ObjectiveTo investigate the anti‑pancreatic fibrosis mechanism of Klotho‑derived peptide 7 （KL7） by observing its effect on a mouse model of chronic pancreatitis （CP） induced by cerulean， and to provide a basis for clinical medication. MethodsA total of 40 male BALB/c mice were randomly divided into control group， model group， low-dose KL7 group （2 mg/kg）， and high-dose KL7 group （4 mg/kg）， with 10 mice in each group. All mice except those in the control group were given intraperitoneal injection of cerulean （50 μg/kg） 6 times a day at an interval of 1 hour， twice a week for 4 consecutive weeks to establish a model of CP. The mice in the low-dose KL7 group and the high-dose KL7 group were treated with different doses of KL7 once a day for 4 consecutive weeks. In vivo imaging was used to observe the accumulation of KL7 in the pancreas； molecular docking was used to detect the binding of KL7 to transforming growth factor-β type Ⅱ receptor （TβRⅡ）； the mice were measured in terms of body weight and pancreatic weight； HE staining was used to observe the pathological changes of pancreatic tissue； Masson staining was used to observe the degree of pancreatic fibrosis； immunohistochemical staining was used to measure the expression of α-smooth muscle actin （α-SMA） and type Ⅰ collagen （COL1A1）； Western blotting was used to measure the protein expression levels of α-SMA， TβRII， and phosphorylated small mothers against decapentaplegic homolog 2/3 （p-Smad2/3） in pancreatic tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test and the Dunnett’s-T3 test were used for further comparison between two groups. ResultsKL7 was significantly enriched in the pancreatic tissue of CP mice， and there was a strong binding activity between KL7 and TβRⅡ. Compared with the control group， the model group had significant reductions in pancreatic mass and relative pancreatic mass （P<0.000 1）， with disordered structure of pancreatic tissue， an increase in inflammatory cell infiltration， and significant increases in fibrosis degree， the positive areas of α-SMA and COL1A1 （P<0.000 1）， and the protein expression levels of α-SMA， TβRⅡ， and p-Smad2/3 （P<0.05）. Compared with the model group， the high-dose KL7 group had significant increases in pancreatic mass and relative pancreatic mass （P<0.01）， with alleviation of structural damage of pancreatic tissue and inflammatory cell infiltration， a significant reduction in fibrosis degree， and significant reductions in the positive areas of α-SMA and COL1A1 （P<0.001） and the protein expression levels of α-SMA， TβRⅡ， and p-Smad2/3 （P<0.01）. ConclusionKL7 has a significant targeted therapeutic effect on pancreatic fibrosis in CP mice through specific binding of KL7 to TβRⅡ， thereby inhibiting the activation of the TGF-β/Smad signaling pathway.

OBJECTIVE To study the protective effect and potential mechanism of chikusetsu saponin Ⅳ a （chsⅣ） on renal function in diabetic nephropathy （DN） model rats. METHODS DN rat model was established by high-fat diet combined with streptozotocin injection. Thirty-six model rats were randomly divided into model group （i.g. administration of normal saline， high-fat diet）， chsⅣ low-dose and high-dose groups （i.g. administration of 90， 180 mg/kg chsⅣ， high-fat diet）， with 12 rats in each group. Additionally， 10 normal rats were set as the control group （i.g. administration of normal saline， regular diet）. From the 5th to the 12th week after streptozotocin injection， they were given intragastric administration of relevant drug or normal saline， once a day. After the last medication， the levels of fasting blood glucose， fasting insulin， blood urea nitrogen， serum creatinine and urine protein as well as the levels of reduced glutathione （GSH）， superoxide dismutase （SOD） and malondialdehyde （MDA） in renal tissues were measured. Additionally， the insulin resistance index was calculated. Hematoxylin-eosin， periodic acid-Schiff， and Masson staining techniques were employed to examine the histopathological alterations in the renal tissue. The expressions of Notch signaling pathway-related proteins in renal tissue were detected by immunohistochemical staining and Western blot methods. RESULTS Compared with model group， the histomorphological of renal tissues in the chsⅣ low- and high-dose groups were significantly improved， with significant decreases in renal histological scores， mesangial expansion index， and glomerulosclerosis scores （ P ＜0.05）； the levels of fasting blood glucose， fasting insulin， blood urea nitrogen， serum creatinine， urine protein and homeostasis model assessment for insulin resistance， as well as MDA content， the expression levels of Notch1， Notch intracellular domain， hairy and enhancer of Split 1 and Delta-like protein 1 in renal tissue were all significantly decreased （ P ＜0.05）. The levels of GSH and SOD in renal tissue were significantly elevated （ P ＜0.05）. Moreover， the improvement in these indicators was significantly more pronounced in the chsⅣ high-dose group compared to the chsⅣ low-dose group （ P ＜0.05）. CONCLUSIONS ChsⅣ can ameliorate renal pathological damage and functional impairment in DN rats. Its underlying mechanisms include restoration of glucose homeostasis and insulin sensitivity， attenuation of renal oxidative stress， and suppression of aberrant Notch signaling pathway activation.

