ObjectiveTo investigate the therapeutic effect of Astragali Radix-mediated changes in gut microbiota on treating type 2 diabetes （T2DM）. MethodsA 12-week randomized， placebo-controlled clinical trial enrolled eighty patients with newly diagnosed type 2 diabetes and poor glycemic control in the Qi deficiency type. All patients received insulin therapy. The observation group （40 cases） was administered with Astragali Radix Granules， while the control group （40 cases） received a placebo. Both treamtents were taken orally twice daily. Changes in gut microbiota were assessed by 16s rDNA sequencing. Serum glucagon-like peptide-1 （GLP-1） levels were measured using enzyme-linked immunosorbent assay （ELISA）. Glucose metabolism indicators including fasting blood glucose （FPG）， 2-hour postprandial blood glucose （2 h PG），glycated albumin（GA）， and glycated hemoglobin （HbA1c） were evaluated. Pancreatic function was evaluated using fasting C-peptide （FCP）， 2-hour postprandial C-peptide （2 h CP）， and C-peptide area under the curve （AUC_cp）. Traditional Chinese medicine （TCM） syndrome scores， clinical efficacy， and safety indicators were also observed. ResultsIn terms of glucose metabolism indicators， compared with the baseline， both groups exhibited significantly lower FPG， 2 h PG， GA and HbA1C （P<0.01），while FCP， 2 h CP and AUC_cp were significantly higher （P<0.01）. Compared with the control group after the treatment， the observation group showed significantly lower FPG， 2 h PG， GA and HbA1C（P<0.05， P<0.01），and significantly higher FCP， 2 h CP and AUC_cp （P<0.05， P<0.01）， indicating that Astragali Radix can improve glucose metabolism. In terms of the diversity of gut microbiota， no significant differences were detected in the Chao1， Shannon and Simpson indexes of the two groups compared with their respective baselines. However， compared with the post-treatment control group， the observation group demonstrated significant increases in the Chao1， Shannon and Simpson indexes （P<0.05， P<0.01）. The β-diversity analysis showed significant separation in gut microbiota composition before and after treatment in both groups， indicating that Astragali Radix can significantly alter the structure and improve the diversity of gut microbiota. At the phylum level， compared with the baseline， both groups showed a significant increase in the relative abundance of Bacteroidota（P<0.01）. The relative abundance of the potentially harmful phylum Proteobacteria was significantly lower in the observation Group after treatment （P<0.01）. Compared with the post-treatment control group， the observation group had a significantly higher relative abundance of Bacteroidota（P<0.01）. No significant difference was found in Firmicutes/Bacteroidota （F/B） ratio between the two groups after treatment， and other phyla showed no significant differences. At the genus level， compared with the baseline， the observation group exhibited a significant increase in Bacteroides （P<0.01） and a significant decrease in Escherichia-Shigella （P<0.01）， whereas no significant difference was seen in the control group . Compared with the control group after treatment， the observation group after treatment had a significantly higher relative abundance of Bacteroides （P<0.01）. No significant differences were seen in other genera. Linear discriminant analysis （LDA） identified potential characteristics taxa： in the observation group， Bacteroidota at the phylum level and Bacteroides and Dubosiella at the genus level， in the control group， Proteobacteria at the phylum level as well as Barnesiella and Staphylococcus at the genus level. Correlation analysis based on a heatmap revealed that GLP-1 levels were positively correlated with Firmicutes， F/B ratio and Fusobacterium， and negatively correlated with Bacteroidota， Proteobacteria， Bacteroides and Escherichia-Shigella. In terms of clinical efficacy， compared with the control group， the total effective rate of the observation group was significantly higher （P<0.05）. Compared with the baseline， the scores for shortness of breath， fatigue， weakness， spontaneous sweating and reluctance to speak significantly decreased in both groups （P<0.01）. Compared with the control group after treatment， the score for weakness was significantly lower in the observation group （P<0.01），indicating that Astragali Radix could improve clinical symptoms and alleviate weakness symptoms. In terms of safety， compared with the baseline， alanine aminotransferase （ALT） levels significantly decreased in both groups （P<0.05，P<0.01），indicating that Astragali Radix did not induce any significant abnormalities in liver and kidney functions. ConclusionAstragali Radix demonstrates the potential to significantly improve the gut microbiota environment in patients of newly diagnosed type 2 diabetes with Qi deficiency. The therapeutic effect may contribute to glycemic control， possibly mediated by an elevation in GLP-1 level. These findings may support its further clinical investigations and potential applications.

