1.Efficacy and safety of CM310 in moderate-to-severe atopic dermatitis: A multicenter, randomized, double-blind, placebo-controlled phase 2b trial
Yan ZHAO ; Jianzhong ZHANG ; Bin YANG ; Jingyi LI ; Yangfeng DING ; Liming WU ; Litao ZHANG ; Jinyan WANG ; Xiaohong ZHU ; Furen ZHANG ; Xiaohua TAO ; Yumei LI ; Chunlei ZHANG ; Linfeng LI ; Jianyun LU ; Qingchun DIAO ; Qianjin LU ; Xiaoyong MAN ; Fuqiu LI ; Xiujuan XIA ; Hao CHENG ; Yingmin JIA ; Guoqing ZHAO ; Jinchun YAN ; Bo CHEN
Chinese Medical Journal 2024;137(2):200-208
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.
2.Experience in diagnosis and treatment of 6 cases of renal Ewing's sarcoma with venous thrombus
Binshuai WANG ; Min QIU ; Qianjin ZHANG ; Maofeng TIAN ; Lei LIU ; Guoliang WANG ; Min LU ; Xiao-Jun TIAN ; Shudong ZHANG
Journal of Peking University(Health Sciences) 2024;56(4):636-639
Objective:To review and analyze the clinical diagnosis and treatment of renal Ewing's sar-coma with venous tumor embolus,to follow up the survival and prognosis of the patients,and to provide help for the diagnosis and treatment of the disease.Methods:Clinical data(including general data,sur-gical data and postoperative pathological data)of patients diagnosed with renal Ewing's sarcoma with ve-nous tumor embolus in Peking University Third Hospital from June 2016 to June 2022 were collected,and the prognosis of the patients was followed up to analyze the influence of diagnosis and treatment process on the prognosis of the disease.Results:There were 6 patients,including 1 male and 5 females.There were 4 cases of left renal tumor and 2 cases of right renal tumor.The median age at diagnosis was 28 years(16-52 years).The imaging findings were all exogenous tumors with internal necrotic tissue and hemorrhage.The mean maximum tumor diameter was 12.6 cm,and the mean tumor thrombus length was 7.8 cm.Four patients underwent open surgery and 2 patients underwent laparoscopic surgery.The post-operative pathological results were renal Ewing sarcoma.Immunohistochemical results showed 3 cases of CD99(+),2 cases of FLI-1(+),and 1 case of CD99,FLI-1(-).3 patients received chemothera-py(cyclophosphamide,doxorubicin,vincristine/ifosfamide,etoposide),1 case received chemotherapy combined with radiotherapy,and 2 cases received no adjuvant therapy.The mean overall survival(OS)of the 6 patients was 37 months,and the mean OS of the 4 patients(47 months)who received chemo-therapy was significantly higher than that of the 2 patients(16 months)who did not receive chemotherapy(P=0.031).Conclusion:Renal Ewing's sarcoma with venous tumor embolus is rare in clinic,and it is common in young female patients.The operation is difficult and the prognosis is poor.Surgical resection,adjuvant radiotherapy and chemotherapy can improve the overall survival rate of the patients.
3.Effect and Mechanism of S-adenosylmethionine on Reversing Chemotherapy Resistance in Pancreatic Cancer
Yan LIU ; Ziming DING ; Qianjin ZHANG
Journal of Medical Research 2024;53(7):146-151
Objective To studyexplore the reversal effect of S-adenosylmethionine(SAM)on chemotherapy resistancechemoresis-tance of pancreatic cancer and explore its related mechanisms.Methods After treatment of human pancreatic cancer resistant cell lines PANC-1/GEM with SAM,the cell proliferation activity of PANC-1/GEM cells and their resistance to gemcitabine(GEM)were ana-lyzed by MTT assay;The the effect of SAM on apoptosis rate of PANC-1/GEM cells was detected by flow cytometry;the change of SAM on the migration activity of drug-resistant cell lines was detected by cell scratch assay;the expression of NEDD4-1 protein in drug-re-sistant cell lines and the changes of NEDD4-1,p-JAK2,p-STAT3 and P-gp protein levels after SAM treatment were detected by Western blot.Results SAM could inhibit the activity of pancreatic cancer PANC-1/GEM resistant cell lines and significantly decreased its resistance to GEM chemotherapy.The IC50 value decreased from 1557.50±201.10nmol/L to 218.39±20.61 nmol/L(P<0.01);SAM can obviously induced the apoptosis of drug-resistant cell lines and inhibited their migration activity;the expression of NEDD4-1 protein was up-regulated in drug-resistant cell lines,and SAM could inhibit the activation levels of NEDD4-1,p-JAK2,p-STAT3 and P-gp proteins.Conclusion SAM can reduce the chemotherapy resistance of PANC-1/GEM cells to GEM by regulating NEDD4-1 to inhibit the activity of JAK2/STAT3 pathway and regulate the activity of P-gp protein,which provides some experimental evidence for the clinical application of SAM in the treatment of chemotherapy resistance in tumor patients.
