The Therapeutic potential of interferon-gamma in tuberculosis

Tuberculosis is one of the critical health problems worldwide. The search for ways to improve the results of tuberculosis treatment and overcome drug resistance lies in understanding the pathogenesis of the development of the infectious process. The interferon system, particularly the role of interferon-gamma, has been identified as the main link in the immune response in tuberculosis. The clinical efficacy of interferon-gamma has been studied and evaluated in clinical trials since the end of the last century. There was obtained evidence of the clinical efficacy of interferon-gamma as part of complex therapy. Recent experimental data make it possible to consider interferon-gamma as a promising therapeutic option for the treatment of multidrug-resistant tuberculosis as part of complex therapy worthy of further studies.

Short-Term Clinical Efficacy of Femoral Neck System Versus Multiple Cannulated Compression Screws in the Treatment of Garden III and IV Femoral Neck Fractures

Femoral neck system (FNS) , as a novel minimally invasive internal fixation device, has been gradually applied in the treatment of femoral neck fracture.However, there are few related clinical studies on FNS at present, especially there is no clinical report on FNS in treating GardenIII and IV femoral neck fractures. The aim of the present study was to compare the short-term clinical efficacy of FNS and multiple cannulated compression screws (MCCS) in the treatment of Garden III and IV femoral neck fractures. The data of 78 patients with femoral neck fracture who were admitted to three teaching hospitals affiliated to Anhui Medical University and received internal fixation with FNS and MCCS from June 2019 to December 2020 were collected for a retrospective study. There were 39 patients in both the FNS and MCCS groups. The basic data, perioperative data were recorded and compared between the two groups of patients. The results of the study are encouraging. The operation time was shorter in FNS group than that in MCCS group (p<0.001). The post-operative partial and complete weight-bearing time was earlier in FNS group than that in MCCS group (p<0.001). The Harris hip score in FNS group was higher than that in MCCS group (p<0.001). The incidence rate of lateral thigh irritation in FNS group and MCCS group was 0 (0/39) and 33.3% (13/39), respectively (χ2=15.600, p<0.001). The length of femoral neck shortening was significantly shorter in FNS group than that in MCCS group (t=-5.093, p<0.001). In conclusion, The application of FNS for Garden III and IV femoral neck fractures can shorten the operation time, reduce the frequency of intraoperative fluoroscopy, and facilitate the recovery of hip joint function, so it provides a novel choice for the treatment of Garden III and IV femoral neck fractures in young people.

Efficacy of Yigu® versus Aclasta® in Chinese postmenopausal women with osteoporosis: a multicenter prospective study

Summary Zoledronic acid (ZOL) is a therapy inhibiting bone resorption. In this study, generic ZOL (Yigu®) showed its clinical efficacy consistency with original ZOL (Aclasta®) in Chinese postmenopausal women with osteoporosis. This study provides a practical basis for the application of Yigu® in Chinese population. Introduction Yigu® has been approved its bioequivalence to Aclasta®. However, the clinical efficacy and safety of Yigu® have not been evaluated yet. Here, we compared the effectiveness and safety between Yigu® and Aclasta® in Chinese postmenopausal women with osteoporosis and assessed the efficacy of intravenous infusion of ZOL. Methods This was a randomized open-label, active-controlled study in postmenopausal women with osteoporosis of 14 clinical centers in China. Postmenopausal women with osteoporosis were recruited and randomized to receive a single infusion of 5 mg Yigu® or Aclasta®. The primary endpoint was the percentage change in bone mineral density (BMD) at lumbar spine after 12 months of treatment and was assessed for equivalence. The secondary endpoint was the percentage change in BMD at proximal femur after 12 months. Additional secondary endpoints were percentage changes in BMD at the above sites after 6 months of treatment and changes in bone turnover biomarkers during ZOL treatment. Safety was also evaluated and compared between two groups. Results A total of 458 postmenopausal women with osteoporosis were enrolled (n = 227, Yigu®; n = 231, Aclasta®). The mean percentage change in the BMD had no statistical difference at the lumbar spine (5.32% vs 5.18%), total hip (2.72% vs 2.83%), and femoral neck (2.37% vs 2.81%) between Yigu® and Aclasta® groups after 12 months of treatment. The mean difference of BMD change at the lumbar spine after 12 months between two groups was 0.15% (95% CI: − 0.71 to 1.00, equivalence margin: − 1.5%, 1.5%), demonstrating the treatments were equivalent. Meanwhile, the decreases in the P1NP and β-CTX showed no difference between two groups after 14 days and 6 and 12 months of treatment. As regards the whole sample, BMD significantly increased after 12 months of treatment. Also, serum C-terminal telopeptide of type 1 collagen (β-CTX) and procollagen 1 N-terminal peptide (P1NP) significantly decreased at each visit period. The overall adverse events were comparable and quite well between two groups. Conclusion Intravenous infusion of zoledronic acid achieved the potent anti-resorptive effects which led to significant increase in BMD of Chinese postmenopausal women with osteoporosis. Yigu® was equivalent to Aclasta® with respect to efficacy and safety.