ObjectiveTo investigate the role of runt-related transcription factor 3 （RUNX3） in transforming growth factor-β₁ （TGF-β₁）-induced activation of mouse primary pulmonary fibroblasts （PFs）， and its effects on fibroblast activation protein （FAP） expression， cell proliferation， and collagen synthesis. MethodsPFs were isolated from C57BL/6 mice and cultured. A RUNX3 knockdown model was established using small interfering RNA （siRNA）. Cells were assigned to the control group （Control）， TGF-β₁-treated group （TGF-β₁）， negative control group （TGF-β₁+siRNA-NC）， and RUNX3-silenced group （TGF-β₁+si-RUNX3）. In addition， a RUNX3 overexpression rescue experiment was performed based on TGF-β₁ stimulation. Protein and mRNA levels of RUNX3， FAP， and typeⅠcollagen （COL1A1） were measured by Western blot and reverse transcription quantitative real-time PCR （RT-qPCR）. Cell proliferation was assessed using CCK-8 and EdU assays. Co-expression of COL1A1 and FAP was examined by double immunofluorescence staining. ResultsCompared with the Control group， RUNX3， FAP， and COL1A1 expression levels were upregulated in PFs in the TGF-β₁ group （P<0.01）. The CCK-8 assay showed that the absorbance value was reduced in the RUNX3 knockdown group compared with the negative control group （P<0.01）. Consistently， the EdU assay demonstrated a lower proportion of EdU-positive cells in the RUNX3 knockdown group than in the negative control group （P<0.01）. Immunofluorescence double staining revealed decreased fluorescence intensities of COL1A1 and FAP in the RUNX3 knockdown group relative to the negative control. Under RUNX3 overexpression conditions， these fluorescence signals exhibited a partial rebound （P<0.01）. ConclusionRUNX3 in TGF-β1-induced PFs may promote cell proliferation and collagen synthesis by positively regulating FAP expression. Targeting the RUNX3/FAP axis may represent a potential therapeutic strategy for pulmonary fibrosis.

Objective:To systematically evaluate the global disease burden of neonatal sepsis and other neonatal infections（NSNIs），providing scientific basis for their prevention and control.Methods:Using the Global Burden of Disease（GBD）2021 database，this article calculated the incidence，mortality，and age-standardized rates for NSNIs. Trends were evaluated with Joinpoint regression model，and compared at different socio-demographic index（SDI）levels.Results:From 1990 to 2021，the global age-standardized incidence rate（ASIR）of NSNIs decreased from 78.98 to 62.70 per 100 000 with an with average annual percentage change（AAPC）of -0.73%（ P<0.01）. The age-standardized mortality rate（ASMR）declined from 4.77 to 3.76 per 100 000 with an AAPC of -0.76%（ P<0.01）. In particular，the disease burden was consistently higher among male neonates. Low birth weight was the primary risk factor globally，followed by preterm birth. Regions with lower SDI levels exhibited higher ASIR and ASMR，and household solid fuel air pollution contributed more to NSNIs-related mortality. Conclusion:Although the overall disease burden of NSNIs has declined，male neonates and low-SDI regions still face substantial challenges. Continuous efforts to improve air quality are warranted，and low-SDI regions should further strengthen healthcare infrastructure to enhance diagnostic and treatment quality.

