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.Trial Registration::ClinicalTrials.gov, NCT04805411.

Objective:To investigate the changes of Toll-like receptor 4(TLR4) level in peripheral blood of endometriosis (EMT) patients with infertility and its relationship with clinicopathological types and pregnancy outcomes.Methods:A total of 150 patients with EMT complicated with infertility (study group) admitted to Huangzhou District People′s Hospital of Huanggang City from May 2019 to March 2021 and 50 healthy married women (control group) who participated in physical examination during the same period were selected as the research objects. Reverse transcription polymerase chain reaction (RT-PCR) was used to determine the level of TLR4 in peripheral blood of the two groups, and different pathological types of EMT were compared. The receiver operating characteristic (ROC) curve was used to evaluate the predictive efficacy of TLR4 expression for postoperative pregnancy in EMT patients with infertility. At the same time, the relationship between changes in TLR4 level in peripheral blood and pregnancy outcomes was analyzed according to the TLR4 cut-off value.Results:The expression of TLR4 mRNA in peripheral blood in the study group was higher than that in the control group: 98.65 ± 10.63 vs. 1.27 ± 0.20, there was statistical difference ( t = 64.66, P<0.01). After treatment, the expression of TLR4 mRNA in peripheral blood of patients with simple peritoneal type, internal cystic type and adenomyosis type EMT complicated were decreased :81.13 ± 8.89 vs. 64.31 ± 6.44, 103.58 ± 10.01 vs. 85.40 ± 8.78, 118.69 ± 12.76 vs. 96.38 ± 9.96, There were statistical differences ( P<0.05); No matter before or after treatment, the expression of TLR4 mRNA in peripheral blood of patients with adenomyosis was higher than that of patients with internal cystic type and simple peritoneal type, while the expression of TLR4 mRNA in peripheral blood of patients with internal cystic type was higher than that of simple peritoneal type, and there were statistical differences ( P<0.05). The results of ROC curve analysis showed that when the area under the curve (AUC) was 0.787(95% CI 0.701 - 0.863, P<0.05) and the best cut-off value was 41.75, the sensitivity, specificity and accuracy of TLR4 mRNA expression in peripheral blood to predict postoperative pregnancy in EMT patients with infertility were 80.12%, 81.57% and 80.30%, respectively. Using the peripheral blood TLR4 mRNA expression of 41.75 as the cut-off value, 143 patients with EMT and infertility with complete follow-up data were divided into high expression group (58 cases, TLR4 mRNA≥41.75) and low expression group (85 cases, TLR4 mRNA < 41.75). The postoperative intrauterine pregnancy rate and total pregnancy rate in the high expression group were lower than those in the low expression group: 44.83% (26/58) vs. 70.59% (60/85), 58.62% (34/58) vs. 81.18% (69/85), and there were statistical differences ( χ2 = 9.54, 8.71, P<0.05). Conclusions:There is abnormal expression of TLR4 in peripheral blood of EMT patients with infertility, and its high expression is closely related to adverse clinicopathological features and pregnancy outcomes. Effective intervention of treatment and postoperative recovery according to the expression level of TLR4 mRNA can further improve the natural pregnancy rate of such patients.