Clinical Efficacy Evaluation and Potential Mechanism of Zhishe Tongluo Capsule in the Treatment of Cerebral Infarction by Meta-Analysis Associated with Network Pharmacology

Objective. By integrating meta-analysis and network pharmacology strategy, the clinical efficacy of Zhishe Tongluo capsule in the treatment of cerebral infarction was evaluated, and the intervention mechanism was preliminary explored. Methods. Through meta-analysis, the Chinese and English literature of the randomized controlled trial (RCT) of Zhishe Tongluo capsule in the treatment of cerebral infarction was comprehensively searched. Based on the standard of Na Pai, the quantitative literature was determined and the Review Manager data were statistically analyzed. Results. A total of 10 RCTs literatures were included. These literatures included a total of 1278 subjects, of which 670 were in the treatment group and 608 were in the control group. In terms of indicators of efficiency and adverse reaction rate, the treatment group was better than the control group. There was a statistical difference P < 0.05 ; a total of 559 chemical constituents and 2306 potential targets were obtained from the online database. Of these, 201 components, 145 targets, and 185 pathways were closely related to cerebral infarction. Conclusions. The available evidence indicates that the addition of Zhishe Tongluo capsule to the conventional treatment of Western medicine can improve the clinical efficacy of cerebral infarction and has some advantages in regulating blood lipids and hemorheology, but the overall evidence level is low, which still needs to be further supported by large-scale and multicenter RCTs; intervention of brain infarction by Zhishe Tongluo capsule is a comprehensive result of multicomponent and multi-target interactions. On the basis of the combined meta-analysis and network pharmacology in scientific attempts, it also provides a reference for the clinical evaluation of other drugs and mechanism research.

Efficacy of Combined Therapy with Nitroimidazole Drugs and Broad-Spectrum Antibiotics on Intra-Abdominal Infection: A 10 Years Real-World Cohort Study

Background: Abdominal infection still has a high mortality rate, and whether the combination of nitroimidazoles against obligate anaerobe could improve the outcome of abdominal infection remains controversial. Objective: This study aimed at exploring the clinical efficacy of broad-spectrum antibiotics combined with nitroimidazoles in the treatment of abdominal infection. Methods: Clinical data of patients with abdominal infection who received broad-spectrum antibiotics alone (BSA) or broad-spectrum antibiotics in combination with nitroimidazole (NCBSA) at a single center from June 2010 to May 2020 were retrospectively reviewed. One-to-one propensity score matching (PSM) was performed to adjust the potential differences in age, gender, APACHE II score and SOFA score of the two groups. Clinical effective rate, hospitalization days and total hospitalization costs were compared between the two groups. Meanwhile, subgroup efficacy was analyzed according to disease severity (APACH II score) and whether abdominal surgery was performed. Result: A total of 149 propensity score-matched case pairs were included in this study. There was no statistical difference in clinical effective rates between the two groups (P = 0.236). The patients in BSA group had shorter hospital stays (18d vs 27d, P = 0.001) and lower hospitalization costs (85185.7 yuan vs 187898.3 yuan, P < 0.001). However, the body temperature and PCT in patients in NCBSA group were higher than those in BSA group (P = 0.007 and P = 0.045, respectively), and CRP and WBC values in NCBSA group also were higher, but there were no significant differences between the two groups (P = 0.105 and P = 0.170, respectively). And more patients (92 vs 38) in NCBSA group underwent abdominal surgery, which indicated the infection and clinical conditons in NCBSA group were probably more severe. Subgroup analysis showed that the severity of the disease and whether the patient suffered postoperative co-infection did not affect the therapeutic effect of the two groups (P > 0.05). Conclusion: The clinical efficacy of broad-spectrum antibiotics combined with nitroimidazoles for abdominal infection was similar to that of broad-spectrum antibiotics alone, and whether the combination of nitroimidazoles in these conditions still needs more lcinical evidence.

