Comparing the efficacy of different intra-articular injections for knee osteoarthritis: A network analysis

Background:The findings on the effectiveness of platelet-rich plasma, ozone, and hyaluronic acid in the treatment of osteoarthritis of the knee are controversial, and the existing original studies and meta-analyses are mostly comparisons of a single joint cavity injection method, lacking direct and indirect comparisons of different drugs in the joint cavity. The lack of direct and indirect comparisons of different drugs in the joint cavity makes it difficult to have a clearer and more comprehensive understanding of joint cavity injection methods. In this study, the efficacy of platelet-rich, ozone, sodium hyaluronate, and combined knee cavity injections were compared directly or indirectly using a reticulated meta-analysis in this field, and the efficacy of treatment measures was ranked to provide more comprehensive and reliable evidence-based clinical evidence for the selection of knee cavity injections in osteoarthritis of the knee.Objective:To compare the effects of platelet-rich plasma, ozone, and sodium glassate injection interventions on the efficacy of osteoarthritis of the knee through reticulated Meta-analysis, and to comprehensively compare the clinical effectiveness of platelet-rich plasma, ozone, and sodium glassate injection joint cavity injection for the treatment of osteoarthritis of the knee.Methods:The PubMed, CBM, CNKI, VIP, and Wan-Fang databases were searched for information on the effectiveness of platelet-rich plasma, ozone, and sodium vitrate injection for the comparative treatment of osteoarthritis of the knee, with a search time frame of each database from the date of creation to July 20, 2021. Two investigators independently screened the literature, extracted data according to inclusion and exclusion criteria, and evaluated the quality of the literature in parallel. Statistical analysis was performed using Stata 16.0 software to compare the differences in the efficacy of each treatment measure using the ratio and 95% confidence interval as effect indicators and to rank the efficacy.Results:Thirty-three RCTs with 7003 patients with osteoarthritis of the knee were included, involving 5 therapeutic measures. Meta-analysis showed that the efficacy of platelet-rich plasma injection was superior to both ozone and hyaluronic acid therapies. Hyaluronic acid+ozone and platelet-rich plasma+hyaluronic acid were both superior to ozone and hyaluronic acid monotherapy. The differences in efficacy between hyaluronic acid and ozone compared with platelet-rich plasma were statistically significant, and the differences in efficacy between the 2 combination therapies (platelet-rich plasma+hyaluronic acid, hyaluronic acid+ozone) and the 3 monotherapies (platelet-rich plasma, ozone, hyaluronic acid) were statistically significant. Platelet-rich plasma+hyaluronic acid, hyaluronic acid+ozone compared with 3 monotherapies (platelet-rich plasma, ozone, hyaluronic acid) were statistically significant, except for the difference in efficacy with platelet-rich plasma, which was not statistically significant, indicating that this platelet-rich plasma+hyaluronic acid and Hyaluronic acid+ozone combination therapy was superior to monotherapy. Also, the efficacy of platelet-rich plasma was better than hyaluronic acid and ozone and the difference was statistically significant, indicating that platelet-rich plasma was more effective than ozone and sodium glass in the treatment of osteoarthritis of the knee in monotherapy.Conclusion:It is believed that in the course of clinical practice, hyaluronic acid+ozone or platelet-rich plasma+hyaluronic acid combination therapy or platelet-rich plasma therapy can be preferred for patients with osteoarthritis of the knee.     

Vitamin D Enhances Neutrophil Generation and Function in Zebrafish (Danio rerio)

Vitamin D (VD) is a major regulator of calcium metabolism in many living organisms. In addition, VD plays a key role in regulating innate and adaptive immunity in vertebrates. Neutrophils constitute an important part of the first line of defense against invading microbes; however, the potential effect of VD on neutrophils remains elusive. Thus, in this study zebrafish in different developmental stages were utilized to identify the potential role of VD in the basal homeostasis and functions of neutrophils. Our results showed that addition of exogenous VD₃ promoted granulopoiesis in zebrafish larvae. Reciprocally, neutrophil abundance in the intestine of adult zebrafish with a cyp2r1 mutant, lacking the capacity to 25-hydroxylate VD, was reduced. Moreover, VD-mediated granulopoiesis was still observed in gnotobiotic zebrafish larvae, indicating that VD regulates neutrophil generation independent of the microbiota during early development. In contrast, VD was incapable to influence granulopoiesis in adult zebrafish when the commensal bacteria were depleted by antibiotic treatment, suggesting that VD might modulate neutrophil activity via different mechanisms depending on the developmental stage. In addition, we found that VD₃ augmented the expression of il-8 and neutrophil recruitment to the site of caudal fin amputation. Finally, VD₃ treatment significantly decreased bacterial counts and mortality in zebrafish infected with Edwardsiella tarda (E. tarda) in a neutrophil-dependent manner. Combined, these findings demonstrate that VD regulates granulopoiesis and neutrophil function in zebrafish immunity.     

