1.Tildrakizumab for moderate-to-severe plaque psoriasis in Chinese patients: A 12-week randomized placebo-controlled phase III trial with long-term extension
Chen YU ; Songmei GENG ; Bin YANG ; Yunhua DENG ; Fuqiu LI ; Xiaojing KANG ; Mingye BI ; Furen ZHANG ; Yi ZHAO ; Weili PAN ; Zhongwei TIAN ; Jinhua XU ; Zhenghua ZHANG ; Nan YU ; Xinsuo DUAN ; Shuping GUO ; Qing SUN ; Weiquan LI ; Juan TAO ; Zhijun LIU ; Yuanyuan YIN ; Gang WANG
Chinese Medical Journal 2024;137(10):1190-1198
Background::There is a need for effective and safe therapies for psoriasis that provide sustained benefits. The aim of this study was to assess the efficacy and safety of tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, for treating moderate-to-severe plaque psoriasis in Chinese patients.Methods::In this multi-center, double-blind, phase III trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned (1:1) to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and 4. Patients initially assigned to placebo were switched to receive tildrakizumab at weeks 12, 16, and every 12 weeks thereafter. Patients in the tildrakizumab group continued with tildrakizumab at week 16, and every 12 weeks until week 52. The primary endpoint was the Psoriasis Area and Severity Index (PASI 75) response rate at week 12.Results::At week 12, tildrakizumab demonstrated significantly higher PASI 75 response rates (66.4% [73/110] vs. 12.7% [14/110]; difference, 51.4% [95% confidence interval (CI), 40.72, 62.13]; P <0.001) and Physician’s Global Assessment (60.9% [67/110] vs. 10.0% [11/110]; difference, 49.1% [95% CI, 38.64, 59.62]; P <0.001) compared to placebo. PASI 75 response continued to improve over time in both tildrakizumab and placebo-switching to tildrakizumab groups, reaching maximal efficacy after 28 weeks (86.8% [92/106] vs. 82.4% [89/108]) and maintained up to 52 weeks (91.3% [95/104] vs. 87.4% [90/103]). Most treatment-emergent adverse events were mild and not related to tildrakizumab. Conclusion::Tildrakizumab demonstrated durable efficacy through week 52 and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.Trial registration::ClinicalTrials.gov, NCT05108766.
2.Advances in neutrophil extracellular traps in bronchopulmonary dysplasia
Ziwei YU ; Jing YIN ; Yun QIAN ; Shuping HAN
International Journal of Pediatrics 2023;50(4):257-261
Due to the development of neonatal intensive care, the survival rate of very preterm infants and very low birth weight infants has been significantly improved, and the incidence of bronchopulmonary dysplasia (BPD) has been obviously increasing year by year.The pathogenesis of BPD has not been clear, it is considered that inflammation is an important link in the occurrence and development of BPD at present.Neutrophils can use their neutrophil extracellular traps (NETs) to capture and kill pathogens and reduce inflammation, but excessive formation of NETs is easy to induce inflammatory imbalance, so as to damage normal cells or tissues and participate in the pathophysiological process of BPD.This paper reviews the structure, formation, function and regulatory role of NETs in BPD, and the targeted treatment strategies and potential research directions of NETs in BPD.
3.Effects of Naikan cognitive-music reminiscence therapy on coping style for female patients with chronic schizophrenia
Hui YU ; Yufei YIN ; Guiping PAN ; Wei LUO ; Guijun MA ; Jing SHAO ; Shuping TAN ; Fude YANG
Chinese Journal of Rehabilitation Theory and Practice 2022;28(3):350-355
Objective To explore the effect of Naikan cognitive-music reminiscence therapy on coping style in female patients with chronic schizophrenia.Methods In May, 2020, 72 female patients with chronic schizophrenia from Beijing Huilongguan Hospital were assigned into control group (n = 48) and music group (n = 24) after trait matching. Both groups accepted routine medicine, while the control group accepted Naikan cognitive therapy, and the music group accepted Naikan cognitive therapy combined music reminiscence, for twelve weeks. They were blind assessed with Simplified Coping Style Questionnaire, Self-rating Depression Scale and Self-rating Anxiety Scale before and after intervention.Results There were five cases in the control group removed for erroneous response. The main effects of group were not significant for all the assessments (F < 0.567, P > 0.05). The main effect of time was significant for negative coping style score (F = 6.968, P = 0.01), and the interaction effects were significant for positive coping style score and Self-rating Depression Scale score (F > 4.227, P < 0.05).Conclusion Combining with music reminiscence, Naikan cognitive therapy may be advantageous for the coping style of female patients with chronic schizophrenia.
