Efficacy and safety of CM310 in moderate-to-severe atopic dermatitis: A multicenter, randomized, double-blind, placebo-controlled phase 2b trial / 中华医学杂志(英文版)

BACKGROUND@#Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.@*METHODS@#This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.@*RESULTS@#At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs . placebo, 95% CI 31%-69%) and 45% (low vs . placebo, 95% CI 26%-64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator's Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310.@*CONCLUSION@#CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.

Expression profiles of Th17 pathway-related genes in patients with syphilis serofast reaction analyzed by PCR-Array technique / 中华微生物学和免疫学杂志

Objective To detect the expression of Th17 pathway-related genes in patients with syphilis serofast reaction and to investigate the mechanism of Th17 cells in syphilis serofast reaction. Meth-ods Peripheral blood samples were collected from patients with syphilis serofast reaction ( n=8 ) , patients who were syphilis-seronegative after treatment (n=8) and healthy subjects (n=8). Total RNA was extrac-ted from each blood sample and then reversely transcribed into cDNA. PCR-Array analysis was performed to quantify the expression levels of Th17 pathway-related genes. Results The expression levels of genes with a fold change >2 (up or down regulated) were defined as differentially expressed. (1) Compared with the control group, the patients with syphilis serofast reaction showed increased expression of genes encoding fork-head box protein 3 (Foxp3) and IL-10, but decreased expression of genes encoding C-C motif chemokine 22 (CCL22), colony stimulating factor 2 (CSF2), CSF3, chemokine (C-X-C motif) ligand 6 (CXCL6), IL-17A, IL-17D, IL-21, IL-23R, IL-9, interferon regulatory factor 4 (IRF4), RAR-related orphan receptorα( RORα) , RAR-related orphan receptor γ ( RORγ) and signal transducer and activator of transcription 3 (STAT3). (2) Compared with the seronegative syphilis group, the expression levels of genes encoding Foxp3 and IL-10 in patients with syphilis serofast reaction were up-regulated, while the expression of genes encoding CCL22, CSF2, CSF3, IL-17A, IL-21, IL-23R, IRF4, RORγ and STAT3 were down-regulated. (3) The expression levels of genes encoding CXCL6 and IL-9 in seronegative syphilis group were lower than those in control group. Conclusion The abnormal expression of Th17 pathway-related genes might relate to the pathogenesis of serofast state of syphilis.

Research on the current situation of re-visiting at 4 traditional Chinese clinics in urban area of Beijing / 国际中医中药杂志

ObjectiveTo research the current situation at traditional Chinese clinics in urban area of Beijing,and to propagate the importance of re-visiting.Methods500 outpatients were selected randomly from 4 traditional Chinese clinics in urban area of Beijing from April 1st in 2010 to March 31st in 2011.Questionnaires were undertaken by these patients,including 120 first visitors and 380 re-visitors,then SPSS17.0 was used to statistically analyze the re-visiting proportion,influence factors and reasons for re-visiting.Results The highest re-visiting proportion was 56.7％ in 4 clinics and the total was 47.0％; 13.6％ patients who didn't have re-visit choice for their having no significant curative effect,12.6％ for having no time,10.3％ for having been recovered; patients who had curative effect and doctor's advice to re-visit may be the related influence factors of re-visiting; in the investigation of reasons,73.0％ patients made re-visit choice for having curative effect,35.9％ for doctors' good medical ethics,35.9％ for doctors' advice.ConclusionThere was a low re-visiting proportion in these 4 traditional Chinese clinics in urban area of Beijing; the top three non-revisiting reasons were no significant curative effect,having no time and having recovered.Having curative effect and doctor's advice to re-visit may be the related influence factors of re-visiting; the top three re-visiting reasons were curative effect,doctor's good medical ethics and doctor's exhortation.

