Background: Visceral white adipose tissue (vWAT) inflammation is a critical pathology of obesity-caused heart damage and is closely associated with adipocyte endoplasmic reticulum (ER) dysfunction. Serine (or cysteine) peptidase inhibitor, clade A, member 3C (Serpina3c) has been identified as an adipokine with anti-vWAT inflammatory effects. However, it remains unclear whether Serpina3c deficiency promotion of vWAT inflammation involves adipocyte ER dysfunction and whether it further contributes to heart damage in obesity. Methods: Wild type and Serpina3c knockout (Serpina3c–/–) mice were fed a high-fat diet (HFD) for 12 weeks. An adeno-associated virus (AAV) was injected locally into epididymal white adipose tissue (eWAT) of Serpina3c–/– mice to induce eWAT-adipocyte- specific overexpression of Serpina3c (AAV-Serpina3c) or knockdown of hypoxia-inducible factor 1α (AAV-shHIF1α). In vitro experiments were performed in 3T3-L1 adipocytes. Results: Serpina3c–/– mice exhibited more severe eWAT, serum and heart inflammation after HFD feeding. Consistently, these adverse phenotypes were mitigated in AAV-Serpina3c and AAV-shHIF1α mice. Mechanistically, ER oxidoreductase 1α (Ero1α) and protein disulfide isomerase (PDI) family members PDIA3 and PDIA4 were found to be target genes of HIF1α. In the obese mice, Serpina3c deficiency caused adipocyte more hypertrophy, and activated HIF1α-Ero1α/PDI mediated ER overoxidation and ER stress in eWAT. Subsequently, this led to increased adipocyte apoptosis and chemokine production and decreased adiponectin expression, which promoted macrophage infiltration and M1 polarization in eWAT, thus exacerbating eWAT inflammation and ultimately facilitating serum and distal heart inflammation. Conclusion These findings indicate that Serpina3c is a significant regulator of adipocyte ER redox homeostasis, thus highlighting Serpina3c as a potential therapeutic target for obesity-related eWAT inflammation and heart damage.

Childhood simple obesity has become a significant public health issue in China. Modern medicine primarily relies on lifestyle interventions and often suffers from poor long-term compliance， while pharmacological options are limited and associated with potential adverse effects. Traditional Chinese Medicine （TCM） has a long history in the prevention and management of this condition， demonstrating eight distinct advantages， including systematic theoretical foundation， diversified therapeutic approaches， definite therapeutic efficacy， high safety profile， good patient compliance， comprehensive intervention strategies， emphasis on prevention， and stepwise treatment protocols. Additionally， TCM is characterized by six distinctive features： the use of natural medicinal substances， non-invasive external therapies， integration of medicinal dietetics， simple exercise regimens， precise syndrome differentiation， and diverse dosage forms. By combining internal and external treatments， TCM facilitates individualized regimen adjustment and holistic regulation， demonstrating remarkable effects in improving obesity-related metabolic indicators， regulating constitutional imbalance， and promoting healthy behaviors. However， challenges remain， such as inconsistent operational standards， insufficient high-quality clinical evidence， and a gap between basic research and clinical application. Future efforts should focus on accelerating the standardization of TCM diagnosis and treatment， conducting multicenter randomized controlled trials， and fostering interdisciplinary integration， so as to enhance the scientific validity and international recognition of TCM in the prevention and treatment of childhood obesity.