4.Analysis of the effect and symptom progression of hybird surgery for cerebral arteriovenous malformation:a single-center retrospective cohort study
Qianjin DING ; Zihao SONG ; Yongjie MA ; Jiaxing YU ; Peng HU ; Hongqi ZHANG
Chinese Journal of Cerebrovascular Diseases 2024;21(10):664-670
Objective To investigate the safety and efficacy of bybrid surgery in the treatment of cerebral arteriovenous malformation(CAVM)and possible factors for postoperative symptom progression.Methods A total of 61 patients with CAVM admitted to the Department of Neurosurgery,Xuanwu Hospital,Capital Medical University from January 1,2016 to December 31,2021 who underwent bybrid surgery were retrospectively included.Demographic information(sex,age),incidence(first diagnosis of CAVM by imaging and/or first appearance of CAVM-related symptoms such as hemorrhage and epilepsy),time from onset to hybrid surgery,modified Rankin scale(mRS)score at admission,history of previous CAVM treatment(surgical removal of previous CAVM and intravascular treatment),CAVM imaging data(lesion location,size,drainage),Spetzler-Martin grade,lesion density(loose,dense),CAVM combined with aneurysm or aneurysmal structure,surgical method(microsurgery+intraoperative DSA,microsurgery+intraoperative DSA+endovascular embolism),treatment-related complications(intracranial hemorrhage and/or ischemic events and/or edema in surgery-related areas,puncture site hematoma and/or fistula and/or pseudoaneurysm,gastrointestinal and/or gingival bleeding and/or epistaxis,contrast hypersensitivity,all-cause death),clinical and radiological follow-up data were recorded.The safety(treatment-related complications,symptom progression[positive difference between the mRS score at 6 months postoperatively and the baseline mRS score])and effectiveness(occlusion,complete absence of the malformation on DSA at 6 months postoperatively;good prognosis,mRS score≤2 at 6months postoperatively)of hybrid surgery treatment were evaluated.Based on the clinical follow-up results at 6 months after surgery,patients who underwent hybrid surgery for CAVM were divided into the progressive group and the non-progressive group,and their baseline and clinical characteristics were compared.Results(1)Among the 61 patients who underwent hybrid surgery for CAVM,37(60.7%)were male,with a median age of 25(13,42)years;11(18.0%)were asymptomatic,and 39(63.9%)had hemorrhage as their initial symptom,while 11(18.0%)had seizures as their initial symptom.At admission,54(88.5%)patients had an mRS score of ≤2,including 38(62.3%)patients who had undergone previous endovascular embolization and had residual or recurrent CAVM;the Spetzler-Martin grade of the CAVM lesion was Ⅰ,Ⅱ,Ⅲ,or Ⅳ in 13(21.3%),22(36.1%),21(34.4%),and 5(8.2%)patients,respectively;24 patients underwent DSA verification during surgery using a hybrid surgical platform,and 37 patients underwent DSA verification and assisted endovascular embolization using a hybrid surgical platform.(2)Clinical follow-up completion rate was 77.0%(47/61);the follow-up time ranged from 6 to 24 months and the median follow-up time was 12(6,24)months.The good prognosis rate was 91.5%(43/47),there was no death.The incidence of treatment-related complications was 10.6%(5/47).The completion rate of imaging follow-up was 72.1%(44/61)and the median follow-up time was 15(10,22)months.There were 40(90.9%)of CAVM occlusion,2(4.5%)of residual CAVM and 2(4.5%)of recurrent CAVM.(3)Among the 47 patients who completed clinical follow-up,15 patients developed symptoms and 32 patients did not develop symptoms.There were no significant differences in sex,age,onset symptoms,mRS score at admission,lesion location,lesion density and aneurysm or aneurysmal structure between the two groups(all P>0.05).In the progressive group,the proportion of lesions with the largest diameter<3 cm,3-6 cm and>6 cm were 3/15,10/15 and 2/15,respectively,and the largest diameter was mainly 3-6 cm.In the non-progressive group,the proportion of the largest diameter<3 cm and 3-6 cm were 18/32 and 14/32,respectively,and the largest diameter<3 cm was the main proportion(x2=8.321).Deep venous drainage(x2=11.937)and residual and/or recurrence(x2=8.507)were present in the progressive group,and the differences between the groups were statistically significant(all P<0.05).Conclusions Hybrid surgery has certain safety and effectiveness in the treatment of CAVM.Patients with CAVM who experienced progression after undergoing composite surgery have characteristics such as larger maximum diameter,the presence of deep venous drainage and residual and/or recurrence,and the factors affecting progression need to be further explored in the future.
