May Traditional Chinese Medicine Reduce the Risk of Developing Rheumatoid Arthritis?An One-armed Prospective Study

Background:Rheumatoid arthritis(RA)is a worldwide public health problem.Intervention and prevention before the onset of rheumatic diseases is a new direction in current research.Objective:The aim of this study was to evaluate the potential and feasibility of traditional Chinese medicine(TCM)in the prevention of RA.Methods:This was a single-armed prospective clinical trial.All participants were recruited from a single center in Guangdong,China.Adults who were tested positive for anti-cyclic citrullinated peptide antibody(anti-CCP)and/or rheumatoid factor(RF),had no synovitis and never been treated with disease-modifying anti-rheumatic drugs(DMARDs),were enrolled to take the Huayu-Qiangshen-Tongbi(HQT)decoction orally twice daily,200 mL each time for 24 weeks.Primary outcome was the proportion of patients who met 2010 ACR(American College of Rheumatology)/EULAR(European League Against Rheumatism)classification criteria of RA during observation.Secondary outcomes included levels of anti-CCP,RF,erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),assessment of signs and symptoms,and radiographic progression by magnetic resonance imaging(MRI).Results:19 individuals were enrolled in the study,4 of which withdrew because of the epidemic of COVID-19.During the observation period,3 individuals(20%)developed RA and they had longer morning stiffness(P=0.009)and more obvious synovial enhancement in MRI(P=0.041)at baseline when compared with those who did not develop RA.After 24 weeks of intervention,there were improvements in 28-swollen joint count(SJC28)(P=0.046),Visual Analog Scale(VAS)(P=0.019),Patient’s Global Assessment(PtGA)(P=0.019)and Physician’s Global Assessment(PGA)(P=0.031),but no statistical significance was observed in the levels of anti-CCP,RF,ESR,CRP,morning stiffness,28-tender joint count(TJC28),Health Assessment Questionnaire(HAQ)and magnetic resonance imaging(MRI)analysis(P>0.05).Conclusion:The HQT formula is safe and could improve joint symptoms and signs in these at-risk individuals,but it remains to be investigated in futher study to see if it might potentially reduce the risk of developing RA.Besides,for individuals at high risk to develop RA,morning stiffness and synovial enhancement in MRI might be predictive factors and warning signs.

Systematic review on the adverse reactions of oral administration of Indigo Naturalis and its preparations

Objective:This article systematically analyses the effects of adverse drug events/adverse drug reactions(ADEs/ADRs)of oral Indigo Naturalis(Qingdai)preparations in order to provide references for its rational clinical application.Methods:All clinical studies reporting ADE/ADR related to the oral administration of Qingdai preparations were searched through electronic databases,including PubMed,the Cochrane Library,Embase,China National Knowledge Infrastructure(CNKI),China Biology Medicine disc(CBM),VIP Information Chinese Journal Service Platform(VIP),and Wanfang database,from inception to September 27,2020.Information were extracted from these literatures,including primary disease,type of adverse reactions,dose,treatment,outcomes and so on.Incidence of ADE/ADR was estimated,as well as distribution of primary diseases and victim organs and systems were analyzed.Results:A total of 682 articles were included,with 651 clinical population studies and 31 case reports.Among them,604 detailed ADR/AE involving 33459 patients using oral Qingdai preparations,and a total of 5061 cases were found to present adverse events,including 2827 cases of digestive system(abdominal pain,diarrhea,etc.),469 cases of blood system damage(thrombocytopenia,leukopenia,anemia,etc.),313 cases of liver damage(abnormal liver function,liver toxicity,elevated liver enzymes,etc.),327 cases of nervous system reactions(headache,dizziness,poor sleep,etc.)and 1186 cases of other systems and organs.Severe adverse events(SAEs)mainly were liver damage,and could be relived after symptomatic treatment.Conclusion:From the systematic information retrieval and analysis,it is found that oral Qingdai preparations application may clinically cause ADEs/ADRs in terms of gastrointestinal tract and liver damage.Therefore,when using oral Qingdai preparations,liver and stomach protection should be done.At the same time,pay close attention to various biochemical indicators and the patient's drug response during the treatment process,and,if necessary,deal with it in time so as not to deteriorate the condition.Moreover,active surveillance system should be conducted to monitor ADE/ADR,so as to establish a clearer causal relationship between the drug and the adverse event.

IGF2BP3-induced activation of EIF5B contributes to progression of hepatocellular carcinoma cells

In this study,we investigated the functional role of eukaryotic initiation factor 5B(EIF5B)in hepatocellular carcinoma(HCC)and the underlying mechanisms.Bioinformatics analysis demonstrated that the EIF5B transcript and protein levels as well as the EIF5Bcopy number were significantly higher in the HCC tissues compared with the non-cancerous liver tissues.Down-regulation of EIF5B significantly decreased proliferation and invasiveness of the HCC cells.Furthermore,EIF5B knockdown suppressed epithelial-mesenchymal transition(EMT)and the cancer stem cell(CSC)phenotype.Down-regulation of EIF5B also increased the sensitivity of HCC cells to 5-fluorouracil(5-FU).In the HCC cells,activation of the NF-kappa B signaling pathway and IkB phosphorylation was significantly reduced by EIF5B silencing.IGF2BP3 increased the stability of the EIF5B mRNA in an m6A-dependent manner.Our data suggested that EIF5B is a promising prognostic biomarker and therapeutic target in HCC.

