ObjectiveTo evaluate the effects and safety of the optimized new Shengmai Powder （优化新生脉散方） on exercise tolerance in patients with chronic heart failure （CHF） of qi deficiency， blood stasis， and fluid retention syndrome. MethodsA randomized， double-blind， placebo-controlled trial was conducted. A total of 78 CHF patients with qi deficiency， blood stasis， and fluid retention syndrome were recruited and randomly assigned to a treatment group （39 cases） and a control group （39 cases）. On the basis of conventional western medical therapy， patients in the treatment group additionally received the optimized new Shengmai Powder granules， while the control group was given an oral placebo of optimized new Shengmai Powder granules. Patients in both groups took 30.6 g each time， twice a day， mixed with water for administration， with a total treatment course of 4 weeks. The primary outcomes were 6-minute walk distance （6MWD） and peak oxygen uptake （Peak VO₂） measured by cardiopulmonary exercise testing. Secondary outcomes included New York Heart Association （NYHA） functional classification， B-type natriuretic peptide （BNP） levels， cardiac function indexes including left ventricular ejection fraction （LVEF）， left ventri-cular end-systolic diameter （LVESD） and left ventricular end-diastolic diameter （LVEDD）， Minnesota Living with Heart Failure Questionnaire （MLHFQ） scores， and scores of four diagnostic information of traditional Chinese medicine （TCM）. All indicators were assessed once before and after treatment respectively. Safety indicators were evaluated， and adverse events during the trial were recorded. ResultsAll patients in both groups were included in the full ana-lysis set （FAS） and safety set （SS）. Compared with baseline， the 6MWD and Peak VO₂ of cardiopulmonary exercise test in the treatment group significantly increased after treatment， while the MLHFQ scores， serum BNP levels and scores of TCM four diagnostic information significantly decreased， and the NYHA cardiac function grade significantly improved （P＜0.01）. After treatment， the 6MWD and Peak VO₂ of cardiopulmonary exercise test， as well as their changes from baseline in the treatment group were higher than those in the control group； the MLHFQ scores， serum BNP levels and scores of TCM four diagnostic information in the treatment group were lower than those in the control group； and the improvement of NYHA cardiac function grade in the treatment group was superior to that in the control group （P＜0.01）. There was no statistically significant differences in all indicators after treatment in the control group （P＞0.05）. The incidence of adverse events was 5.1% （2/39） in the treatment group and 2.6% （1/39） in the control group， with no statistically significant difference between groups （P＞0.05）. ConclusionOn the basis of conventional western medicine treatment， the addition of the optimized new Shengmai Powder can further improve exercise tolerance， cardiac function and quality of life in patients with CHF of qi deficiency， blood stasis and fluid retention syndrome， and show good safety.

In response to the clinical needs of cancer treatment and rehabilitation, Professor Lin Hongsheng proposed the Wuzhi Wuyang (five treatments and rehabilitation) concept on the basis of years of clinical experience and the Guben Qingyuan (consolidate the foundation and clear the source) theory. Wuzhi Wuyang emphasizes the importance of treatment and rehabilitation and aims to provide personalized and stage-specific treatment and rehabilitation plans by integrating the advantages of traditional Chinese medicine (TCM) and modern medicine to achieve comprehensive life-cycle management for patients with cancer. The proposal of Wuzhi Wuyang has provided new ideas and methods for the treatment, prevention, and rehabilitation of cancer, along with valuable references for clinical practice and academic research. This article summarizes the connotation of Wuzhi Wuyang and its application in the comprehensive management of cancer prevention and treatment with TCM.