Objective: To understand the microclimate in primary and secondary school classrooms for the study period during the winter heating season, so as to provide a reference for the revision and improvement of relevant health standards. Methods: In December 2024, stratified random sampling was used to select 30 primary and secondary schools and 180 classrooms from the northern regions with centralized heating (Liaoning Province, Tianjin City) and the southern regions without centralized heating (Shanghai City, Anhui Province, and Jiangxi Province). Indoor temperature, relative humidity, wind speed, CO 2 and other indicators were measured on site. Variance analysis, t-test, Mann-Whitney U test and Kruskal-Wallis H test were used to analyze the differences in the microclimate of classrooms among regions and urban and rural differences. Results: The average temperature in the middle of the classrooms tested on site was (16.47±4.72)℃, and the variance analysis showed that the difference between the regions was statistically significant ( F=27.80, P <0.01). Among them, Tianjin had the highest average temperature of (20.43± 2.12 )℃, followed by Liaoning (19.03±2.23)℃, Shanghai (15.33±5.32)℃, Anhui (12.79±1.74)℃, and Jiangxi (11.69± 1.68 )℃. Horizontal temperature difference was 0.90 (0.50, 1.60)℃, the vertical temperature difference was 0.20 (0.10,0.60)℃, the average relative humidity was (44.39±16.16)%, the wind speed was 0.03(0.01,0.11)m/s, and the differences among different provinces and cities were statistically significant ( H/F =40.62, 82.69, 95.06, 55.28, all P <0.01). The average CO 2 volume concentration in urban areas of Tianjin, Liaoning, and Shanghai was 0.21(0.16,0.30)%, and there was no statistically significant difference ( H=4.65, P =0.10). There were grade differences in relative humidity ( F =3.71, 6.21) and CO 2 ( H =14.72, 12.92) in the north and the south (all P <0.05). In addition, the temperature, relative humidity, wind speed and CO 2 in the middle of the classroom were 42.8%, 67.8%, 100.0% and 22.2% respectively. Conclusions The temperature in the middle of the classroom in the non centralized heating area is lower than the standard, the relative humidity of classroom in the centralized heating area is lower than the standard，and the CO 2 in the classroom in winter is lower than the standard. It is recommended to install heating facilities in schools with low temperatures to increase the temperature and increase the frequency of ventilation in classrooms or adopt mechanical ventilation strategies to reduce CO 2 volume concentration.

ObjectiveTo investigate the current awareness and optimization recommendations on pneumonia with unknown etiology (PUE) surveillance among Shanghai healthcare professionals, and to provide evidence for the improvement of the surveillance system. MethodsIn December 2024, healthcare professional participants from diverse medical and health institutions were randomly selected within each stratum using a stratified cluster sampling method in all 16 districts of Shanghai for questionnaire surveys on their knowledge and suggestions for optimization of the PUE surveillance system. Descriptive statistics analyses, multivariate logistic regressions, and content analyses were used for data analyses. ResultsA total of 385 survey subjects were involved in the study, including 119 professional staffs from disease prevention and control centers and 266 from medical institutions. Those who understood the case definition for PUE correctly accounted for 67.01% (258/385). Multivariate regression model analyses showed that female gender (aOR=2.22, 95%CI: 1.36‒3.66), professionals from disease control institutions (aOR=2.02, 95%CI: 1.12‒3.72), and those who self-assessed as being familiar with the monitoring system (aOR=2.18, 95%CI:1.23‒3.89) had better understanding of the definition. Overall, 89.61% (345/385) of the survey subjects acknowledged the necessity of the surveillance system. Small number of cases meeting the case definition (54.46%, 214/379), insufficient diagnostic awareness (39.84%, 151/379), and lack of incentives for case reporting (29.29%, 111/379) were major problems for the current surveillance system, with variations observed across different types of institutions. Suggested segments for optimizing the surveillance system included monitoring purpose, case definition, form of monitoring and reporting procedure, organization mechanism, and epidemiological investigation and response. ConclusionThe necessity of PUE surveillance is commonly recognized among healthcare workers. However, the existing system falls short in terms of mastery of case definition and overall surveillance adaptability. There is an urgent need for optimization and improvement to enhance the capacity for preventing and controlling emerging and sudden respiratory infectious diseases.

Objective:To analyze the correlation between blood glucose index and peripheral neuropathy in type 2 diabetes patients under continuous blood glucose monitoring.Methods:A total of 110 patients with type 2 diabetes admitted to the Lu′an Hospital Affiliated to Anhui Medical University from November 2022 to January 2024 were retrospectively observed, and the blood glucose indexes of patients were monitored by continuous glucose meter [glucose time in range (TIR), mean blood glucose (MBG), estimated hemoglobin A 1c (eHbA 1c), blood glucose standard deviation (SD), coefficient of variation (CV), largest amplitude of glycemic excursions (LAGE), mean amplitude of glycemic excursions (MAGE), means of daily differences (MODD), etc ]. All patients with type 2 diabetes were grouped according to whether they had peripheral neuropathy or not, and were divided into the developing group and the non-developing group. General data and blood glucose indexes of the two groups were collected and sorted out. Receiver operating characteristic (ROC) curve was used to analyze the value of various blood glucose indicators in predicting peripheral neuropathy in patients with type 2 diabetes. Spearman correlation analysis was also used to evaluate the correlation between blood glucose index and peripheral neuropathy. Results:The disease course, TIR, MBG, eHbA 1c, SD, CV, LAGE, MAGE and MODD of the occurrence group were significantly different from those of the non-occurrence group (all P<0.05). By plotting the ROC curve, It was found that the area under the curve (AUC) of TIR, MBG, eHbA 1c, SD, CV, LAGE, MAGE and MODD predicting peripheral neuropathy in patients with type 2 diabetes were 0.942, 0.840, 0.705, 0.759, 0.819, 0.813, 0.857 and 0.677, respectively. The AUC of the combined prediction was 0.971(95% CI: 0.946-0.997), which was higher than that of the single indicator (all P<0.05). Spearman correlation assessment showed a negative correlation between TIR and peripheral neuropathy ( r=-0.738, P<0.05). MBG, eHbA 1c, SD, CV, LAGE, MAGE and MODD were positively correlated with peripheral neuropathy ( r=0.554, 0.376, 0.452, 0.490, 0.527, 0.625, 0.272, all P<0.05). Conclusions:Based on continuous blood glucose monitoring, the blood glucose index of type 2 diabetes patients is closely related to peripheral neuropathy, and the above blood glucose index can accurately predict peripheral neuropathy, providing a reference for reducing or preventing the occurrence of peripheral neuropathy.