ObjectiveTo investigate the expression characteristics of serum HBV RNA in patients with low-level viremia （LLV） and its value in the diagnosis of LLV. MethodsA total of 402 chronic hepatitis B （CHB） patients who attended Affiliated Hospital of Zunyi Medical University from December 2023 to May 2025 were enrolled， and according to their viral load， they were divided into complete virologic response （CVR） group （190 patients with HBV DNA <20 IU/mL） and LLV group （212 patients with an HBV DNA level of ≥20 IU/mL and <2 000 IU/mL）. The two groups were analyzed in terms of age， sex， disease type， serum HBV RNA， HBeAg， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and total bilirubin （TBil）， and according to HBeAg status， the patients in the LLV group were further divided into HBeAg-negative group with 140 patients and HBeAg-positive group with 72 patients. The chi-square test was used for comparison of categorical data between two groups， and the Mann-Whitney U test was used for comparison of continuous data between two groups. A multivariate Logistic regression analysis was used to investigate the influencing factors for LLV in CHB patients， and a Spearman’s rank correlation analysis was used to analyze the correlation of HBV RNA with HBV DNA， ALT， AST， and TBil in the LLV group. The receiver operating characteristic （ROC） curve was plotted to evaluate the efficacy of HBV RNA in the diagnosis of LLV. ResultsCompared with the CVR group， the LLV group had a significantly higher serum level of HBV RNA ［3 （1　—　5） log₁₀ copies/mL vs 2 （1　—　3） log₁₀ copies/mL， Z=-2.346， P=0.019］ and a significantly higher proportion of patients with hepatitis B cirrhosis （31.13% vs 22.11%， χ²=4.155， P=0.042） or hepatocellular carcinoma （9.91% vs 4.74%， χ²=3.876， P=0.049）. The multivariate Logistic regression analysis showed that HBV RNA （odds ratio=1.163， 95% confidence interval： 1.058　—　1.278， P=0.002） was an independent risk factor for the onset of LLV in CHB patients. Among the patients with LLV， HBeAg-positive patients had a significantly higher level of HBV RNA than HBeAg-negative patients ［6 （4　—　7） log₁₀ copies/mL vs 2 （1　—　3） log₁₀ copies/mL， Z=-9.962， P<0.001］. The correlation analysis showed that HBV RNA level had no significant correlation with HBV DNA， ALT， AST， or TBil in the patients with LLV （all P>0.05）. The ROC curve analysis showed that HBV RNA had an AUC of 0.567 for the diagnosis of LLV （P=0.021）， with an optimal cut-off value of 4.5 log₁₀ copies/mL， a sensitivity of 30.7%， and a specificity of 85.8%. ConclusionSerum HBV RNA level is an independent risk factor for the development of LLV in CHB patients， and there is a significant increase in the expression of HBV RNA in HBeAg-positive patients. Therefore， it may serve as a potential biomarker for clinical risk assessment.

