ObjectiveTo observe the clinical efficacy of Tangshen Dihuang decoction in treating diabetic kidney disease （DKD） with liver-kidney Yin deficiency and blood stasis syndrome and its impact on gut microbiota. MethodsA randomized controlled clinical trial was conducted， in which 102 DKD patients with liver-kidney Yin deficiency and blood stasis syndrome were randomly assigned to the Tangshen Dihuang decoction group and the control group. Each group consisted of 51 cases， and the treatment period was 3 months. The primary efficacy indicators included urinary albumin-to-creatinine ratio （UACR）， fasting blood glucose （FBG）， 2-hour postprandial blood glucose （2 hPBG）， glycated hemoglobin （HbA₁C）， serum creatinine （SCr）， blood urea nitrogen （BUN）， angiotensinⅡ （AngⅡ）， serum cystatin C （Cys-C）， urinary N-acetyl-β-D-glucosaminidase （NAG）， urinary β₂-microglobulin （Uβ₂-MB）， traditional Chinese medicine （TCM） symptom scores， and gut microbiota. ResultsAfter treatment， the total response rate in the Tangshen Dihuang decoction was 87.23% （41/47）， which was higher than that （69.57%， 32/46） in the control group （Z=4.30， P<0.05）. After treatment， the TCM symptom scores decreased in both groups （P<0.01） and were lower in the Tangshen Dihuang decoction group than in the control group （P<0.01）. After treatment， the control group showed decreases in UACR， Uβ₂-MG， AngⅡ， and FBG （P<0.05） as well as 2 hPBG and HbA₁C （P<0.01）， and no significant differences in BUN， Cys-C， eGFR， SCr， and NAG. The Tangshen Dihuang decoction group showed increased eGFR （P<0.05）， declined levels of UACR， BUN， Cys-C， Uβ₂-MB， AngⅡ， FBG， 2 hPBG， NAG， and HbA₁C （P<0.01）， and no significant difference in SCr. The Tangshen Dihuang decoction group had lower BUN （P<0.05）， Cys-C （P<0.05）， AngⅡ （P<0.05）， 2 hPBG （P<0.05）， Uβ₂-MG （P<0.01）， and NAG （P<0.01） and higher eGFR level （P<0.05） than the control group. After treatment， the control group showed declines in Shannon， Observed_species， and Chao1 indices （P<0.05）. The samples from both groups showed statistically significant differences in the principal coordinates analysis （PCoA） plot based on Anosim analysis （P<0.05）. After treatment， the Tangshen Dihuang decoction group showed decreased relative abundance of Actinobacteria （P<0.05）. Moreover， the relative abundance of Actinobacteria was significantly lower in the Tangshen Dihuang decoction group than in the control group （P<0.05）. At the genus level， the control group showed decreased relative abundance of Bifidobacterium （P<0.05）， and the Tangshen Dihuang decoction group presented increased relative abundance of Bifidobacterium and Blautia_A （P<0.05）. After treatment， the Tangshen Dihuang decoction group had higher relative abundance of Bifidobacterium than the control group （P<0.01）. ConclusionTangshen Dihuang decoction has a significant therapeutic effect on DKD patients with liver-kidney Yin deficiency and blood stasis syndrome. It can markedly relieve clinical symptoms and reduce proteinuria and postprandial blood glucose by antagonizing the local renin-angiotensin system （RAS） and alleviating gut microbiota dysbiosis.

