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

OBJECTIVETo analyze the risk factors for deep vein thrombosis (DVT) of the lower extremity in patients with bone metastases.

METHODSNinety patients with bone metastases were admitted to our hospital From January 2010 to December 2011, and their clinical data were retrospectively analyzed. There were 57 males and 33 females with a mean age of 61 years (range, 27 to 78 years). On admission, all cases were detected by color Doppler ultrasonography for DVT of bilateral lower extremities. Univariate and multivariate analyses were performed to determine the probable risk factors including gender, age, body weight, tumor location, bed confinement and etc.

RESULTSAmong the 90 patients, DVT was found in 24 patients on admission and the DVT incidence was 26.7% (24/90). The univariate analysis showed that bed confinement, multiple metastasis, pathological fracture, primary lesion detected, blood group, fibrinogen and hematocrit were significantly related to the incidence of DVT (P < 0.05). The logistic multivariate regression analysis showed that bed confinement, pathological fracture and fibrinogen were independent risk factors for the incidence of DVT.

CONCLUSIONSBed confinement, pathological fracture and fibrinogen are independent risk factors for the incidence of DVT for patients with bone metastases. Patients with bed confinement >3 days, pathological fracture or fibrinogen >4 g/L should be routinely screened for lower extremity DVT on admission. Once identified, the DVT patients should be treated as early as possible.

Adult ; Aged ; Bone Neoplasms ; epidemiology ; secondary ; Female ; Humans ; Incidence ; Lower Extremity ; Male ; Middle Aged ; Neoplasm Metastasis ; Retrospective Studies ; Risk Factors ; Ultrasonography, Doppler, Color ; Venous Thrombosis ; epidemiology

BACKGROUND:The risk of lower extremity deep venous thrombosis was high in patients with bone metastases. Major surgery is a major risk factor for thrombosis. There was no standard prophylactic regimen available.
OBJECTIVE:To investigate the efficacy and safety of low molecular weight heparins versus rivaroxaban in the postoperative prevention of lower extremity deep venous thrombosis in patients with bone metastases.
METHODS:From January 2010 to December 2013, a total of 73 patients with bone metastasis in spine, pelvis and lower extremities, who underwent open surgery in the Department of Musculoskeletal Tumor, Third Hospital, Hebei Medical University, China, were retrospectively analyzed. The patients were divided into low molecular weight heparins group (n=41) and rivaroxaban group (n=32) according to the prophylactic drugs after surgery.
RESULTS AND CONCLUSION:Nine cases (22%) in the low molecular weight heparins group were found lower extremity deep venous thrombosis, and six cases (19%) in the rivaroxaban group suffered from lower extremity deep venous thrombosis, showing no significant differences (χ2=0.11, P=0.74). The incidences of bleeding events in both groups were respectively 7.32%and 6.25%, showing no significant differences (correctionχ2=0.083, P>0.05). There were no significant differences regarding the levels of platelet, activated partial thromboplastin time and prothrombin time between both groups preoperatively or postoperatively (P>0.05). Therefore, the efficacy and safety of low molecular weight heparins and rivaroxaban in the postoperative prevention of lower extremity deep venous thrombosis were similar. Both could effectively reduce the incidence of deep venous thrombosis, with a relative low risk of bleeding.