Objective To detect the PM_2.5 pollution situation during heating season in Xinxiang university town, analyze the contents of 10 elements in PM_2.5, and evaluate its health risks, so as to provide data support for the subsequent environmental governance of college town. Methods PM_2.5 were collected during heating season. The contents of 10 elements were detected by ICP-MS after PM_2.5 was digested. The source was analyzed using enrichment factor method. The ecological risk and health risk of PM_2.5 was evaluated by applying the potential survival hazard index method and health risk assessment method. Results The average contents of Al, Mg, Mn, Cr, Zn, Se, Cu, Pb, Cd and As were respectively 165.59，203.37，7.75，328.93，133.61，8.24，30.82，7.09，2.77and 9.15 ng/m³. The average contents of Cr, Pb, and As all exceeded their air environment targets. The enrichment factors of Pb, Cu, As, Zn, Cd, Cr and Se were all more than 10, and their sources were affected by human activities. The potential ecological risk index of PM_2.5 was 352.42, which was strong ecological hazard factor. PM_2.5 had carcinogenic risk to human, and the risk in adults was higher than that in children. Conclusion During heating season in Xinxiang college town mainly, PM_2.5 may have short-term health risks on environment and human. When the air quality is poor, it is recommended to reduce outdoor activities while taking personal protective measures to minimize the potential health risks to the population in the university town.

ObjectiveTo investigate the mechanism through which miR‑21 improves chronic renal fibrosis in mice via targeted modulation of the phosphatase and tensin homolog （PTEN）/protein kinase B （AKT）/mammalian target of rapamycin （mTOR） pathway. MethodsThirty‑two chronic kidney disease model mice were randomly divided into four groups （n=8 each group）： model group， miR‑21 overexpression group， miR‑21 inhibition group， and miR‑21 inhibition + MK‑2206 group. Eight healthy mice were included as the control group. The miR‑21 overexpression， miR‑21 inhibition， and miR‑21 inhibition + MK‑2206 groups received tail‑vein injections of lentivirus （50 μL， 1×10⁸ TU per mouse） once weekly for three weeks. The control and model groups were injected with an equal volume of empty vector （LV‑NC）. The miR‑21 inhibition + MK‑2206 group additionally received gavage of the AKT/mTOR pathway inhibitor MK‑2206 （480 mg/kg） once weekly for three weeks. The expressions of miR‑21， 24 h urinary protein， serum creatinine （Scr）， blood urea nitrogen （BUN）， and renal tissue levels of collagen Ⅰ， collagen Ⅲ， α‑smooth muscle actin （α‑SMA）， and PTEN protein， as well as p‑AKT/AKT and p‑mTOR/mTOR ratios， were compared among groups. HE staining was used to observe pathological changes in renal tissue， and Masson staining was used to observe the degree of renal fibrosis. A dual‑luciferase assay was performed to verify the targeting relationship between miR‑21 and PTEN. ResultsCompared with the model group， miR‑21 expression in renal tissue increased in the miR‑21 overexpression group （P<0.05） and decreased in the miR‑21 inhibition group （P<0.05）. Compared with the model group， the miR‑21 overexpression group showed increased 24 h urinary protein， Scr， BUN， and renal tissue expression of collagen Ⅰ， collagen Ⅲ， and α‑SMA （all P<0.05）， while these indicators decreased in the miR‑21 inhibition group （P<0.05）. Compared with the miR‑21 inhibition group， the miR‑21 inhibition + MK‑2206 group exhibited lower 24‑h urinary protein， Scr， BUN， and renal tissue expression of Collagen Ⅰ， Collagen Ⅲ， and α‑SMA （all P<0.05）. Compared with the model group， the miR‑21 overexpression group showed decreased PTEN protein expression （P<0.05） and increased p‑AKT/AKT and p‑mTOR/mTOR ratios （P<0.05）， while the miR‑21 inhibition group showed increased PTEN expression （P<0.05） and decreased p‑AKT/AKT and p‑mTOR/mTOR ratios （P<0.05）. Compared with the miR‑21 inhibition group， the miR‑21 inhibition + MK‑2206 group had lower p‑AKT/AKT and p‑mTOR/mTOR ratios （P<0.05）， with no significant difference in PTEN protein expression. HE and Masson staining showed normal kidney structure and almost no fibrosis in the control group. The model group exhibited glomerular enlargement， capillary loop adhesion， and focal fibrosis. The miR-21 overexpression group showed severe destruction of glomerular structure， accompanied by extensive fibrosis and renal tubular atrophy. The pathological changes and degree of fibrosis were alleviated in the miR-21 inhibition group. The miR-21 inhibition + MK-2206 group showed only mild pathological changes and mild fibrosis， with the interstitium being largely normal. Compared with PTEN-WT + NC mimics 1， the relative luciferase activity in the PTEN-WT + miR-21 mimics group decreased （P<0.001）. There was no statistically significant difference in relative luciferase activity between PTEN-WT + NC mimics group and PTEN-MUT + miR-21 mimics group. ConclusionmiR‑21 may improve renal function indicators and alleviate renal fibrosis in chronic kidney disease mice via targeted modulation of PTEN and subsequently inhibiting the AKT/mTOR pathway.