Edaravone activates the GDNF/RET neurotrophic signaling pathway and protects mRNA-induced motor neurons from iPS cells

Background Spinal cord motor neurons (MNs) from human iPS cells (iPSCs) have wide applications in disease modeling and therapeutic development for amyotrophic lateral sclerosis (ALS) and other MN-associated neurodegenerative diseases. We need highly efficient MN differentiation strategies for generating iPSC-derived disease models that closely recapitulate the genetic and phenotypic complexity of ALS. An important application of these models is to understand molecular mechanisms of action of FDA-approved ALS drugs that only show modest clinical efficacy. Novel mechanistic insights will help us design optimal therapeutic strategies together with predictive biomarkers to achieve better efficacy. Methods We induce efficient MN differentiation from iPSCs in 4 days using synthetic mRNAs coding two transcription factors (Ngn2 and Olig2) with phosphosite modification. These MNs after extensive characterization were applied in electrophysiological and neurotoxicity assays as well as transcriptomic analysis, to study the neuroprotective effect and molecular mechanisms of edaravone, an FDA-approved drug for ALS, for improving its clinical efficacy. Results We generate highly pure and functional mRNA-induced MNs (miMNs) from control and ALS iPSCs, as well as embryonic stem cells. Edaravone alleviates H2O2-induced neurotoxicity and electrophysiological dysfunction in miMNs, demonstrating its neuroprotective effect that was also found in the glutamate-induced miMN neurotoxicity model. Guided by the transcriptomic analysis, we show a previously unrecognized effect of edaravone to induce the GDNF receptor RET and the GDNF/RET neurotrophic signaling in vitro and in vivo, suggesting a clinically translatable strategy to activate this key neuroprotective signaling. Notably, edaravone can replace required neurotrophic factors (BDNF and GDNF) to support long-term miMN survival and maturation, further supporting the neurotrophic function of edaravone-activated signaling. Furthermore, we show that edaravone and GDNF combined treatment more effectively protects miMNs from H2O2-induced neurotoxicity than single treatment, suggesting a potential combination strategy for ALS treatment. Conclusions This study provides methodology to facilitate iPSC differentiation and disease modeling. Our discoveries will facilitate the development of optimal edaravone-based therapies for ALS and potentially other neurodegenerative diseases. Graphical abstract

CLINICAL EFFICACY OF DASHMOOL KWATH NASYA IN THE MANAGEMENT OF MANYASTAMBHA WITH SPECIAL REFERENCE TO CERVICAL SPONDYLITIS

Background: Nasya is an essential therapeutic procedure as many of the courses of Ayurvedic treatment. It comes under the Panchashodhana karmas. It is necessary in all Urdhwa jathru vikaras. Nasya is effective for inducing immediate results and serves as a permanent cure. Cervical spondylotic change is frequently found in many asymptomatic adults, with 25 the age of 40, 50% of adults over the age of 40 and 85% of adults over the age of 60 showing evidence of disc degeneration. Cervical spondylosis can be compared with Manyastambha based on signs & symptoms. Nasya is the simple techniques and ingredients are readily available & economical. Also, these are indicated in the management of Manyastambha and have no proven adverse effects. This study was intended to assess the efficacy of the Dashmool Kwath Nasya in the management of this disease. Method: Randomly, 30 patients of Manyastambha were selected and paired “t” test was used. Result: Statistically significant improvement was found in this study on post-follow-up. Conclusion: Dashmool Kwath Nasya is having a prolonged action as it is having highly significant results post follow up of treatment as compared to after treatment.