The pathogenic mechanism of syndactyly type V identified in aHoxd13Q50R knock-in mice

Syndactyly type V (SDTY5) is an autosomal dominant extremity malformation characterized by fusion of the fourth and fifthmetacarpals. In the previous publication, we first identified a heterozygous missense mutation Q50R in homeobox domain (HD) ofHOXD13 in a large Chinese family with SDTY5. In order to substantiate the pathogenicity of the variant and elucidate the underlyingpathogenic mechanism causing limb malformation, transcription-activator-like effector nucleases (TALEN) was employed togenerate a Hoxd13Q50R mutant mouse. The mutant mice exhibited obvious limb malformations including slight brachydactyly andpartial syndactyly between digits 2-4 in the heterozygotes, and severe syndactyly, brachydactyly and polydactyly in homozygotes.Focusing on BMP2 and SHH/GREM1/AER-FGF epithelial mesenchymal (e-m) feedback, a crucial signal pathway for limbdevelopment, we found the ectopically expressed Shh, Grem1 and Fgf8 and down-regulated Bmp2 in the embryonic limb bud atE10.5 to E12.5. A transcriptome sequencing analysis was conducted on limb buds (LBs) at E11.5, revealing 31 genes that exhibitednotable disparities in mRNA level between the Hoxd13Q50R homozygotes and the wild-type. These genes are known to be involvedin various processes such as limb development, cell proliferation, migration, and apoptosis. Our findings indicate that the ectopicexpression of Shh and Fgf8, in conjunction with the down-regulation of Bmp2, results in a failure of patterning along both theanterior-posterior and proximal-distal axes, as well as a decrease in interdigital programmed cell death (PCD). This cascadeultimately leads to the development of syndactyly and brachydactyly in heterozygous mice, and severe limb malformations inhomozygous mice. These findings suggest that abnormal expression of SHH, FGF8, and BMP2 induced by HOXD13Q50R may beresponsible for the manifestation of human SDTY5.

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.

Survival of people living with HIV after treatment with Traditional Chinese Medicine in Henan province of China: a retrospective cohortstudy

OBJECTIVE: To provide survival estimates of people living with human immunodeficiency virus(PLHIV) after treatment with Traditional Chinese Medicine(TCM) in rural China, to identify the prognostic factors at enrollment, and to explore the effectiveness of TCM intreating PLHIV.METHODS: PLHIV who enrolled in national TCM HIV treatment trial program in October 2004 were analyzed in this study and followed up to October 2010. Survival time was estimated by the Kaplan-Meier curve and hazard ratios, and identifying prognostic factors were computed through Cox proportional hazard models.RESULTS:A total of 1666 PLHIV were included with 102 591 person-months of follow-up. Overall, 312(18.7%) patients died. The total mortality rate over the study period was 3.6 per 100 person-years,which was lower than the worldwide rate. The cumulative survival rate was 95.9% at 1 year[95% confidence interval(CI)(94.8-96.8)] and 80.4% at 6years [95% CI(78.4-82.3)]. Elevated death risks emerged among males, older individuals, and thosewithlowerCD4+T-cellcounts.CONCLUSION: TCM could increase survival and lengthen the life span of PLHIV in Henan province of China, as shown by our retrospective cohort study. Factors such as sex, age, education, and CD4+ T-cell counts correlated to survival. However,retrospective cohorts bias the data, so more prospective studies should be performed to confirm our primary results.

Reliability and validity of dermatology life quality index: assessment of quality of life in human immunodeficiency virus/acquired immunodeficiency syndrome patients with pruritic papular eruption

OBJECTIVE: To test the reliability and validity of dermatology life quality index(DLQI) in simplified Chinese language by assessing the quality of life(QoL) in HIV(human immunodeficiency virus)/AIDS(Acquired immunodeficiency syndrome) patients with pruritic papular eruption(PPE). METHODS: A study of simplified-Chinese-versiond from10 questions with the principal component analysis and the contribution rate of the 3 common factors was 59.95%. CONCLUSION: The simplified-Chinese-version DIQL is an acceptable and valid scale for HIV/AIDS patients with PPE. It can be used to evaluate the QoL of HIV/AIDS patients with PPE in China.