[摘 要] 目的：探讨乙醛脱氢酶1A1（ALDH1A1）mRNA负载树突状细胞（DC）疫苗体外诱导抗鼻咽癌干细胞免疫反应的能力。方法：体外转录ALDH1A1 mRNA并电转染至人外周血DC，构建ALDH1A1-DC疫苗，转染EGFP mRNA为对照。流式细胞术检测DC表型、淋巴细胞亚群、细胞毒性T 淋巴细胞（CTL）增殖和细胞因子分泌。分选ALDH+和ALDH- C666-1细胞，检测干细胞标志物（CD24、CD133）和干性基因（OCT4、SOX2、Nanog）的表达水平，采用CCK-8法评估ALDH1A1-DC疫苗诱导的特异性免疫杀伤能力。结果：EGFP-DC荧光表达率显著高于未转染DC（P < 0.000 1），ALDH1A1-DC抗原提呈分子HLA-ABC、共刺激分子CD86、CD40和CCR7表达与未转染DC相比显著增强（P = 0.001 3、P = 0.005 9、P = 0.000 4及P = 0.001 9）。与单独淋巴细胞组（T）及空载DC诱导的淋巴细胞组（DC-T）相比，ALDH1A1-DC诱导的CTL比例最高（均P < 0.000 1），分裂指数最高（P = 0.000 2、P = 0.000 3），且CD8+CD69+（P = 0.000 5、P < 0.000 1）和CD8+ IFN-γ+（P = 0.012 6、P = 0.001 9）细胞亚群比例均显著提高。ALDH1A1-DC-T细胞对ALDH+C666-1悬浮细胞球的杀伤效果显著优于ALDH-细胞球（P = 0.001 0），且与其他各组淋巴细胞相比表现出较强的抗ALDH+C666-1悬浮细胞球的免疫效应（P = 0.001 0，P < 0.000 1）。然而，HLA-ABC阻断后其对ALDH+C666-1细胞的特异性杀伤效应显著降低（P < 0.000 1）。结论：mRNA转染DC后可翻译蛋白并促进DC成熟，增强其诱导特异性CTL免疫反应的能力。

Triptolide （TP）， the core active component of the traditional Chinese medicine Tripterygium wilfordii ， exhibits remarkable pharmacological activities including anti-inflammatory， immunosuppressive and anti-tumor effects， and holds broad application prospects in the treatment of major diseases such as autoimmune diseases and malignant tumors. However， TP has a narrow therapeutic window and causes multi-organ toxicities including liver， kidney and reproductive toxicities， which severely restrict its safe clinical application and new drug development. Therefore， toxicity reduction and efficacy enhancement has become a core scientific problem urgently to be solved in this field. This paper systematically reviews the four core strategies for TP toxicity reduction and efficacy enhancement， including structural modification， dosage form improvement， herbal compatibility， and external therapies of traditional Chinese medicine. Among them， structural modification optimizes the toxic and efficacy characteristics of TP from the molecular structure level， with typica l derivatives including （5 R ）-5-hydroxy triptolide， ZT01， PG490-88， etc. Dosage form modification achieves toxicity reduction and efficacy enhancement via targeted and sustained-controlled drug release of diverse delivery systems. It includes triptolide preparations such as nanoparticles， liposomes， microemulsion gels and liquid crystals， possessing favorable clinical transformation potential. The herbal compatibility and external therapies of traditional Chinese medicine conform to the holistic view of traditional Chinese medicine and have a profound clinical application foundation， but their mechanisms of action are insufficiently elucidated， and they lack unified standardized specifications and high-quality evidence-based proof. In the future， we should rely on multi-omics technology to elucidate the toxic and efficacy mechanisms， integrate technologies to optimize preparations， improve the evaluation system and promote clinical transformation.

