ObjectiveTo investigate the molecular mechanisms by which Wenyang Jiedu granules （WYJD） alleviate influenza A virus （IAV）-induced pneumonia based on single-cell transcriptome sequencing. MethodsThirty female BALB/c mice were randomly divided into a blank control group （Control）， IAV group， and WYJD low-， medium-， and high-dose groups （WYJD-L， WYJD-M， WYJD-H； 2.925， 5.85， 11.7 g·kg^-1， n=6）. Except for the Control group， all other groups were intranasally inoculated with IAV subtype H1N1 （A/PR/8/34） to establish an infection model. Two hours after modeling， drug administration was initiated and continued for 5 consecutive days， with daily monitoring of body weight and general condition. On day 6， mice were sacrificed and samples were collected. Lung index was calculated， and histopathological examination of lung tissue was performed. Lung tissues from the Control， IAV， and WYJD-H groups were subjected to single-cell transcriptome sequencing （n=3）， focusing on type I alveolar epithelial cells （AT1） to analyze changes in gene expression and signaling pathways. Western blot was used to detect the expression changes of relevant proteins to validate the single-cell sequencing results. ResultsCompared with the Control group， the IAV group exhibited significantly decreased body weight （P<0.05） and significantly increased lung index （P<0.05）. Compared with the IAV group， all WYJD-treated groups exhibited significantly increased body weight （P<0.01） and significantly decreased lung index （P<0.01）. Single-cell sequencing analysis revealed that WYJD inhibited overactivation of interferon and inflammatory signaling pathways in AT1 cells after IAV infection， including interferon-γ response， interferon-α response， tumor necrosis factor-α/nuclear factor-κB （TNF-α/NF-κB）， and interleukin-6/Janus kinase/signal transducer and activator of transcription 3 （IL-6/JAK/STAT3） pathways. Compared with the Control group， the number of AT1 cells in the IAV group showed a decreasing trend. Compared with the IAV group， the WYJD-H group showed an increasing trend， although neither difference was statistically significant. Further analysis of AT1 cell subpopulation gene expression showed that， compared with the Control group， the IAV group exhibited increased expression of pro-apoptotic genes FAS cell surface death receptor （FAS） and cyclin-dependent kinase inhibitor 1A （CDKN1A）， a significant increase in tumor protein p53 （Tp53） expression （P<0.05）， and significant decreases in expression of the AT1 marker gene advanced glycosylation end-product-specific receptor （AGER） and membrane structural gene caveolin1 （CAV1） （P<0.05， P<0.01）. Compared with the IAV group， the WYJD-H group showed significantly decreased expression of FAS， CDKN1A， and Tp53 （P<0.05， P<0.01）， and significantly increased expression of AGER and CAV1 （P<0.05， P<0.01）. Regarding interferon response-related genes， compared with the Control group， the IAV group showed increased expression of interferon-stimulated gene 15 （ISG15）， interferon-induced protein with tetratricopeptide repeats 3 （IFIT3）， signal transducer and activator of transcription 2 （STAT2）， bone marrow stromal cell antigen 2 （BST2）， and C-X-C motif chemokine ligand 10 （CXCL10）， with a significant increase in 2′，5′-oligoadenylate synthetase-like protein 1 （OASL1） （P<0.05）. Compared with the IAV group， the WYJD-H group showed significantly decreased expression of all the above genes， with highly significant differences for ISG15， IFIT3， STAT2， BST2， and OASL1 （P<0.01）， and a significant difference for CXCL10 （P<0.05）. Among inflammation-related genes， compared with the Control group， the IAV group showed significantly increased expression of intercellular adhesion molecule 1 （ICAM1）， tumor necrosis factor alpha-induced protein 3 （TNFAIP3）， keratin 8 （KRT8）， tumor necrosis factor receptor superfamily member 1A （TNFRSF1A）， and TNFRSF1B （P<0.01）， and increased expression of NFKBIA， a negative regulator of NF-κB （P<0.05）. Compared with the IAV group， the WYJD-H group showed significantly decreased expression of KRT8 and TNFRSF1B （P<0.05）， while ICAM1， NFKBIA， TNFAIP3， and TNFRSF1A showed decreasing trends without statistical significance. Western blot validation showed that， compared with the Control group， protein expression levels of ISG15， FAS， p53， and phosphorylated p65 （p-p65） in lung tissue of the IAV group were significantly increased （P<0.05， P<0.01）. Compared with the IAV group， the WYJD-H group showed significantly decreased expression of these proteins （P<0.05， P<0.01）. ConclusionWYJD may alleviate viral pneumonia by targeting gene expression in AT1 cells， inhibiting overactivated interferon and inflammatory signaling pathways after IAV infection， and downregulating pro-apoptotic signaling， thereby reducing alveolar epithelial injury.

