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.

Cryotherapy ; Humans ; Hypopharynx ; Respiratory System

Few studies have described the key features and prognostic roles of lung microbiota in patients with severe community-acquired pneumonia (SCAP). We prospectively enrolled consecutive SCAP patients admitted to ICU. Bronchoscopy was performed at bedside within 48 h of ICU admission, and 16S rRNA gene sequencing was applied to the collected bronchoalveolar lavage fluid. The primary outcome was clinical improvements defined as a decrease of 2 categories and above on a 7-category ordinal scale within 14 days following bronchoscopy. Sixty-seven patients were included. Multivariable permutational multivariate analysis of variance found that positive bacteria lab test results had the strongest independent association with lung microbiota (R² = 0.033; P = 0.018), followed by acute kidney injury (AKI; R² = 0.032; P = 0.011) and plasma MIP-1β level (R² = 0.027; P = 0.044). Random forest identified that the families Prevotellaceae, Moraxellaceae, and Staphylococcaceae were the biomarkers related to the positive bacteria lab test results. Multivariable Cox regression showed that the increase in α-diversity and the abundance of the families Prevotellaceae and Actinomycetaceae were associated with clinical improvements. The positive bacteria lab test results, AKI, and plasma MIP-1β level were associated with patients' lung microbiota composition on ICU admission. The families Prevotellaceae and Actinomycetaceae on admission predicted clinical improvements.
Acute Kidney Injury/complications* ; Bacteria/classification* ; Chemokine CCL4/blood* ; Community-Acquired Infections/microbiology* ; Humans ; Lung ; Microbiota/genetics* ; Pneumonia, Bacterial/diagnosis* ; Prognosis ; RNA, Ribosomal, 16S/genetics*

Eubhorbia neriifolia L. is a plant of Euphorbia family.Five known lignans were isolated from the aerial parts of E. neriifolia L. by silica gel for column chromatography and preparative high-performance liquid chromatography (HPLC).Their potential antitumor activities were evaluated in vitro.Compound 2 exhibited proliferation inhibition and cytotoxicity against esophageal squamous cancer cells, especially KYSE-410 and KYSE-450 cells.Further analyses showed that compound 2 could significantly induce apoptosis through the activation of caspase 3/9 and down-regulation of the Bcl-2/Bax protein ratio.These results suggested that compound 2 had a significant inhibitory effect on the esophageal squamous cancer cells, especially KYSE-410, which deserves further research as a potential antitumor agent.

Objective To analyze the effect of 30 min action observation training combined with rehabilita－tion therapy on resting state visual analogue score ( R －VAS), passive movement state visual analogue score (P－VAS) and Beck depression index (BDI) scores in early stroke patients with hemiplegia .Methods From June 2016 to December 2017,86 patients with early stroke and hemiplegia treated in the Affiliated Hospital of Tai 'an Medical College were selected in the research .According to the random number table method , the patients were randomly divided into control group and combined group ,with 43 cases in each group.The control group was given routine rehabilitation treatment ,and the combined group was given 30 min action observation training on the basis of the control group.The differences of BDI,R－VAS and P－VAS were compared between the two groups before and after 1 month of treatment.Results The scores of P－VAS[(5.14 ±1.47)points]and R－VAS[(8.14 ±1.53)pionts] in the combined group were significantly lower than before treatment (t＝11.42,10.31,all P＜0.01),and the scores of the combined group were significantly lower than those of the control group (t＝9.27,8.94,all P＜0.01).The P－VAS and R －VAS scores in the control group after treatment showed no statistically significant differences compared with those before treatment(t ＝0.78,1.69,all P＞0.05).After treatment,the BDI scale scores of the combined group and control group were significantly lower than those before treatment (t＝6.43,2.29,all P＜0.05), and the score of the combined group was significantly lower than that of the control group (t＝4.44,P ＜0.05). Conclusion The 30 min exercise observation and training combined with rehabilitation therapy can effectively relieve the pain and other discomfort of early stroke patients with hemiplegia ,and can accelerate the recovery of upper limb movement function,so it has good clinical value .

OBJECTIVETo summarize the treatment status of gastric gastrointestinal stromal tumor (GIST) in Shandong province,by analyzing the clinicopathological features and prognostic factors.