人工晶状体断襻的术中处理

目的：探讨人工晶状体植入时出现断襻的术中处理方法。方法：回顾总结2006-03/2011-05的25例25眼人工晶状体植入时出现断襻的术中处理方法：其一是将断襻人工晶状体植入囊袋内（23眼）,其二是一期或二期更换断襻人工晶状体（2眼）。结果：在25眼中,其中1眼术中进行人工晶状体的更换,1眼术后第3d人工晶状体向下发生严重脱位,进行了人工晶状体的更换,2眼人工晶状体发生轻微移位,余21眼未发生人工晶状体移位;术后1mo矫正视力0.8～1.0者8眼,0.5～者14眼,0.2者1眼（合并有糖尿病视网膜病变）,23眼均未发生人工晶状体明显移位;术后6mo随访的15眼均未发生人工晶状体明显移位。结论：将断襻人工晶状体植入囊袋内合适的位置,大多数人工晶状体不发生移位或不影响术后视力的提高,可以作为手术应急的一种选择。     

Drug D,a Diosgenin Derive,Inhibits L-Arginine-Induced Acute Pancreatitis through Meditating GSDMD in the Endoplasmic Reticulum via the TXNIP/HIF-1α Pathway

Acute pancreatitis (AP) is one of the most common causes of hospitalization for gastrointestinal diseases, with high morbidity and mortality. Endoplasmic reticulum stress (ERS) and Gasdermin D (GSDMD) mediate AP, but little is known about their mutual influence on AP. Diosgenin has excellent anti-inflammatory and antioxidant effects. This study investigated whether Diosgenin derivative D (Drug D) inhibits L-arginine-induced acute pancreatitis through meditating GSDMD in the endoplasmic reticulum (ER). Our studies were conducted in a mouse model of L-arginine-induced AP as well as in an in vitro model on mouse pancreatic acinar cells. The GSDMD accumulation in ER was found in this study, which caused ERS of acinar cells. GSDMD inhibitor Disulfiram (DSF) notably decreased the expression of GSDMD in ER and TXNIP/HIF-1α signaling. The molecular docking study indicated that there was a potential interaction between Drug D and GSDMD. Our results showed that Drug D significantly inhibited necrosis of acinar cells dose-dependently, and we also found that Drug D alleviated pancreatic necrosis and systemic inflammation by inhibiting the GSDMD accumulation in the ER of acinar cells via the TXNIP/HIF-1α pathway. Furthermore, the level of p-IRE1α (a marker of ERS) was also down-regulated by Drug D in a dose-dependent manner in AP. We also found that Drug D alleviated TXNIP up-regulation and oxidative stress in AP. Moreover, our results revealed that GSDMD^-/- mitigated AP by inhibiting TXNIP/HIF-1α. Therefore, Drug D, which is extracted from Dioscorea zingiberensis, may inhibit L-arginine-induced AP by meditating GSDMD in the ER by the TXNIP /HIF-1α pathway.     

Clinical Impact of Empirical Antibiotic Therapy in Patients With Coronavirus Disease 2019 Requiring Oxygen Therapy

Despite the low prevalence of secondary bacterial infection in coronavirus disease 2019 (COVID-19) patients, most of them were administered antibiotic therapy empirically. However, the prognostic impact of empirical antibiotic therapy has not been evaluated. We conducted retrospective propensity score-matched case-control study of 233 COVID-19 patients with moderate to severe illnesses who required oxygen therapy and evaluated whether empirical antibiotic therapy could improve clinical outcomes. Empirical antibiotic therapy did not improve clinical outcomes including length of stay, days with oxygen requirement, the proportion of patients with increased oxygen demand, the proportion of patients who required mechanical ventilation, and overall mortality. This finding implies that routine administration of antibiotics for the treatment of COVID-19 is not essential and should be restricted.     

A Comparison of Pseudorabies Virus Latency to Other α-Herpesvirinae Subfamily Members

Pseudorabies virus (PRV), the causative agent of Aujeszky’s disease, is one of the most important infectious pathogens threatening the global pig industry. Like other members of alphaherpesviruses, PRV establishes a lifelong latent infection and occasionally reactivates from latency after stress stimulus in infected pigs. Latent infected pigs can then serve as the source of recurrent infection, which is one of the difficulties for PRV eradication. Virus latency refers to the retention of viral complete genomes without production of infectious progeny virus; however, following stress stimulus, the virus can be reactivated into lytic infection, which is known as the latency-reactivation cycle. Recently, several research have indicated that alphaherpesvirus latency and reactivation is regulated by a complex interplay between virus, neurons, and the immune system. However, with those limited reports, the relevant advances in PRV latency are lagging behind. Therefore, in this review we focus on the regulatory mechanisms in PRV latency via summarizing the progress of PRV itself and that of other alphaherpesviruses, which will improve our understanding in the underlying mechanism of PRV latency and help design novel therapeutic strategies to control PRV latency.     