Objective To investigate the value of first platelet count(PLT)to respiratory rate(RR)ratio(PLT/RR)on admission in the diagnosis and prognosis of secondary sepsis in pneumonia patients.Methods A total of 100 patients with pneumonia admitted to the First Affiliated Hospital of Army Medical University from May 2023 to August 2024 were selected as subjects.According to the presence or absence of pneumonia sepsis,they were divided into sepsis group(63 cases)and non-sepsis group(37 cases).The secondary sepsis in pneumonia pa-tients were followed up continuously for 30 d.According to the survival situation,they were divided into sur-vival group(54 cases)and death group(9 cases).PLT in peripheral blood was measured,vital signs were col-lected on the first day of admission,and PLT/RR was calculated.The receiver operating characteristic curve was used to evaluate the predictive value of PLT,RR and PLT/RR for secondary sepsis in pneumonia pa-tients.The systemic inflammatory response syndrome(SIRS)score,modified early warning score(MEWS)and quick sequential organ failure assessment(qSOFA)score on admission were calculated,and the clinical predictive value of SIRS score,MEWS and qSOFA score was compared.Results PLT and PLT/RR in sepsis group were lower than those in non-sepsis group(P<0.000 1),RR was higher than that in non-sepsis group(P<0.01).The area under the curve(AUC,95%CI)of PLT,RR and PLT/RR were 0.858(0.785-0.931),0.693(0.589-0.796)and 0.902(0.843-0.962),respectively.The optimal cut-off values were 146.5×109/L,20.5 per minute and 8.075,respectively.The specificity were 8.1%,83.8%and 2.7%,respec-tively.The sensitivity was 33.3%,50.8%and 30.2%,respectively.Compared with the non-sepsis group,the sepsis group had a significantly higher SIRS score(P<0.001),a significantly lower MEWS(P<0.000 1),and no significant difference in qSOFA score between the two groups(P>0.05).The AUC(95%CI)of SIRS score,MEWS and qSOFA score in predicting secondary sepsis in pneumonia patients were 0.717(0.616-0.818),0.748(0.650-0.846)and 0.505(0.389-0.622),respectively.The optimal cut-off values were 4.5,2.5 and 1.5 points,respectively.The specificity were 91.9%,2.7%and 100.0%,respectively.The sensitivity was 42.9%,33.3%and 6.3%,respectively.PLT and PLT/RR in death group were lower than those in sur-vival group(P<0.05),RR was higher than that in survival group(P<0.05).Secondary sepsis in pneumonia patients were followed up for 30 d,Kaplan-Meier survival curve showed that patients with PLT≤138.5×109/L had a lower 30 d survival rate(P=0.007 8).Patients with RR>24.5 per minute had a lower 30 d sur-vival rate(P=0.016 1).Patients with PLT/RR≤6.375 had a lower 30 d survival rate(P=0.002 3).Conclu-sion PLT/RR can be used as a biological index to predict secondary sepsis in pneumonia patients,which is better than SIRS score,MEWS and qSOFA score,and the prognosis of secondary sepsis in pneumonia patients with low PLT/RR is worse.

Liquid biopsy,as an emerging minimally invasive early detection method for tumors,has shown great potential;however,several challenges limit its application in tumor diagnosis.Tetrahedral framework nucleic acids(tFNAs)have garnered significant attention in the biomedical field due to their structural stabili-ty,programmability,and superior intracellular endocytosis and tissue penetration capabilities.These properties make tFNAs an ideal candidate for constructing advanced biosensing platforms for liquid biopsy applications.tFNAs significantly enhance the binding efficiency of circulating tumor cells(CTCs),circulating tumor DNA(ctDNA),and extracellular vesicles(EVs),thereby improving the sensitivity and detection capability of the liquid biopsy biosensing platform.This review provides a comprehensive overview of tFNAs-based biosensors in the liquid biopsy field.It elaborates on the synthesis,characteristics,and applications of tFNAs in detecting CTCs,ctDNA,and EVs.Additionally,it discusses the diverse strategies and advantages of tFNAs in biosens-ing applications,highlighting how these features significantly enhance the performance and reliability of bio-sensors.Finally,this review addresses the current challenges faced by tFNAs in liquid biopsy and explores their future prospects,aiming to facilitate early screening,precise diagnosis,and integrated diagnostic-treat-ment approaches for tumors.