METHODSClinicopathological and follow-up data of 1 165 patients with gastric GIST between January 2000 and December 2013 from 23 tertiary referral hospitals in Shandong Province were collected to establish a database. The risk stratification of all cases was performed according to the National Institutes of Health(NIH) criteria proposed in 2008. Kaplan-Meier method was used to calculate the survival rate. Log-rank test and Cox regression model were used for univariate and multivariate prognostic analyses.

RESULTSAmong 1 165 cases of gastric GIST, 557 were male and 608 were female. The median age of onset was 60 (range 15-89) years. Primary tumors were located in the gastric fundus and cardia in 623 cases(53.5%), gastric body in 346 cases(29.7%), gastric antrum in 196 cases(16.8%). All the cases underwent resection of tumors, including endoscopic resection (n=106), local resection (n=589), subtotal gastrectomy(n=399), and total gastrectomy(n=72). Based on the NIH risk stratification, there were 256 cases (22.0%) at very low risk, 435 (37.3%) at low risk, 251 cases (21.5%) at intermediate risk, and 223 cases (19.1%) at high risk. A total of 1 116 cases(95.8%) were followed up and the median follow-up period was 40 (range, 1-60) months. During the period, 337 patients relapsed and the median time to recurrence was 34 (range 1-60) months. The 1-, 3-, and 5-year survival rates were 98.6%, 86.1% and 73.4%, respectively. The 5-year survival rates of patients at very low, low, intermediate, and high risk were 93.1%, 85.8%, 63.0% and 42.3% respectively, with a statistically significant difference (P=0.000). Multivariate analysis showed that primary tumor site (RR=0.580, 95%CI:0.402-0.835), tumor size (RR=0.450, 95%CI:0.266-0.760), intraoperative tumor rupture(RR=0.557, 95%CI:0.336-0.924), risk classification (RR=0.309, 95%CI:0.164-0.580) and the use of imatinib after surgery (RR=1.993, 95%CI:1.350-2.922) were independent prognostic factors.

CONCLUSIONSThe choice of surgical procedure for gastric GIST patients should be based on tumor size. All the routine procedures including endoscopic resection, local excision, subtotal gastrectomy and total gastrectomy can obtain satisfactory curative outcomes. NIH classification has a high value for the prediction of prognosis. Primary tumor site, tumor size, intraoperative tumor rupture, risk stratification and postoperative use of imatinib are independent prognostic factors in gastric GIST patients.

Objective To summarize and analyze the epidemiological and clinical characteristics of patients with subacute thyroiditis (SAT),so as to provide a basis for prevention and treatment of the disease.Methods The epidemiological and clinical datas of 121 SAT patients,who were treated at the Shandong Provincial Institute for Endemic Disease Prevention and Control in 2015,were collected.The SAT patient's age,sex,lived in urban or rural areas,occupation and time of onset distributions were analyzed retrospectively.According to the clinical manifestations,the SAT patients were divided into types Ⅰ (mild/nodule type),Ⅱ (medium/normal),Ⅲ (severe/hyperthyroidism),and Ⅳ (delay),and clinical manifestations,auxiliary examination findings,treatment and outcome were summarized.Results Average age of the 121 cases of SAT patients was 41.36 years old,the youngest was 10 years old and the oldest was 76 years old.Most of the patients were 30-＜ 50 years old,which was accounted for 55.37％ (67/121).Most of the patients were female,which was accounted for 90.08％ (109/121).Most of the patients lived in rural areas,which was accounted for 59.50％ (72/121).Majority of the SAT patients were farmers,which was accounted for 43.80％ (53/121).Most onset of the disease was in November,accounted for 19.83％ (24/121),and the least was in June,accounted for 2.48％ (3/121),the peak of the incidence of SAT lied in autumn,and it was sporadic in the rest of the year.From the clinical classification,the mild type (61) and the medium type (46) were the largest part,a total of 107 cases,accounted for 88.43％ (107/121);while the severe type had 5 cases,accounted for 4.13％ (5/121);the delay type had 9 cases,accounted for 7.44％ (9/121).The clinical manifestations were as follows:anterior neck discomfort was 109 cases,accounted for 90.08％ (109/121);sore throat was 93 cases,accounted for 76.86％ (93/121).Auxiliary examination findings were as follows:thyroid iodine taken rate reduced in 121 cases,accounted for 100.00％ (121/121);thyroid nodule 96 cases,accounted for 79.34％ (96/ 121);total number of white blood cells increased in 52 cases,accounted for 42.98％ (52/121);neutrophil increased in 61 cases,accounted for 50.41％ (61/121);blood sedimentation significantly speed up in 49 cases,accounted for 40.50％ (49/121).All of the 121 patients were cured.Conclusions Majority of the patients are female,young aduhs and farmers.The peak of the incidence of SAT lies in autumn.The proportion of mild,medium type is the highest,we suggest this disease should be early diagnosis and treatment.