5.Clinical treatment guideline for pulmonary blast injury (version 2023)
Zhiming SONG ; Junhua GUO ; Jianming CHEN ; Jing ZHONG ; Yan DOU ; Jiarong MENG ; Guomin ZHANG ; Guodong LIU ; Huaping LIANG ; Hezhong CHEN ; Shuogui XU ; Yufeng ZHANG ; Zhinong WANG ; Daixing ZHONG ; Tao JIANG ; Zhiqiang XUE ; Feihu ZHOU ; Zhixin LIANG ; Yang LIU ; Xu WU ; Kaican CAI ; Yi SHEN ; Yong SONG ; Xiaoli YUAN ; Enwu XU ; Yifeng ZHENG ; Shumin WANG ; Erping XI ; Shengsheng YANG ; Wenke CAI ; Yu CHEN ; Qingxin LI ; Zhiqiang ZOU ; Chang SU ; Hongwei SHANG ; Jiangxing XU ; Yongjing LIU ; Qianjin WANG ; Xiaodong WEI ; Guoan XU ; Gaofeng LIU ; Junhui LUO ; Qinghua LI ; Bin SONG ; Ming GUO ; Chen HUANG ; Xunyu XU ; Yuanrong TU ; Liling ZHENG ; Mingke DUAN ; Renping WAN ; Tengbo YU ; Hai YU ; Yanmei ZHAO ; Yuping WEI ; Jin ZHANG ; Hua GUO ; Jianxin JIANG ; Lianyang ZHANG ; Yunfeng YI
Chinese Journal of Trauma 2023;39(12):1057-1069
Pulmonary blast injury has become the main type of trauma in modern warfare, characterized by externally mild injuries but internally severe injuries, rapid disease progression, and a high rate of early death. The injury is complicated in clinical practice, often with multiple and compound injuries. Currently, there is a lack of effective protective materials, accurate injury detection instrument and portable monitoring and transportation equipment, standardized clinical treatment guidelines in various medical centers, and evidence-based guidelines at home and abroad, resulting in a high mortality in clinlcal practice. Therefore, the Trauma Branch of Chinese Medical Association and the Editorial Committee of Chinese Journal of Trauma organized military and civilian experts in related fields such as thoracic surgery and traumatic surgery to jointly develop the Clinical treatment guideline for pulmonary blast injury ( version 2023) by combining evidence for effectiveness and clinical first-line treatment experience. This guideline provided 16 recommended opinions surrounding definition, characteristics, pre-hospital diagnosis and treatment, and in-hospital treatment of pulmonary blast injury, hoping to provide a basis for the clinical treatment in hospitals at different levels.
