ObjectiveTo observe the effect of M1 bone marrow-derived macrophages （M1-BMDM） with Wnt5a knockdown on liver fibrosis and regeneration in a rat model of liver cirrhosis， and to investigate its gain-of-function effect compared with unmodified M1-BMDM. MethodsPrimary bone marrow-derived macrophages were isolated from rats and were polarized to M1 phenotype to construct M1-BMDM^Wnt5a-KD cells. A rat model of liver cirrhosis induced by CCl₄/2-AAF was established， and at the end of week 8， rats were randomly divided into model group， M1-BMDM group， M1-BMDM Wnt5a-knockdown empty vector group （M1-BMDM^KD-EV group）， and M1-BMDM Wnt5a-knockdown group （M1-BMDM^Wnt5a-KD group）， with 6 rats in each group. On the first day of week 9， the rats in each group were given a single injection of the corresponding cells via the caudal vein， along with an intraperitoneal injection of a CCR2 inhibitor. Six rats without any treatment were used as normal control group. Samples were collected at the end of week 12 to assess liver histopathology， serum liver function parameters， hepatic stellate cell activation， and the expression levels of mature hepatocyte markers. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the model group， all cell treatment groups had significant alleviation of liver inflammatory response and significant reductions in the activities of alanine aminotransferase and aspartate aminotransferase （AST） in serum （all P<0.01）， and the M1-BMDM^Wnt5a-KD group had a significantly lower serum level of AST than the M1-BMDM group （P<0.05）. The semi-quantitative analysis based on immunohistochemical staining showed that compared with the model group， all cell treatment groups had a significant reduction in the percentage of CD68-positive area （all P<0.05）， and compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had a significant reduction in the percentage of CD68-positive area and a significant increase in the percentage of CD163-positive area （both P<0.05）. Compared with the model group， all cell treatment groups had significant reductions in the mRNA expression levels of CD68 and tumor necrosis factor-α （all P<0.05） and the protein expression level of CD68 （all P<0.01）； compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had significant increases in the protein and mRNA expression levels of CD163 （both P<0.05）， significant reductions in the protein and mRNA expression levels of CD68 （both P<0.05）， and a significant reduction in the protein expression level of tumor necrosis factor-α （P<0.01）. Sirius Red collagen staining and alpha-smooth muscle actin （α-SMA） immunohistochemical staining showed that compared with the model group， all cell treatment groups had significant alleviation of liver collagen deposition and α-SMA-positive area， with the most significant changes in the M1-BMDM^Wnt5a-KD group， and compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had significantly smaller Sirius Red-positive area and α-SMA-positive area and a significantly lower content of hydroxyproline in liver tissue （all P<0.05）. Compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had significant reductions in the protein and mRNA expression levels of α-SMA and the mRNA expression level of COL-I and TGF-β （all P<0.05）. Compared with the model group， all cell treatment groups had a significant increase in the protein expression level of HNF-4α in liver tissue （all P<0.05）， and the M1-BMDM^Wnt5a-KD group had significantly higher protein and mRNA expression levels of HNF-4α and hepatocyte specific antigen than the M1-BMDM^KD-EV group （both P<0.05）. The M1-BMDM^Wnt5a-KD group had a significantly higher serum level of albumin than the M1-BMDM^KD-EV group （P<0.01）. Immunofluorescence co-staining showed that compared with the model group， all cell treatment groups had a significant increase in the number of cells stained positive for HNF and HNF-4α and Ki67 （all P<0.01）， and the M1-BMDM^Wnt5a-KD group had a significantly higher number of such cells than the M1-BMDM^KD-EV group （P<0.05）. ConclusionInhibition of Wnt5a expression enhances the therapeutic effect of M1-BMDM on rats with liver cirrhosis induced by CCl₄/2-AAF， which provides new ideas for enhancing the anti-cirrhotic effect of M1-BMDM through genetic modification.

