Objective To investigate the role and potential mechanism of secreted phosphoprotein 1 (SPP1)⁺ macrophages in the formation of chronic renal allograft fibrosis. Methods The expression features of SPP1⁺ macrophages in renal allografts of chronic allograft dysfunction (CAD) patients were analyzed based on single-cell transcriptome data of renal tissues from patients with CAD. Transcription factor VIPER analysis and DoRothEA transcription factor activity analysis were performed on the single-cell transcriptome data. Renal tissue samples were collected from kidney transplant recipients, including the CAD group (n=5) and the non-renal allograft fibrosis group (CTL group, n=5). A mouse model of chronic allograft rejection was established and divided into the allogeneic kidney transplantation group (CAD group, n=3) and the syngeneic kidney transplantation group (SYN group, n=3). Hematoxylin-eosin staining was used to detect renal tissue injury in mice, and Masson staining was used to detect renal tissue fibrosis. Immunofluorescence staining was performed to detect SPP1 expression in renal tissues of transplant recipients and mouse renal allografts. Bone marrow-derived macrophages (BMDMs) were extracted from mice and subjected to hypoxia stimulation. The expression of hypoxia-inducible factor (HIF)-1α and SPP1 was detected by Western blot, and SPP1 expression was detected by flow cytometry. BMDMs were transfected with HIF-1α overexpression plasmid and HIF-1α small interfering RNA (siRNA) followed by hypoxia intervention, and the expression of HIF-1α and SPP1 was detected by Western blot. Mouse aortic endothelial cells (MAECs) were co-cultured with the supernatant of BMDMs, and the expression of endothelial-mesenchymal transition (EndMT)-related markers was detected by Western blot and immunofluorescence. Results Single-cell transcriptome analysis showed that the proportion of SPP1⁺ macrophages in renal allograft tissues was significantly higher in the CAD group than in the CTL group (P<0.05). The renal injury score and the percentage of interstitial fibrotic area in the CAD group were significantly higher than those in the SYN group (both P<0.05). Immunofluorescence staining showed that the proportion of SPP1⁺ macrophages was increased in the CAD group compared with the CTL group, and also increased in the CAD group compared with the SYN group (both P<0.05). VIPER analysis and DoRothEA transcription factor activity analysis revealed activation of the hypoxia pathway and upregulated expression of transcription factors such as HIF-1α in SPP1⁺ macrophages. SPP1 expression was elevated in BMDMs under hypoxic conditions. Knockdown of HIF-1α inhibited hypoxia-induced SPP1 protein expression, whereas overexpression of HIF-1α upregulated SPP1 protein levels. After co-culture of hypoxia-induced BMDMs with MAECs, the expression levels of EndMT-related markers were increased. Conclusions SPP1⁺ macrophages differentiated under hypoxia are significantly infiltrated in the formation of chronic renal allograft fibrosis, and may promote renal allograft fibrosis by inducing EndMT in renal vascular endothelial cells.

Since the promulgation of the first Drug Administration Law of the People's Republic of China 40 years ago in 1984, China has undergone four main stages in the traditional Chinese medicine(TCM) regulation: the initial establishment of TCM regulation rules(1984-1997), the formation of a modern TCM regulatory system(1998-2014), the reform of the review and approval system for new TCM drugs(2015-2018), and the construction of a scientific regulation system for TCM(2019-2024). Over the past five years, a series of milestone achievements of TCM regulation in China have been achieved in the six aspects, including its strategic objectives and the establishment of a science-based regulatory system, the reform of the review and approval system for new TCM drugs, the optimization and improvement of the TCM standard system and its formation mechanism, comprehensive enhancement of regulatory capabilities for TCM safety, international harmonization of TCM regulation and its role in promoting innovation. Looking ahead, centered on advancing TCMRS to establish a sound regulatory framework tailored to the unique characteristics of TCM, TCM regulation will evolve into new reform patterns, advancing and extending across eight critical fronts, including the legal framework and policy architecture, the review and approval system for new TCM drugs, the quality standard and management system of TCM, the comprehensive quality & safety regulation and traceability system, the research and transformation system for TCMRS, AI-driven innovations in TCM regulation, the coordination between high-quality industrial development and high-level regulation, and the leadership in international cooperation and regulatory harmonization. In this way, a unique path for the development of modern TCM regulation with Chinese characteristics will be pioneered.
Humans ; China ; Drugs, Chinese Herbal/standards* ; History, 20th Century ; History, 21st Century ; Medicine, Chinese Traditional/trends*

