Objective To investigate the clinical efficacy of Zhikang Capsules plus Compound Huangbai Lotion for retention enema in the treatment of patients with mild to moderate distal ulcerative colitis(UC)of damp-heat in large intestine type,and to observe their effects on the serum levels of pro-inflammatory cytokines of tumor necrosis factor α(TNF-α),interleukin 6(IL-6)and C-reactive protein(CRP).Methods A total of 110 patients with mild to moderate distal UC of damp-heat in large intestine type who were treated in the Outpatient Clinics and Wards of the Third Affiliated Hospital of Henan University of Traditional Chinese Medicine from October 2022 to December 2023 were randomly divided into an observation group and a control group according to random number table method,with 55 patients in each group.The control group was given retention enema with 1 g of Xilei Powder and 50 mL of Compound Huangbai Lotion before going to bed every night,while the observation group was given retention enema with 2.4 g of Zhikang Capsules and 50 mL of Compound Huangbai Lotion before going to bed every night The course of treatment for the two groups covered 14 days.The changes in the serum inflammation factors,coagulation function indicators,traditional Chinese medicine(TCM)syndrome scores,and the Inflammatory Bowel Disease Quality of Life Questionnaire(IBDQ)scores in the two groups were observed before and after treatment.After treatment,the clinical efficacy and drug safety in the two groups were evaluated.Results(1)After 14 days of treatment,the total effective rate of the observation group was 90.91％(50/55)and that of the control group was 80.00％(44/55),and the intergroup comparison(tested by rank sum test)showed that the therapeutic efficacy of the observation group was significantly superior to that of the control group(P＜0.01).(2)After treatment,the serum levels of inflammation factors of TNF-α,IL-6,and CRP patients in the two groups were decreased compared with those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.05 or P＜0.01).(3)After treatment,the prothrombin time(PT)and fibrinogen(FIB)of the two groups of patients were improved compared with those before treatment(P＜0.05),while the improvement of thrombin time(TT)and activated partial thromboplastin time(APTT)were not obvious when compared with those before treatment(P＞0.05);the comparison between the two groups showed that the improvement of PT and FIB in the observation group was significantly superior to that in the control group(P＜0.05 or P＜0.01).(4)After treatment,the scores of TCM symptoms of diarrhea,mucous-purulent and bloody stool,tenesmus,scorching sensation of the anus in the two groups were decreased compared with those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.05 or P＜0.01).(5)After treatment,the scores of IBDQ items of general symptoms,intestinal symptoms,social functioning,emotional role functioning in the two groups were increased compared with those before treatment(P＜0.05),and the increase in the observation group was significantly superior to that in the control group(P＜0.01).(6)During the treatment,no obvious adverse reactions occurred in the two groups,with higher safety.Conclusion Zhikang Capsules plus Compound Huangbai Lotion for retention enema are effective and safe in treating mild to moderate distal UC of damp-heat in large intestine type.The therapy can effectively control the illness of UC,alleviate the clinical symptoms and negative emotions,improve the inflammatory response and coagulation function,and enhance the quality of life of the patients.

Objective To investigate the mechanism of E26 transformation-specific sequence 4(ETV4)affecting the proliferation and migration of colon cancer cells through the nuclear factor-κB(NF-κB)signaling pathway.Methods The expression level of ETV4 in normal colon tissues and cancer tissues was analyzed by the user-friendly interactive cancer transcriptome data analysis resource(UALCAN)database.Reverse transcription quantitative polymerase chain reaction(qRT-PCR)and Western blot were used to detect the expression level of ETV4 in normal intestinal epithelial cells and colon cancer cell lines.After silencing ETV4 in SW480 cells,qRT-PCR and Western blot were per-formed to detect the expression of ETV4 to assess transfection efficiency;colony formation and Tran-swell assays were conducted to explore the effects of ETV4 silencing on the proliferation and migration of colon cancer cells;the Western blot was used to detect the effects of ETV4 silencing on the protein expression of protein 65(p65)and phosphorylated protein 65(p-p65)in the NF-κB pathway.Results The UALCAN database analysis revealed high expression of ETV4 in colon cancer tissues.The qRT-PCR and Western blot showed that ETV4 expression was significantly higher in the colon cancer cell lines SW480,Lovo,Caco-2,and SW620 than in normal intestinal epithelial cells HIEC-6,with the highest expression in SW480 cells(P＜0.001).Colony formation and Transwell assay results indicated that silencing ETV4 significantly inhibited the proliferation and migration of colon cancer SW480 cells(P＜0.001).Western blot results showed that silencing ETV4 significantly inhibited the expression of p-p65 protein in the cells(P＜0.001).Conclusion Silencing ETV4 may inhibit the activation of the NF-κB signaling pathway,thereby inhibiting the proliferation and migration of colon cancer cells.