ObjectiveTo investigate the effect and mechanism of transplantation of human umbilical cord mesenchymal stem cell （hUC-MSC） with overexpression of the Numb gene in the treatment of cholestatic liver fibrosis （CLF）. MethodsThe technique of lentiviral transfection was used to induce the overexpression of the Numb gene in hUC-MSC （hUC-MSC^Numb-OE）， and hUC-MSC transfected with empty vector （hUC-MSC^OE-EV） was used as negative control. Bile duct ligation （BDL） was performed to establish a rat model of CLF， and then the rats were randomly divided into BDL group， hUC-MSC group， hUC-MSC^OE-EV group， and hUC-MSC^Numb-OE group， while a sham-operation group was also established. The rats in the intervention groups were given a single splenic injection of the corresponding cells after BDL， and samples were collected at the end of week 4. Related indicators were measured， including serum biochemistry， liver histopathology， the content of hydroxyproline （Hyp） in the liver， hepatic stellate cell activation， ductular reaction， liver regeneration， and the expression levels of key molecules in the Numb-p53 signaling axis. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the BDL group， the hUC-MSC group and the hUC-MSC^OE-EV group had significant reductions in the levels of serum biochemical parameters （aspartate aminotransferase， gamma-glutamyl transpeptidase， total bile acid， total bilirubin， and direct bilirubin）， liver fibrosis markers （the content of Hyp and the expression levels of alpha-smooth muscle actin， tumor necrosis factor-α， and transforming growth factor-beta 1）， and ductular reaction markers （the expression levels of CK7 and CK19） （all P <0.05）， and compared with the hUC-MSC^OE-EV group， the hUC-MSC^Numb-OE group had significantly greater improvements in the above indicators （all P <0.05）. In addition， compared with the hUC-MSC^OE-EV group， the hUC-MSC^Numb-OE group had significant improvements in the expression levels of liver regeneration-related markers （albumin and hepatocyte nuclear factor 4α） and the molecules associated with the Numb-p53 signaling axis （Numb， pNumb， Mdm2， and p53） （all P <0.05）. ConclusionOverexpression of the Numb gene can enhance the therapeutic effect of hUC-MSC on CLF， possibly by activating the Numb-PTB^L-p53-HNF4α axis， promoting the hepatic differentiation of hUC-MSCs and subsequently enhancing liver regeneration.

Objective Based on the visualization graph analysis of the research hotspots of Angelica sinensis, predict the future research trends, and provide references for the next step of Angelica sinensis research. Methods Chinese and English literatures on Angelica sinensis collected from CNKI, WanFang, VIP and Web of Science from 2012 to 2022 were retrieved. CiteSpace 6.1.R6 software was used to perform visualization econometrics analysis on the number of publications, authors, institutions, journals, keywords and other topics. Results 3490 Chinese literatures and 409 English literatures were included. Visual knowledge map analysis showed that Gansu University of Chinese Medicine and Nanjing University of Chinese Medicine were the research institutions with the largest number of literature publications in Chinese and English respectively. Journals published mainly include Shizhen Traditional Chinese Medicine and Materia medica, Evidence-based Complementary and Alternative Medicine. Current research hotspots include the effects of Angelica sinensis polysaccharides, volatile oils, and ferulic acid on the hematopoietic system, chronic diseases, and cognitive impairment, as well as clinical efficacy evaluations of classic prescriptions containing Angelica sinensis and their modified formulations. The research trend was characterized by a focus on the pharmacological study of Danggui Buxue Tang,employing various experimental approaches such as network pharmacology, serum pharmacology, and metabolomics to elucidate the mechanisms of Angelica sinensis. Conclusion The pharmacological effects of Angelica sinensis and its compound were extensive, which should be further researched.

Objective To investigate the association between low-level ionizing radiation exposure and peripheral blood parameters in medical radiation workers, and to provide evidence for radiation protection strategies and occupational health surveillance. Methods A total of 1261 medical radiation workers from medical institutions in Heze City, Shandong Province, China, were enrolled. Individual monitoring of occupational external exposure was performed. Demographic characteristics and physical examination data were collected. According to the median annual effective dose, the subjects were stratified into a low-dose group (0.10-0.43 mSv) and a high-dose group (>0.43-5.24 mSv). Logistic regression was used to assess the association between ionizing radiation and peripheral blood parameters. Subgroup analyses were conducted by gender, age, and exposure duration. Results A total of 1261 subjects were enrolled, of whom 893 (70.82%) were male and 368 (29.18%) were female. The median age was 39.00 (32.00, 47.00) years and the median exposure duration was 11.00 (5.00, 22.00) years. No statistically significant differences in baseline characteristics were observed between the two groups. The radiation dose ranged from 0.104 to 5.239 mSv, all below the occupational exposure limit (20 mSv). Basophil count, hematocrit, and mean corpuscular volume in the high-dose group were significantly higher than those in the low-dose group, while mean corpuscular hemoglobin concentration was lower (P<0.05). Logistic regression analysis showed that ionizing radiation primarily affected erythrocyte parameters, with abnormal hematocrit (OR=1.449, 95%CI: 1.148-1.831), abnormal mean corpuscular volume (OR=1.407, 95%CI: 1.119-1.771), and abnormal mean corpuscular hemoglobin concentration (OR=1.608, 95%CI: 1.278-2.025) positively associated with ionizing radiation exposure. Subgroup analyses further revealed differences that were not observed in the total population These findings suggest that gender, age, and exposure duration may modify the effect of ionizing radiation on peripheral blood parameters. Conclusion Long-term low-level ionizing radiation exposure can affect peripheral blood parameters in medical radiation workers, particularly erythrocyte parameters. Enhanced occupational health monitoring and protection measures are warranted.