7-Dehydrocholesterol protects against circadian disruption and experimental colitis:potential role of RORα/γ

Dear Editor,Circadian rhythms are physical,behavioral,and mental changes that follow a roughly 24-h cycle.Our prior researches have estab-lished a significant correlation between the disruption of the cir-cadian rhythm and the severity of experimental colitis,an animal model replicating inflammatory bowel disease(IBD)in humans[1,2].IBD is a chronic inflammatory disease of the gastrointesti-nal tract and is divided into ulcerative colitis and Crohn’s disease.Approximately 0.5%of the population in the Western world suf-fers from IBD[3].

Nagilactone E increases PD-L1 expression through activation of c-Jun in lung cancer cells

Nagilactone E(NLE),a natural product with anticancer activities,is isolated from Podocarpus nagi.In this study,we reported that NLE increased programmed death ligand 1(PD-L1)expressions at both protein and mRNA levels in human lung cancer cells,and enhanced its localization on the cell membrane.Mechanistically,NLE increased the phosphorylation and expression of cJun,and promoted the localization of c-Jun in the nucleus,while silencing of c-Jun by small interfering RNA(siRNA)reduced NLEinduced PD-L1.Further study showed that NLE activated the c-Jun N-terminal kinases(JNK),the upstream of c-Jun,and its inhibitor SP600125 reversed the NLE-increased PD-L1.Moreover,NLE-induced PD-L1 increased the binding intensity of PD-1 on the cell surface.In summary,NLE upregulates the expression of PD-L1 in lung cancer cells through the activation of JNK-c-Jun axis,which has the potential to combine with the PD-1/PD-L1 antibody therapies in lung cancer.

感染新型冠状病毒的2型糖尿病患者的临床特征和结果——一项回顾性研究

据报道,糖尿病及其相关的代谢性疾病是新型冠状病毒肺炎(coronavirus disease 2019,COVID-19)患者的主要合并症。这项临床研究旨在调查有或没有合并糖尿病的COVID-19患者的临床特征、影像学和实验室检查、并发症、治疗方法以及临床结局。这项回顾性研究纳入2020年1月12日至3月25日208例经实验室确认的COVID-19的住院患者(≥45岁)。分析病历信息包括临床特征、影像学和实验室检查、并发症、治疗和临床结果。其中,96名(46.2%)患者患有2型糖尿病。在COVID-19合并2型糖尿病患者中,高血压(58.3%vs.31.2%)、冠心病(17.1%vs.8.0%)和慢性肾脏病(6.2%vs.0%)的共存率明显高于没有2型糖尿病的COVID-19患者。COVID-19合并2型糖尿病患者的CT胸部扫描异常频率和程度显著增加,包括毛玻璃样混浊(85.6%vs.64.9%,P<0.001)和双侧斑片状阴影(76.7%vs.37.8%,P<0.001)。此外,患有糖尿病的COVID-19患者的血糖水平[7.23 mmol·L^-1(IQR:5.80~9.29)vs.5.46 mmol·L^-1(IQR:5.00-6.46)]、血液中低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)[2.21 mmol·L^-1(IQR:1.67~2.76)vs.1.75 mmol·L^-1(IQR:1.27~2.01)]和收缩压[130 mmHg(IQR:120~142)vs.122 mmHg(IQR:110~137),P<0.001]显著高于没有糖尿病的患者(P<0.001)。2型糖尿病和其他代谢性疾病共存于COVID-19患者中,这可能会增加发病率并加重COVID-19的病情。血糖和脂质代谢的最佳管理是确保更好的临床结果的关键。对于患有糖尿病及其他基础和慢性代谢性疾病的COVID-19患者,应提高临床警惕性。

Herbal formula BaWeiBaiDuSan alleviates polymicrobial sepsis-induced liver injury via increasing the gut microbiota Lactobacillus johnsonii and regulating macrophage anti-inflammatory activity in mice

Sepsis-induced liver injury(SILI)is an important cause of septicemia deaths.BaWeiBaiDuSan(BWBDS)was extracted from a formula of Panax ginseng C.A.Meyer,Lilium brownie F.E.Brown ex Miellez var.viridulum Baker,Polygonatum sibiricum Delar.ex Redoute,Lonicera japonica Thunb.,Hippophae rhamnoides Linn.,Amygdalus Communis Vas,Platycodon grandiflorus(Jacq.)A.DC.,and Cortex Phelloderdri.Herein,we investigated whether the BWBDS treatment could reverse SILI by the mechanism of modulating gut microbiota.BWBDS protected mice against SILI,which was associated with promoting macrophage anti-inflammatory activity and enhancing intestinal integrity.BWBDS selectively promoted the growth of Lactobacillus johnsonii(L.johnsonii)in cecal ligation and puncture treated mice.Fecal microbiota transplantation treatment indicated that gut bacteria correlated with sepsis and was required for BWBDS anti-sepsis effects.Notably,L.johnsonii significantly reduced SILI by promoting macrophage anti-inflammatory activity,increasing interleukin-10+M2 macrophage production and enhancing intestinal integrity.Furthermore,heat inactivation L.johnsonii(HI-L.johnsonii)treatment promoted macrophage anti-inflammatory activity and alleviated SILI.Our findings revealed BWBDS and gut microbiota L.johnsonii as novel prebiotic and probiotic that may be used to treat SILI.The potential underlying mechanism was at least in part,via L.johnsonii-dependent immune regulation and interleukin-10+M2 macrophage production.