Objective: To investigate the potential therapeutic mechanisms of kaempferol , an active component in the traditional Chinese medicine gardenia , for lung cancer treatment using a network pharmacology approach . Methods: The main active ingredients and potential targets of Gardenia jasminoides were obtained through the Tra⁃ditional Chinese Medicine Pharmacology Database and Analysis Platform (TCMSP) , and combined with the lung cancer related target information collected from Gene Cards and OMIM databases , the intersection targets of Garde⁃nia jasminoides and lung cancer treatment were determined by drawing Venn diagrams . Further screening of core targets was conducted through PPI network analysis , and gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes ( KEGG) pathway enrichment analysis were performed using the Metascape platform . Auto dock software was used to evaluate the binding affinity between the active ingredients of Gardenia jasminoides and target proteins . In terms of experiments , cell proliferation ability was evaluated through CCK⁃8 assay , cell migration and invasion ability were detected through cell scratch healing assay and Transwell assay , and the expression levels of epithelial mesenchymal transition ( EMT) protein and inflammatory factors were detected by Western blot and RT⁃qPCR . Results: The active ingredient kaempferol in Gardenia jasminoides exhibited significant binding ability invasion of lung cancer cells . The results of Western blot and RT⁃qPCR further confirmed that kaempferol could promote an increase in E ⁃cadherin , a decrease in N ⁃cadherin and Vimentin , and reduce the expression of inflam⁃matory factors . Conclusion The active ingredient of Gardenia jasminoides , kaempferol , inhibits the proliferation ,migration and invasion of lung cancer cells by targeting BCL⁃2 , while reversing EMT progression and suppressing the expression levels of inflammatory cytokines in lung cancer cells , thus preventing lung cancer progression .

Objective:To investigate the effect of armadillo repeat containing X-linked 3(ARMCX3)on the proliferation,migration,and invasion of breast cancer cells and its potential molecular mechanism.Methods:Immunohistochemistry was used to measure the expression of ARMCX3 in breast cancer tissue and adjacent tissue,and Western blot was used to measure the expression of ARMCX3 in breast cancer cells.Breast cancer cells were transfected with lentivirus to establish a model of breast cancer cells with low expres-sion of ARMCX3,and flow cytometry,colony formation assay,scratch assay,and Transwell assay were used to observe the effect of ARMCX3 on the proliferation,migration,and invasion of breast cancer cells.TCGA and GTEx databases were used to analyze the ex-pression of SRY-box transcription factor 9(SOX9)in breast cancer tissue,and GEO database was used to analyze the correlation be-tween SOX9 and ARMCX3.Western blot was used to measure the expression levels of E-cadherin,N-cadherin,vimentin,and SOX9 in breast cancer cells.Results:Compared with adjacent tissue and human normal breast epithelial cells,there was a significant in-crease in the expression level of ARMCX3 in breast cancer tissue and most breast cancer cell lines(P<0.05).Compared with the con-trol group,the low expression of ARMCX3 inhibited the prolifera-tion,migration,and invasion of MCF-7 and MDA-MB-231 cells,promoted the expression of E-cadherin,and inhibited the expres-sion of N-cadherin and vimentin(P<0.05).Compared with the nor-mal tissue,there was a significant increase in the expression level of SOX9 in breast cancer tissue(P<0.001),which was correlated with ARMCX3,and the low expression of ARMCX3 also significantly in-hibited the expression of SOX9.Conclusion:ARMCX3 is highly ex-pressed in breast cancer tissue and breast cancer cells,and it may regulate the proliferation,migration,and invasion of breast cancer cells through SOX9.