BACKGROUND:Irisin plays a crucial role in the physiological regulation of the body,advancing the browning process of white adipose tissue cells and exerting significant effects on the regulation of energy metabolism,thermogenesis,reduction of oxidative stress,and body mass loss.OBJECTIVE:To summarize the latest research progress in irisin and related diseases.METHODS:A computerized search of PubMed,MedReading,Web of Science,CNKI,WanFang,and VIP was performed to collect studies on the effect of irisin on relevant diseases.The search time was from January 1,2011 to April 13,2024.The search terms were"irisin,physical exercise,FNDC5,disease"in Chinese and English.According to the inclusion and exclusion criteria,71 papers were finally included for review.RESULTS AND CONCLUSION:Irisin has important roles in anti-inflammation,fat metabolism,bone metabolism,brain health,cancer,diabetes,cardiovascular disease and kidney disease.Moreover,exercise can promote the expression of irisin,and different forms of exercises have different effects on irisin levels.Acute exercise,long-term exercise,resistance exercise and high-intensity exercise can all enhance irisin levels.The discovery of irisin provides a new potential basis for exercise therapy,which is a promising therapeutic target due to the multiple biological functions of irisin,and shows potential therapeutic value in the treatment of human metabolic diseases and their complications,obesity,and cancer.Irisin has a promising application as a potential target for the treatment of obesity,cognitive function,cardiovascular,cancer and other diseases in clinical practice.However,its specific mechanism of action still needs to be studied in depth,and there may be side effects.In the future,an in-depth understanding of the mechanism of irisin is needed to provide a more adequate basis for the treatment of obesity,cognitive dysfunction,cardiovascular disease,and cancer.

AKT,also known as Protein Kinase B(PKB),plays a critical role in cell proliferation and metabolism.There are three isoforms of AKT:AKT1,AKT2,and AKT3.The effects of these isoforms on the pluripotency and differentiation of mouse embryonic stem cells(mESCs)remain unclear.This study aims to explore the impact of three AKT isoform-specific knockouts on the self-renewal and differen-tiation of mouse embryonic stem cells.Using CRISPR/Cas9 gene-editing technology,AKT isoform-spe-cific knockout cell lines were established.The phenotypic and molecular changes were analyzed through Western blotting,flow cytometry,qRT-PCR,CCK-8 assays,Alkaline Phosphatase(AP)staining,and RNA-seq.The construction of AKT isoform-specific knockout cell lines was successful.The loss of AKT1 and AKT2 inhibited the proliferation of mESCs.The knockout of any single AKT isoform did not affect the expression of pluripotency genes at both mRNA or protein levels.However,during embryoid body forma-tion,the deletion of any of the three AKT isoforms affected the mRNA expression levels of genes in all three germ layers.Transcriptome analysis showed that compared to wild-type mESCs,995,547,and 429 differentially expressed genes(|log2FC|≧1,P＜0.05)were identified inAKT1,AKT2,and AKT3 isoform-specific knockout cells,respectively.There was some overlap in the differentially expressed genes regulated by these three isoforms.In conclusion,the independent knockout of AKT isoforms does not af-fect the maintenance of pluripotency in mouse embryonic stem cells,but they are crucial for differentia-tion.The three AKT isoforms can collectively regulate gene expression while retaining their own regulato-ry specificity.This study provides a foundation for understanding the unique and overlapping roles of AKT isoforms in stem cell biology,highlighting their importance in maintaining stem cell function and differen-tiation.