4.The effect of mentalization-based family therapy on adolescents with depressive disorder and its related brain regions
Jiuju LI ; Shuping TAN ; Yanli ZHAO ; Yin QI ; Fan ZHANG ; Huaqing LIU ; Lina LI
Chinese Journal of Behavioral Medicine and Brain Science 2022;31(1):43-49
Objective:To explor the effects of mentalization-based family therapy (MBFT) on the emotions of anxiety and depression, reflective functions, and related brain regions of adolescents with depression.Methods:Thirty-two adolescent patients with depression were selected in Beijing Huilongguan Hospital.Among them, fifteen patients treated with conventional drugs were defined as the control group, the other seventeen patients served as the observation group.On the basis of routine drug treatment, patients in the observation group were treated with 1.5 h MBFT once a week, for a total of 3 months.Among them, 10 patients underwent resting functional magnetic resonance imaging(rs-fMRI) scans before and after the intervention.SPSS 23.0 was used for statistical analysis of scale evaluation data by using chi-square test and repeated-measure analysis of variance, and pairwise Pearson correlation was used to construct a brain network matrix for the MRI results.The patient's brain network matrix was put into Gretna to calculate, and then use repeated measures analysis of variance and t test for judgment. Results:(1)Repeated measurement analysis of variance showed, over time and group, before and after intervention, the group×time interactions of patients' reflective function, anxiety, depression were statistically significant ( F=5.113, 9.350, 5.264, all P<0.05). Further simple effect analysis showed, in the observation group, there were statistically significant differences in patients' anxiety ((55.09±14.35) vs (30.58±3.62)), depression ((61.58±16.81) vs (31.00±3.48)) before and after intervention (all P<0.01). There was no significant difference in reflective function ((8.71±0.51) vs (8.87±0.50) ) in the observation group before and after intervention( P> 0.05). The reflective function((8.92±0.33) vs (8.73±0.35)) and anxiety((50.67±13.88) vs (45.78±12.89)) scores of the control group were not statistically significant different before and after intervention(all P>0.05), and the depression scores of the control group before and after inter-vention((69.33±9.11) vs (50.94±7.99)) were statistically significant different( P<0.01). (2)rs-fMRI showed that, using the posterior parietal lobe and the medial prefrontal lobe as seed points, the group×time interactions with right inferior frontal gyrus, right fusiform gyrus, right superior temporal gyrus, left middle temporal gyrus and right superior frontal gyrus were statistically significant ( F=29.56, 20.63, 8.69, 9.49, 8.62, all P<0.05). The further simple effect analysis showed in the observation group, the pre-test was less than the post-test, and the difference was statistically significant( P<0.05). In the control group, there were not statistically significant differences in the functional connection strength before and after the test(all P>0.05). (3)The brain network analysis of 264 regions of interest (ROIs) in the whole brain showed that the number of modules in the observation group was less than that in the control group, and the difference was statistically significant ( t=-2.64, P=0.046). Conclusion:MBFT can improve the anxiety and depression of adolescent patients with depression.It enhances the functional link between mentalization related brain regions and the whole brain, and enhances the activity of the whole brain link to become more integrated.
5.Research progress of mono-(ADP-ribosyl) transferase family and their inhibitors in tumor therapy
Yin LI ; Hongfeng GU ; Yi ZOU ; Shuping WANG ; Yungen XU
Journal of China Pharmaceutical University 2021;52(6):643-652
Poly-adenosine diphosphate ribose polymerases (PARPs) play an important role in DNA repair and apoptosis.Among them, mono-(ADP-ribosyl) transferase (MARTs) can regulate various cell reactions by catalyzing and transferring single ADP-ribose.Most MARTs are highly expressed in cancers, which is closely related to the occurrence and progression of cancers.This review introduces the MARTs that are highly expressed in cancers, classifies them according to the differences of their structural domains, and reviews their known mechanism, their close relationship with cancers, their potential value in cancer therapy and the research progress of corresponding inhibitors.These targets are expected to provide new research ideas for cancer therapy in the era of precision medicine.