ObjectiveTo observe the clinical efficacy of electroacupuncture in treatment of simple obesity patients and its effects on the metabolism-inflammation network. MethodsSeventy-two patients with simple obesity were randomly divided into a electroacupuncture group and a sham electroacupuncture group， with 36 patients in each group. In the electroacupuncture group， conventional acupuncture was applied at Zhongwan （CV 12）， bilateral Tianshu （ST 25）， bilateral Daheng （SP15）， Qihai （CV 6）， Guanyuan （CV 4）， bilateral Zusanli （ST 36） and Fenglong （ST 40）. The sham electroacupuncture group used placebo needle at same acupoints as the electroacupuncture group. Both groups were given sparse-dense waves with a frequency of 2/10 Hz， 30 minutes per session， 3 times a week， for a total of 8 weeks of treatment. The changes of human body parameters including body weight， body mass index （BMI）， waist circumference， and body fat percentage （BFP）， metabolic factors including serum fasting blood glucose （FBG）， triglyceride （TG）， total cholesterol （TC）， high density lipoprotein （HDL）， low density lipoprotein （LDL）， leptin， and ghrelin， and inflammatory factors including interleukin-6 （IL-6） and tumor necrosis factor α （TNF-α） were compared before and after treatment. Correlations between changes in leptin， ghrelin and inflammatory factors were further analyzed. ResultsWaist circumference was significantly reduced after treatment in both groups compared with baseline （P＜0.05）， and the post-treatment waist circumference was lower in the electroacupuncture group than in the sham electroacupuncture group （P＜0.05）； body weight， BMI and BFP decreased significantly after treatment compared to pretreatment levels in the electroacupuncture group （P＜0.05）. Serum leptin， IL-6 and TNF-α declined significantly after treatment in both groups versus baseline （P＜0.05）； the electroacupuncture group had lower post-treatment levels of leptin， IL-6 and TNF-α as well as larger pre-post changes than the sham group （P＜0.05）； ghrelin increased markedly after treatment in both groups （P＜0.05）， with higher post-treatment ghrelin and greater pre-post variation observed in the electroacupuncture group （P＜0.05）. In the electroacupuncture group， changes in ghrelin were negatively correlated with IL-6 and positively correlated with TNF-α （P＜0.01）； in the sham electroacupuncture group， ghrelin changes were negatively correlated with both IL-6 and TNF-α， whereas leptin changes were positively correlated with the two inflammatory markers （P＜0.01）. ConclusionElectroacupuncture can effectively improve clinical manifestations， as well as regulate serum metabolic and pro-inflammatory factors in patients with simple obesity， and discrepant correlation patterns of metabolism-inflammation are observed between the two groups.

The core pathogenesis of childhood IgA vasculitis nephritis （IgAVN） lies in the intermingled conditions of heat， stasis and deficiency. Deficiency is the fundamental cause， while heat acts as the predominant manifestation at the initial stage， and stasis serves as the key factor leading to protracted illness. Based on this understanding， the overall therapeutic principle of clearing heat and cooling blood， dissolving stasis and unblocking collaterals， reinforcing healthy qi and consolidating the root is established. A self-formulated Qingre Zhixue Formula （清热止血方） is used as the basic prescription. According to the characteristics of different disease stages， childhood IgAVN is further classified into three main syndrome types， including blood heat with stasis obstruction， deficiency of both qi and yin， and deficiency of both spleen and kidney， with corresponding syndrome-based treatments. Throughout the treatment process， emphasis is placed on dissolving stasis and unblocking collaterals， while protecting the spleen and stomach of children and maintaining healthy qi. This paper provides new perspectives for diagnosis and treatment of childhood IgAVN with traditional Chinese medicine.