Objective To analyze the proportion and clinicopathological characteristics of HER2-positive breast cancer patients with BRCA1/2 pathogenic variants, and their response to neoadjuvant anti-HER2 targeted therapy. Methods The clinicopathological data of 531 breast cancer patients with germline BRCA1/2 pathogenic variants (201 with BRCA1 variants and 330 with BRCA2 variants) were analyzed. Results Among the 201 BRCA1 and 330 BRCA2 variants, 17 (8.5%) and 42 (12.7%) HER2-positive breast cancer cases were identified, respectively, accounting for 11.1% of all BRCA1/2-mutated breast cancers. Compared with BRCA1/2-mutated HR-positive/HER2-negative patients, HER2-positive patients did not present any significant differences in clinicopathological features; however, compared with triple-negative breast cancer patients, HER2-positive patients had a later onset age and lower tumor grade. Among the 17 patients who received neoadjuvant anti-HER2 targeted therapy, 10 cases achieved pCR (58.8%), whereas 7 cases did not (41.2%). Conclusion HER2-positive breast cancer accounts for more than 10% of BRCA1/2-mutated patients. Approximately 40% of these patients fail to achieve pCR after neoadjuvant targeted therapy. This phenomenon highlights the possibility of combining anti-HER2 targeted agents with poly (adenosine diphosphate-ribose) polymerase inhibitors.

Objective:To assess the predictive value of acute liver failure (ALF) for sepsis-free survival (SFS) in burn patients and to identify associated risk factors.Methods:A retrospective cohort study was conducted on burn patients meeting inclusion criteria from the 2014 Kunshan aluminum dust explosion disaster (August 2, 2014 - April 13, 2015). Eligible patients were stratified into ALF and non-ALF groups based on the development of ALF. Demographic characteristics, total burn surface area, organ dysfunction, time to sepsis onset, and clinical outcomes were collected and compared between groups. Kaplan-Meier survival analysis and multivariate Cox regression were performed to assess the impact of ALF on SFS. A nomogram model was constructed for individualized risk prediction.Results:Among 185 enrolled patients (ALF group:21, non-ALF group:164), ALF incidence was 11.35%. The ALF group demonstrated higher mortality (85.71% vs. 34.15%, P<0.001) and SFS failure rates (100.00% vs. 61.59%, P<0.001) compared to non-ALF patients. Multivariate Cox analysis identified ALF as an independent sepsis predictor ( HR=1.68, 95% CI: 1.00-2.80, P<0.05). Time-dependent ROC analysis showed AUCs of 0.626, 0.714, 0.703, and 0.706 for SFS prediction at 2, 4, 8, and 12 weeks respectively. The nomogram model demonstrated that ALF combined with other parameters effectively predicted sepsis risk within 2-12 weeks post-injury. ALF development showed significant associations with concurrent organ dysfunction including acute kidney injury, acute heart failure, and acute respiratory distress syndrome (all P<0.001). A higher proportion of ALF patients received hemodialysis ( P<0.001) and pre-hospital central venous catheterization ( P=0.017). Conclusions:ALF independently predicts SFS failure and correlates strongly with poor prognosis in burn patients. Early ALF recognition and targeted interventions may facilitate sepsis risk stratification and precision prevention strategies.