Objective To investigate the clinical effect of dapagliflozin combined with sacubitril-valsar-tan in the treatment of non-reduced ejection fraction type heart failure(non-HFrEF).Methods A total of 120 patients with non-HFrEF diagnosed and treated in this hospital from January to December 2022 were selected as the study subjects and divided into the observation group and control group by the random number method,60 cases in each group.The both groups were treated with conventional treatments such as β-receptor blockers and diuretics,the patients in the control group were treated with sacubitril-valsartan(Noxinto),and the pa-tients in the observation group were treated with dapagliflozin on the basis of the control group for 6 months.The clinical efficacy,serum N-terminal B-type natriuretic peptide precursor(NT-proBNP),hypersensitivity-C-reactive protein(hs-CRP),serum creatinine(SCr),serum potassium,cardiac color Doppler ultrasound param-eters,6 min walk test(6MWT)distance before treatment and in 6 months after treatment,and the occurrence of major adverse cardiovascular events(MACE)during treatment were compared between the two groups.Re-sults After 6 months of treatment,the total effective rate in the observation group was 93.3%,which was higher than 80%in the control group,and the difference was statistically significant(P=0.032).After 6 months of treatment,the levels of NT-proBNP and hs-CRP in the two groups were significantly decreased compared with those before treatment,moreover the observation group was lower than the control group,and the difference was statistically significant(P<0.05).After 6 months of treatment,LVEF and 6MWT dis-tance in the two groups were increased compared with those before treatment,LVEDV and LVESV were de-creased compared with those before treatment,moreover the change amplitude of the above indexes in the ob-servation group were greater than those in the control group,and the differences were statistically significant(P<0.05).The incidence rate of MACE in the observation group was lower than that in the control group(16.7%vs.5.0%),and the difference was statistically significant(P<0.05).Conclusion Dapagliflozin combined with sacubitril-valsartan in the treatment of non-HFrEF could significantly reduce the levels of NT-proBNP and hs-CRP,improve the cardiac function,increase the exercise tolerance,decrease the incidence rate of MACE and improve the prognosis.

Objective To compare the application effect of platelet rich fibrin(PRF)prepared at different centrifugal speeds in tooth extraction wounds using network meta-analysis statistical method.Methods PubMed,Co-chrane Library,Embase,Web of Science,CNKI,Wanfang,VIP and China Biology Medicine disc(CBM)databases were searched to collect the randomized controlled trials on the effect of PRF in tooth extraction from January 1,2024.Note-Express software was used to select literatures,RevMan5.3 was used to evaluate the quality of the included literatures,and Stata14.0 software was used to perform mesh meta-analysis on outcome indicators such as bone mineral density,bone height loss,visual analog scale of pain(VAS),dry groove,and bleeding after tooth extraction.Results A total of 31 randomized controlled trials were included,including 2 824 extraction sites,involving 7 rotational speeds for PRF preparation(3 000,2 800,2 700,2 300,1 500,1 400,1 300 r/min).The results of cu-mulative sequencing showed that PRF prepared by 2 700 r/min centrifugation had the best effect in improving bone mineral density.In terms of improving the buccal bone height,the PRF prepared by 2 700 r/min centrifu-gation had the best effect.In terms of pain improvement,PRF prepared by 1 500 r/min centrifugation had the best effect;PRF prepared by 2 500 r/min centrifugation had the best effect in reducing the incidence of dry trough.PRF prepared by 2 500 r/min centrifugation was the most effective in reducing bleeding.Conclusion Based on the available evidence,PRF prepared with 2 700 r/min has the best effect on improving bone density and bone height after tooth extraction.In terms of pain improvement,1 500 r/min was the most effective;2 500 r/min was the most effective in improving the incidence of dry trough and bleeding.