Sjögren's syndrome （SS）， a disorder of immune system， is one of the dominant diseases treated by traditional Chinese medicine （TCM）. China Association of Chinese Medicine organized experts in the field of TCM and western medicine rheumatology and pharmacology to discuss the advantages and optimal regimens of TCM for the treatment of SS. The experts generally agreed on the low early diagnosis rate of SS and the lack of targeted therapeutic drugs. In addition， autoimmune abnormality is the key factor in the occurrence of SS and deficiency of both Qi and Yin is the core pathogenesis. SS has unique tongue manifestations， which is expected to allow for the early diagnosis and treatment with integrated traditional Chinese and western medicine. TCM has advantages in treating SS in terms of alleviating clinical symptoms and systemic involvement， individualized treatment， relieving sleep and mood disorders， preventing the occurrence in the early stage， and enhancing the effectiveness and reducing toxicity in the treatment by integrated TCM and western medicine. In general， TCM has advantages in different stages of SS. Internal and external use of TCM， acupuncture， and acupotome are all available options. The optimal regimens should be determined on the basis of pattern identification， stage of disease， and the advantages of TCM. Clinical characteristics and biomarkers of SS should be studied to classify patients， so as to design precision evidence-based TCM regimens for SS. On the basis of unique tongue manifestations of SS， models for early diagnosis and poor prognosis identification of SS should also be established to achieve early prevention and treatment and to improve the prognosis. In the future， we should vigorously carry out high-quality evidence-based medical research on the treatment of SS by TCM and integrated traditional Chinese and western medicine and develop relevant guidelines to optimize and standardize current diagnosis and treatment， thereby laying a basis for clarifying and explaining the advantages of TCM in treating SS.

Objective:To explore the prolonged therapeutic regimen for patients with plaque psoriasis, who showed a positive response to 4-week treatment with tazarotene/betamethasone dipropionate cream, but were not completely cured.Methods:A multicenter, randomized, open-labelled, parallel-controlled clinical study was conducted. A total of 232 patients with plaque psoriasis were collected, who showed a positive response to previous 4-week treatment with 0.05%/0.05% tazarotene/betamethasone dipropionate cream, but were not completely cured with the psoriasis area and severity index[PASI] improvement rate being 50%-90%. At week 5, they were randomly and equally divided into 2 groups: test group receiving treatment with 0.05%/0.05% tazarotene/betamethasone dipropionate cream once a day, and control group receiving a sequential regimen of 0.05% tazarotene gel on weekdays once a day followed by 0.05%/0.05% tazarotene/betamethasone dipropionate cream on weekends once a day. After 2-and 4-week prolonged treatment, the efficacy and safety of the 2 therapeutic regimens were evaluated and compared. Measurement data were compared between 2 groups by using covariance analysis or t test, and enumeration data were compared by using chi-square test. Results:From the 5th to the 8th week, 200 out of the 232 patients completed the treatment. Data collected from 110 patients in the test group and 112 in the control group were enrolled into the full analysis set, and those from both 113 patients in the test group and control group were enrolled into safety analysis set. After consecutive 6-and 8-week treatment, the decline rates of the PASI score were 73.05% ± 16.69% and 78.46% ± 15.40% respectively in the test group, which were significantly higher than those in the control group (66.73% ± 21.77%, 67.02% ± 34.19%, respectively, both P < 0.05) . After 6-week treatment, the proportion of subjects who achieved PASI90 was significantly higher in the test group (14 cases, 12.7%) than in the control group (5 cases, 4.5%, χ2=4.842, P=0.028) ; After 8-week treatment, the proportions of subjects who achieved PASI75 and PASI90 (61.8%, 23.6%, respectively) were significantly higher in the test group than in the control group (48.2%, 12.5%, respectively, both P < 0.05) . During the consecutive 8-week treatment, there was no significant difference in the incidence rate of adverse reactions between the test group (15.0%) and control group (23.9%, χ2=2.822, P=0.093) . Conclusion:For patients who showed a positive response to 4-week treatment with 0.05%/0.05% tazarotene/betamethasone dipropionate cream, but were not completely cured, the continuous use of 0.05%/0.05% tazarotene/betamethasone dipropionate cream for 4 weeks is a superior therapeutic regimen compared with the sequential regimen of 0.05% tazarotene gel followed by 0.05%/0.05% tazarotene/betamethasone dipropionate cream.

