Objective To evaluate the surgical efficacy of unilateral pneumonectomy for the treatment of tuberculous destroyed lung, analyze the causes of severe postoperative complications, and explore clinical management strategies. Methods A retrospective analysis was conducted on the clinical data of patients with tuberculous destroyed lung who underwent unilateral pneumonectomy at the Public Health Clinical Center of Chengdu from 2017 to 2023. Postoperative severe complications were statistically analyzed. Patients were divided into a non-severe complication group and a severe-complication group, and the causes, management, and outcomes of complications were analyzed. Results A total of 134 patients were included, comprising 69 males and 65 females, with a mean age of 17-73 (40.43±12.69) years. There were 93 patients undergoing left pneumonectomy and 41 patients undergoing right pneumonectomy. Preoperative sputum smear was positive in 35 patients, all of which converted to negative postoperatively. There were 58 patients with hemoptysis preoperatively, and none experienced hemoptysis postoperatively. Postoperative incisional infection occurred in 8 (5.97%) patients, and postoperative pulmonary infection in 26 (19.40%) patients. Severe postoperative complications occurred in 17 (12.69%) patients, including empyema in 9 (6.72%) patients, bronchopleural fistula with empyema in 1 (0.75%) patient, severe pneumonia in 3 (2.24%) patients, postpneumonectomy syndrome in 1 (0.75%) patient, chylothorax in 1 (0.75%) patient, ketoacidosis in 1 (0.75%) patient, and heart failure with severe pneumonia in 1 (0.75%) patient. Perioperative mortality occurred in 2 (1.49%) patients, both of whom underwent right pneumonectomy. Multivariate logistic regression analysis revealed that a history of ipsilateral thoracic surgery, concomitant Aspergillus infection, and greater blood loss were independent risk factors for severe complications following unilateral pneumonectomy for tuberculous destroyed lung (P<0.05). Conclusion Unilateral pneumonectomy for patients with tuberculous destroyed lung can significantly improve the clinical cure rate, sputum conversion rate, and hemoptysis cessation rate. However, there is a certain risk of severe perioperative complications and mortality, requiring thorough perioperative management and appropriate management of postoperative complications.

The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that evade immunity elicited by vaccination has posed a global challenge to the control of the coronavirus disease 2019 (COVID-19) pandemic. Therefore, developing countermeasures that broadly protect against SARS-CoV-2 and related sarbecoviruses is essential. Herein, we have developed a lipid nanoparticle (LNP)-encapsulated mRNA (mRNA-LNP) encoding the full-length Spike (S) glycoprotein of SARS-CoV-2 (termed RG001), which confers complete protection in a non-human primate model. Intramuscular immunization of two doses of RG001 in Rhesus monkey elicited robust neutralizing antibodies and cellular response against SARS-CoV-2 variants, resulting in significantly protected SARS-CoV-2-infected animals from acute lung lesions and complete inhibition of viral replication in all animals immunized with low or high doses of RG001. More importantly, the third dose of RG001 vaccination elicited effective neutralizing antibodies against current epidemic XBB and JN.1 strains and similar cellular response against SARS-CoV-2 Omicron variants (BA.1, XBB.1.16, and JN.1) were observed in immunized mice. All these results together strongly support the great potential of RG001 in preventing the infection of SARS-CoV-2 variants of concern (VOCs).

Acute kidney injury (AKI) is a critical clinical condition characterized by rapid renal function decline, with high morbidity, mortality, and healthcare costs. Traditional Chinese medicine (TCM) has shown potential effects on mitigating oxidative stress and programmed cell death in AKI models. Scutellaria barbata D. Don (SB) and Scleromitrion diffusum (Willd.) R. J. Wang (SD), a classic TCM herbal pair exhibited anti-inflammatory and antioxidant activities. Using advanced chromatographic separation technology, we enriched the effective fractions of water extracts from SB-SD, obtaining self-assembled herbal nanoparticles (SB and SD nanoparticles, SSNPs) rich in flavonoids and terpenoids. These SSNPs demonstrated robust antioxidant properties in vitro and mitigated AKI progression in vivo by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. Oral administration of SSNPs in mice resulted in absorption into the bloodstream, formation of a protein corona, reduced macrophage phagocytosis, and enhanced bioavailability and renal targeting. Furthermore, we investigated the self-assembly principle of SSNPs using representative flavonoids and terpenoids. Kinetic studies and in situ transmission electron microscopy (in situ TEM) revealed that these compounds self-assemble via supramolecular forces like hydrogen bonding and π-π interactions, forming stable nanostructures. This study elucidates the renoprotective effects and mechanisms of SB and SD, and provides a novel approach for the development of TCM-based nanomedicines, highlighting the potential of nano-TCM in AKI treatment.