The core pathogenesis of childhood IgA vasculitis nephritis （IgAVN） lies in the intermingled conditions of heat， stasis and deficiency. Deficiency is the fundamental cause， while heat acts as the predominant manifestation at the initial stage， and stasis serves as the key factor leading to protracted illness. Based on this understanding， the overall therapeutic principle of clearing heat and cooling blood， dissolving stasis and unblocking collaterals， reinforcing healthy qi and consolidating the root is established. A self-formulated Qingre Zhixue Formula （清热止血方） is used as the basic prescription. According to the characteristics of different disease stages， childhood IgAVN is further classified into three main syndrome types， including blood heat with stasis obstruction， deficiency of both qi and yin， and deficiency of both spleen and kidney， with corresponding syndrome-based treatments. Throughout the treatment process， emphasis is placed on dissolving stasis and unblocking collaterals， while protecting the spleen and stomach of children and maintaining healthy qi. This paper provides new perspectives for diagnosis and treatment of childhood IgAVN with traditional Chinese medicine.

OBJECTIVE To investigate the effects of MIR149 rs2292832 and MIR499 rs3746444 gene polymorphisms on the efficacy of tofacitinib combined with iguratimod in the treatment of moderate‑to‑severe rheumatoid arthritis （RA）， to provide genetic reference for individualized treatment of moderate‑to‑severe RA patients.METHODS This was a prospective cohort study， and patients were grouped according to genotyping results. A total of 320 patients with moderate-to-severe RA diagnosed in the department of immunology of our hospital between January 2023 and January 2024 were enrolled. All patients received standardized treatment with tofacitinib （5 mg twice daily） combined with iguratimod （25 mg twice daily） for 24 weeks treatment course. Clinical efficacy outcomes， including American College of Rheumatology （ACR） 20/50/70 responses， disease activity score‑28 based on C‑reactive protein （DAS28-CRP）， erythrocyte sedimentation rate （ESR） and C-reactive protein （CRP）， were compared among patients with different genotypes. Combined-genotype analysis and multivariate Logistic regression analysis were also performed.RESULTS The MIR149 rs2292832 CC-genotype patients exhibited significantly higher ACR20， ACR50 and ACR70 response rates （88.90%， 67.78%， 45.56%） than those carrying CT- and TT-genotypes （ P ＜0.05）. After 24 weeks treatment， the reductions in DAS28‑CRP， ESR and CRP were significantly greater in CC‑genotype patients than in CT‑ and TT‑genotype patients （ P ＜0.05）， and the 24‑week DAS28‑CRP was significantly lower in the CC‑genotype patients than in CT‑ and TT‑genotype patients （ P ＜0.05）. The MIR499 rs3746444 GG-genotype showed significantly higher ACR20， ACR50 and ACR70 response rates （91.46%， 73.17%， 52.44%） than those carrying AG‑ and AA‑genotypes （ P ＜0.05）. After 24 weeks of treatment， the reductions in DAS28‑CRP， ESR and CRP were significantly greater in GG‑genotype patients than in AG- and AA-genotype patients and the 24‑weeks DAS28‑CRP was significantly lower in the GG‑genotype patients than in AG- and AA-genotype patients （ P ＜0.05）. Among the nine combined‑genotyps， the CC+GG genotype yielded the best treatment response. The MIR149 rs2292832 CC and MIR499 rs3746444 GG genotypes were independent predictors of clinical remission （ P ＜0.01）， whereas baseline DAS28‑CRP ≥ 6.5 served as a negative predictor of clinical remission （ P ＜0.05）.CONCLUSIONS Gene polymorphisms of MIR149 rs2292832 and MIR499 rs3746444 significantly influence the therapeutic effect of tofacitinib combined with iguratimod in patients with moderate-to-severe RA. Patients carrying CC and GG genotypes achieve better treatment responses.