6.Clinical characteristics of Guillain-Barré syndrome combined with hyponatremia in Southern China and its risk factors for prognosis: a multi-center retrospective analysis
Sijia PAN ; Bei SHAO ; Can LUO ; Hongyuan DAI ; Bo YANG ; Na WANG ; Jiajia YAO ; Yin LIU ; Shuping LIU ; Man DING ; Zuneng LU
Chinese Journal of Neuromedicine 2021;20(7):716-724
Objective:To investigate the clinical characteristics of Guillain-Barré syndrome (GBS) combined with hyponatremia in Southern China and its risk factors for prognosis.Methods:The retrospective cohort study involved patients who met the diagnostic criteria of GBS from 18 upper first-class hospitals of 6 provinces/cities in southern China (south of Huaihe River) from January 1, 2013 to September 30, 2016. The clinical data of these patients were collected. According to serum sodium levels, they were divided into hyponatremia group (serum sodium concentration<135 mmol/L) and normal serum sodium group (serum sodium concentrations≥135 mmol/L). Based on Medical Research Coucil sum scores at nadir, these patients were divided into mild GBS group (>40), moderate GBS group (30-40), and severe GBS group (<30). Furthermore, according to the Hughes GBS disability scale (H-GBS-DS) scores at discharge, these GBS patients with hyponatremia were divided into favorable prognosis group (H-GBS-DS<3) and poor prognosis group (H-GBS-DS≥3). The incidence of hyponatremia in patients from the mild GBS group, moderate GBS group, and severe GBS group were compared. Multivariate Logistic regression analysis was performed to determine the clinical risk factors for hyponatremia in GBS patients. The clinical data of hyponatremia patients from favorable prognosis group and poor prognosis group were compared; multivariate Logistic regression analysis was used to determine the risk factors for poor prognosis in GBS patients with hyponatremia.Results:(1) Among the 570 patients, 354 had mild GBS, 94 had moderate GBS, and 122 had severe GBS; 134 GBS patients were combined with hyponatremia, 436 GBS patients had normal serum sodium. The hyponatremia incidence in mild, moderate and severe GBS groups increased successively, ( P<0.05). Multivariate Logistic regression analysis showed that facial paralysis ( OR=1.979, 95%CI: 1.172-3.342, P=0.011), respiratory muscle paralysis ( OR=3.218, 95%CI: 1.611-6.428, P=0.001), secondary pulmonary infection ( OR=4.822, 95%CI: 2.835-8.201, P=0.000), severe GBS ( OR=2.611, 95%CI: 1.444-4.721, P=0.001) and length of hospital stay ( OR=1.029, 95%CI: 1.009-1.050, P=0.004) were risk factors for hyponatremia in GBS patients. (2) Among 134 GBS patients with hyponatremia, 80 had poor prognosis and 54 had favorable prognosis. As compared with the favorable group, the poor prognosis group had significantly lower proportion of patients with extraocular muscle paralysis, statistically higher proportions of patients with respiratory muscle paralysis and secondary pulmonary infection, significantly different severities of GBS, signficantly higher proportion of patients accepted intravenous immunoglobulin (IVIG) and hormone treatments, statistically longer length of hospital stay ( P<0.05). Respiratory muscle paralysis ( OR=25.590, 95%CI: 9.433-69.423, P=0.000), moderate GBS ( OR=17.030, 95%CI: 8.441-34.361, P=0.000), and severe GBS ( OR=51.042, 95%CI: 24.596-105.926, P=0.000) were independent risk factors for poor short-term prognosis of GBS patients with hyponatremia. Conclusions:Severe GBS patients with facial paralysis, respiratory muscle palsy, secondary pulmonary infection, and long hospital stay trend to have hyponatremia. Hyponatremia patients with respiratory muscle paralysis and moderate/severe GBS have poor short-term prognosis.