OBJECTIVE To analyze the influential factors for clinical efficacy of polymyxin B combined with other antibiotics in the treatment of carbapenem-resistant Acinetobacter baumannii （CRAB） pulmonary infection. METHODS A retrospective analysis was conducted on the clinical data of patients with CRAB pulmonary infection in our hospital from May 2021 to October 2024. Information such as age， gender， admitting department， infection status， underlying medical conditions， mechanical ventilation time， combination anti-infective treatment regimens， and the Acute Physiology and Chronic Health Evaluation Ⅱ （APACHE-Ⅱ） score 24 h before medication was compiled. Based on the effectiveness of the treatment， patients were divided into treatment-effective group and treatment-ineffective group. Univariate analysis and multivariate Logistic regression analysis were employed to identify independent factors influencing clinical efficacy. RESULTS A total of 156 patients were included， and 108 patients were treated effectively， with an effective rate of 69.23%. The results of univariate analysis indicated that there were statistically significant differences between 2 groups in terms of the duration of mechanical ventilation time， APACHE-Ⅱ score 24 h before medication， the number of complication types， the proportion of abnormal coagulation function， anti-infective treatment course， and hospital stay before medication （P＜0.05）. The results of multivariate Logistic regression analysis showed that APACHE-Ⅱ score≥15 points 24 h before medication [OR＝2.965， 95%CI （1.284， 6.845）， P＝0.020]， mechanical 20251606） ventilation time≥10 d [OR＝3.577， 95%CI （1.185， 10.793）， P＝0.037] and hospital stay≥14 d before medication [OR＝2.422， 95%CI （1.036， 5.654）， P＝0.041] were independent 15120420253@139.com risk factors， and anti-infective treatment course＞7 d was a protective factor [OR＝0.445， 95%CI （0.221， 0.895）， P＝0.043]. CONCLUSIONS This study shows that the effective rate of polymyxin B combined with other antibiotics in the treatment of CRAB pulmonary infection is less than 70%. The mechanical ventilation time≥10 d， APACHE-Ⅱ score≥15 points 24 h before medication， and hospital stay≥14 d before medication may lead to treatment failure， whereas anti-infective treatment course＞7 d may be associated with treatment success.

Hepatocellular carcinoma （HCC）， as the sixth most common malignant tumor worldwide， poses a serious threat to human health due to its insidious onset and high mortality rate. This article reviews the molecular mechanisms and intervention strategies of gut microbiota （GM） homeostasis in the development and progression of HCC， in order to provide new ideas for the intervention and treatment of HCC. Studies have shown that GM dysbiosis， intestinal leakage， microbial-associated molecular pattern， bacterial translocation， and metabolic products play key roles in the progression of HCC. GM imbalance may lead to immune escape， thereby promoting tumor cell proliferation and metastasis. This article elaborates on the association between GM and HCC， deeply analyzes the mechanism of action of GM in the development and progression of HCC， investigates the role of bile acid-related metabolites， short-chain fatty acid-related metabolites， and other metabolites in HCC， and explores the strategies for targeting GM in the treatment of HCC， including probiotics， prebiotics， antibiotics， Toll-like receptor 4 antagonists， and fecal microbiota transplantation. This article emphasizes that maintaining the integrity of the intestinal barrier and GM homeostasis is of great significance in the prevention and treatment of HCC， which provides a direction for developing new diagnosis and treatment strategies.