BACKGROUND:Bone defects can directly affect the success rate and long-term stability of dental implants.Studies have shown that salidroside has the ability to promote the proliferation and differentiation of osteoblasts,but less is reported on its pathways related to osteogenic differentiation. OBJECTIVE:To investigate the effects of salidroside on the proliferation and differentiation of MC3T3-E1 cells and the expression of related genes and proteins through in vitro cell experiments. METHODS:Cell counting kit-8 test and alkaline phosphatase test were used to determine the optimal concentration of salidroside(0.5,1,5,10,and 50 μmol/L)in promoting the proliferation and differentiation of MC3T3-E1 cells.There were four groups in the experiment:control group,salidroside group,salidroside+LY294002 group,and LY294002 group,which were cultured with osteogenic induction solution,osteogenic induction solution containing 10 μmol/L salidroside,osteogenic induction solution containing 10 μmol/L salidroside+10 μmol/L LY294002,and osteogenic induction solution containing 10 μmol/L LY294002,respectively.The effects of salidroside and LY294002,an inhibitor of the PI3K/Akt signaling pathway,on the expressions of genes and proteins related to osteogenesis were observed. RESULTS AND CONCLUSION:Cell counting kit-8 assay and alkaline phosphatase assay showed that salidroside promoted the proliferation of MC3T3-E1 cells most significantly at 10 μmol/L.Compared with the control group,salidroside could promote mineralization,promote cell adhesion,reduce cell death,increase mRNA expression of Runx-2,osteocalcin and osteopontin(P<0.01),and increase protein expression of Runx-2 and p-Akt(P<0.01).However,the addition of LY294002 reversed the above results.These findings indicate that salidroside can promote the mineralization of MC3T3-E1 cells and the expression of osteogenesis-related genes and proteins,which may be related to the activation of PI3K/Akt signaling pathway.

OBJECTIVE: To investigate the effects of the combined Yiqi Huoxue Jiedu formula (YHJF) on intestinal microbiota in elderly patients with pulmonary-derived sepsis and identify potential microbial targets. METHODS: A prospective randomized double-blind controlled trial was conducted. Elderly patients with pulmonary infection-induced sepsis admitted to the emergency department of Guangdong Provincial Hospital of Traditional Chinese Medicine (TCM), intensive care unit (ICU) of Fangcun Hospital, and ICU of Daxuecheng Hospital, from November 2020 to October 2021 were enrolled and randomized into two groups. Both groups received conventional Western medicine treatment. The observation group additionally received YHJF (composed of 15 g of Panax ginseng, 9 g of Panax notoginseng, and 3 g of Rheum palmatum, dissolved in 50 mL warm water) orally or via nasogastric tube twice daily for 7 days; while the control group received a placebo. Clinical data and fresh fecal samples were collected before treatment and on days 5-7 of treatment. Intestinal microbiota diversity and structure were analyzed via 16S rDNA sequencing and bioinformatics [α diversity, β diversity, and linear discriminant analysis effect size (LEfSe)]. RESULTS: Fifty-five patients were included (29 in the control group, 26 in the observation group). There were no significantly differences in gender, age, comorbidities, and baseline sequential organ failure assessment (SOFA), acute physiology and chronic health evaluation II (APACHE II), acute gastrointestinal injury (AGI) classification score, and gastrointestinal failure (GIF) score between the two groups. Compared to the control group, the observation group showed significantly lower serum procalcitonin, APACHE II score, and greater reduction in GIF score by day 7. Thirty fecal samples were collected pre-treatment (baseline group), 29 post-treatment from the control group, and 26 from the observation group. Gut microbiota α diversity analysis revealed that Simpson index in the observation group and control group were significantly decreased compared to the baseline group [0.75 (0.53, 0.91), 0.81 (0.32, 0.91) vs. 0.88 (0.87, 0.89), both P < 0.05], but there was no significantly difference between the observation group and the control group. There were no significantly differences in Chao1, Ace, and Shannon indices among three groups. β diversity analysis indicated that distinct microbiota structures among three groups (R² = 0.096, P = 0.026). Species difference analysis showed that, at the phylum level, Firmicutes (53.69%), Actinobacteria (16.23%), Proteobacteria (15.39%), and Bacteroidetes (9.57%) dominated, with no significant intergroup differences. At the genus level, 38 taxa showed significant differences. Compared to the control group, the observation group exhibited increased Erysipelatoclostridium (P = 0.014) and Faecalibacterium (P = 0.013), and decreased Bacteroides (P = 0.009), Bilophila (P = 0.005), Eggerthella (P = 0.002), and Collinsella (P = 0.043). LEfSe analysis highlighted Lactobacillus salivarius, Erysipelatoclostridium, Collinsella, Cloacibacillus, and Bacteroides as key discriminators. CONCLUSION YHJF combined with conventional therapy alters intestinal microbiota structure in patients with elderly pulmonary-derived sepsis, with Bacteroides, Erysipelatoclostridium, and Collinsella identified as potential microbial targets.
