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.A multi-constraint optimal puncture path planning algorithm for percutaneous interventional radiofrequency thermal fusion of the L5/S1 segments
Hu LIU ; Zhihai SU ; Chengjie HUANG ; Lei ZHAO ; Yangfan CHEN ; Yujia ZHOU ; Hai LÜ ; Qianjin FENG
Journal of Southern Medical University 2024;44(9):1783-1795
Objective To minimize variations in treatment outcomes of L5/S1 percutaneous intervertebral radiofrequency thermocoagulation(PIRFT)arising from physician proficiency and achieve precise quantitative risk assessment of the puncture paths.Methods We used a self-developed deep neural network DWT-UNet for automatic segmentation of the magnetic resonance(MR)images of the L5/S1 segments into 7 key structures:L5,S1,Ilium,Disc,N5,Dura mater,and Skin,based on which a needle insertion path planning environment was modeled.Six hard constraints and 6 soft constraints were proposed based on clinical criteria for needle insertion,and the physician's experience was quantified into weights using the analytic hierarchy process and incorporated into the risk function for needle insertion paths to enhance individual case adaptability.By leveraging the proposed skin entry point sampling sub-algorithm and Kambin's triangle projection area sub-algorithm in conjunction with the analytic hierarchy process,and employing various technologies such as ray tracing,CPU multi-threading,and GPU parallel computing,a puncture path was calculated that not only met clinical hard constraints but also optimized the overall soft constraints.Results A surgical team conducted a subjective evaluation of the 21 needle puncture paths planned by the algorithm,and all the paths met the clinical requirements,with 95.24%of them rated excellent or good.Compared with the physician's planning results,the plans generated by the algorithm showed inferior DIlium,DS1,and Depth(P<0.05)but much better DDura,DL5,DN5,and AKambin(P<0.05).In the 21 cases,the planning time of the algorithm averaged 7.97±3.73 s,much shorter than that by the physicians(typically beyond 10 min).Conclusion The multi-constraint optimal puncture path planning algorithm offers an efficient automated solution for PIRFT of the L5/S1 segments with great potentials for clinical application.
3.A multi-constraint optimal puncture path planning algorithm for percutaneous interventional radiofrequency thermal fusion of the L5/S1 segments
Hu LIU ; Zhihai SU ; Chengjie HUANG ; Lei ZHAO ; Yangfan CHEN ; Yujia ZHOU ; Hai LÜ ; Qianjin FENG
Journal of Southern Medical University 2024;44(9):1783-1795
Objective To minimize variations in treatment outcomes of L5/S1 percutaneous intervertebral radiofrequency thermocoagulation(PIRFT)arising from physician proficiency and achieve precise quantitative risk assessment of the puncture paths.Methods We used a self-developed deep neural network DWT-UNet for automatic segmentation of the magnetic resonance(MR)images of the L5/S1 segments into 7 key structures:L5,S1,Ilium,Disc,N5,Dura mater,and Skin,based on which a needle insertion path planning environment was modeled.Six hard constraints and 6 soft constraints were proposed based on clinical criteria for needle insertion,and the physician's experience was quantified into weights using the analytic hierarchy process and incorporated into the risk function for needle insertion paths to enhance individual case adaptability.By leveraging the proposed skin entry point sampling sub-algorithm and Kambin's triangle projection area sub-algorithm in conjunction with the analytic hierarchy process,and employing various technologies such as ray tracing,CPU multi-threading,and GPU parallel computing,a puncture path was calculated that not only met clinical hard constraints but also optimized the overall soft constraints.Results A surgical team conducted a subjective evaluation of the 21 needle puncture paths planned by the algorithm,and all the paths met the clinical requirements,with 95.24%of them rated excellent or good.Compared with the physician's planning results,the plans generated by the algorithm showed inferior DIlium,DS1,and Depth(P<0.05)but much better DDura,DL5,DN5,and AKambin(P<0.05).In the 21 cases,the planning time of the algorithm averaged 7.97±3.73 s,much shorter than that by the physicians(typically beyond 10 min).Conclusion The multi-constraint optimal puncture path planning algorithm offers an efficient automated solution for PIRFT of the L5/S1 segments with great potentials for clinical application.