OBJECTIVE To systematically evaluate the influential factors for the clinical efficacy of tigecycline in the treatment of severe infections caused by multidrug-resistant Gram-negative bacteria （MDR-GNB）. METHODS Retrieved from PubMed， Embase， The Cochrane Library， CNKI database， Wanfang database and VIP database， the studies about the influential factors for the clinical efficacy of tigecycline in the treatment of adult patients with severe infections caused by MDR-GNB from the database construction to April 30， 2025. After screening literature， extracting data and evaluating the quality of literature， systematic review was performed by using RevMan 5.3 software. RESULTS A total of 14 studies involving 2 033 patients were included， of which 1 355 patients showed effective treatment outcomes. The meta-analysis results showed that Acute Physiology and Chronic Health Evaluation （APACHE）-Ⅱ ＞ 20 [OR＝4.50， 95%CI （2.28， 8.85）， P＜0.001]， malignant tumor [OR＝1.96， 95%CI （1.41， 2.72）， P＜0.001]， hemodialysis [OR＝2.09， 95%CI （1.40， 3.12）， P＜0.001]， septic shock [OR＝3.07， 95%CI （2.00， 4.72）， P＜0.001]， mechanical ventilation [OR＝2.31， 95%CI （1.57， 3.39）， P＜0.001]， coagulation dysfunction [OR＝ 3.03， 95%CI （2.09， 4.37）， P＜0.001]， glucocorticoids use＞3 days [OR＝2.26， 95%CI （1.14， 4.45）， P＝0.020]， and longer hospitalization time before using tigecycline [OR＝3.33， 95%CI （1.34， 8.30）， P＝0.010] were risk factors for the clinical efficacy of tigecycline in treatment of severe infections caused by MDR-GNB. Tigecycline initial double-dose regimen [OR＝0.23， 95%CI （0.13， 0.42）， P＜0.001]， combination therapy [OR＝0.15， 95%CI （0.05， 0.48）， P＝0.001]， and prolonged treatment course [OR＝0.91， 95%CI （0.88， 0.95）， P＜0.001] were protective factors. CONCLUSIONS There are many influential factors for the clinical efficacy of tigecycline in the treatment of severe infections caused by MDR-GNB， among which APACHE-Ⅱ score＞20， malignant tumor， hemodialysis， septic shock， mechanical ventilation， coagulation dysfunction， glucocorticoids＞3 d and longer hospitalization time before using tigecycline before tigecycline （No.20251606） use are risk factors； tigecycline double dose， combined medication and longer treatment course are protective factors.

OBJECTIVES: To explore the association of the expression of WW domain-containing ubiquitin E3 ligase 1 (WWP1) with immune infiltration in tumor microenvironment (TME) of ovarian cancer. METHODS: Ovarian cancer patient data from The Cancer Genome Atlas (TCGA) were used to analyze the association of WWP1 expression with patient prognosis. TISCH2 was utilized to analyze the changes in immune cell subtypes in TME of metastatic tumor and after chemotherapy. The impact of WWP1 on immune cell infiltration, somatic copy number alterations of WWP1 and evolution of immune cell subtypes was evaluated using TIMER and TIGER pseudo-time analysis. A deep learning model was used to analyze TCGA pathological images to investigate the effect of WWP1 on TME of ovarian cancer. RNA-seq analysis was conducted to identify the differentially expressed genes in WWP1-overexpressing SKOV3 cells and validate immune infiltration. Multicolor immunofluorescence assay was used to analyze the immune markers in SKOV3 and SKOV3/DDP cell xenografts in nude mice. RESULTS: The patients with high WWP1 expression levels had significantly lower overall survival rate (P=0.0012). High WWP1 expression levels and Stage IV disease were both associated with a poor prognosis (P<0.05). In metastatic ovarian cancer or after chemotherapy, the percentages of malignant tumor cells and tumor-associated fibroblasts increased in the TME, accompanied by elevated WWP1 levels. WWP1 expression level was positively correlated with pro-tumorigenic immunosuppressive cells (r=0.1323-0.3955, P<0.05) and negatively with tumor-inhibiting immune cells (r=-0.1949- -0.1333, P<0.05). Specific copy number alterations of WWP1 also influenced CD8⁺ T cell percentage and neutrophil infiltration levels in the TME. RNA-seq analysis of WWP1-overexpressing SKOV3 cells and immunofluorescence assay of the tumor-bearing mice yielded findings consistent with those of bioinformatics analysis. CONCLUSIONS WWP1 may serve as a prognostic biomarker and a potential target for immune regulation in the TME of ovarian cancer.
