multi-modal EUS-AI system.

Objective To explore the epidemiological characteristics of 45 year-old or older human immunodeficiency virus (HIV)-infected persons and patients with acquired immune deficiency syndrome (AIDS) in Chengdu. Methods Epidemiological methods were used to analyze the data of 45 year-old or older patients with HIV/AIDS reported in Chengdu from 2018 to 2020. Results From 2018 to 2020, there were 219 newly reported cases aged 45 and above (35.67%) with HIV/AIDS in Chengdu, and the differences among them were statistically significant (χ²=6.45, P<0.05). Among the subjects, HIV infected cases accounted for 72.60%, males accounted for 75.80%, most subjects were 56 - 65 years old (48.86%), living in Jinjiang District (39.73%), working in service industries (36.99%), divorced or widowed (67.58%), and Han people (72.15%). There were no significant differences in above characteristics of HIV-infected persons and patients with AIDS from 2018 to 2020 (χ²=0.29, 0.22, 5.65, 1.92, 5.68, 1.12, 2.12, 0.39, P>0.05). 75.34% of the patients were infected through heterosexual transmission, and 50.68% were detected at treatment. The proportion of patients whose first CD4 cell test result was lower than 200/μL was relatively higher (43.84%). Nearly 81.28% of the patients received antiviral therapy, and the mortality reached 16.89%. From 2018 to 2020, the difference in transmission route, sample source, the first examination results of CD4 cells, antiviral treatment, or prognosis was not statistically significant (χ²=1.29, 3.59, 1.56, 0.01, 0.35, P>0.05). Fever (62.10%), fatigue (42.01%), and lymph node enlargement (28.77%) were main symptoms of the patients. 51.14% were detected in outpatient examinations, and most patients were accompanied by at least one opportunistic infection. Cytomegalovirus infection (56.16%) and Mycobacterium tuberculosis infection (36.53%) were main virus infection types. From 2018 to 2020, there was no significant difference in symptoms, visiting departments or combined infection (χ²=0.07-3.00, 3.00, 0.20-2.61, P>0.05). Conclusion The prevalence of HIV/AIDS is relatively severe in 45 year-old or older people in Chengdu. The constituent ratio and the incidence rate show an upward trend. Therefore, individualized prevention and control strategies should be formulated for 45 year-old or older people to effectively suppress the transmission of HIV/AIDS in the middle-aged and the elderly.

Objective To investigate whether Danhong injection can enhance the therapeutic effect of neural stem cell (NSC) transplantation in repairing cerebral ischemia injury by regulating the nuclear factor E2-related factor 2 (Nrf2) signaling pathway. Methods Forty male SD rats were randomly divided into the NSC transplantation group (NSC group), Danhong injection group (DH group), NSC+ Danhong injection group (N+D group), NSC+ Danhong injection group +ML385 group(N+D+M group) and PBS control group (PBS group), 8 rats in each group. All rat models of cerebral ischemia were established by embolization of the middle cerebral artery. Reperfusion was performed at 1.5 h after embolization. All rats in each group received corresponding interventions at 3 d after reperfusion. The neurological function score was evaluated before and 1, 2, 4 weeks after NSC transplantation. All rats were sacrificed at 4 weeks after NSC transplantation. The parameters related to oxidative stress were detected. The expression levels of neuron-specific nuclear protein (NeuN) and von Willebrand factor (vWF) were determined by immunofluorescence staining. Results Before NSC transplantation, the neurological function scores did not significantly differ among different groups (all P > 0.05). At postoperative 1, 2 and 4 weeks, the neurological function scores in the NSC, DH and N+D groups were significantly lower than those in the PBS and N+D+M groups (all P < 0.05). Compared with the PBS and N+D+M groups, the malondialdehyde (MDA) levels were significantly decreased, whereas the superoxide dismutase (SOD) and glutathione peroxidase (GPX) levels were considerably increased in the NSC, DH and N+D groups (all P < 0.05). The GPX level in the N+D+M group was significantly lower than that in the PBS group (P < 0.05). Immunofluorescence staining showed that the transplant NSC in the rat brain migrated to the surrounding area of cerebral infarction and survived, and expressed neuronal marker NeuN and neovascularization marker vWF. However, the number of living NSC in the N+D+M group was significantly lower compared with those in the remaining groups. Conclusions Danhong injection may improve the microenvironment of stem cell transplantation, enhance the survival rate of transplant NSC and improve the therapeutic effect of NSC transplantation for cerebral ischemia injury probably by regulating the Nrf2 signaling pathway.