4.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.
5.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.
6.Study on mechanism of action of Fuke duanhongyin capsule on the improvement of dysfunctional uterine bleeding in rats
Ying HE ; Yonggen LING ; Hongqing ZHAO ; Mengyao WU ; Lu BAI ; Qian CHEN ; Haohan ZHOU ; Yuhong WANG
China Pharmacy 2022;33(23):2840-2844
OBJECTIVE To investigate the mechanism of Fuke duanhongyin capsule in improving dysfunctional uterine bleeding (DUB) in rats. METHODS Pregnant SD rats were randomly divided into blank control group (distilled water), model control group (distilled water) and Fuke duanghongyin capsule group (1.296 g/kg), with 6 rats in each group. Except for blank control group, DUB model was established in other groups. After modeling, they were given relevant medicine/distilled water 10 mL/kg intragastrically, once a day, for consecutive 14 d. After medication, uterine index, ovary index and hemorheology indexes (whole blood high shear relative index, whole blood low shear relative index, erythrocyte aggregation index, Carson viscosity) of rats were all determined. The pathological changes of uterus and ovary tissues were observed; mRNA relative expression levels of epidermal growth factor (EGF), hypoxia-inducible factor 1α (HIF-1α), epidermal growth factor receptor (EGFR) and serine/ threonine-protein kinase 1(AKT1), and protein relative expression levels of EGF and EGFR in uterine tissue were all measured. RESULTS Compared with model control group, the uterine index, ovary index, erythrocyte aggregation index were all decreased significantly in Fuke duanghongyin capsule group (P<0.05 or P<0.01); whole blood high shear relative indexes, mRNA relative expression levels of EGF, HIF-1α and EGFR and protein relative expression levels of EGF and EGFR in uterine tissue were all increased significantly (P<0.05 or P<0.01). The pathological changes of ovary and uterus were improved. CONCLUSIONS Fuke duanhongyin capsule can improve DUB in rat, the mechanism of which may be related to the activation of EGF-EGFR signaling pathway.
7.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.
8.Study on non-flavonoids chemical constituents from Spatholobi Caulis.
Xiao-Yan LIU ; Wei XU ; Xiu-Wei YANG ; Peng ZHANG ; Wei ZHAO ; Yun GONG ; Ni-Fu LIU
China Journal of Chinese Materia Medica 2020;45(5):1120-1127
To study the non-flavonoids chemical constituents in water extract of Spatholobi Caulis. Some purification and analysis techniques like silica gel, D101-macroporous adsorptive resins, and Sephadex LH-20 column chromatographies as well as reversed phase high-performance liquid chromatography were used to isolate and analyze the phenolic acid esters and other type compounds from Spatholobi Caulis integrally. The structures of these compounds were identified by spectroscopic techniques such as nuclear magnetic resonance and high resolution mass spectrometries. Twenty-seven compounds, including phenolic acid, coumarin, lignan, terpene, alkaloid, and steroid compounds, were isolated from ethyl acetate and n-butanol fractions in water extract of Spatholobi Caulis, and they were identified as β-sitosterol(1), feruli acid methyl ester(2), syringaresinol(3),(+)-medioresinol(4),(+)-epipinoresinol(5), p-acetylphenol(6), bolusanthin Ⅳ(7), evofolin B(8), salicylic acid(9), trans-p-hydroxy-cinnamic acid(10), abscisic acid(11), m-hydroxyphenol(12), C-veratroylglycol(13), p-hydroquinone(14), 8,9-dihydroxymegastigma-4,6-dien-3-one(15), p-hydroxybenzoic acid(16), 6,9-dihydroxymegastigma-4,7-dien-3-one(17), protocatechuic acid(18), protocatechuic acid methyl ester(19), 5,7-dihydroxycoumarin(20), isolariciresinol(21), nicotinic acid(22), daucosterol(23),(+)-pinoresinol(24), stigmasterol(25), allantoin(26) and koaburaside(27), respectively. Furthermore, compounds 2-15, 19-22, 24 and 26 were isolated from genus Spatholobus for the first time.