Approximately 30%-40% of epilepsy patients do not respond well to adequate anti-seizure medications (ASMs), a condition known as pharmacoresistant epilepsy. The management of pharmacoresistant epilepsy remains an intractable issue in the clinic. Its early prediction is important for prevention and diagnosis. However, it still lacks effective predictors and approaches. Here, a classical model of pharmacoresistant temporal lobe epilepsy (TLE) was established to screen pharmacoresistant and pharmaco-responsive individuals by applying phenytoin to amygdaloid-kindled rats. Ictal electroencephalograms (EEGs) recorded before phenytoin treatment were analyzed. Based on ictal EEGs from pharmacoresistant and pharmaco-responsive rats, a convolutional neural network predictive model was constructed to predict pharmacoresistance, and achieved 78% prediction accuracy. We further found the ictal EEGs from pharmacoresistant rats have a lower gamma-band power, which was verified in seizure EEGs from pharmacoresistant TLE patients. Prospectively, therapies targeting the subiculum in those predicted as "pharmacoresistant" individual rats significantly reduced the subsequent occurrence of pharmacoresistance. These results demonstrate a new methodology to predict whether TLE individuals become resistant to ASMs in a classic pharmacoresistant TLE model. This may be of translational importance for the precise management of pharmacoresistant TLE.
Epilepsy, Temporal Lobe/diagnosis* ; Animals ; Drug Resistant Epilepsy/drug therapy* ; Electroencephalography/methods* ; Rats ; Anticonvulsants/pharmacology* ; Neural Networks, Computer ; Male ; Humans ; Phenytoin/pharmacology* ; Adult ; Disease Models, Animal ; Female ; Rats, Sprague-Dawley ; Young Adult ; Convolutional Neural Networks

OBJECTIVE: This study aims to elucidate the therapeutic potential of osthole for the treatment of atopic dermatitis (AD), focusing on its ability to alleviate chronic pruritus (CP) and the underlying molecular mechanisms. METHODS: In this study, we investigated the anti-inflammatory effects of osthole in both a 2,4-dichloronitrobenzene (DNCB)-induced AD mouse model and tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) stimulated huma immortalized epidermal (HaCaT) cells. The anti-itch effect of osthole was specifically assessed in the AD mouse model. Using methods such as hematoxylin and eosin (HE) staining, enzyme-linked immunosorbent assay (ELISA), western blot (WB), quantitative real-time PCR (qRT-PCR), and immunofluorescence staining. RESULTS: Osthole improved skin damage and clinical dermatitis scores, reduced scratching bouts, and decreased epidermal thickness AD-like mice. It also reduced the levels of interleukin (IL)-31 and IL-31 receptor A (IL-31 RA) in both skin tissues and HaCaT cells. Furthermore, Osthole suppressed the protein expression levels of phosphor-p65 (p-p65) and phosphor-inhibitor of nuclear factor kappa-Bα (p-IκBα). Meanwhile, it increased the protein expression levels of peroxisome proliferator-activated receptor α (PPARα) and PPARγ in HaCaT cells. CONCLUSION These findings indicated that osthole effectively inhibited CP in AD by activating PPARα, PPARγ, repressing the NF-κB signaling pathway, as well as the expression of IL-31 and IL-31 RA.