Analysis of antimicrobial susceptibility and mutations of genes associated with rifampicin and isoniazid resistance in Mycobacteria tuberculosis isolates from 7 patients with cutaneous tuberculosis / 中华皮肤科杂志

Objective To assess the antimicrobial resistance and resistance-related mutations in rpoB and katG genes in Mycobacteria tuberculosis isolates from patients with cutaneous tuberculosis. Methods Seven strains of Mycobacteria were isolated from lesions or secretions of patients with cutaneous tuberculosis and identified as M. tuberculosis. Proportion method was used to test the susceptibility of M. tuberculosis isolates to rifampicin, isoniazid, streptomycin and ethambutol. PCR and sequencing were performed to analyze the mutations in rpoB and katG genes. Results Of the 7 isolates of M. tuberculosis, 1 was resistant to rifampicin,isoniazid and ethambutol simultaneously, and the other 6 were sensitive to rifampicin, isoniazid, streptomycin and ethambutol. All the 7 isolates were positive for the amplification of rpoB and katG genes by PCR. DNA sequencing revealed two mutations at codon 531 (TCG to TTG) and codon 315 (AGC to ACC) in the multi-drug resistant strain, which were absent in the other 6 strains. Conclusion Multi-drug resistance has emerged in M. tuberculosis isolates from patients with cutaneous tuberculosis, which is likely to be related to improper treatment.

Efficacy and safety of long-term repeated treatment of facial wrinkles with botulinum toxin A / 中华医学美学美容杂志

Objective To evaluate the clinical efficacy and safety of long-term repeated treatment of facial wrinkles with application of botulinum toxin A (BTXA). Methods A total of 52 patients had received 8 injections in seven years with BTXA against facial wrinkles, including forehead wrinkles, fishtail lines, glabellas wrinkles, and nasal dorsum transverse wrinkles. Besides day 1 (baseline) and day for the next injection (end-point), follow-up visits were scheduled on 1 week, 1 month, and 3 months after every injection. The therapy effect and safety were evaluated. Results For all the patients, it began to take effect on day 3 or 4 after the treatment and best effect appeared on 1 month post-treatment. Patients' selfevaluation as grade 1 for the improvement of forehead wrinkles, fishtail lines, glabellas wrinkles and nasal dorsum transverse wrinkles, accounted for 100%, 97.1%, 99.8% and 99%, respectively. Correspondingly, cases as grade 2 accounted for 0, 2.9%, 0.2% and 1.0%. Grades 3 to 5 had not been reported. With the repetition of treatment, the efficiency increased. The average of effective duration was (7.8±1.1) months, which lasted longer with the injection times increased (r= 0.256, P= 0.02). Adverse reactions observed in the previous several injections, including ecchymosis, feeling of tightness, rigid expression and severer wrinkles near the injected site, which were mild and the incidence rate decreased after the following injections (r= 0.850, P= 0.01). Severe adverse effects, such as allergic reaction,headache, blepharoptosis and dysraphism of eyes had not happened in all the 52 patients. Conclusion Long-term repeated application of BTXA against facial wrinkles is safe and the efficacy is confirmed. The approach can be applied repeatedly to those who have indications and good tolerance.

Sequence analysis and genotyping of genital Chlamydia trachomatis among patients with suspected-Neisseria gonorrhoeae / 中华微生物学和免疫学杂志

Objective To understand the prevalence rate of genital Chlamydia trachomatis among a population with suspected-Neisseria gonorrhoeae infection,the distribution of Chlamydia trachomatis genotypes,assess changes in omp1 sequences among patients with Neisseria gonorrhoeae and Chlamydia trachomatis coinfections.Methods Four hundred and one swabs were collected.Chlamydia trachomatis and Neisseria gonorrhoeae were detected by Roche Amplicor System.DNA were extracted from those samples and were amplified by nested PCR.PCR products were sequencing and analyzed by software Mega4.0.Results The prevalence of genital Chlamydia trachomatis infection,Neisseria gonorrhoeae infection and coinfection with genital gonorrhoea and genital chlamydia were 82.3%,24.2% and 21.7% each.Eight genotypes were identified in 73 sequences,including E(27.4%),G/Ga(23.3%),D/Da(16.4%),F(13.7%),J (11.0%),H(5.5%),B and K(each 1.4%).Sequencing analysis showed that 3 cases(4.1%) had missense mutation,including genotype D/Da,E,G/Ga.Genotypes F,H,J and K were more variable,however,most of them were silent mutation.Conclusion The prevalence rate of genital Chlamydia trachomatis among a population with Neisseria gonorrhoeae infection was high.The most common genotypes were genotype E,G/Ga,D/Da and F; Sequencing analysis has provided a tool for the molecular epidemiology of genital Chlamydia trachomatis infections.