ObjectiveTo evaluate the clinical efficacy of Huangqin Qingre Chubi capsules （HQC） in patients with rheumatoid arthritis （RA） and the syndrome of dampness-heat obstruction and investigate the mechanism by which HQC restore clinical and laboratory parameters in RA patients through regulation of the long non-coding RNA （LncRNA） endogenous Bornavirus-like nucleoprotein 3 pseudogene （EBLN3P）/miR-369-3p/nuclear factor I X（NFIX）-Janus kinase（JAK）/signal transducer and activator of transcription （STAT） signaling pathway，thereby providing new experimental evidence and potential therapeutic targets for the traditional Chinese medicine （TCM） treatment of RA. MethodsA randomized controlled trial design was adopted，with 100 RA patients meeting the criteria assigned into an observation group （n=50） and a control group （n=50）. In addition，50 healthy controls were enrolled. The control group received leflunomide plus meloxicam，while the observation group additionally received HQC. Efficacy was assessed after 4 weeks of treatment. Observation indicators including Western medicine indicators （DAS28，CPRI-RA，SF-36，VAS，PGA，PhGA，and SAS/SDS），TCM syndrome scores （TCMSS-RADHP，TCMSS-RASDP），and laboratory indicators （ESR，CRP，RF，anti-CCP antibody，VEGF，bFGF，MMP-2/9，p-JAK2/STAT3，and LncRNA EBLN3P/miR-369-3p/NFIX expression） were measured to comprehensively explore the therapeutic mechanism of HQC. ResultsThe study included 45 healthy controls （34 males and 11 females） and 87 RA patients （22 males and 65 females）. The median age，median disease duration，and median BMI of patients were 56 years old，10 years，and 21.51 kg·m^-2，respectively. Compared with healthy controls，the RA group exhibited a typical state of immune-inflammatory activation as manifested by elevated levels of ESR，anti-CCP antibodies，CRP，and RF （P<0.01），raised clinical symptom scores （DAS28，VAS，PGA，PhGA，CPRI-RA，and TCM symptoms） （P<0.05，P<0.01），and reduced SF-36 domain scores （P<0.01）. Molecular detection revealed abnormal expression of LncRNA EBLN3P and miR-369-3p，upregulated expression of key proteins in the JAK/STAT pathway （JAK2/p-JAK2 and STAT3/p-STAT3） and angiogenesis markers （VEGF，bFGF，and MMP-2/9），and downregulated expression of NFIX （P<0.05，P<0.01） in the RA group. Spearman correlation analysis further demonstrated associations of key molecules in the LncRNA EBLN3P/miR-369-3p/NFIX-JAK/STAT pathway with immune-inflammatory markers and clinical symptom scores （P<0.05，P<0.01）. Regarding treatment response，both groups showed reductions in ESR，anti-CCP，CRP，and RF levels compared with baseline （P<0.01） and restored scores of DAS28，CPRI-RA，VAS，PGA，PhGA，TCM symptoms，SAS，SDS，and all SF-36 domains （P<0.01）. The observation group outperformed the control group in restoring the scores of SAS，SDS，PGA，TCMSS-SDP，and SF-36 domains （PF，BP，GH，VT，and SF） （P<0.05）. Real-time PCR analysis revealed that post-treatment expression levels of LncRNA EBLN3P，miR-369-3p，NFIX，JAK2，p-JAK2，STAT3，p-STAT3，VEGF，bFGF，MMP-2，and MMP-9 were recovered compared with pre-treatment levels （P<0.01）. Notably，the observation group demonstrated superior regulatory effects on p-JAK2，STAT3，p-STAT3，and MMP-9 compared with the control group （P<0.05）. Apriori association rule analysis revealed that HQC treatment was significantly correlated with reduced TCMSS-RADHP，ESR，SF，DAS28，SAS，and SDS scores，as well as increased VT，GH，and RP scores （confidence >80%，support >50%）. Regarding safety，two patients in the observation group experienced mild gastrointestinal discomfort，and one patient in the control group developed a rash. All the symptoms resolved after symptomatic treatment. ConclusionHQC target and regulate the LncRNA EBLN3P/miR-369-3p/NFIX-JAK/STAT axis to inhibit angiogenesis and inflammatory responses，reduce immune inflammatory markers，alleviate clinical symptoms，and improve the quality of life in RA patients，exerting synergistic effects on symptoms and quality of life.