Objective: To compare the efficacy and safety of combining diosmin with Jiuhua hemorrhoid suppository versus diosmin alone for the treatment of hemorrhoid hemorrhage. Methods: The Jiuhua hemorrhoid suppository study was conducted in 10 medical centers across China from April 1, 2019 to June 30, 2020. Patients with hemorrhoid bleeding were randomized in a ratio of 1 : 1 to either receive Jiuhua hemorrhoid suppository and diosmin tablets (the study group) or diosmin tablets alone (the control group). The suppository was used once a day after defecation or at bedtime after rinsing the anus with warm water. Diosmin tablets were administered only once a day (0.9 g). The primary endpoint of the study was the assessment of hemorrhoid bleeding relief 7 ± 2 days after treatment, classified as “very effective” “effective” and “ineffective”. The secondary endpoint included the evaluation of pain alleviation using the visual analogue scale (VAS, with scores ranging from 0 to 10) and edema (with scores ranging from 0 to 3). The safety of the two treatment regimens was evaluated 14 ± 2 days after drug administration. Results: The full analysis set (FAS) comprised 107 participants in the study group and 111 in the control group, while the per-protocol set (PPS) included 106 participants in the study group and 111 in the control group. In terms of hemorrhoid bleeding, the proportion of very effective and effective cases in the study group were significantly higher than that in the control group [106 (99.06%) vs. 91 (81.98%), P < 0.0001] in the FAS, and the PPS results [105 (99.06%) vs. 91 (81.98%), P < 0.0001] were comparable to the FAS results. The pain VAS scores at day 7 after treatment were comparable between the two groups (0.80 ± 1.17 vs. 0.80 ± 1.20, P = 0.2177). The majority of the participants in both groups had an edema score of 0 at day 7 after treatment [96 (89.72%) vs. 99 (91.67%), P = 0.370 5]. Adverse events (AEs) occurred in 9 patients (8.4%) in the study group and 3 patients (2.7%) in the control group. In addition, 5 AEs in the study group and 1 AE in the control group were possibly in association with the study drug. Conclusion Compared with the administration of diosmin oral tablets alone, the addition of Jiuhua hemorrhoid suppository to the tablets demonstrates enhanced efficacy in addressing hemorrhoid bleeding, with satisfactory patient adherence and acceptable safety.

Diabetic nephropathy (DN) is considered the primary causes of end-stage renal disease (ESRD) and is related to abnormal glycolipid metabolism, hemodynamic abnormalities, oxidative stress and chronic inflammation. Antagonism of vascular endothelial growth factor B (VEGF-B) could efficiently ameliorate DN by reducing renal lipotoxicity. However, this pharmacological strategy is far from satisfactory, as it ignores numerous pathogenic factors, including anomalous reactive oxygen species (ROS) generation and inflammatory responses. We found that the upregulation of VEGF-B and downregulation of interleukin-22 (IL-22) among DN patients were significantly associated with the progression of DN. Thus, we hypothesized that a combination of a VEGF-B antibody and IL-22 could protect against DN not only by regulating glycolipid metabolism but also by reducing the accumulation of inflammation and ROS. To meet these challenges, a novel anti-VEGFB/IL22 fusion protein was developed, and its therapeutic effects on DN were further studied. We found that the anti-VEGFB/IL22 fusion protein reduced renal lipid accumulation by inhibiting the expression of fatty acid transport proteins and ameliorated inflammatory responses

The Hedgehog (HH) signaling pathway plays important roles in gastrointestinal carcinogenesis and the gastrointestinal tumor microenvironment (TME). Aberrant HH signaling activation may accelerate the growth of gastrointestinal tumors and lead to tumor immune tolerance and drug resistance. The interaction between HH signaling and the TME is intimately involved in these processes, for example, tumor growth, tumor immune tolerance, inflammation, and drug resistance. Evidence indicates that inflammatory factors in the TME, such as interleukin 6 (IL-6) and interferon-