Effects of simvastatin on the mouse model of sclerotic skin / 中华皮肤科杂志

Objective To study the effect of simvastatin on the mouse model of sclerotic skin. Methods A total of 44 mice were divided into two groups, i.e., early administration group (n=24) and post-induction administration group (n=20), and the former was classified into three subgroups, including negative group, model group and simvastatin-treated group, and the latter into two groups, namely blank control group, simvastatin-treated group. The mouse model of sclerotic skin was established by local injec-tions of bleomycin in the back of BALB/c mice. Simvastatin was administered by gavage at a dose of 5 μg per kilogram body weight per day for 4 weeks to mice at the same time when bleomycin was injected in the early group or after 4-week bleomycin injection in the post-induction group. Skin sections were prepared 24 hours after the last administration of simvastatin for histopathological examination and measurement of derma l thickness with HE staining, determination of hydroxyproline content via colorimetry, and mRNA expression of procollagen α1 (Ⅰ) by RT-PCR. Results In the early administration group, a significant increment was observed in the diameter of dermal collagen, skin thickness, and hydroxyproline content in model group compared with the negative control group (all P <0.01), whereas decreased dermal thickness, hydroxyproline content and mRNA expression of procollagen α1(Ⅰ) were noticed in simvastatin-treated group in comparison with the model group (P<0.05, 0.01 and 0.05, respectively). No obvious improvement was achieved in dermal thickness or hydroxyproline content in simvastatin-treated group compared with blank control group (both P0.05), but the mRNA expression of procollagen α1 (Ⅰ) was inhibited in the former group (P<0.05). Conclusion Skin sclerosis is relieved significantly by administration of simvastatin at the induction of scle- rosis but not by that after the induction of sclerotic skin.

Expression level and significance of Src-homology2 domain phosphatase-1 and -2 in condyloma acuminatum / 中华传染病杂志

Objective To investigate the different expression pattern of Src-homology2 domain phosphatase (SHP)-1 and SHP-2 in human papiilomavirus (HPV)6/11 infected condyloma acuminatum (CA) and the significance of the difference. Methods HPV6/11 related CA cases were diagnosed by in situ hybridization. The expression and distribution of SHP-1 and SHP-2 were examined by SP immunohistochemistry technique in skin samples from 40 HPV 6/11 positive CA cases and 20 healthy control (foreskins). Results The positive rates of SHP-1 and SHP-2 were 80% and 85% respectively in CA, which were significantly higher than those in healthy control cases (only 35% and 30%, respectively, X2=11.87,P<0.01; X2 =18. 15,P<0. 01) . The SHP-1 and/or SHP-2 positive cells in CA skin lesions were mainly distributed in prickle layer, showing as brown yellow, with the positive staining located in cytoplasm. Contrastively, the SHP-1 and/or SHP-2 positive cells in healthy controls were rare and mainly distributed in basal layer, showing as pale yellow with the positive staining located in cytoplasm. There was no significant correlation between the expression of SHP-1 and SHP-2 in CA( rs = 1.0, P>0.05 ). Conclusion The expressions of SHP-1 and SHP-2 increase in HPV6/11 positive CA, which suggest that with the infection of HPV6/11, SHP-1 and SHP-2 may play a regulatory role in the proliferation of keratinocytes.