6.Clinical effect of right minithoracotomy approach on tricuspid regurgitation after the left-sided valve surgery: A retrospective study of a single center
Daokuo ZHENG ; Baocai WANG ; Zhaoyun CHENG ; Yong ZHAO ; Qiao ZHANG ; Huakun ZHANG ; Lu MA ; Qianjin LIU ; Zhenwei GE
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2022;29(06):742-747
Objective To analyze the clinical efficacy of right minithoracotomy approach in the treatment of patients with regurgitation after left-sided valve surgery (LSVS). Methods The clinical data of 77 patients who suffered tricuspid regurgitation (TR) after LSVS and received surgical treatment in the Heart Center of Henan Provincial People's Hospital from 2012 to 2019 were selected. According to the operation method, the patients were divided into a right minithoracotomy group (n=32), including 13 (40.6%) males, aged 57.3±5.3 years and a median sternotomy group (n=45), including 17 (37.8%) males, aged 55.7±6.6 years. Preoperative and postoperative clinical data of the two groups were compared and analyzed. Results There was no significant difference in preoperative data between the two groups. There were 24 patients of tricuspid valvuloplasty (TVP) and 8 patients of tricuspid valve replacement (TVR) in the right minithoracotomy group. There were 29 patients of TVP and 16 patients of TVR in the median sternotomy group. The operation time, postoperative hospitalization time, intubation time and ICU stay time of the right minithoracotomy group were shorter than those of the median sternotomy group (P<0.001). The operative bleeding, postoperative drainage in 24 hours, postoperative blood transfusion rate and incision poor healing of the right minithoracotomy group were significantly decreased compared with those of the median sternotomy group (P<0.05). The extracorporeal circulation time between the two groups was not significantly different (P=0.382). The postoperative complications and mortality of the righ minithoracotomy group were significantly lower than those of the median sternotomy group (P<0.05). Conclusion The procedure of right minithoracotomy access can reduce perioperative morbidity and mortality compared with the median sternotomy, and results in satisfied clinical efficacy.
7.Correlation between gross motor function and spinal range of motion for children with bilateral spastic cerebral palsy
Sijia LI ; Qi ZHANG ; Yan HE ; Qianjin LIU ; Yanqing ZHANG ; Tiantian ZHOU
Chinese Journal of Rehabilitation Theory and Practice 2022;28(10):1211-1216
ObjectiveTo explore the correlation between gross motor function and spinal range of motion (ROM) in children with bilateral spastic cerebral palsy. MethodsA total of 33 children with bilateral spastic cerebral palsy in Beijing Bo'ai Hospital from December, 2019 to March, 2022 were selected and divided into group 1 (grade Ⅰ, n = 12), group 2 (grade Ⅱ, n = 11) and group 3 (grade Ⅲ, n = 10) according to Gross Motor Function Classification System (GMFCS). SpinalMouse (spine morphometric machine) was used to measure the ROM of forward and backward flexion, and left and right lateral flexion of trunk, respectively, in sitting. Their gross motor ability was then further tested using the Gross Motor Function Measure (GMFM) 88 item. ResultsThe ROM of backward flexion, the left and right lateral flexion, and the total ROM of sagittal and coronal plane were positively correlated with the scores of GMFM88 (r > 0.424, P < 0.05), and were negatively correlated with the grade of GMFCS (|r| > 0.424, P < 0.05). ConclusionSpinal ROM correlates with gross motor function in children with bilateral spastic cerebral palsy.