Objective To summarize and analyze the epidemiological and clinical characteristics of patients with subacute thyroiditis(SAT),so as to provide a basis for prevention and treatment.Methods The epidemiological and clinical data of 1 865 patients with SAT,who were treated in the Shandong Institute of Prevention and Control for Endemic Disease in 2015-2006,were collected.The SAT patients' sex,age,urban and rural areas,occupation and time of onset distributions,summary onset clinical manifestations,laboratory findings,treatment and outcome were analyzed retrospectively.Results The average age of the 1 865 patients with SAT was 42.16 years old,the youngest was 9 years old,and the oldest was 74 years old.Most of the patients were 21-50 years old,which was accounted for 62.36％ (1 163/1 865),and most of the patients were female,which was accounted for 83.70％ (1 561/1 865).Most of the patients lived in rural areas,which was accounted for 60.54％ (1 129/1 865).Most patients were onset in January,accounted for 20.48％ (382/1 865),and the least in July,accounted for 1.77％ (33/1865).For the clinical classification,the moderate type and the light type were the largest part with 1 716 cases,accounted for 92.01％,while the severe type was 149 cases,accounted for 7.99％.The clinical manifestations were as follows:the neck discomfort in 1 701 cases,accounted for 91.21％;neck pain,sore throat and palpitate in 1 439 cases,1 351 cases and 1 341 cases,accounted for 77.16％,72.44％ and 71.90％,respectively.Laboratory test results were as following:1 865 cases of thyroid 131I absorption rate reduced(100％);1 396 cases of thyroid nodules increased(74.85％);532 cases of FT3 and FT4 significantly increased,while TSH significandy decreased (28.53 ％);949 cases of FT3 and FT4 increased,while TSH decreased (50.88％);53 cases of FT3 and FT4 decreased,while TSH increased (2.84％);331 cases of FT3,FT4 and TSH in the normal range(17.75％).The thyroid 13I absorption rate significantly increased and thyroid nodules significantly reduced with treatment,the difference was statistically significant (t =-34.93,133.2,all P ＜ 0.001).1 813 patients were cured,while 52 cases arised hypothyroidism.Conclusion Majority of SAT patients are young women.The peak of the incidence of SAT lies in autumn and winter.The proportion of the moderate type is the highest.Early diagnosis and treatment is the key to improve the prognosis of patients with SAT.

Objective To explore the association between complement C3 and the prevalence of simple fatty liver disease and nonalcoholic steatohepatitis. Methods A total of 2 799 health check-up participants were recruited from Tianjin Medical University General Hospital-Health Management Centre. Serum C3 levels were measured using immunoturbidimetry method and simple fatty liver disease and nonalcoholic steatohepatitis were diagnosed by liver ultrasonography and serum alanine aminotransferase concentration. Multiple logistic regression analysis was used to examine the association between quartiles of serum C3 levels and the prevalence of simple fatty liver disease and nonalcoholic steatohepatitis. Results After adjusting for covariates, the odds ratios (95% confidence interval) of simple fatty liver disease and nonalcoholic steatohepatitis for increasing quartiles of C3 were: 1.00 (reference), 2.15 (1.55, 3.01), 3.28 (2.35, 4.6) and 4.31 (3.11, 6.02); and 1.00 (reference), 4.54 (1.68, 15.91), 7.81 (3.02, 26.67) and 14.91 (5.94, 50.14) (both P for trend<0.000 1), respectively. Conclusions The study found that the elevated C3 levels were significantly associated with the prevalence of simple fatty liver disease and nonalcoholic steatohepatitis. Further study is needed to clarify whether C3 has a predictive value for the occurrence of nonalcoholic fatty liver disease.