Objective    To analyze the clinical features and prognosis of coronavirus disease 2019 (COVID-19) patients. Methods    A total of 379 confirmed COVID-19 patients admitted to Public Health Clinical Center of Chengdu from January 16 to November 30, 2020 were divided into two groups including an elderly group (42 patients, ≥60 years) and a non-elderly group (337 patients, <60 years) by age. The epidemiology, clinical features, laboratory tests, treatment and prognosis of the two groups were compared. Results    Among the 379 patients, 286 (75.5%) were males and 93 (24.5%) were females, aged from 2 months to 87 years, with an average age of 41.2 years. The average age of the elderly group was 69.5 years, and 61.9% of them were females. They were imported from Wuhan or local secondary patients (73.8%), mainly common or critical type (88.1%). While, the average age of the non-elderly group was 37.8 years, and males were more common (80.1%). There were mostly from foreign input (75.7%), mainly mild or ordinary type (95.0%). A total of 179 patients (47.2%) had one or more underlying diseases. Hypertension (15 patients, 35.7%) and diabetes (11 patients, 26.2%) were more common in the elderly group, while non-alcoholic steatohepatitis (132 patients, 39.2%) was more frequent in the non-elderly group. The most common clinical manifestations were fever (138 patients, 36.4%) and cough (129 patients, 34.0%). Fever, cough, dyspnea, and fatigue were more common in the elderly group than those in the non-elderly group (P<0.05). Compared with the non-elderly group, the elderly group had lower total lymphocyte count, CD4+ and CD8+ T-cell count, higher level of myocardial injury or inflammation markers (P<0.05). Abnormal echocardiography in 139 patients (36.7%) was mainly caused by decreased left ventricular diastolic function (22.7%) and heart valve regurgitation (14.0%), and the rate in the elderly group was significantly higher than that in the non-elderly group (85.7% vs. 30.6%, P<0.05). After treatment, 3 patients in the elderly group died, and the others were cured and discharged. The hospitalization duration of the elderly group was longer than that of the non-elderly group (22.1 d vs. 18.8 d, P=0.033). Conclusions    Elderly COVID-19 patients are mainly imported from Wuhan or secondary to the local population, mainly common or critical type, often associated with basic diseases such as hypertension or diabetes. While, non-elderly COVID-19 patients are mainly imported from abroad, mainly mild or common type, often associated with non-alcoholic steatohepatitis. After treatment, most of the patients have a good prognosis.

Objective To analyze the application of intraoperative neurophysiological monitoring combined with neuronavigation multi-modal fusion technology in the brainstem glioma resection. Methods One hundred twenty patients with brainstem glioma were divided into observation group and control group. The control group was treated by traditional operation, while the observation group was treated by intraoperative nerve electrophysiological monitoring combined with neuronavigation multimodal fusion technology. The general condition, clinical efficacy, KPS score, complications and survival rate of the two groups were compared. Results The effect was significantly better in the observation group(76.66%)than in control group(53.33%)( x2=11.962,P=0.001).KPS scores were significantly higher in the observation group (27.91 ±1.98) than in the control group (12.11 ±2.13)(t=32.669, P<0.001). Conclusions Intraoperative nerve electrophysiological monitoring plus neuronavigation multimodality fusion technology can improve clinical efficacy and quality of life in patients with brainstem glioma.