[Purpose]To analyze the trends of cancer incidence and mortality in Changsha City from 2018 to 2022.[Methods]Based on the annual cancer registry data of Changsha City from 2018 to 2022,SAS 9.2 software was used to calculate the crude incidence/mortality rates and age-standardized incidence/mortality rates by Chinese standard population(ASIRC/ASMRC).The age-standardized rate was standardized using the population composition of China in 2000.Join-point 4.9.0.0 software was used to fit a Log-linear regression model to calculate the average annual percentage change(AAPC)and its 95％confidence interval(CI)for trend analysis.A linear regression model was applied to calculate the contribution rate of each cancer type to the trend change,with a significance level of α=0.05.[Results]From 2018 to 2022,the crude incidence rate of malig-nant tumors in Changsha City was 367.98/105(ASIRC:232.28/105),and the crude mortality rate was 192.36/105(ASMRC:106.11/105).Both incidence and mortality rates were higher in male than those in female.The incidence and mortality rates remained relatively low before age 50 but rose rapidly thereafter:the incidence peaked in the age group of 80～84 years old,while mortality peaked in the age group of 85 years old and above.The top 5 cancers by incidence were lung cancer,female breast cancer,colorectum cancer,cervical cancer,and thyroid cancer;while the top 5 cancers by mortality were lung cancer,colorectum cancer,liver cancer,female breast can-cer,and cervical cancer.The ASIRC increased significantly in the total population(AAPC=4.71％,95％CI:3.20％～6.23％),male(AAPC=2.44％,95％CI:0.35％～4.58％),and female(AAPC=7.17％,95％CI:4.00％～10.43％).The ASMRC increased significantly in the total population(AAPC=2.94％,95％CI:0.73％～5.20％)and male(AAPC=3.37％,95％CI:1.63％～5.15％),but the trend in female was not statistically significant(P＞0.05).Contribution rate analysis showed that thyroid cancer(51.25％),female breast cancer(12.18％),lymphoma(6.02％),and oral cavity and pharyngeal can-cer(5.28％)were the main cancer types contributing to the increased ASIRC;lung cancer(26.10％),colorectum cancer(14.89％),oral cavity and pharyngeal cancer(5.73％),lymphoma(5.60％),and thyroid cancer(2.08％)were the main ones contributing to the increased ASMRC;liver cancer(49.82％)and esophageal cancer(19.55％)were the main causes of decreased ASIRC,with their contribution rates to decreased ASMRC reaching 77.69％and 11.16％,respectively.[Conclusion]The disease burden of malignant tumors in Changsha City continued to increase from 2018 to 2022.It is necessary to strengthen prevention and control for cancers with a signifi-cant upward trend(such as thyroid cancer,lung cancer,and colorectum cancer)and high-risk populations(such as male and middle-aged and elderly people),while consolidating the prevention and control effects for liver cancer and esophageal cancer.

In the context of aging population, the issue of polypharmacy among elderly patients with mental disorders has become increasingly prominent.Cognitive decline and depressive symptoms render these patients more vulnerable to medication-related risks, while poorly managed physical illnesses further complicate their treatment.To address these challenges, this paper proposes a series of management strategies that emphasize the critical role of pharmacists in conducting medication reviews.A comprehensive assessment of drug risks, benefits, and patient adherence is essential.The proposed strategies not only require careful consideration of patients' clinical needs and individual preferences but also highlight the importance of multidisciplinary team collaboration to reach a consensus on medication therapy.The use of clinical decision support systems as an auxiliary tool is recommended to enhance the scientific rigor of medication decision-making.Furthermore, pharmacists can optimize medication regimens through scientifically validated methods and promote patient or family involvement in self-management to improve acceptance and adherence to treatment adjustments.