Objective:To investigate the effect of oxidized-low density lipoprotein (ox-LDL) on contrast-induced renal tubular epithelial cell apoptosis and its mechanism.Methods:Human renal proximal tubular epithelial HK-2 cells were cultured in vitro and divided into four groups using the random number table method, including a control group, an ox-LDL group (50 μg/ml ox-LDL), an iohexol group (100 mg I/ml iohexol) and an ox-LDL+iohexol group (50 μg/ml ox-LDL+100 mg I/ml iohexol). Apoptosis rates were detected using the in situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay. Western blotting was used to detect the level of apoptosis by evaluating the presence of cleaved cysteine aspartic acid specific protease-3 (cleaved Caspase-3) protein. Mitochondrial membrane potential was detected using the JC-1 method. Mitochondrial/cytoplasmic cytochrome C (Cyt C) levels were detected by Western blotting to assess mitochondrial damage. Western blotting was used to detect the levels of the mitochondrial fission-related dynamin-related protein 1 (Drp1) and the mitochondrial fusion-related optic atrophy protein 1 (OPA1) to evaluate mitochondrial fusion/fission. Independent sample t test and one-way analysis of variance were used for data analysis. Results:The apoptosis rate [(30.12±3.19)%] and the relative expression of cleaved Caspase-3 protein (0.34±0.07) in the iohexol group were higher than those in the control group [(4.77±1.68)%, 0.23±0.05] ( P<0.05, 0.01). The apoptosis rate [(48.81±4.96)%] and the relative expression of cleaved Caspase-3 protein (0.53±0.05) in the ox-LDL+iohexol group were higher than those in the iohexol group (both P<0.01). The mitochondrial membrane potential (1.61±0.15) and mitochondrial/cytoplasmic Cyt C ratio (1.09±0.14) in the iohexol group were lower than those in the control group (6.15±0.52 and 3.09±0.45) (both P<0.01). The mitochondrial membrane potential (0.27±0.01) and the mitochondrial/cytoplasmic Cyt C ratio (0.24±0.04) in the ox-LDL+iohexol group were lower than those in the iohexol group (both P<0.01). The relative expression of Drp1 protein in the iohexol group (0.49±0.05) was higher than that in the control group (0.29±0.03), the relative expression of long OPA1 protein (0.24±0.03) was lower than that of the control group (0.40±0.03) (both P<0.01). The relative expression of Drp1 protein in the ox-LDL+iohexol group (0.64±0.02) was higher than that in the iohexol group, the relative expression of long OPA1 protein (0.07±0.02) was lower than that in the iohexol group (both P<0.01). Conclusions:ox-LDL can exacerbate contrast-induced renal tubular epithelial cell apoptosis, and its mechanism may be due to an imbalance in mitochondrial fusion and division caused by the contrast agent, leading to the increase mitochondrial damage.

Objective:To analyze the incidence and mortality of pancreatic cancer in China from 1992 to 2021, and to explore the effects of age, period, and cohort on pancreatic cancer incidence and mortality.Methods:Data from the Global Burden of Disease Study (GBD) 2021 database were used to analyze the incidence and mortality of pancreatic cancer in China from 1992 to 2021. The Joinpoint software was applied to analyze the time trends of standardized incidence and mortality rates, and to calculate the average annual percentage change. An age-period-cohort model was constructed to analyze the effects of age, period, and birth cohort on the trends of pancreatic cancer incidence and mortality. The disease burden of pancreatic cancer deaths attributed to risk factors such as hyperglycemia and smoking was analyzed.Results:In 2021, the incidence of pancreatic cancer in China was 8.34/100 000, and the mortality rate was 8.41/100 000, representing increases of 150.45% and 145.19%, respectively, compared to 1992 (3.33/100 000 and 3.43/100 000) . By sex, the incidence (9.93/100 000) and mortality (9.91/100 000) rates in males in 2021 were higher than those in females (6.68/100 000 and 6.83/100 000) . From 1992 to 2021, the standardized incidence and mortality rates of pancreatic cancer in China