Humans ; Gastrointestinal Microbiome/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Double-Blind Method ; Sepsis/drug therapy* ; Aged ; Prospective Studies ; RNA, Ribosomal, 16S/genetics* ; Male ; Female ; Panax notoginseng ; Rheum

Aim To investigate the effect of cumulative non-high density lipoprotein cholesterol/high density lip-oprotein cholesterol(non-HDLC/HDLC)exposure on atherosclerotic cardiovascular disease(ASCVD).Methods A prospective cohort study was conducted.A total of 50 777 employees of Kailuan Group who participated in three physical examinations in 2006-2007,2008-2009 and 2010-2011 were selected as the study subjects.Groups were divided into Q1,Q2,Q3 and Q4 according to the cumulative non-HDLC/HDLC exposure quartiles.Kaplan-Meier curve was used to calculate the cumulative incidence of ASCVD in different cumulative non-HDLC/HDLC groups,and Log-rank test was used to compare the differences among groups.Cox proportional risk model was used to analyze the effect of cumulative non-HDLC/HDLC exposure on ASCVD.Results The average follow-up was(10.19±2.21)years,and 5 003 new cases of ASCVD occurred.The cumulative incidence of ASCVD in groups Q1 to Q4 was 6.49％,8.71％,10.86％and 14.85％,respectively(Log-rank P＜0.01).Multivariate Cox regression analysis showed that compared with group Q1,the HR(95％CI)of ASCVD in groups Q2,Q3 and Q4 were 1.13(1.03～1.24),1.18(1.07～1.29),1.22(1.12～1.34),respectively;the HR(95％CI)of myocardial infarction were 1.15(0.87～1.53),1.44(1.10～1.88),1.67(1.29～2.17),respectively;the HR(95％CI)of revascularization were 1.21(0.99～1.49),1.31(1.07～1.60)and 1.49(1.22～1.81),respectively;the HR(95％CI)of ischemic stroke were 1.17(1.03～1.32),1.17(1.04～1.33)and 1.21(1.06～1.37),respectively;but the above association was not found when heart failure and atrial fibrillation were used as the outcome events.The restricted cubic spline showed that cumulative non-HDLC/HDLC values were line-arly associated with the risk of ASCVD.Conclusion Cumulative non-HDLC/HDLC exposure was positively associated with the risk of ASCVD.

Objective:To explore the impact of the stimulator of interferon genes(STING)-interferon regulatory factor 3(IRF3)pathway on the senescence of rapid pacing HL-1 myocytes.Methods:HL-1 cells were divided into five groups: the control group(HL-1 cells without any treatment), pacing group(HL-1 cells paced for 48 hours), STING siRNA group(HL-1 cells paced for 48 hours and transfected with STING siRNA), NC siRNA group(HL-1 cells paced for 48 hours and transfected with NC siRNA), and H151 inhibitor group(HL-1 cells paced for 48 hours with the addition of 1 μmol/L STING inhibitor H151). Mitochondrial membrane potential was assessed in control and pacing group cells, and mitochondrial MitoTracker and TFAM co-localization staining was performed on these cells.Cellular senescence was evaluated using β-galactosidase staining in each group, and the positive rate of cellular senescence was observed and calculated.Western blotting was employed to detect the expression levels of STING, IRF3, P-IRF3, P16, P21, and P53 proteins in all groups.Immunofluorescence was utilized to examine the expression distribution of STING and P21 across the various groups.ELISA was performed to measure the concentrations of interleukin(IL)-1β, IL-6, and IL-8 in the cell supernatants from each group as part of the senescence-associated secretory phenotype(SASP).Results:Compared with the control group, the ratio of mitochondrial JC-1 multimer to monomer was significantly decreased in the pacing group( t=16.42, P<0.05), the co-localization of mitochondrial MitoTracker and TFAM in the cells was significantly weakened, the proportion of cells with positive cellular senescence-associated β-galactosidase staining significantly increased in the pacing group, the expression levels of STING, P-IRF3/IRF3, P16, P21, and P53 proteins were significantly elevated in the pacing group, and the concentrations of IL-1β, IL-6, and IL-8 in the cell supernatants were markedly increased.Compared with the pacing group, the proportion of cells with positive cellular senescence-associated β-galactosidase staining decreased in the STING siRNA group and H151 inhibitor group ( F= 18.13, P<0.05), the expression levels of STING, P-IRF3/IRF3, P16, P21, and P53 were reduced in the STING siRNA group and H151 inhibitor group ( F=16.84, 26.56, 74.70, 31.80, 31.23, all P<0.05), and the concentrations of IL-1β, IL-6, and IL-8 in the cell supernatants decreased( F=197.80、1 339.00、1 308.00, all P<0.001). Conclusions:Rapid pacing of HL-1 cells can promote mtDNA release into the cytoplasm, activate the STING-IRF3 pathway, accelerate cellular senescence, and enhance the secretion of SASP.Inhibiting the expression of STING can delay the senescence induced by the rapid pacing of HL-1 cells and reduce SASP secretion.