Female ; Ovarian Neoplasms/genetics* ; Humans ; Ubiquitin-Protein Ligases/metabolism* ; Tumor Microenvironment/immunology* ; Animals ; Mice ; Cell Line, Tumor ; Mice, Nude ; Prognosis ; Gene Expression Regulation, Neoplastic

Breast cancer (BC) is one of the most prevalent malignant tumors affecting women worldwide, with its incidence rate continuously increasing. As a result, treatment strategies for this disease have received considerable attention. Research has highlighted the crucial role of the Hedgehog (Hh) signaling pathway in the initiation and progression of BC, particularly in promoting tumor growth and metastasis. Therefore, molecular targets within this pathway represent promising opportunities for the development of novel BC therapies. This study aims to elucidate the therapeutic mechanisms by which natural compounds modulate the Hh signaling pathway in BC. By conducting a comprehensive review of various natural compounds, including polyphenols, terpenes, and alkaloids, we reveal both common and unique regulatory mechanisms that influence this pathway. This investigation represents the first comprehensive analysis of five distinct mechanisms through which natural compounds modulate key molecules within the Hh pathway and their impact on the aggressive behaviors of BC. Furthermore, by exploring the structure-activity relationships between these compounds and their molecular targets, we shed light on the specific structural features that enable natural compounds to interact with various components of the Hh pathway. These novel insights contribute to advancing the development and clinical application of natural compound-based therapeutics. Our thorough review not only lays the groundwork for exploring innovative BC treatments but also opens new avenues for leveraging natural compounds in cancer therapy.

Objective To explore the effects of combined exposure to bisphenol A (BPA) and high-fat diet on liver lipid metabolism and hepatocyte senescence in mice, and to elucidate the potential mechanisms of the onset and development of non-alcoholic fatty liver disease (NAFLD). Methods Specific pathogen free C57BL/6J mice were randomly divided into six groups, with 10 mice with equal numbers of each sex in each group. The mice in the control group and the simple BPA group were fed with regular diet, while others four groups of mice were fed with high-fat diet. At the same time, the mice in the simple BPA group were intragastric administered with BPA at a dose of 50 μg/kg body weight, while the mice in the low-, medium- and high-dose BPA+high-fat groups were intragastric administered with BPA at doses of 5, 50 and 500 μg/kg body weight respectively. The mice in the control group and the high-fat group were intragastric administered with the same volume of corn oil once per day for 90 consecutive days. Liver tissues were subjected to hematoxylin-eosin (HE) and Oil Red O staining. Liver coefficients and lipid-stained area ratios were calculated. Serum level of total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, and the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined using an automatic biochemical analyzer. The hepatic tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-10 levels were quantified by enzyme-linked immunosorbent assay. The relative expression of cholesterol regulatory element binding protein 1 (SREBP1), CCAAT enhancer binding protein α, P16, and phosphorylated histone H2AX (γ-H2AX) in liver tissues was detected using Western blotting. The interaction effect of the combined exposure to BPA and high-fat diet was observed based on the result of mice in the control group, the simple high-fat group, the simple BPA group, and the medium-dose BPA group+high-fat group (the combined exposure group) using a 2×2 factorial design. The results of mice in the simple high-fat group and the low-, medium-, and high-dose BPA+high-fat groups were used to observe the effect of BPA exposure dose under high-fat diet conditions. Results i) The interactive effect of combined exposure to BPA and high fat. The HE and Oil Red O staining results indicated that the combined exposure to BPA and high-fat diet successfully established NAFLD in mice. The interactive effect of combined exposure to BPA and high-fat diet on serum ALT activity and the relative expression of P16 in the liver tissue of female mice, as well as the serum ALT and AST activities and the relative expression of SREBP1 in the liver tissue