OBJECTIVE: Cassiae Semen (CS, Juemingzi in Chinese) is a widely used traditional Chinese medicine with a variety of pharmacological effects. This study aimed to investigate the potential therapeutic effects and molecular mechanisms of anthraquinones of CS (AQS) for adiposity. METHODS: The chemical components of the AQS were determined using high-performance liquid chromatography (HPLC). Network pharmacology analysis was used to predict potential anti-obesity targets of action for AQS. We constructed high fat with high sugar water diet-induced obese mice and observed their body weight and whole-body lipid metabolism to evaluate the efficacy of AQS in promoting lipid metabolism. Subsequently, the epidermal temperature at the brown adipose tissue (BAT) before and after cold stimulation was observed and the expression of lipid metabolism-related genes in the liver and BAT tissues was detected to clarify the mechanism of action of AQS. RESULTS: Network pharmacology analysis showed that AQS was involved in the regulation of liver and adipose tissue function under obesity. Pathological and biochemical results showed that AQS reduced lipid accumulation in the liver and adipose tissue induced by an unhealthy diet. With the increase of cold tolerance, the volume and weight of BAT were increased by AQS, suggesting that it regulated the body heat production dominated by BAT. After AQS treatment, the levels of genes related to uncoupling protein1 (UCP1)-mediated adaptive thermogenesis in BAT tissues and lipid metabolism in the liver were also increased, which further proved that AQS activated BAT function to promote lipid metabolism in the whole body. CONCLUSION This study revealed the pharmacological effects of AQS, thereby providing a scientific basis for regulating BAT thermogenesis and liver lipid metabolism to alleviate obesity and providing clues for further exploring the application of natural active ingredients in the treatment of metabolism-related diseases.

AIM:To investigate the effect of Huangqi-Danggui decoction(HQDG)on the brain tissue of rats with cerebral ischemia/reperfusion(I/R)injury for 7 d by regulating macroautophagy and chaperone-mediated autophagy(CMA),and to explore its mechanism.METHODS:Male SD rats were randomly divided into sham group,model group,HQDG group and Xuesaitong(XST)group.Determination of main chemical components of HQDG by liquid chro-matography-mass spectrometry.The model of middle cerebral artery occlusion/reperfusion in rats was established by the left modified thread embolism method,and the changes of cerebral blood flow were observed by laser speckle blood flow imager.Zea Longa score was used to observe the neurological deficit.HE staining was used to observe the degree of nerve cell injury.The changes of neurovascular unit and autophagosomes in brain tissue were observed by transmission electron microscopy.Immunohistochemical method was used to detect the expression of LC3,P62,lysosome-associated membrane protein-2A(LAMP-2A),heat shock protein 70(HSP70)and myocyte enhancer factor 2D(MEF2D)proteins.Western blot was used to detect the expression of autophagy-related proteins P62 and LC3-Ⅱ/LC3-I.RESULTS:Compared with the sham group,the neurological deficit score in model group was significantly higher(P<0.01).A large number of nerve cells showed necrosis and nuclear dissolution,with the cell arrangement being disordered.The number of autophagosomes increased.The protein expression levels of LC3,LAMP-2A,HSP70 and MEF2D in brain tissue increased,while the ex-pression level of P62 protein decreased(P<0.05 or P<0.01).Compared with the model group,the scores of neurological deficit in brain tissue in HQDG and XST groups were significantly lower(P<0.01).Cell damage was significantly re-duced.The number of autophagosomes further increased.The expression levels of LAMP-2A,HSP70,MEF2D and P62 proteins in brain tissue decreased,while the expression levels of LC3-Ⅱ/LC3-I protein increased(P<0.05 or P<0.01).CONCLUSION:HQDG can alleviate cerebral ischemia/reperfusion injury in rats and exert neuroprotective effects by ac-tivating macroautophagy and reducing CMA.