Drugs, Chinese Herbal/analysis*
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Esters/analysis*
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Fabaceae/chemistry*
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Hydroxybenzoates/analysis*
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Mass Spectrometry
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Phytochemicals/analysis*
9.Isolation and identification of flavonoids from Spatholobi Caulis.
Xiao-Yan LIU ; Wei XU ; Xiu-Wei YANG ; Peng ZHANG ; Wei ZHAO ; Yun GONG ; Ni-Fu LIU
China Journal of Chinese Materia Medica 2020;45(6):1384-1392
The chemical compounds in water extract of Spatholobi Caulis were further studied. The compounds were systematically isolated and purified by using various separation and analysis techniques including silica gel, macroporous adsorptive resins and Sephadex LH-20 column chromatographies, as well as reversed phase high-performance liquid chromatography(RP-HPLC). Twenty-three flavonoids and one chromone were identified by the spectroscopic analysis techniques combining their physicochemical properties, they were identified as isoduartin(1), sativan(2), 8-O-methylretusin(3), 7-hydroxydihydroflavone(4), odoratin(5), butesuperin A(6), biochanin A(7), 3'-methoxydaidzein(8), 7-hydroxychromone(9), calycosin(10), naringenin(11), dihydrocajanin(12),(6 aR,11 aR)-maackiain(13), 2'-hydroxygenistein(14),(6 aR,11 aR)-medicarpin-3-O-glucopyranoside(15),(-)-epiafzelechin(16),(-)-catechin(17),(-)-epicatechin(18), 4',8-dimethoxy-7-O-β-D-glucopyranosylisoflavone(19), ononin(20),(-)-gallocatechin(21), rutin(22), daidzin(23) and sphaerobioside(24). Compounds 4, 6, 8, 9, 11, 12, 14-16, 19 and 22-24 were isolated from Spatholobi Caulis for the first time.
Chromatography, High Pressure Liquid
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Drugs, Chinese Herbal/chemistry*
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Fabaceae/chemistry*
;
Flavonoids/isolation & purification*
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Phytochemicals/isolation & purification*
10.Efficacy of combined lymphoplasma exchange for the treatment of severe refractory immune-related skin diseases: a clinical observation
Shijia RAO ; Bijuan LI ; Ji LI ; Hongfu XIE ; Mingliang CHEN ; Shuang ZHAO ; Yaling WANG ; Wei SHI ; Qianjin LU
Chinese Journal of Dermatology 2019;52(1):16-19
Objective To evaluate the clinical efficacy of lymphoplasma exchange (LPE) for the treatment of severe refractory immune-related skin diseases.Methods From May 2013 to October 2015,8 patients with toxic epidermal necrolysis,drug-induced hypersensitivity syndrome (DIHS),pemphigus vulgaris,pemphigoid or paraneoplastic pemphigus were enrolled from Department of Dermatology,Xiangya Hospital,Central South University,who showed no response to conventional therapy or presented with multiple organ dysfunction.After the treatment with LPE,the efficacy was evaluated,and adverse reactions were observed.Results After one session of LPE therapy,6 patients received marked improvement,and were cured at last.In 1 patient with pemphigus vulgaris who was resistant to the treatment with high doses of glucocorticoids and immunosuppressive agents,the rashes regressed during the treatment with LPE,but recurred after the end of treatment.One patient with bullous pemphigoid presented with eruptive blisters on the next day after the treatment with LPE,which were considered as allergic reactions to allogeneic plasma.There were no obvious differences in white blood cell count,lymphocyte count,neutrophil count and blood platelet count in the peripheral blood of 8 patients before and after the treatment with LPE.During the follow-up of 3-5 years,all of the patients were recovered without recurrence,except 1 patient with bullous pemphigoid who died of disseminated tuberculosis after 1 year.Conclusion LPE is effective for the treatment of severe immune-related skin diseases,but attention should be paid to potential transfusion reaction and allergic reactions.

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