showed upward trends, with average annual increases of 0.80% and 0.62%, respectively, both of which were statistically significant (both P<0.001) . Age effect results indicated a general increasing trend in pancreatic cancer incidence, with a steady rise in the 15-49 age group, a sharp increase after the age of 50, and a peak in the over 85 age group at 68.64/100 000. The mortality rate showed a slow increase in the 15-79 age group, with a marked rise and peak in the 80-84 age group at 196.51/100 000. Period effect results showed an overall upward trend in the period relative risk ( RR) for pancreatic cancer incidence, with the highest risk in 2017-2021 ( RR=1.09, 95% CI: 1.05-1.13, P=0.012) , compared to the reference period 2002-2006 ( RR=1) . The RR for pancreatic cancer mortality showed a fluctuating trend, with the highest risk in 2012-2016 ( RR=1.60, 95% CI: 1.07-2.38, P=0.021) , compared to the reference period 2002-2006 ( RR=1) . The results of cohort effect showed that the incidence and mortality risk of pancreatic cancer in China generally increased with the increase of years. With the 1952-1956 birth cohort as the reference cohort ( RR=1) , the incidence ( RR=1.18, 95% CI: 0.99-1.40, P=0.032) and mortality ( RR=1.63, 95% CI: 0.12-11.53, P=0.042) risk of pancreatic cancer were the highest in the 1987-1991 birth cohort, and showed decreasing trends after the 1992-1996 birth cohort. The proportion of pancreatic cancer deaths attributable to high blood glucose showed an increasing trend, while those attributable to smoking showed a decreasing trend. Conclusions:From 1992 to 2021, the standardized incidence and mortality rates of pancreatic cancer in China have continued to rise, with males having higher incidence and mortality rates than females. Age, period, and cohort all significantly influence the trends in pancreatic cancer incidence and mortality. The trend in pancreatic cancer deaths attributable to high blood glucose is increasing.

Objective To analyze the medication rules of Chinese herbal concentrated-granule for the treatment of hypertension nationwide using data mining and knowledge graph methods,thus to provide evidence for expanding its application in treating hypertension.Methods From January 2022 to March 2023,Chinese herbal concentrated-granule prescriptions for hypertension prescribed by traditional Chinese medicine experts nationwide were collected.Microsoft Excel was used to analyze the frequency,properties and flavors,meridian tropism,and efficacy categories of the medicinals.Hierarchical clustering was applied for cluster analysis,and the Neo4j graph database was utilized to construct an information knowledge graph illustrating the relationships between regions and medicinals.Results A total of 2 600 Chinese herbal concentrated-granule prescriptions were included,involving 370 medicinals.The top six frequently-used medicinals were Poria(Fuling),Glycyrrhizae Radix et Rhizoma(Gancao),Atractylodis Macrocephalae Rhizoma(Baizhu),Citri Reticulatae Pericarpium(Chenpi),Paeoniae Radix Alba(Baishao),and Angelicae Sinensis Radix(Danggui).The properties of the medicinals were mainly warm and mild,and their flavors were usually sweet,pungent,and bitter.The medicinals frequently have the meridian tropism of the spleen,lung,and liver meridians.Hierarchical clustering yielded seven clusters.The information knowledge graph of region-medicinals relationships revealed that medicinals used in five or more regions were Baishao,Baizhu,Chenpi,Pinelliae Rhizoma(Banxia),Fuling,Gastrodiae Rhizoma(Tianma),Bupleuri Radix(Chaihu),Chuanxiong Rhizoma(Chuanxiong),Salviae Miltiorrhizae Radix et Rhizoma(Danshen),Danggui,Gancao,and Astragali Radix(Huangqi).Conclusion Chinese herbal concentrated-granule for hypertension usually consist of tonifying medicinals,with sweet and warm properties,and having the meridian tropism of the spleen meridian.And the medicinals composed of the prescriptions often have the actions of calming the liver and suppressing yang,strengthening the spleen and removing dampness,and nourishing the liver and kidney.