8.Value of contrast-enhanced ultrasound combined with serum CXCL8 and CXCR2 in the evaluation of postoperative efficacy of transcatheter arterial chemoembolization for primary liver cancer
Yumin ZHANG ; Xianwei ZHAO ; Qianjin HE ; Jieneng CHEN
Journal of International Oncology 2022;49(10):592-596
Objective:To investigate the application value of contrast-enhanced ultrasound combined with serum CXC chemokine ligand 8 (CXCL8) and CXC chemokine receptor 2 (CXCR2) levels detection in the efficacy evaluation of patients with primary liver cancer after transcatheter arterial chemoembolization (TACE) .Methods:A total of 80 patients with primary liver cancer who were diagnosed and treated in Huanggang Central Hospital of Hubei Province from June 2019 to January 2022 were selected as the research objects. The therapeutic efficacy was evaluated 2 months after TACE treatment. According to the pathological diagnosis, the patients were divided into complete inactivation group ( n=30) and residual lesion group ( n=50) . The levels of serum CXCL8 and CXCR2 were measured by enzyme linked immunosorbent assay (ELISA) double antibody sandwich method, and contrast-enhanced ultrasonography was performed on the patients. Receiver operating characteristic (ROC) curve was applied to analyze the value of serum CXCL8 and CXCR2 in evaluating the efficacy of TACE in patients with primary liver cancer. Kappa test was applied to test the consistency of contrast-enhanced ultrasound and contrast-enhanced ultrasound combined with serum CXCL8 and CXCR2 in evaluating the efficacy of TACE in patients with primary liver cancer and the results of pathological diagnosis. Results:Compared with the complete inactivation group, the levels of serum CXCL8 [ (7.12±1.68) ng/ml vs. (5.07±1.25) ng/ml] and CXCR2 [ (3.62±0.79) ng/ml vs. (2.43±0.67) ng/ml] in the residual lesion group were obviously higher ( t=5.79, P<0.001; t=6.89, P<0.001) . The areas under the curve of CXCL8 and CXCR2 in evaluating the efficacy of TACE in patients with primary liver cancer were 0.827 and 0.801 respectively, the specificities were 73.3% and 76.7%, and the sensitivities were 70.0% and 72.0% respectively. The concordance between contrast-enhanced ultrasound and pathological diagnosis was moderate, and the Kappa value was 0.49 ( P<0.001) . The concordance between contrast-enhanced ultrasound combined with serum CXCL8 and CXCR2 and pathological diagnosis was high, and the Kappa value was 0.62 ( P<0.001) . The sensitivity of contrast-enhanced ultrasound combined with serum CXCL8 and CXCR2 in evaluating the efficacy of TACE in patients with primary liver cancer was 90.0%, which was higher than the sensitivity of contrast-enhanced ultrasound (72.0%, χ2=5.26, P=0.022) , CXCL8 (70.0%, χ2=6.25, P=0.012) and CXCR2 (72.0%, χ2=5.26, P=0.022) . Conclusion:Contrast-enhanced ultrasound can detect residual lesions after TACE in patients with primary liver cancer to a certain extent, and its combination with serum CXCL8 and CXCR2 can effectively improve the evaluation efficiency of the efficacy of TACE treatment in patients with primary liver cancer.
9.Recent advances in systemic lupus erythematosus and microbiota: from bench to bedside.
Yijing ZHAN ; Qianmei LIU ; Bo ZHANG ; Xin HUANG ; Qianjin LU
Frontiers of Medicine 2022;16(5):686-700
Systemic lupus erythematosus (SLE) is a complicated autoimmune disease affecting multiple systems and organs. It is highly heterogeneous, and it preferentially affects women at childbearing age, causing worldwide social burden. The pathogenesis of SLE mostly involves genetic predisposition, epigenetic dysregulation, overactivation of the immune system, and environment factors. Human microbiome, which is mostly composed of microbiota colonized in the gut, skin, and oral cavity, provides a natural microbiome barrier against environmental risks. The past decade of research has demonstrated a strong association between microbiota and metabolic diseases or gastrointestinal diseases. However, the role of microbiota in autoimmunity remains largely unknown until recently, when the technological and methodological progress facilitates further microbiota research in SLE. In this review, the latest research about the role and mechanisms of microbiota in SLE and the advances in the development of diagnostic and therapeutic strategies based on microbiota for SLE were summarized.
Humans
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Female
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Gastrointestinal Microbiome
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Lupus Erythematosus, Systemic/therapy*
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Microbiota
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Autoimmunity
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Immune System
10.Diagnosis and treatment of adult-onset Still′s disease
Xiaoqing YI ; Shuaihantian LUO ; Guiying ZHANG ; Qianjin LU
Chinese Journal of Dermatology 2021;54(2):165-169
Adult-onset Still′s disease (AOSD) is a type of systemic inflammatory disease of unknown etiology, with diverse clinical manifestations, and there are some difficulties in its diagnosis and treatment. In recent years, it has been found that some new markers, such as heme oxygenase 1, calreticulin, inflammatory cytokines and advanced glycation end products, can be used for a comprehensive assessment of the activity and severity of AOSD. Moreover, new biological agents, such as tumor necrosis factor inhibitors, interleukin-1 (IL-1) inhibitors, IL-6 inhibitors and recombinant IL-18 binding proteins, bring new hope for the treatment of AOSD. This review mainly summarizes progress in the diagnosis and treatment of AOSD.

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