ObjectiveTo observe the effectiveness and safety of modified Taohong Siwu Decoction （桃红四物汤） for patients of chronic heart failure with lower limb deep vein thrombosis in the chronic stage of blood stasis syndrome. MethodsA total of 120 patients of chronic heart failure with lower limb deep vein thrombosis in chronic stage of blood stasis syndrome were randomly divided into 60 cases each in control group and observation group. Both groups were given basic treatment of western medicine， and the observation group was additionally given modified Taohong Siwu Decoction （桃红四物汤） for oral administration， one dose per day. The treatment course for both groups lasted for 4 weeks. The total effective rate and the incidence of adverse reactions were compared between the two groups after treatment. Cardiac function indexes including left ventricular ejection fraction （LVEF）， and left ventricular end-systolic internal diameter （LVESd）， left ventricular end-diastolic internal diameter （LVEDd）， serological indexes including N-terminal natriuretic natriuretic peptide precursor （NT-proBNP）， high sensitivity C-reactive protein （hs-CRP） and vascular endothelial growth factor （VEGF）， score of traditional Chinese medicine （TCM） symptom including chest pain， swelling of the affected limb， fixed tenderness， and bruising， haemodynamics indicators including high cut whole blood viscosity， low cut whole blood viscosity， and erythrocyte pressure， and coagulation indices including activated partial thromboplastin time （APTT）， plasminogen time （PT）， and fibrinogen （FIB） levels were compared before and after treatment. ResultsDuring the study， 3 cases were excluded and 2 cases lost follow-up in the observation group， while 2 cases were excluded and 3 cases lost follow-up in the control group. A total of 110 patients completed the trial， 55 cases in each of the two groups. The total effective rate in the observation group was 92.73% （51/55）， which was significantly higher than that of the control group， 78.18% （43/55， P＜0.05）. Compared within group before treatment， LVEF， APTT and PT levels increased， LVESd， LVEDd， NT-proBNP， hs-CRP， VEGF， high cut whole blood viscosity， low cut whole blood viscosity， erythrocyte pressure volume and FIB levels decreased， chest pain， swelling of the affected limbs， stationary pressure pain and bruising score decreased in both groups after treatment， and the improvement of all above indexes was better in the observation group than that in control group （P＜0.05 or P＜0.01）. The incidence of adverse reactions was 7.27% （4/55） in the observation group and 21.82% （12/55） in the control group， and the incidence of adverse reactions in the observation group was significantly lower than that in the control group （P＜0.05）. ConclusionModified Taohong Siwu Decoction （桃红四物汤） as adjuvant treatment for patients of chronic heart failure with lower limb deep vein thrombosis in the chronic stage of blood stasis syndrome showed better clinical effectiveness when compared with western basic treatment， which can improve the clinical symptoms， cardiac function， haemodynamics， and coagulation， with good safety.

Azvudine and nirmatrelvir/ritonavir (Paxlovid) are recommended for COVID-19 treatment in China, but their safety and efficacy in the elderly population are not fully known. In this multicenter, retrospective, cohort study, we identified 5131 elderly hospitalized COVID-19 patients from 32,864 COVID-19 patients admitted to nine hospitals in Henan Province, China, from December 5, 2022, to January 31, 2023. The primary outcome was all-cause death, and the secondary outcome was composite disease progression. Propensity score matching (PSM) was performed to control for confounding factors, including demographics, vaccination status, comorbidities, and laboratory tests. After 2:1 PSM, 1786 elderly patients receiving azvudine and 893 elderly patients receiving Paxlovid were included. Kaplan-Meier and Cox regression analyses revealed that compared with Paxlovid group, azvudine could significantly reduce the risk of all-cause death (log-rank P = 0.002; HR: 0.71, 95% CI: 0.573-0.883, P = 0.002), but there was no difference in composite disease progression (log-rank P = 0.52; HR: 1.05, 95% CI: 0.877-1.260, P = 0.588). Four sensitivity analyses verified the robustness of above results. Subgroup analysis suggested that a greater benefit of azvudine over Paxlovid was observed in elderly patients with primary malignant tumors (P for interaction = 0.005, HR: 0.32, 95% CI: 0.18-0.57) compared to patients without primary malignant tumors. Safety analysis revealed that azvudine treatment had a lower incidence of adverse events and higher lymphocyte levels than Paxlovid treatment. In conclusion, azvudine treatment is not inferior to Paxlovid treatment in terms of all-cause death, composite disease progression and adverse events in elderly hospitalized COVID-19 patients.