Premature ovarian insufficiency （POI） is a reproductive endocrine disorder that severely affects female reproductive health. However， there remains a lack of clinically effective and safe therapeutic options to restore ovarian function. Traditional Chinese medicine （TCM）， with its advantages of multi-component and multi-target holistic regulation， has shown unique potential in the prevention and treatment of POI. Among TCM monomers， curcumin， resveratrol， and icariin exert antioxidant， anti-inflammatory， and anti-ovarian granulosa cell apoptosis effects by regulating signaling pathways such as nuclear factor-erythroid 2-related factor 2/heme oxygenase-1， phosphoinositide 3-kinase/protein kinase B， and mitogen-activated protein kinase. Single TCM herbs， including American ginseng， Cuscutae Semen， and Cistanches Herba， can regulate sex hormone levels， and alleviate ovarian oxidative stress and immune damage. TCM compound formulas such as Yijing decoction， Siwu decoction， Zuogui pill， and Kuntai capsule modulate multiple signaling pathways， including vascular endothelial growth factor/vascular endothelial growth factor receptor-2， phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin， and silence information regulator 1/p53， thereby promoting angiogenesis， inhibiting mitochondrial apoptosis， and regulating autophagy and ferroptosis， which ultimately delay follicular atresia and improve ovarian reserve function. Further studies are suggested to apply artificial intelligence to deeply explore the underlying mechanisms and carry out high-quality clinical trials， so as to promote the standardized application of TCM in the prevention and treatment of POI.

Rheumatoid arthritis （RA） is an autoimmune disease characterized by chronic synovial inflammation and joint destruction， with a complex pathogenesis. Macrophage polarization plays a pivotal role in disease progression. Recent studies demonstrate that microRNA （miRNA）， as critical post-transcriptional regulators， can participate in the inflammatory response process by regulating the polarization state of macrophages， thereby aggravating RA joint damage. This review summarizes the mechanism of action of various miRNA in regulating macrophage polarization， and emphasizes their potential therapeutic value in RA.

Objective: To evaluate oral health status and knowledge, attitude and practice (KAP) among third grade primary school students after the implementation of the Comprehensive Intervention Project for Childhood Oral Diseases in Guizhou Province, so as to provide evidence for program optimization. Methods: Using a multistage cluster sampling method, oral examinations and questionnaire surveys were conducted among third grade primary school students in schools covered by the Comprehensive Intervention Project for Childhood Oral Diseases in Guizhou Province (intervention group, n =1 030) and schools not covered by the program (control group， n =1 130) in November 2023. A follow up survey was conducted one year after the project s implementation (December 2024) to evaluate the differences in oral health status and KAP between the two groups. The t-test and χ 2 test were used to compare means and rates, respectively. Results: One year after implementation, the permanent caries prevalence, caries filling ratio, mean dmft/DMFT, and mean simplified debris index in the intervention group were 33.3%, 22.3 %, 3.44±3.10, 0.77±0.56, which were all better than those in the control group (39.8%, 17.3%, 3.89±2.85, and 0.87± 0.63 ) ( χ 2/ t =9.87, 8.78, -2.59, -3.91,all P <0.05). After intervention, the levels of oral health knowledge, attitude and behaviors in the intervention group were better than those in the control group ( Z =7.69, 2.35, 2.10, all P <0.05). Except for the item "fluoride has no protective effect on teeth", the correct response rates of other oral health knowledge items in the intervention group were higher than those in the control group ( χ 2=3.92-163.94, all P <0.05). The reported rates of tooth brushing related behaviors and sugary beverage consumption were higher in the intervention group than in the control group ( χ 2=4.02-11.42，all P <0.05). Conclusions The Comprehensive Intervention Project for Childhood Oral Diseases improves children s oral health status, oral health knowledge, and some oral health behaviors, but has limited effects on some behaviors and oral health attitudes. Future efforts should focus on the factors influencing the transformation of children s oral health attitudes and behaviors, along with strengthening long term follow up evaluations.