Occupational pneumoconiosis remains the most common occupational disease in China, with occupational mineral dust exposure being its primary causative factor. Although national standards for online monitoring and early warning systems of coal mine dust concentrations have been established, national occupational health standards for rapid and online monitoring of dust concentration and particle size distribution in other industries are still limited. Among dust concentration sensor technologies, the light scattering method is the preferred choice for online dust monitoring owing to its wide measurement range and low cost. The beta-ray absorption method is mature but highly sensitive to humidity. The electrostatic induction method offers high sensitivity, simple structure, and low maintenance costs but exhibits high errors in low-concentration dust monitoring. The tapered element oscillating microbalance method is highly sensitive but costly. Multi-sensor data fusion technology can improve monitoring reliability, however, mature domestic products are not yet available. For monitoring dust particle size distribution, sieving and sedimentation methods are cumbersome. The aerodynamic method shows broad prospects in the online monitoring of respirable dust but has obvious measurement errors for larger dust particles. The use of optical measurement method is limited by dust morphology and is not suitable for monitoring coal dust particle size distribution. The electrical mobility method is primarily applicable to submicron dust. Future research should focus on promoting the application of monitoring technology for respirable dust particle size distribution in online monitoring of industrial dust. By integrating Internet of Things, data mining, and artificial intelligence technologies, along with multi-sensor data fusion and numerical simulation, dust concentration prediction models can be established to achieve accurate dust concentration monitoring and early warning of exceedances. The advancements of technologies will provide scientific support for the assessment of industrial dust hazards and the prevention and control of occupational pneumoconiosis.

Objective To explore the traditional Chinese medicine(TCM)syndrome characteristics of patients with Chikungunya hemorrhagic fever and to provide empirical data to support the application of TCM in diagnosing and treating Chikungunya hemorrhagic fever.Methods A cross-sectional survey was conducted to collect clinical data(sex,age,days since onset,and comorbidity underlying disease conditions)and TCM with four-examination information(symptoms,tongue manifestations,and pulse manifestations)from 255 patients with Chikungunya hemorrhagic fever who visited Lecong Hospital of Shunde,Foshan,the Third People's Hospital of Shunde District of Foshan,Shunde Hospital of Southern Medical University Affiliated Chencun Hospital between July 23 and July 29,2025.Factor and cluster analyses were used to summarize TCM syndrome characteristics and analyze core pathogenesis in conjunction with clinical features.Results Among the 255 patients with Chikungunya hemorrhagic fever,131 were male and 124 were female,with a age of(49.05±17.93)years and a disease duration of(3.26±1.78)days.Among the four types of examination information in TCM,35 items exhibited a frequency exceeding 10%.The most prevalent symptoms were arthralgia(180 patients,70.59%),exanthem(153 patients,60.00%),fatigue(99 patients,38.82%),anhidrosis(98 patients,38.43%),pruritus(96 patients,37.65%),and fever(92 patients,36.08%).Tongue and pulse manifestations were primarily white fur(155 patients,60.78%),pink tongue(111 patients,43.53%),slippery pulse(143 patients,56.08%),and greasy fur(134 patients,52.53%).Patients with disease onset≤3 d had a higher incidence of arthralgia,fatigue,fever,aversion to cold,generalized muscle