Objective To analyze the relationship between serum exosomal microRNA(miR)-7-5p expression levels in children with asthma and their short-term prognosis.Methods A total of 132 asthmatic children(asthma group)and 30 healthy children(control group)from Tangshan Vocational & Technical College Affiliated Hospital between October 2021 and May 2023 were included as study subjects.These asthmatic children were categorized into a good prognosis group(n=91)and a poor prognosis group(n=41)based on their Childhood Asthma Control Test results.The levels of allergy history,forced vital capacity(FVC),fractional exhaled nitric oxide(FeNO),and miR-7-5p level among groups were compared,and logistic regression analysis was conducted to identify risk factors for the short-term prognosis of asthmatic children.The Kappa test,receiver operating characteristic(ROC)curve,and mean absolute error(MAE)value were used to evaluate indicators in predicting short-term prognosis in children with asthma.Results The level of miR-7-5p in the asthma group[0.53(0.49,0.64)]was lower than that in the control group[1.03(0.97,1.10)],with significant difference(Z=8.548,P＜0.001).The poor prognosis group exhibited a higher proportion of allergy history(68.29％)and FeNO[38(36,41)ppb]levels,and lower FVC[1.86(1.84,2.05)L]and miR-7-5p levels[0.47(0.43,0.52)]compared to the good prognosis group[46.15％,35(30,40)ppb,1.94(1.87,2.06)L,0.60(0.50,0.68)],and the differences were significant(x2/Z=2.854～6.450,all P＜0.05).Multivariate logistic regression analysis revealed that a history of allergies(OR=3.388,95％CI:1.328～8.643,P=0.011)and high FeNO levels(OR=1.161,95％CI:1.064～1.267,P=0.001)were independent risk factors,while a high level of miR-7-5p(OR=0.090,95％CI:0.033～0.248,P＜0.001)was an independent protective factor for the short-term prognosis of asthmatic children.The area under the ROC curve for miR-7-5p+allergy history+FeNO in predicting the short-term prognosis of asthmatic children was 0.851,which was higher than that for miR-7-5p alone(0.851,Z=2.097,P=0.036)and allergy history+FeNO(0.726,Z=4.239,P＜0.001).The Kappa value for miR-7-5p+allergy history+FeNO was 0.67,which was higher than miR-7-5p(0.44)and allergy history+FeNO(0.41).The MAE for miR-7-5p+allergy history+FeNO was 0.022,which was lower than miR-7-5p alone(0.067)and the combination of allergy history+FeNO(0.035).Conclusion Elevated level of miR-7-5p in the serum exosomes of asthmatic children is linked to a favorable short-term prognosis.The combination of miR-7-5p,allergy history,and FeNO may have certain value in evaluating the short-term prognosis of asthmatic children.

Objective To investigate the effects of allergens on the expressions of IL-18,IL-18BPa and IL-18Rα protein in peripheral blood CD4+Th1 cells of healthy control subjects(HC)and patients with allergic rhi-nitis(AR),and on the expressions of IL-18,IL-18BPa and IL-18Rα mRNA in the peripheral blood CD4+T cells.Methods Blood samples were collected from patients with rhinitis for negative skin prick test(AR-),rhinitis for positive skin prick test(AR+)and HC.Flow cytometry was used to evaluate the effects of allergens on the expres-sions of IL-18,IL-18BPa and IL-18Rα protein in CD4+Th1 cells.The expressions of IL-18,IL-18BPa and IL-18Rα mRNA in CD4+T cells were determined by qPCR.Results Compared with HC,increased IL-18 while de-creased IL-18BPa expressions in Th1 cells of AR-and AR+patients were observed,increased IL-18Rα expression in Th1 cells of AR+patients was also found.Additionally,allergens induced elevated expression of IL-18Rα pro-tein in Th1 cells of HC,and induced elevated mRNA expressions of IL-18,IL-18BPa and IL-18Rα in isolated blood CD4+T cells of AR+patients and HC.Conclusion Allergens may be involved in the pathogenesis of AR by inducing the expressions of IL-18 and IL-18Rα in blood CD4+Th1 cells.

Objective:To investigate the effect of inhibitory activity of high mobility group protein B1 (HMGB1), signal transduction and activator of transcription 3 (STAT3) on myocardial ischemia-reperfusion injury in rats.Methods:In vivo and in vitro models of MIRI were established. SD rats were randomly divided into a sham group, a model group, a glycyrrhizic acid group, and a NSC74859 group, with 6 rats in each group. Rats in the sham group were not ligation, and rats in the sham group and model group were not given medication. The rats in the glycyrrhizic acid group and the NSC74859 group were injected with HMGB1 antagonist glycyrrhizic acid or STAT3 inhibitor NSC74859 5 mg/kg in the tail vein at 12 h 30 min before ischemia/reperfusion and 30 min after ischemia, respectively. Left ventricular shortening fraction (FS) and left ventricular ejection fraction (EF) were evaluated by echocardiography, and apoptosis of cardiomyocytes was evaluated by hematoxylin-eosin (HE) and TUNEL staining. The expression levels of HMGB1, STAT3, and phosphorylated STAT3 (p-STAT3) were detected by real-time fluorescence quantitative PCR and Western Blot. The viability of H9C2 cells was determined by the MTS assay, intracellular ATP content was determined, and the mitochondrial membrane potential of H9C2 cells was measured by flow cytometry to evaluate the survival of cardiomyocytes. The action mode of HMGB1/STAT3 was studied by the immunoprecipitation method. The expression and migration of HMGB1/STAT3 in the nucleus and cytoplasm were detected by immunostaining. Results:After inhibiting the expression of HMGB1 or STAT3, EF and FS were increased, and immune infiltration and apoptosis of cardiomyocytes were decreased. Inhibition of HMGB1 expression could decrease the expression of STAT3, but inhibition of STAT3 expression didn’t affect the expression of HMGB1. Hypoxia could lead to increased expression of HMGB1 and p-STAT3, and decreased expression of STAT3. After 8 hours of hypoxia, the expression level of STAT3 suddenly increased. After reoxygenation, the expression of HMGB1 and STAT3 decreased, and the expression of p-STAT3 increased, but p-STAT3 (Ser 727) didn’t participate in this process. After ischemia-reperfusion injury, HMGB1 and STAT3 binded firmly in cardiomyocytes, but inhibition of STAT3 or HMGB1 weakened this binding. Inhibition of HMGB1 or STAT3 expression could reduce myocardial ischemia-reperfusion injury. The expression of HMGB1 in reoxygenated cardiomyocytes increased after hypoxia, and HMGB1 migrated from the nucleus to the cytoplasm.Conclusions:Inhibiting the activity of the HMGB1/STAT3 axis effectively reduces MIRI in rats.