OBJECTIVE To develop evidence-based clinical practice recommendations for the use of hemostatic drugs in special populations， so as to improve the efficacy and safety of medication.METHODS Led by the Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital， a working group of 79 experts covering clinical pharmacy， obstetrics and gynecology， pediatrics and other fields was established. Clinical questions regarding the efficacy and safety of hemostatic drugs in special populations were screened through literature review and two rounds of Delphi questionnaire surveys. Intervention questions were structured using the population， intervention， comparison， and outcome framework， while management questions were additionally described using the population， clinical setting, management measure， and outcome framework. Databases including Medline， Embase， Cochrane Library， CNKI， Wanfang Data， and VIP were systematically searched to collect and screen relevant evidence. Recommendations were formulated through recommendation questionnaire surveys and expert consensus meetings， and the quality of evidence and strength of recommendations were graded according to the Grading of Recommendations Assessment， Development and Evaluation system. RESULTS &CONCLUSIONS A total of 8 clinical questions were finally determined， the consensus rates of all clinical questions and recommendations were more than 90%， and 8 recommendations on the use of hemostatic drugs in special populations were formulated. These recommendations cover special populations including children， women during pregnancy/puerperium/lactation， the elderly， patients with hepatic impairment， patients in the perioperative period of liver transplantation， patients with renal impairment/on dialysis/in the perioperative period of kidney transplantation， immunocompromised patients， and patients with hematological diseases. The recommendations specify the applicable scenarios， dose adjustment principles， monitoring indicators， and safety management strategies of hemostatic drugs in different special populations， which can provide a reference for the clinical application of hemostatic drugs in special populations and help clinicians and pharmacists develop individualized medication plans.

OBJECTIVE To investigate the current status of contamination with carbapenem-resistant gram-negative bacteria in environment of intensive care units(ICU)of tertiary hospitals in Shanghai and find out the potential contamination sources so as to provide bases for prevention and control of multidrug-resistant organisms infec-tions in the ICUs.METHODS The surroundings of the ICU patients detected with CRGNB and environmental ob-jects surfaces in public area were sampled by mSuperCARBA chromogenic media from Dec.2024 to Jan.2025,the strains were isolated,and the targeted strains were identified by matrix-assisted laser desorption/ionization time-of-flight(MALDI-TOF)mass spectrometer.RESULTS A total of 653 samples were collected in the survey,76 of which were positive for bacterial culture,60 were detected with CRGNB,and the isolation rate of CRGNB was 9.19％.The isolation rate of CRGNB was 53.40％in the water-source group,0.91％in the non-water-source group,and there was significant difference(x2=286.450,P＜0.001).The result of whole genome sequencing for 17 strains of CRKP showed that ST11 and ST15 were the two major types of multilocus typing(MT),respective-ly carrying 2-12 types of drug resistance genes.CONCLUSIONS The CRGNB strains are detected in some environ-mental sites of the ICUs of 15 tertiary hospitals in Shanghai,and the isolation rate of CRKP is highest among them.The colonization rate of CRGNB is relatively low on the highly frequent-contact object surfaces of the ICUs,however,sink drain holes poses a risk of hospital-acquired CRGNB infections transmissions.Additionally,the ba-sins and towels of the CRGNB patients are hard to be thoroughly cleaned,disinfected and dried,resulting in a high contamination rate.