pain,aversion to wind,insomnia,headache,sweating,low-grade fever,poor appetite,loose stool,hyperhidrosis,and red tongue than those with disease onset≥4 d(P<0.05).Patients with disease onset≥4 d had a higher incidence of pink tongue and thick fur than those with disease onset≤3 d(P<0.05).The syndrome elements in patients with Chikungunya hemorrhagic fever predominantly manifested on the defensive exterior,with involvement of the sinew-bone joints,skin-muscle,and spleen.Pathogenic factors were primarily characterized by external winds,dampness,and heat.Factor and cluster analysis result indicated three TCM pathogenesis progression patterns:imbalance of the defensive exterior with wind-dampness conflict and heat transformation;dampness-heat flowing into muscles and meridians causing joint obstruction and qi blood stasis;and dampness-heat congelation resulting in qi mechanism obstruction,consumption of body fluids,and infiltration of the skin.Conclusion Patients with Chikungunya hemorrhagic fever primarily present with fever,joint pain,and rashes.In TCM,this condition falls under the category of"dampness-warmth"syndrome.Its etiology is attributed to pathogens,with transmission occurring through mosquito bites.The core pathogenesis of TCM is the invasion of the defensive exterior and dampness-toxic heat accumulation.The therapeutic principles focus on clearing heat pathogens,resolving dampness pathogens,dispersing wind pathogens,and promoting the resolution of rashes.

Objective To investigate whether ginsenoside Rg3 can ameliorate glomerular endothelial injury in diabetic nephropathy(DN)mice through Ras homologous gene family member A(Rho A)/Rho-associated coiled-coil forming protein kinase,(ROCK1)/NLR family pyrin domain protein 3(NLRP3)pathway.Methods Forty mice were randomly divided into 4 groups:control group,DN group,ginsenoside(ginsenoside Rg3)group and RhoA/ROCK pathway inhibition(FD)group,with 10 mice in each group.Fasting blood glucose(FBG)was measured by glucose meter.The levels of urinary protein,urea nitrogen(BUN)and serum creatinine(SCr)were detected by ELISA.PAS staining was used to detect glomerular morphology and structure and to evaluate glomerular injury index(GDI).The expression of platelet-endothelial cell adhesion molecule(PECAM-1 or CD31),von Willefibrilia factor(vWF),RhoA,ROCK and NLRP3 protein related to pyrodeath were detected by immunofluorescence staining.Western blotting detected the expression of intercellular adhesion molecule-1(ICAM-1),vascular cell adhesion molecule-1(VCAM-1),the inflammatory factor interleukin-1β(IL-1β)and IL-18 protein in the glomerulus.Results Compared with the control group,the levels of FPG,urinary protein,BUN and SCr in DN group were increased,and the differences were statistically significant(t=17.59～43.81,all P<0.05).The glomerular structure was significantly damaged and GDI was increased(t=20.73,P<0.05).The expressions of CD31,RhoA,ROCK and NLRP3 in glomeruli were increased,while the expression of vWF was decreased.The expressions of ICAM-1,VCAM-1,IL-1β and IL-18 in renal tissues were increased,and the differences were statistically significant(t=27.95～40.10,all P<0.05).Compared with the DN group,the levels of FPG,urinary protein,BUN and SCr in ginsenoside group were decreased,and the differences were statistically significant(t=14.87～20.33,all P<0.05).The damage of glomerular structure was improved and GDI was decreased(t=19.80,P<0.05),the expression of CD31,RhoA,ROCK and NLRP3 in glomerular was decreased,and the expression of vWF was increased.The expressions of ICAM-1,VCAM-1,IL-1β and IL-18 in renal tissues of FD group were decreased,and the differences were statistically significant(t=12.62～39.68,all P<0.05).Conclusion Ginsenosides Rg3 can improve the level of glomerular endothelial injury and pyroptosis in DN mice by down-regulating RhoA/ROCK/NLRP3 pathway.