ObjectiveTo investigate the protective effect of Lycium barbarum polysaccharide (LBP) combined with aerobic exercise (AE) on the liver of rats with nonalcoholic steatohepatitis (NASH) induced by high-fat diet based on the p38 mitogen-activated protein kinase (p38 MAPK)-nuclear factor-κB (NF-κB) pathway. MethodsAfter 1 week of adaptive feeding, 45 Sprague-Dawley rats, aged 8 weeks, were randomly divided into control group (10 rats fed with normal diet) and high-fat group (35 rats fed with high-fat diet). At the end of week 28, the high-fat group was randomly divided into model group, LBP group, AE group, and LBP+AE group, with 8 rats in each group, and intervention was performed for 10 weeks. At the end of the experiment, fasting blood glucose was measure for all rats, and serum samples, liver tissue, and visceral fat were collected. Biochemical kits were used to measure the serum levels of triglyceride (TG), total cholesterol (TC), alanine aminotransferase (ALT), and aspartate aminotransferase (AST); ELISA kits were used to measure the serum levels of fasting insulin (FINS), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and monocyte chemotactic protein-1 (MCP-1); quantitative real-time PCR and Western blot were used to measure the mRNA and protein expression levels of Toll-like receptor 4 (TLR4), p38 MAPK, and NF-κB in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the control group, the model group had significant increases in TG, TC, AST, ALT, FINS, and homeostasis model assessment of insulin resistance (HOMA-IR) (all P ＜0.05), a tendency of increases in the serum levels of the inflammatory factors MCP-1, TNF-α, and IL-6 (all P ＜0.05), and significant increases in the mRNA and protein expression levels of TLR4, p38 MAPK, and NF-κB in liver tissue (all P ＜0.05). Compared with the model group, each intervention group had significant reductions in TG, TC, AST, ALT, FINS, and HOMA-IR (all P ＜0.05), a tendency of reductions in the serum levels of the inflammatory factors MCP-1, TNF-α, and IL-6 (all P ＜0.05), and significant reductions in the mRNA and protein expression levels of TLR4, p38 MAPK, and NF-κB (all P ＜0.05). Compared with LBP group, the LBP+AE group had significant reductions in TG, ALT, FINS, HOMA-IR, MCP-1, the mRNA expression level of TLR4, protein expression levels of p38 MAPK and NF-κB(all P＜0.05). Compared with Ae group, the LBP+AE group had significant reductions in FINS, HOMA-IR, IL-6, MCP-1, the mRNA expression level of TLR4 (all P＜0.05). ConclusionLBP combined with AE may improve inflammation in NASH rats by regulating the p38 MAPK/NF-κB pathway.

To investigate Streptococcus suis ( S.suis) isolated from patients in Shandong province using genomic epidemiology and pathogenologic analysis. To provide the foundation to establish reasonable and accurate prevention and control measures of human S. suis infection. Molecular typing, whole genome phylogenetic tree, virulence gene typing, antibiotic resistance profile and mobile genetic elements carrying antibiotic resistance genes of isolated S. suis strains were investigated. The pathogenicity of isolated strains was also evaluated by comparing their capacity to induce pro-inflammatory cytokine production in vitro. S. suis infections in Shandong province were predominantly due to serotype 2 and sequence type 1 strains. The major symptoms were meningitis. The studied strains could be divided into five lineages. All strains belong to highly pathogenic type in Shandong province,Strains from lineage 2 possessed higher capacity to stimulate pro-inflammatory cytokine production than other strains did, even though other strains belong to highly pathogenic strains. In addition, multiple antibiotic resistance genes and corresponding mobile genetic elements werewidespread in S. suis strains from Shandong province, except strains from lineage 3. High diversities in genome, evolutionary path and pathogenicity of S. suis strains from Shandong province were revealed. It was necessary to surveillant the S. suis strain in genomic level.