Objective To explore the value of CT-based radiomics and machine learning in predicting the severity of community acquired pneumonia(CAP)in children.Methods The clinical and imaging data of 158 patients diagnosed with CAP in children were analyzed retrospectively.All patients were randomly divided into training set(n=110)and validation set(n=48)in a ratio of 7︰3.Radiomics features were outlined and extracted using 3D Slicer software,and feature selection was achieved using maximum relevance and minimum redundancy(MRMR)and least absolute shrinkage and selection operator(LASSO)algorithms.The construction of the nomogram model and the machine learning combined model was performed by combining clinical features and Radiomics score(Radscore),and its performance was evaluated and validated.Results The area under the curve(AUC)of the clinical model,the radiomics model and the nomogram model in the validation set were classified as 0.82,0.86 and 0.91,respectively.The AUC of the combined multi-layer perceptron(MLP),random forest(RF),and adaptive boosting(ADB)models were 0.926,0.934 and 0.917,respectively in the validation set.Conclusion Radiomics combined with clinical data is expected to be a novel predictor of the severity of CAP in children.MLP,RF and ABD machine learning algorithms can further enable model performance.

Objective:To observe any effect of combining transcranial magnetic stimulation (rTMS) with aerobic exercise on the cognitive functioning of early stage Parkinson′s disease (PD) patients.Methods:A total of 120 PD patients in the early stage were randomly divided into an observation group and a control group, each of 60. Both groups received conventional drug treatment and moderate-intensity aerobic exercise training, while the observation group was additionally provided with high-frequency rTMS treatment. Before and after 3 months of the treatments, everyone′s cognitive and motor functioning was evaluated using the Montreal Cognitive Assessment Scale (MoCA) and the third part of the Unified Parkinson′s Disease Rating Scale (UPDRS-Ⅲ), respectively. Negative emotions were evaluated using the Hamilton Anxiety Scale (HAMA) and the Hamilton Depression Scale (HAMD). Auditory event-related potentials were also detected, and the latency and amplitude of P300 were analyzed.Results:The average MoCA, UPDRS-Ⅲ, HAMA and HAMD scores, as well as the amplitude and latency of P300 had improved significantly in both groups after the treatment. At that point the observation group′s performance was significantly better than that of the control group in terms of the MoCA′s visuospatial and executive function, attention and delayed recall indicators, and also total score. The observation group′s average HAMA score (10.55±3.11), HAMD score (9.78±4.10), the P300 amplitude [(11.29±2.21)μV] and latency [(384.75±48.26)ms] were also significantly better. The UPDRS-Ⅲ scores were negatively correlated with the visuospatial and executive function scores of the MoCA scale in the observation group before and after treatment, while the average HAMA score was negatively correlated with the attention and delayed recall scores.Conclusions:Supplementing aerobic exercise with rTMS can significantly improve the cognition and motor functioning of early stage PD patients. The combination is more effective than aerobic exercise alone. Such combined therapy is worthy of popularization and clinical application.

Objective To develop an objective and precise prognostic model for assessing severity and prognosis in elderly patients with community-acquired pneumonia(CAP)admitted to the emergency department.Methods A retrospective analysis was conducted on elderly patients with CAP admitted to Department of Emergency,Minhang Hospital,Fudan University between Jun 2018 and Dec 2020.With the primary outcome being the 30-day in-hospital mortality rate of elderly CAP patients,four systemic inflammatory response markers,including the neutrophil-to-lymphocyte ratio(NLR),monocyte-to-lymphocyte ratio(MLR),platelet-to-lymphocyte ratio(PLR),and systemic immune-inflammation index(SII)were evaluated using univariate and multivariate Logistic regression analyses.The predictive performance of different scoring systems was compared.Results A total of 421 elderly CAP cases were enrolled.The results of the multivariate Logistic regression analysis demonstrated that NLR was an independent risk factor for elderly inpatients with CAP.We combined NLR with the existing CURB-65 score for joint optimization to construct a scoring system or a clinical prognosis model,by quantifying and assigning optimal cut-off value of 11.4 for NLR,and established the NLR+CURB-65 score.The ROC curve was constructed to compare the areas under the curve of the three different scoring systems(NLR,CURB-65,and NLR+CURB-65).The area under the curve of the NLR+CURB-65 score was significantly higher than that of the CURB-65 score.Based on the optimal cut-off value of 3 for NLR+CURB-65 score,the patients were stratified into high-risk group(n=188)and low-risk group(n=233).The K-M survival curve was utilized and indicated that compared with high-risk group,low-risk group had a lower mortality rate and a higher discharge rate.Conclusion For elderly emergency hospitalized patients with CAP,the combination of NLR and CURB-65 score showed high predictive value for assessing disease severity and prognosis.