Objective:To explore the clinical efficacy of targeted epidural space block combined with acupotomy in the treatment for lumbar disc herniation(LDH)under the monitor of X-ray image,and to analyze the safety of its operation.Methods:A total of 60 LDH patients who admitted to Department of Pain,Jiangyin Affiliated Hospital of Nanjing University of Chinese Medicine from January 2022 to September 2023 were selected,and they were randomly divided into observation group and control group as random number table,with 30 cases in each group.The observation group adopted targeted epidural space block combined with acupotomy under monitor with X-ray for anterior epidural space,while the control group adopted conventionally epidural block,all of which were treated only once.The Visual Analogue Scale(VAS)scores and Oswestry Disability Index(ODI)scores of two groups before treatment and at the 3rd day,7th day and 30th day after treatment were compared.At the 30th day after treatment,the curative effects of two groups were evaluated according to ODI scores,at the same time,the safe distance between puncture and acupotomy in patients of observation group was analyzed.Results:The effective rates of the treatment of observation group and control group were respectively 96.67%and 70%,and the difference of that between the two groups was statistically significant(x2=7.680,P<0.05).The VAS scores of the two groups at the 3rd day,7th day and 30th day after treatment were lower than those before treatment,and the observation group(2.30±0.87),(1.53±0.86)and(1.47±0.81)were lower than the control group(4.43±0.89),(2.23±0.89)and(4.27±0.82),the difference was statistically significant(t=9.374,3.098,13.306,P<0.05).The ODI scores of the two groups were at the 3rd day,7th day and 30th day after treatment were lower than those before treatment,and the differences of them between two groups were statistically significant(t=7.112,10.690,10.151,P<0.05).In 30 patients of observation group,the gap between the dural sac and the inner edge of facet joint on the affected side was larger than 4.0mm in 25 cases,and all of them can safely conduct puncture with targeting.Conclusion:The targeted epidural space block combined with acupotomy by adopting monitor with X-ray image can effectively improve the symptom of pain,and activities of daily life of LDH patients,which treatment is safe and effective.

Objective To observe the therapeutic effect of regulating intestinal acupuncture combined with fire-dragon cupping in the treatment of slow transit constipation(STC)after stroke in the elderly.Methods A total of 132 patients with STC after stroke who were diagnosed and treated in Hangzhou Hospital of Traditional Chinese Medicine from January 2023 to June 2024 were selected and divided into control group and observation group according to the random number table method,with 66 cases in each group.Patients in control group received defecation training,while patients in observation group were treated with regulating intestinal acupuncture combined with fire-dragon cupping on the basis of control group.Both groups of patients were treated continuously for 2 weeks.The therapeutic effects,Cleveland clinic constipation score(CCS),Bristol stool form scale(BSFS)scores and serum intestinal neurotransmitter levels of two groups of patients were compared,and the recurrence rate was statistically analyzed.Results The clinical effective rate of patients in observation group was significantly higher than that in control group(x2=5.893,P=0.015).After 2 weeks of treatment,the CCS,BSFS score and serum vasoactive intestinal peptide(VIP)level of two groups of patients were significantly lower than those before treatment in same group,and 5-hydroxytryptamine(5-HT)level was significantly higher than that before treatment in same group(P＜0.05).The CCS,BSFS score and serum VIP level of patients in observation group were significantly lower than those in control group,and 5-HT level was significantly higher than that in control group(P＜0.05).The recurrence rate of patients in observation group was significantly lower than that in control group(x2=3.986,P＜0.05).Conclusion The treatment of regulating intestinal acupuncture combined with fire-dragon cupping can effectively alleviate the constipation degree of STC after stroke in the elderly,and its effectiveness may be related to the regulation of intestinal neurotransmitters.

Objective Biomarkers associated with liver cancer CD8+T cells identified and prognostic models established by single-cell RNA sequencing and Bulk RNA sequencing.Methods Single-cell datasets of liver cancer were downloaded from the GEO database and differentially expressed genes in CD8+T cells between patients and controls were extracted by single-cell RNA sequencing.Gene expression profiling data and clinical data of liver cancer were downloaded from the TCGA database,and modular genes with relevance to CD8+T cells were screened using the CIBERSORT algorithm and WGCNA technology.Differential genes and modular genes were taken as intersecting genes and subjected to GO and KEGG analyses,and a prognostic model was established by applying univariate COX regression analysis and LASSO algorithm.The predictive effectiveness of the model in both internal and external datasets is validated by K-M and ROC curves.The effectiveness of the model's prediction in both internal and external datasets was validated by K-M and ROC curves.High-and low-risk groups were divided according to the median value of the risk score,and the distribution of infiltrating immune cells and tumor mutations between high-and low-risk groups were analyzed.Results A prognostic model with nine genes was constructed,and the K-M and ROC curves showed that the model had good predictive ability in both the internal and external datasets,and there were significant differences in the distribution of infiltrating immune cells and gene mutations in the high-and low-risk groups.Conclusion In this study,a novel prognostic model based on CD8+T cells was developed using bioinformatic method in combination with single-cell RNA sequencing and Bulk RNA sequencing technologies,which provides a reliable theoretical basis for prognostic improvement and survival prediction of liver cancer patients.