[摘 要] 目的：探讨细胞色素c氧化酶铜伴侣蛋白17（COX17）是否参与去甲泽拉木醛（DML）抑制胃癌细胞增殖和侵袭的作用。方法： 采用5、10和20 μmol/L DML处理MGC-803细胞，通过显微镜计数和Transwell实验评价DML对细胞增殖和侵袭的影响；采用非标记定量蛋白质组学比较DML处理组与DMSO组的蛋白表达谱，结合差异表达分析和GO功能富集筛选候选蛋白，并采用Western blotting验证DML处理后COX17蛋白表达变化。分别构建COX17敲低和过表达稳定细胞株，通过细胞计数和Transwell实验评价COX17对MGC-803细胞增殖和侵袭的影响。采用分子对接和50 ns分子动力学模拟分析DML与COX17的潜在结合模式及复合物构象稳定性；进一步通过COX17过表达回复实验评价COX17在DML抑制细胞增殖和侵袭过程中的作用。结果：DML显著抑制MGC-803细胞增殖和侵袭，且随DML浓度升高，抑制作用逐渐增强（均P < 0.000 1）。蛋白质组学共筛选出72个差异表达蛋白，其中21个上调、51个下调；结合差异表达特征、GO功能富集结果及前期研究基础，选取COX17进行后续验证。DML可显著下调MGC-803细胞中COX17蛋白表达（P < 0.000 1）。敲低COX17可抑制细胞增殖和侵袭，过表达COX17则促进上述表型。分子对接提示DML与COX17之间可能存在疏水接触、氢键和盐桥等相互作用，对接评分为−6.8 kcal/mol；分子动力学模拟显示DML-COX17复合物在50 ns模拟过程中整体趋于相对稳定。COX17过表达可部分减弱DML对MGC-803细胞增殖和侵袭的抑制作用（P < 0.01）。结论：DML可抑制MGC-803细胞增殖和侵袭并下调COX17蛋白表达，COX17可能参与DML对胃癌细胞恶性表型的调控。

Objective: To investigate the differences in proliferation and osteogenic differentiation capacities between rat dental socket stem cells (DSCs) and periodontal ligament mesenchymal stem cells (PDLSCs), thereby providing a experimental basis for elucidating the functional characteristics of these two distinct sources of mesenchymal stem cells. Methods: This study was approved by the Institutional Animal Care and Use Committee. Twenty-four 6- to 8-week-old male Sprague-Dawley rats were divided into four groups (n = 6 per group) based on the time points of 0, 1, 3, and 7 days post-extraction by the random number table method. A rat alveolar socket model was established by extracting the left maxillary molars. Hematoxylin and eosin (H&E) staining was performed to observe the histomorphological changes in the alveolar sockets at the specified time points. Immunohistochemistry was used to detect the expression and distribution of the p75 neurotrophin receptor (P75NTR). Based on the staining results, an optimal time point was selected to harvest early healing tissues from the alveolar sockets. DSCs were cultured using a combination of tissue block and enzymatic digestion methods. Concurrently, PDLSCs were isolated from the extracted molars using identical culture protocols. The surface markers CD44, CD45, CD90, and P75NTR were analyzed via flow cytometry. Cell proliferation and clonogenic potential were compared using the Cell Counting Kit-8 (CCK-8) assay and colony formation assays, respectively. After adipogenic induction, Oil Red O staining was conducted to observe lipid droplet formation. Following osteogenic induction, alkaline phosphatase (ALP) activity and alizarin red S (ARS) staining were utilized to evaluate ALP expression and mineralized nodule formation, respectively. Furthermore, the mRNA and protein expression levels of osteogenesis-related factors, including ALP and Runt-related transcription factor 2 (RUNX2), were quantified to comprehensively assess the osteogenic differentiation potential of both cell types. Results: H&E staining revealed that the alveolar sockets were filled with erythrocytes 0 and 1 days post-extraction. By day 3, significant fibroblastic connective tissue proliferation was observed within the sockets, and bone formation increased markedly by day 7. Immunohistochemical analysis showed sparse P75NTR-positive staining limited to the inner socket wall 0 and 1 days post-extraction. On day 3, P75NTR was distributed throughout the fibrous connective tissue of the socket, with slight staining on the bone walls. By day 7, the receptor was expressed in the fibrous connective tissue at the edges of the trabeculae. Consequently, day 3 post-extraction was selected as the optimal time point for DSC isolation. Both PDLSCs and DSCs exhibited similar morphologies in vitro, characterized by high expression of mesenchymal stem cell markers (CD90, CD44) and P75NTR, alongside low expression of the hematopoietic marker CD45. CCK-8 assays demonstrated that the proliferation capacity of the DSCs was significantly higher than that of the PDLSCs (P < 0.05), accompanied by a greater colony formation rate (P < 0.001). Both cell types possessed adipogenic differentiation potential, as evidenced by vacuolar structures in the cytoplasm. Regarding osteogenesis, the DSCs exhibited a larger area and higher density of ALP staining (P < 0.001). ARS staining indicated that both cells formed orange-red mineralized nodules; however, the DSCs produced significantly more calcified nodules (P < 0.0001). Additionally, the mRNA and protein expression levels of ALP and RUNX2 were notably elevated in the DSCs compared with the PDLSCs (all P < 0.05). Conclusion Rat DSCs can be stably cultured in vitro. Compared with PDLSCs, DSCs exhibited superior capabilities in terms of proliferation, colony formation, and osteogenic differentiation.