of male mice was significant (all P<0.05). Specifically, the serum ALT activity of male mice in the combined exposure group was higher than that in the simple high-fat group (P<0.05), while the ALT activity in the serum of female mice in the combined exposure group was lower than that in the simple BPA group (P<0.05). The relative expression of SREBP1 protein in the liver tissue of male mice in the combined exposure group was higher than that in the control group, the simple high-fat group, and the simple BPA group (all P<0.05). For the other indicators, there were no significant differences in the interactive effect of combined exposure to BPA and high-fat diet (all P>0.05). ii) Dose effects of BPA exposure. The HE and Oil Red O staining result showed that the degree of vacuolar steatosis in the liver of female and male mice of medium- and high-dose BPA + high-fat groups was aggravated, and the range of inflammatory cell infiltration was expanded when compared with same-sex mice in the simple high-fat group. The serum ALT activity and the fat stained area ratio, as well as the relative expression of P16 in liver tissue of female mice in high-dose BPA + high-fat group increased (all P<0.05), while the level of IL-10 in liver tissue decreased (P<0.05), compared with the female mice in simple high-fat group. The serum ALT activity, the TNF-α level in liver tissue, and the relative expression of SREBP1, P16 and γ-H2AX proteins in liver tissue of male mice in high-dose BPA + high-fat group increased (all P<0.05), while the IL-6 level in liver tissue decreased (P<0.05), compared with the male mice in simple high-fat group. For the female or male mice in the low- and medium-dose BPA + high-fat groups, only some of the above indicators showed significant changes (all P<0.05). Conclusion The combined exposure to BPA and high-fat diet has a synergistic effect on the onset and development of NAFLD. The mechanism may be related to inducing cellular senescence and modulation of lipid synthesis pathways, thereby affecting liver steatosis. The exposure dose of BPA may affect the synergistic effect.

Objective:To discuss whether safranal affects the proliferation,migration,and phenotypic transformation of the vascular smooth muscle cells(VSMCs)in a high-glucose environment and to clarify the function of safranal in the prevention and treatment of diabetic(DM)vascular complications.Methods:The SD rats were selected as experimental subjects;primary VSMCs were cultured from rat thoracic aortas and divided into control group,25 mmol·L-1 high glucose(HG)group,HG+20 μmol·L-1 safranal group,HG+40 μmol·L-1 safranal group,and HG+80 μmol·L-1 safranal group.The cells in control group received no treatment;the cells in 25 mmol·L-1 HG group were pretreated with 25 mmol·L-1 HG;the cells in HG+20,40,and 80 μmol·L-1 safranal groups were further treated with 20,40,and 80 μmol·L-1 safranal respectively for 48 h on the basis of 25 mmol·L-1 HG group.Cell counting kit-8(CCK-8)method was used to determine the appropriate concentration of safranal and detect the viabilities of the VSMCs in various groups;cell scratch healing assay was used to detect the scratch healing rates of the VSMCs in various groups;Transwell chamber assay was used to detect the numbers of the migration VSMCs in various groups;immunofluorescence method was used to detect the fluorescence intensities of alpha-smooth muscle actin(α-SMA)and rabbit anti-osteopontin(OPN)in the VSMCs in various groups;Western blotting method was used to detect the expression levels of OPN,α-SMA,and proliferating cell nuclear antigen(PCNA)in the VSMCs in various groups.Results:Under microscope,on the 4th day of in vitro culture,the spindle-shaped or triangular cells crawled out from the edge of the thoracic aorta tissue blocks,with long spindle being the most common morphology.On the 14th,the cells gradually covered the bottom of the dish;when cell density reached 80%-90%,the characteristic"hills and valleys"growth pattern appeared.Third-generation cells were taken for immunofluorescence identification;immunofluorescence staining with VSMC-specific marker α-SMA showed positive expression of α-SMA protein in the primarily cultured VSMCs.The CCK-8 assay results showed that compared with control group,the cell viability of the cells in 160 μmol·L-1 safranal group was significantly decreased(P<0.01),indicating toxic damage to the cells.Under the conditions of safranal concentrations at 20,40,and 