To investigate Streptococcus suis ( S.suis) isolated from patients in Shandong province using genomic epidemiology and pathogenologic analysis. To provide the foundation to establish reasonable and accurate prevention and control measures of human S. suis infection. Molecular typing, whole genome phylogenetic tree, virulence gene typing, antibiotic resistance profile and mobile genetic elements carrying antibiotic resistance genes of isolated S. suis strains were investigated. The pathogenicity of isolated strains was also evaluated by comparing their capacity to induce pro-inflammatory cytokine production in vitro. S. suis infections in Shandong province were predominantly due to serotype 2 and sequence type 1 strains. The major symptoms were meningitis. The studied strains could be divided into five lineages. All strains belong to highly pathogenic type in Shandong province,Strains from lineage 2 possessed higher capacity to stimulate pro-inflammatory cytokine production than other strains did, even though other strains belong to highly pathogenic strains. In addition, multiple antibiotic resistance genes and corresponding mobile genetic elements werewidespread in S. suis strains from Shandong province, except strains from lineage 3. High diversities in genome, evolutionary path and pathogenicity of S. suis strains from Shandong province were revealed. It was necessary to surveillant the S. suis strain in genomic level.

Objective To construct a human renal epithelial cell line HEK293T by CRISPR-Cas9-based site-directed knock-in of vascular endothelial growth factor 165 (VEGF165) gene, and avoid the off-target effect caused by lentivirus infection. Methods The VEGF165 expression vector with homologous arm (pUCm-T-VEGF165 plasmid) and the sgRNA expression vector [pSpCas9(BB)-2A-Puro-sgRNA plasmid] were designed and constructed based on the DNA sequence of the EZH2 gene, and then co-transfected into HEK293T cells. The expression of VEGF165 mRNA was detected by qPCR and the expressions of VEGF165 proteins were detected by Western Blot. Results The qPCR and Western Blot results showed that, comparing with the control, the pUCm-T-VEGF165 plasmid and pSpCas9(BB)-2A-Puro-sgRNA plasmid, the expression of the co-transfection plasmid were significantly increased, i.e. 3.42±0.30 vs. 1.02±0.21, 1.13±0.16 and 0.98±0.18 for the VEGF165 mRNA level (all P<0.01), and 1.13±0.16 vs. 1.02±0.06, 0.88±0.03 and 0.80±0.05 for the VEGF165 protein level (all P<0.01), respectively. Besides, the expression of EZH2 was significantly down-regulated, i.e. 0.14±0.06 vs. 1.08±0.11, 1.02±0.12 and 1.13±0.16 for the EZH2 mRNA level (all P<0.01), and 0.23±0.03 vs. 1.05±0.13, 0.91±0.04 and 0.81±0.06 for the EZH2 protein level (all P<0.01), respectively. This result showed that the VEGF165 was successfully inserted into the EZH2 genome, interfering the EZH2 expression. Conclusions VEGF165 gene can be successfully knocked into HEK293T cells by CRISPR/Cas9 system.

In 1930s, Wolf created the first partogram. In 1950s, Friedman proposed the classical model of partogram that has been applied in clinical labor assessment ever since. Over the past ten years, Zhang has made great improvement in this field. Here, we reviewed the three different stages in partogram research (the first proposed stage, Friedman's classical stage and Zhang's stage) in terms of its background, demographic characteristics and clinical application. Moreover, this article also emphasized the necessity of partogram research and discussed the prospects for future research and clinical application based on the recent progress in China.

Objective To identify hot research areas of nursing human caring in PubMed from 2012 to 2016, and to explore the present research status and development directions. Methods PubMed was searched using key words human caring. BICOMB 2.0 and SPSS 11.5 software were used to analyze high-frequency keywords and conduct co-word clustering analysis. Results We searched for 3088 related articles and extracted 42 high-frequency keywords (30.97%). Seven hot research areas were identified,including:human caring in nursing practice;nursing models,nursing theories;nursing education of human caring;hospice care;relationship between human caring and nurse-patient relation;human caring of cancer patients;family system,social support and human caring. Conclusion Analysis of research areas of nursing human caring in past 5 years is beneficial to understanding the present research status and development directions,and providing references for practice,research and education of human caring.