Breast cancer is the most common malignant tumor among women, and early diagnosis, coupled with optimized treatment strategies is crucial for improving the prognosis. In recent years, with the advancement of nanotechnology, manganese-based nanomaterials have shown potential in various aspects of early breast cancer diagnosis, drug delivery, and tumor treatment. Compared to other nanomaterials, manganese-based nanomaterials exhibit excellent biocompatibility and have become a significant focus in the research of breast cancer diagnosis and treatment.

Background The staff in centers for disease control and prevention (CDC) were at a great risk for psychological distress when they were faced with outbreak-related prevention and control work and routine tasks during the COVID-19 period. Psychological resilience and burnout are two key influencing factors on psychological distress. Objective To explore the status and mechanisms of psychological resilience, burnout, and psychological distress among CDC staff. Methods From September to October 2022, a cross-sectional survey was conducted in all CDC staff in Beijing, and 2228 CDC staff from 17 units (including 1 municipality-level CDC and 16 district-level CDCs) participated the questionnaire survey. The basic information questionnaire, Connor-Davidson Resilience Scale (CD-RISC-10) Chinese version, Maslach Burnout Inventory-General Survey (MBI-GS) Chinese version, and the 10-item Kessler Psychological Distress Scale (Kessler10) Chinese version were selected in our study. Mann-Whitney U test or Kruskal-Wallis H test was used to analyze the differences in the scores of psychological resilience, burnout, and psychological distress by demographic and sociological characteristics. The correlations among the three elements were analyzed by Spearman correlation analysis. Potential influencing factors of psychological distress of the CDC staff were evaluated by multiple linear regression. A potential mediating effect of psychological resilience-burnout-psychological distress was analyzed by the mediation package of R 4.2.0, and validated by Bootstrap method. Results Of 2228 questionnaires distributed, 2022 valid questionnaires were collected, and the recovery rate was 90.75%. The median (P₂₅, P₇₅) psychological distress score of CDC staff was 13.00 (8.00, 24.00), and the number of participants with psychological distress levels of 1, 2, 3, and 4 was 358 (17.71%), 546 (27.00%), 362 (17.90%), and 756 (37.39%), respectively. The median (P₂₅, P₇₅) psychological resilience score was 24.00 (20.00, 30.00) and the median (P₂₅, P₇₅) burnout score was 38.00 (25.00, 50.00). The results of the multiple linear regression showed that psychological resilience, burnout, caring for the elderly, having a chronic disease, and monthly income had independent influences on psychological distress (P<0.05), and emotional exhaustion, cynicism, and reduced personal accomplishment (reversed) in the case of burnout had a great effect on psychological distress (P<0.05). After controlling general demographic characteristic variables, total burnout score exerted a partial mediation effect on the relationship between psychological resilience and psychological distress, with a mediation effect value of −0.439 (95%CI: −0.483, −0.397), and a total mediation effect contribution rate of 60.89%. The two dimensions of burnout (emotional exhaustion and cynicism) played a partial mediating role between psychological resilience and psychological distress, with mediating effect contribution rates of 42.44% and 41.41%, respectively. Conclusion Psychological distress among CDC staff in Beijing was prominent during COVID-19. Psychological resilience can act directly on psychological distress or indirectly on psychological distress through burnout. Both emotional exhaustion and cynicism dimensions of burnout have a partial mediating role between psychological resilience and psychological distress. Increasing psychological resilience and decreasing burnout may reduce the occurrence of psychological distress.