Development and Primary Application of an Indirect ELISA Based on Rep Protein to Analyze Antibodies against Porcine Cocirvirus-like Virus (PCLV)

Porcine circovirus-like virus (PCLV) is a member of circovirus that contains a single-strand DNA genome, which may be one of the pathogens that causes diarrheal symptoms in pigs. The Rep protein encoded by the genome of PCLV may be responsible for viral genome replication. The development of serological detection methods for PCLV is of great necessity for clinical diagnosis, as well as epidemiological investigations. Therefore, this study attempted to build an indirect enzyme-linked immunosorbent assay (ELISA) to examine antibodies against PCLV based on the His-tagged recombinant Rep protein. Full-length PCLV Rep protein was induced and expressed in E. coli and was purified as an antigen to establish an ELISA detection kit. The purified Rep protein was used to inject into mice to produce specific antibodies. There was no cross-reaction of Rep-based ELISA with antisera against other porcine viruses. The intra-assay and inter-assay coefficient variations (CVs) were 0.644–8.211% and 0.859–7.246%, respectively, indicating good repeatability. The non-cross-reaction with TGEV, PRRSV and PCV2 testing showed high sensitivity and high specificity for this ELISA assay. A total of 1593 serum samples collected from different pig farms in Jiangxi Province were tested for anti-PCLV Rep antibodies, and 284 (17.83%) of the 1593 samples were Rep antibody positive. Altogether, the indirect ELISA detection tool developed in this study could be applied to examine serum of PCLV antibodies with good repeatability, high sensitivity and high specificity. In addition, field sample detection results suggested that the PCLV antibody has a low prevalence in pig populations in Jiangxi Province of China.     

The role of hypoxia inducible factor-1α in the increased MMP-2 and MMP-9 production by human monocytes exposed to nickel nanoparticles

Nickel is an important economic commodity, but it can cause skin sensitization and may cause lung diseases such as lung fibrosis, pneumonitis, bronchial asthma and lung cancer. With development of nanotechnology, nano-sized nickel (Nano-Ni) and nano-sized titanium dioxide (Nano-TiO?) particles have been developed and produced for many years with new formulations and surface properties to meet novel demands. Our previous studies have shown that Nano-Ni instilled into rat lungs caused a greater inflammatory response as compared with standard-sized nickel (5 μm) at equivalent mass concentrations. Nano-Ni caused a persistent high level of inflammation in lungs even at low doses. Recently, several studies have shown that nanoparticles can translocate from the lungs to the circulatory system. To evaluate the potential systemic effects of metal nanoparticles, we compared the effects of Nano-Ni and Nano-TiO? on matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) gene expression and activity. Our results showed that exposure of human monocyte U937 to Nano-Ni caused dose- and time- dependent increase in MMP-2 and MMP-9 mRNA expression and pro-MMP-2 and pro-MMP-9 activity, but Nano-TiO? did not. Nano-Ni also caused dose- and time- related increase in tissue inhibitor of metalloproteinases 1 (TIMP-1), but Nano-TiO? did not. To determine the potential mechanisms involved, we measured the expression of hypoxia inducible factor 1α (HIF-1α) in U937 cells exposed to Nano-Ni and Nano-TiO?. Our results showed that exposure to Nano-Ni caused HIF-1α accumulation in the nucleus. Furthermore, pre-treatment of U937 cells with heat shock protein 90 (Hsp90) inhibitor, 17-(Allylamino)-17-demethoxygeldanamycin (17-AAG), prior to exposure to Nano-Ni significantly abolished Nano-Ni-induced MMP-2 and MMP-9 mRNA upregulation and increased pro-MMP-2 and pro-MMP-9 activity. Our results suggest that HIF-1α accumulation may be involved in the increased MMP-2 and MMP-9 production in U937 cells exposed to Nano-Ni.     

Development of a placebo effect model combined with a dropout model for bipolar disorder

The aim of this study was to develop a placebo model for bipolar disorder to help optimize clinical trial designs for studies targeting manic episodes in bipolar disorder. A bipolar disease database was built based on individual longitudinal data collected from over 3,000 patients in 11 clinical trials for 5 approved bipolar drugs. An empirical placebo effect model with an exponential decay process plus a linear progression process was developed to quantify the time course of the Young Mania Rating Scale total score based on only placebo data from the database. In order to describe the dropout pattern during the trials, a parametric survival model was developed and the Weibull distribution was identified to be the best distribution to describe the data. Based on the likelihood ratio test, it was found that patients with higher baseline score, slower disease improvement and more rapid disease progression tended to dropout earlier, and the trial features such as trial starting year and trial site were also significant covariates for dropout. A combination of the placebo effect model and the dropout model was applied to simulate new clinical trials through Monte-Carlo simulation. Both the placebo effect model and dropout model described the observed data reasonably well based on various diagnostic plots. The joint placebo response and dropout models can serve as a tool to simulate the most likely level of placebo response with the expected dropout pattern to help design a new clinical trial.