Inflammation plays an important role in the development of acute lung injury (ALI). Severe pulmonary inflammation can cause acute respiratory distress syndrome (ARDS) or even death. Expression of proinflammatory interleukin-1β(IL-1β) and inducible nitric oxide synthase (iNOS) in the process of pulmonary inflammation will further exacerbate the severity of ALI. The purpose of this study was to explore the effect of Palrnatine (Pa) on lipopolysaccharide (LPS)-induced mouse ALI and its underlying mechanism. Pa, a natural product, has a wide range of pharmacological activities with the potential to protect against lung injury. Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) assays were performed to detect the expression and translation of inflammatory genes and proteins in vitro and in vivo. Immunoprecipitation was used to detect the degree of P65 translocation into the nucleus. We also used molecular modeling to further clarify the mechanism of action. The results showed that Pa pretreatment could significantly inhibit the expression and secretion of the inflammatory cytokine IL-1β, and significantly reduce the protein level of the proinflammatory protease iNOS, in both in vivo and in vitro models induced by LPS. Further mechanism studies showed that Pa could significantly inhibit the activation of the protein kinase B (Akt)/nuclear factor-κB (NF-κB) signaling pathway in the LPS-induced ALI mode and in LPS-induced RAW264.7 cells. Through molecular dynamics simulation, we observed that Pa was bound to the catalytic pocket of Akt and effectively inhibited the biological activity of Akt. These results indicated that Pa significantly relieves LPS-induced ALI by activating the Akt/NF-κB signaling pathway.

Vertebral augmentation (VA) is widely used in the clinical treatment of osteoporotic vertebral compression fracture (OVCF), but its clinical efficacy has always been controversial. Since 2009, a total of four high-quality prospective randomized double-blind placebo-controlled studies have been published, but their conclusions on the effectiveness of VA were inconsistent. Latest Cochrane review (2018) and American society for bone and mineral research task report (2019) believed that compared with sham surgery, there is no advantage supporting the use of VA as a routine treatment for patients with OVCF, which triggered a new round of debates. The effectiveness of the VA remains to be determined, which makes it difficult to guide the actual clinical work of surgeons. This paper reviews the key studies in the controversy, sorts out and analyzes the details and latest views in the controversy, summarizes the impact of VA on the mortality rate of OVCF patients, and puts forward the optimal application mode of VA based on the current evidence.

Gene therapy is rapidly emerging as a powerful therapeutic strategy for a wide range of neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD). Some early clinical trials have failed to achieve satisfactory therapeutic effects. Efforts to enhance effectiveness are now concentrating on three major fields: identification of new vectors, novel therapeutic targets, and reliable of delivery routes for transgenes. These approaches are being assessed closely in preclinical and clinical trials, which may ultimately provide powerful treatments for patients. Here, we discuss advances and challenges of gene therapy for neurodegenerative disorders, highlighting promising technologies, targets, and future prospects.

Objective: To investigate the incidence and risk factors of catheter-related venous thrombosis (PICC-DVT) after peripherally inserted central catheter (PICC) in patients with hematologic malignancies, and to analyze the safety of anti-coagulation therapy with low-molecular-weight heparin. Methods: From August 2016 to June 2018, 43 patients with hematologic malignancies received PICC in Baoan District People's Hospital of Shenzhen City were enrolled. The patients were divided into low-molecular-weight heparin anticoagulation group (22 cases) and blank control group (21 cases) according to the random number table method. The blood routine, coagulation quadruple, D-dimer, protein C activity, protein S activity, and antithrombin Ⅲ activity before and after catheterization were compared between the two groups. Results: Of the 43 patients, 5 cases (11.62%) occurred PICC-DVT within 1 month after PICC, including 2 cases (9.09%) in the low-molecular-weight heparin anticoagulation group, and 3 cases (14.29%) in the blank control group, the difference between the two groups was not statistically significant (P = 0.664). No pulmonary embolism occurred in all patients with PICC-DVT. One case in the blank control group developed PICC-DVT and catheter-associated staphylococcus aureus infection, the patient was extubated after anti-infection and thrombolytic therapy, the other patients with PICC-DVT were not extubated, and the thrombus was dissolved after anticoagulant therapy. There were no significant differences in the white blood cell count, platelet count, prothrombin time, activated partial thromboplastin time, D-dimer, protein C activity, protein S activity, and antithrombin Ⅲ activity between the low-molecular-weight heparin anticoagulation group and blank control group (all P > 0.05). The anticoagulant index (protein C, protein S or antithrombin Ⅲ activity) was decreased in 5 patients with PICC-DVT, and in 38 non-thrombotic patients, the anticoagulant index was reduced in 16 patients (42.11%), the difference was statistically significant (P = 0.021). Conclusions The incidence of protein C, protein S or antithrombin Ⅲ activity reduction in hematological malignancies patients with PICC-DVT is higher than that in non-thrombotic patients. Low-molecular-weight heparin anticoagulant therapy can not reduce the occurrence of PICC-DVT within 1 month after PICC in patients with hematological malignancies, but the treatment is safe and has no relevant bleeding event.

Humans ; Leukemia, Promyelocytic, Acute ; Sarcoma, Myeloid