OBJECTIVE: To investigate the association between ABO blood types and gestational diabetes mellitus (GDM) risk. METHODS: A prospective birth cohort study was conducted. ABO blood types were determined using the slide method. GDM diagnosis was based on a 75-g, 2-h oral glucose tolerance test (OGTT) according to the criteria of the International Association of Diabetes and Pregnancy Study Groups. Logistic regression was applied to calculate the odds ratios ( ORs) and 95% confidence intervals ( CIs) between ABO blood types and GDM risk. RESULTS: A total of 30,740 pregnant women with a mean age of 31.81 years were enrolled in this study. The ABO blood types distribution was: type O (30.99%), type A (26.58%), type B (32.20%), and type AB (10.23%). GDM was identified in 14.44% of participants. Using blood type O as a reference, GDM risk was not significantly higher for types A ( OR = 1.05) or B ( OR = 1.04). However, women with type AB had a 19% increased risk of GDM ( OR = 1.19, 95% CI = 1.05-1.34; P < 0.05), even after adjusting for various factors. This increased risk for type AB was consistent across subgroup and sensitivity analyses. CONCLUSION The ABO blood types may influence GDM risk, with type AB associated with a higher risk. Incorporating it-either as a single risk factor or in combination with other known factors-could help identify individuals at risk for GDM before or during early pregnancy.
Humans ; Female ; Pregnancy ; Diabetes, Gestational/etiology* ; ABO Blood-Group System ; Adult ; Prospective Studies ; Risk Factors ; Young Adult

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Aim To explore the material basis and un-derlying mechanism of Qingre Huoxue Formula(QRHXF)in the treatment of non-small cell lung cancer(NSCLC)by applying network pharmacology,molecular docking technology and bioinformatics com-bined with animal experiments.Methods TCMSP,ECTM,and BATMAN databases were used to obtain active components and corresponding targets of QRHXF;GEO and DisGeNENT databases were con-ducted to acquire NSCLC-associated differential expres-sion genes.By intersecting them,the common targets were obtained.It was chosen to construct a herb-com-ponent-disease network and protein-protein interaction(PPI)network.Furthermore,DAVID database was used to perform gene ontology(GO)function and Kyo-to encyclopedia of genes and genomes(KEGG)path-way enrichment analyses.The molecular docking was presented by adopting Autodock Vina program to verify key targets.RNA-seq datawere downloaded from TC-GA database to obtain differential gene expression.Ka-planMeier(KM)analysis was performed to analyze the relationship between gene expression and overall sur-vival.Mouse subcutaneous tumor model of LLC was established.The effects of QRHXF on body weight,tumor volume and weight were monitored for pharmaco-dynamic analysis.Tumor tissues slides were stained with hematoxylin and eosin(HE)for histopathological examination.Immunohistochemistry(IHC)staining was employed for detecting Ki67 and EP300.Western blot was performed to measure the protein expression of TP53,CDK1 and NTRK1.Results The results of net-work pharmacology showed that a total of seven com-mon targets were screened from NSCLC and QRHXF,and the effect of QRHXF on anti-NSCLC may occur via multiple signaling pathways,including cell cycle.The results of molecular docking indicated that the main ac-tive components of QRHXF had low binding energy and stable docking conformation with the molecular target for treating NSCLC.According to bioinformatic analy-sis,there were significant differences in BRCA1,CDK1 and NTRK1 mRNA expression between tumor tissues and normal tissues,which were also prognostic factors for overall survival.Animal experimental research showed QRHXF inhibited subcutaneous tumor growth(P＜0.01)and improved the quality of life in mice with NSCLC.After QRHXF intervention,the density of tumor cells was significantly reduced,and necrotic are-as were increased.The expressions of Ki67 and EP300 were significantly decreased.Compared with the model group,Western blot showed up-regulation of TP53 and NTRKA(P＜0.05),whereas CDK1 were down-regu-lated(P＜0.05).Conclusion QRHXF exerted anti-NSCLC effects by regulating NTRK1,EP300,TP53,CDK1 and inducing cell cycle,cell cycle arrest and in-hibiting tumor growth,metastasis and angiogenesis.