Objective To investigate the epidemiological characteristics and risk factors of non-alcoholic fatty liver disease in Jincheng between 2015 and 2020. Methods Clinical data of 8,578 medical check-ups at Physical Examination Center of ou hospital from January 2015 to December 2020 were retrospectively selected. The prevalence of non-alcoholic fatty liver disease in the last 5 years was recorded, and Logistic regression was utilized to identify the risk factors for the development of non-alcoholic fatty liver disease. Results The overall prevalence of non-alcoholic fatty liver disease in Jincheng was 14.57% in 2015-2020. The prevalence of non-alcoholic fatty liver disease was higher in men than in women (16.99% vs 10.98%) and highest in the 40-59 age group (18.76%). No statistical difference was reported in blood urea nitrogen (BUN) and serum creatinine (Scr) between groups (P>0.05), while statistical difference was found in diabetes, hypertension, body mass index (BMI), waist circumference, weekly exercise frequency, daily vegetable intake, triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (ALT) and uric acid (UA) between two groups (P<0.05). Multivariate Logistic regression analysis denoted that BMI (OR=2.794, 95% CI: 1.745-4.550), waist circumference (OR=2.586, 95% CI: 1.585-4.299), diabetes (OR=0.644, 95% CI: 1.425-2.781), hypertension (OR=1.479, 95% CI: 1.121-2.290), weekly exercise ≥6h (OR=0.617, 95% CI: 0.519-0.709), daily vegetable intake ≥300g (OR=0.590, 95% CI: 0.467-0.652), TG (OR=1.481, 95% CI: 1.122-1.996), TC (OR=1.562, 95% CI:1.143-2.135), LDL-C (OR=1.440, 95% CI: 1.139-2.048), HDL-C (OR=0.656 , 95% CI: 0.587-0.783) , ALT (OR=1.591, 95% CI: 1.056-2.183), and UA (OR=1.412, 95% CI: 1.009-1.887) were risk factors for non-alcoholic fatty liver disease (P<0.05) . Conclusion The prevalence of non-alcoholic fatty liver disease in Jincheng City from 2015 to 2020 is 14.57%, the prevalence of males is higher than that of females, and the prevalence rate is the highest in the 40-59 age group. Moreover , diabetes mellitus , hypertension , BMI , waist circumference , weekly exercise , daily vegetable intake , serum TG, TC, LDL-C, HDL-C, ALT, and UA are all associated with the risk of the disease.

Objective: To investigate the effect of targeted silencing of DNA methyltransferase 3A(DNMT3A) on collagen deposition, proliferation and migration activity of mouse lung fibroblasts(PFs). Methods: In order to ensure the proliferation and migration activity of primary fibroblasts, the lung tissues of neonatal C57 suckling mice were taken, PFs were extracted after being sheared, and the morphology was observed and identified under the microscope. PFs cells were activated by 5 ng/ml TGF-β1for 24 h after cell attachment, and DNMT3A silencing model was constructed by small interfering RNA; The experiment was divided into control group, TGF-β1group, TGF-β1+ siRNA-NC group and TGF-β1+ siRNA-DNMT3A group. The protein expressions of DNMT3A, α-smooth muscle actin(α-SMA) and Collagen Ⅰ were detected by Western blot; Real time quantitative reverse transcription polymerase chain reaction(RT-qPCR) was used to detect the mRNA expression changes ofDNMT3A,α-SMAandCollagenⅠ. The proliferation ability of PFs was detected by CCK-8 and EdU staining; the migration ability of PFs was detected by scratch test and Transwell migration test. Results: Compared with the control group, TGF-β1induced the increase of DNMT3A in the activated PFs cell group(P<0.01), the protein and mRNA levels of fibrosis and proliferation related indicators α-SMA and Collagen Ⅰ also increased(allP<0.05), and the proliferation and migration ability of PFs increased(allP<0.000 1). Compared with the siRNA-NC group, the protein expression levels of DNMT3A(P<0.000 1) and related indicators α-SMA(P<0.01) and Collagen Ⅰ(P<0.01) significantly decreased in the DNMT3A silencing group by Western blot, and the mRNA levels ofDNMT3A,α-SMAandCollagenⅠby RT-qPCR also decreased(allP<0.001), and the proliferation(P<0.01) and migration ability(P<0.05) of PFs cells decreased compared with the control group. Conclusion Silencing DNMT3A can inhibit the deposition of collagen and the proliferation of PFs. DNMT3A can promote the proliferation and migration of PFs, and then promote the activation of PFs and the development of pulmonary fibrosis. This process may be regulated by DNA methylation modification.