80 μmol·L-1 respectively,after 48 h intervention on VSMCs,no significant adverse effect on cell viability was observed;considering both the effect and toxicity of safranal,these three concentrations were used in subsequent cell experiments.After 48 h intervention,compared with control group,the activity of the VSMCs in 25 mmol·L-1 HG group was increased(P<0.001);compared with 25 mmol·L-1 HG group,the activities of the VSMCs in HG+20,40,and 80 μmol·L-1 safranal groups were gradually decreased(P<0.05).The cell scratch healing assay and Transwell assay results showed that after 48 h intervention,the scratch healing rate of the VSMCs in 25 mmol·L-1 HG group was significantly higher than that in control group(P<0.01),and the number of transmembrane cells through the Transwell chamber was significantly increased(P<0.05);compared with 25 mmol·L-1 HG group,the scratch healing rates of the VSMCs in HG+20,40,and 80 μmol·L-1 safranal groups were gradually decreased(P<0.05),and the number of transmembrane cells was decreased(P<0.05).The immunofluorescence staining results showed that compared with control group,the fluorescence intensity of α-SMA protein in the VSMCs in 25 mmol·L-1 HG group was significantly weakened(P<0.001),while the fluorescence intensity of OPN protein was significantly enhanced(P<0.001);compared with 25 mmol·L-1 HG group,the fluorescence intensities of α-SMA protein in the VSMCs in HG+20,40,and 80 μmol·L-1 safranal groups were gradually increased(P<0.05),and the fluorescence intensities of OPN were gradually weakened(P<0.05).The Western blotting method results showed that compared with control group,the expression level of α-SMA protein in the VSMCs in 25 mmol·L-1 HG group was decreased(P<0.05),and the expression levels of PCNA and OPN proteins were increased(P<0.01);compared with 25 mmol·L-1 HG group,the expression level of α-SMA protein in the VSMCs in HG+20,40,and 80 μmol·L-1 safranal groups were increased(P<0.05),and the expression levels of PCNA and OPN proteins were decreased(P<0.05).Conclusion:Safranal can inhibit the proliferation,migration,and phenotypic transformation of the VSMCs induced by high glucose.

Objective:To investigate the correlation between CHA 2DS 2-VASC score and the recurrence risk of paroxysmal atrial fibrillation after radiofrequency ablation. Methods:It was a retrospective cohort study. A total of 150 patients who underwent radiofrequency ablation for paroxysmal atrial fibrillation in Xingtai People′s Hospital from January 2017 to January 2021 were consecutively included in the study. According to the preoperative CHA 2DS 2-VASC score, patients were divided into high score group (≥3 points, n=90) and low score group (<3 points, n=60). Baseline clinical data was collected. All patients underwent circumferential pulmonary vein isolation, and those with atrial flutter before ablation also underwent tricuspid isthmus isolation. Holter and electrocardiogram examinations were performed at 3, 6 months and 1 year after ablation to evaluate whether there was recurrence of atrial fibrillation. Univariate and multivariate Cox regression was used to analyze the risk factors for recurrence of atrial fibrillation after radiofrequency ablation. Results:Among 150 patients 90 were males and 60 were females with a mean age of (64.0±3.6) years. There were no significant differences in age, sex, and proportion of hypertension, diabetes, chronic heart failure and stroke or transient ischemic attack (TIA), medication of antiarrhythmic and anticoagulant drugs between the two groups (all P>0.05). The longest duration of atrial fibrillation in the high score group was significantly longer than that in the low score group (26.0±6.1) hours vs. (10.0±2.1) hours, P<0.05). There were no patients with cardiac tamponade, atrial esophageal fistula and severe vascular puncture complications in the two groups. During the follow-up period, the recurrence rate in the high score group was significantly higher than that in the low score group (16.7% (15/90) vs. 8.3% (5/60), P<0.05). Multivariate Cox regression analysis showed that CHA 2DS 2-VASC score≥3 was an independent risk factor for atrial fibrillation recurrence in patients with paroxysmal atrial fibrillation after radiofrequency ablation ( HR=3.84, 95% CI: 1.87-7.89, P=0.02). Conclusion:CHA 2DS 2-VASC score≥3 is an independent risk factor for atrial fibrillation recurrence in patients with paroxysmal atrial fibrillation after radiofrequency ablation.