In recent decades, the prevalence of hyperuricemia and gout has increased dramatically due to lifestyle changes. The drugs currently recommended for hyperuricemia are associated with adverse reactions that limit their clinical use. In this study, we report that berberine (BBR) is an effective drug candidate for the treatment of hyperuricemia, with its mechanism potentially involving the modulation of gut microbiota and its metabolite, succinic acid. BBR has demonstrated good therapeutic effects in both acute and chronic animal models of hyperuricemia. In a clinical trial, oral administration of BBR for 6 months reduced blood uric acid levels in 22 participants by modulating the gut microbiota, which led to an increase in the abundance of Bacteroides and a decrease in Clostridium sensu stricto_1. Furthermore, Bacteroides fragilis was transplanted into ICR mice, and the results showed that Bacteroides fragilis exerted a therapeutic effect on uric acid similar to that of BBR. Notably, succinic acid, a metabolite of Bacteroides, significantly reduced uric acid levels. Subsequent cell and animal experiments revealed that the intestinal metabolite, succinic acid, regulated the upstream uric acid synthesis pathway in the liver by inhibiting adenosine monophosphate deaminase 2 (AMPD2), an enzyme responsible for converting adenosine monophosphate (AMP) to inosine monophosphate (IMP). This inhibition resulted in a decrease in IMP levels and an increase in phosphate levels. The reduction in IMP led to a decreased downstream production of hypoxanthine, xanthine, and uric acid. BBR also demonstrated excellent renoprotective effects, improving nephropathy associated with hyperuricemia. In summary, BBR has the potential to be an effective treatment for hyperuricemia through the gut-liver axis.

OBJECTIVES: To investigate the inhibitory effect of pirfenidone (PFD) on growth of bladder cancer xenograft and its regulatory effect on Treg cells in tumor-bearing mice. METHODS: Thirty-two C57BL/6 mice bearing ectopic bladder tumors were randomized into control and PFD groups (n=16). In PFD group, PFD was administered orally at the daily dose of 500 mg/kg, and tumor growth and survival of the mice were monitored. After treatment for 21 days, the tumors and vital organs were harvested for analysis. Immunohistochemistry was used to assess CD3, CD4, CD8, and FOXP3 expressions in the tumors. Flow cytometry and RT-qPCR were used to analyze the percentage of CD4⁺CD25⁺FOXP3⁺ Treg cells and IL-2, IL-10, and IL-35 expressions in the tumors and spleens; organ damage of the mice was examined with HE staining. RESULTS: Compared with the control group, the PFD-treated mice exhibited significantly lower tumor growth rate with smaller tumor volumes at day 21, along with improved survival at day 28. Immunohistochemistry revealed no significant differences in the infiltration of CD3⁺ and CD8⁺ cells between the two groups, but the percentages of CD4⁺ and FOXP3⁺ cells were significantly lower in the tumors of PFD-treated mice. Flow cytometric analysis confirmed a decrease in CD4⁺CD25⁺FOXP3⁺ Treg cells in the tumors from PFD-treated mice, which also had reduced expression levels of IL-2, IL-10 and IL-35 mRNAs in the tumors. No significant differences were found in Treg cell populations or cytokine expressions in the spleen tissues between the two groups. HE staining showed obvious organ damage in neither of the groups. CONCLUSIONS PFD inhibits bladder cancer growth and enhances survival of tumor-bearing mice possibly by suppressing Treg cells in the tumor microenvironment.
Animals ; Urinary Bladder Neoplasms/drug therapy* ; Mice ; T-Lymphocytes, Regulatory/metabolism* ; Mice, Inbred C57BL ; Interleukins/metabolism* ; Interleukin-10/metabolism* ; Cell Line, Tumor ; Interleukin-2/metabolism* ; Xenograft Model Antitumor Assays ; Female

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease with a high mortality rate. Many countries worldwide have already reported local transmission, and the number of reported cases has been increasing yearly, with an ever-expanding region. No specific treatment drugs or vaccines have seriously threatened public health safety in epidemic regions. This article reviews the epidemiological characteristics, transmission routes, and control measures of SFTS.