Objective: To analyze the mediating effect of social support between family resilience and quality of life among elderly patients with Alzheimer's disease (AD), so as to provide the basis for improving the quality of life among elderly patients with AD. Methods: Elderly patients with AD who aged >60 years admitted to Wenzhou Seventh People's Hospital from August 2017 to June 2021 were selected. Data on demographic information, the severity of AD, and the profile of the primary caregivers were collected through questionnaire surveys. Social support, family resilience, and quality of life were assessed using the Social Support Rating Scale, the Shortened Chinese Version of the Family Resilience Assessment Scale, and the Chinese Version of the Quality of Life in Alzheimer's Disease Scale, respectively. The Process macro program was used to analyze the mediating effect of social support between family resilience and quality of life. Results: A total of 137 elderly patients with AD were surveyed. The mean age of the participants was (69.26±10.93) years. Among them, there were 63 males (45.99%) and 74 females (54.01%). The mean scores for social support, family resilience, and quality of life were (27.93±4.28), (97.34±10.06), and (27.82±7.27) points, respectively. The results of the mediating effect analysis indicated that family resilience could directly and positively affect the quality of life, with an effect value of 0.319 (95%CI: 0.122-0.491). It could also indirectly and positively affect the quality of life through social support, with an effect value of 0.118 (95%CI: 0.030-0.248). The mediating effect accounted for 26.42% of the total effect. Conclusion Social support plays a positive mediating role between family resilience and quality of life among elderly patients with AD.

ObjectiveBased on ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， network pharmacology and molecular docking techniques， to explore the pharmacodynamic material basis and mechanism of Renshen Wuweizi Tang in treating spleen-lung Qi deficiency syndrome. MethodsThe chemical components in the decoction of Renshen Wuweizi Tang were systematically characterized and identified by UPLC-Q-TOF-MS/MS， and network pharmacology was used to screen potential active ingredients， collect component targets and gene sets related to spleen-lung Qi deficiency syndrome， and obtain protein interaction relationships through STRING. Cytoscape 3.9.1 was used to construct a "formula-syndrome" association network and calculate topological feature values. Gene ontology（GO） function and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analysis were performed on core genes to explore potential pharmacodynamic links， the average shortest path between the formula-drug target network and the pharmacodynamic link gene network was calculated to discover dominant pharmacodynamic links， and MCODE plugin was used to identify core gene clusters from the dominant pharmacodynamic links， which were validated using Gene Expression Omnibus（GEO）， and molecular docking was performed between key components and core targets. ResultsOne hundred and thirty-seven components were identified in the negative ion mode， and eighty components were identified in the positive ion mode. After deduplication， a total of 185 components were identified， mainly composed of triterpenoid saponins（49） and flavonoids（54）. Based on the "formula-syndrome" correlation network analysis， energy metabolism was determined to be the dominant pharmacodynamic link of Renshen Wuweizi Tang in the treatment of spleen-lung Qi deficiency syndrome. The results of molecular docking showed that 7 components（adenosine， atractylenolide Ⅱ， atractylenolide Ⅲ， ginsenoside Rg₁， glycyrrhizin B₂， glycyrrhizin E₂ and campesterol） from 4 medicinal materials（Ginseng Radix et Rhizoma， Atractylodis Macrocephalae Rhizoma， Glycyrrhizae Radix et Rhizoma and Poria） in this formula might regulate energy metabolism by acting on 6 targets， namely cyclic adenosine monophosphate-response element binding protein 1（CREB1）， glyceraldehyde-3-phosphate dehydrogenase（GAPDH）， interleukin（IL）-6， nuclear transcription factor（NF）-κB1， peroxisome proliferator-activated receptor α（PPARα）， and tumor necrosis factor（TNF）， thus improving the symptoms of diseases related to spleen-lung Qi deficiency syndrome. ConclusionThis study established a UPLC-Q-TOF-MS/MS for rapid characterization and identification of chemical components in the decoction of Renshen Wuweizi Tang， expanding the understanding of the material composition of this formula， and found that 7 components might act on the key advantageous pharmacodynamic link "energy metabolism" through 6 targets to improve the related symptoms of spleen-lung Qi deficiency syndrome. This can provide a reference for the subsequent exploration of the material benchmark and mechanism of the famous classical formula.