ObjectiveTo systematically elucidate the accumulation characteristics of secondary metabolites in the stems and leaves of Panax ginseng with different stem colors. MethodsUltra-high-performance liquid chromatography-triple quadrupole-tandem mass spectrometry （UHPLC-QqQ-MS） was employed to determine the of 22 ginsenosides in the stems and leaves of 2- to 5-year-old P. ginseng plants with green and purple stems. Principal component analysis （PCA）， orthogonal partial least squares-discriminant analysis （OPLS-DA）， and one-way analysis of variance （ANOVA） were performed to explore the distribution patterns of ginsenosides from three dimensions： tissue distribution， growth duration， and stem color. Results① Tissue distribution： Leaves served as the primary organ for ginsenoside accumulation， exhibiting significantly higher total ginsenoside content than stems， which indicated distinct tissue-specific distribution of ginsenosides. ② Growth duration： Ginsenoside levels in stems generally peaked in the 2-year-old plants before stabilizing， while those in leaves displayed a declining-rebounding pattern， indicating that the 2-year-old plants （harvest stage） was a critical time point for the resurgence of leaf ginsenosides. ③ Stem color： A stage-specific correlation was observed between stem color and ginsenoside accumulation. In stems， the early-growth stage （2-year-old） of purple-stemmed plants exhibited higher content of specific ginsenosides （e.g.， ginsenoside Rk₁ and notoginsenoside R₁）， which may be associated with its stronger early-stage stress resistance. In leaves， the content of core ginsenosides （e.g.， ginsenosides Re and Rd） in 5-year-old plants with green stems showed a surpassing trend， demonstrating higher potential of resource development. ConclusionThe accumulation of ginsenosides in P. ginseng stems and leaves is multidimensionally regulated by tissue type， growth duration， and stem color phenotypes. Purple-stemmed plants exhibit early-stage specific ginsenoside accumulation and stress resistance potential， whereas green-stemmed plants are more advantageous for core leaf ginsenoside development at the harvest stage. The findings confirm that aboveground stem color can serve as a biomarker for directed breeding and efficient resource utilization of P. ginseng.

ObjectiveTo summarize the research results on the toxic mechanism and the relevant regulatory policies at home and abroad of pyrrolizidine alkaloids （PAs）， the main toxic components， in Senecionis Scandentis Herba， thereby providing insights into the clinical use and scientific regulation of Senecionis Scandentis Herba. MethodsMultiple Chinese and English databases including PubMed， ScienceDirect， Elsevier， China national knowledge infrastructure （CNKI）， Wanfang Data， and VIP were searched， with "Senecio，" "PSenecio scandens，" and "pyrrolizidine alkaloids" as search terms. The relevant articles published from 1959 to 2025 were retrieved and analyzed， and 79 articles were finally selected for review. ResultsThe chemical components of Senecionis Scandentis Herba include alkaloids， flavonoids， volatile oils， sesquiterpenes， jacaranone derivatives， and organic acids， among which alkaloids are the most toxic components， followed by jacaranone derivatives. PAs are metabolized into highly active pyrrole derivatives in the liver， which can cause serious adverse reactions such as sinusoidal obstruction syndrome and DNA damage. The content of PAs varies significantly due to the origin， harvest period， and medicinal parts. There have been reports of clinical liver injury caused by preparations containing Senecionis Scandentis Herba， and some preparations have a daily intake of PAs exceeding the international safety threshold. Currently， international organizations have set limited standards for PAs， while China only controls the content of adonifoline， and the supervision is not yet perfect. ConclusionAlthough Senecionis Scandentis Herba has medicinal value， its PAs have significant toxicological properties. This is a problem that cannot be ignored and needs to be overcome in the use of Senecionis Scandentis Herba. Therefore， it is necessary to strengthen the quality control of raw materials， establish a more comprehensive limited standard for PAs， and optimize the medication strategy in combination with traditional Chinese medicine theory to ensure the safety of clinical medication.