7.Study on the correlation between COX-2, ER, PR and the formation of endometrial polyps and the increased malignant change rate of endometrial polyps after menopause
Miao ZHANG ; Ruying WU ; Shuping YIN ; Limin YANG ; Jie YANG ; Fanlong MENG ; Zengqiang XIE
Chinese Journal of Primary Medicine and Pharmacy 2020;27(20):2448-2452
Objective:To investigate the correlation between cyclooxygenase-2(COX-2), estrogen receptor (ER), progesterone receptor(PR) and the formation of endometrial polyps and the increased malignant rate of postmenopausal endometrial polyps.Methods:From January 2018 to January 2019, a total of 160 postmenopausal women treated in the People's Hospital of Changxing County were selected and divided into endometrial polyps group(83 cases) and oothectomy group(42 cases), normal menopause group(35 cases) according to different diseases.The levels of COX-2, ER, PR in the three groups were measured.The expression of COX-2 in mesenchymal cells and glandular epithelial cells, the expression of ER in mesenchymal cells and glandular epithelial cells, the expression of PR in mesenchymal cells and glandular epithelial cells in the three groups were compared, and the correlation between COX-2, ER, PR and increased malignant rate of endometrial polyps was analyzed.Results:The positive expression rates of COX-2 in mesenchymal cells and glandular epithelial cells in the endometrial polyps group(16.9%, 30.1%) were higher than those in the normal menopause group(0.0%, 11.4%) and the oothectomy group(4.8%, 7.1%)(χ 2=4.568, 5.806, all P<0.05 ). There were no statistically significant differences in the expression of ER in mesenchymal cells and glandular epithelial cells among the three groups(χ 2=1.333, 1.412, all P>0.05). The expression of PR in mesenchymal cells and glandular epithelial cells in the endometrial polyps group was lower than that in the normal menopause group and the oothectomy group(χ 2=4.890, 5.022, all P<0.05). COX-2 was positively correlated with the increase in malignant rate of endometrial polyps( r=4.335, P<0.05), PR was negatively correlated with an increase in the malignant rate of endometrial polyps( r=-4.256, P<0.05), and ER had no significant correlation with an increase in the malignant rate of endometrial polyps( r=1.203, P>0.05). Conclusion:COX-2 and PR are significantly related to the formation of endometrial polyps and the increase in malignant rate of postmenopausal endometrial polyps, but there is no significant expression of ER.Therefore, the detection of COX-2 and PR levels is beneficial to provide a certain scientific basis for clinical treatment.
8.Clinical features and validation of Brighton criteria in Guillain-Barré syndrome in southern China:retrospective analysis of 1358 hospitalized patients in four years
Yin LIU ; Min LOU ; Bei SHAO ; Gan LUO ; Fang JI ; Hongyuan DAI ; Xiaoyi LI ; Bo HU ; Chao QIN ; Jun XU ; Shuping LIU ; Jiajia YAO ; Jingxia GUAN ; Zheman XIAO ; Zuneng LU
Chinese Journal of Neurology 2018;51(2):85-90
Objective To analyze the clinical features and validation of Brighton criteria in Guillain-Barré syndrome (GBS) patients from southern China.Methods The clinical data of hospitalized GBS patients from 69 hospitals of 14 provinces/cities in southern China,the area south of the Huaihe River,between 1 January 2013 and 30 September 2016,were collected and analyzed retrospectively,and patients were classified according to the Brighton criteria of case definition,ranging from a highest (defined as level one) to a lowest (level four) level of diagnostic certainty.Results A total of 1 358 GBS patients were collected,including 51 cases with cranial nerve variants,157 with Miler-Fisher syndrome and 1 150 with classic GBS characterized by flaccid weakness of limbs.Among 1 150 cases of classic GBS,49.57% (570/1 150) patients had antecedent events,with respiratory infection predominated (71.23%,406/570);83.74% (963/1 150) presented limb weakness at onset,99.21% (1 124/1 133) reached the peak within four weeks,with a score of 3.15 ± 1.16 for Hughes Disability Scale;99.56% (1 128/1 133)developed bilateral weakness and 95.39% (1 097/1 150) manifested flexia or hyporeflexia;the cerebrospinal fluid showed albuminocytologic dissociation in 80.58% (772/958) patients whose lumbar puncture was performed;demyelinating GBS accounted for 48.14% (401/833) and axonal subtype 18.01% (150/833) respectively in patients with findings of nerve conduction studies available.According to Brighton criteria,the patients were stratified as level one in 44.09% (507/1 150),level two in 45.74% (526/1 150),level three in 7.57% (87/1 150) and level four in 2.61% (30/1 150) of all the patients,and 69.55% (507/729),28.67% (209/729),0% (0/729) and 1.78% (13/729),respectively in the patients with complete data (n =729).Conclusions In southern China,demyelinating subtype of GBS is predominant,whereas the proportion of axonal subtype is remarkably lower than that in northern China.The Brighton criteria have a high sensitivity for the diagnosis of GBS in southern China,and examination of cerebrospinal fluid and electrodiagnostic studies are necessary for stratified diagnosis.
9.Application of contrast-enhanced ultrasonography in the evaluation of the stability of carotid atherosclerotic plaque
Wenjing WU ; Zhifei BEN ; Hua YIN ; Yunwen CHEN ; Saijun CHEN ; Shuping FU ; Changrui SHENG ; Zhelan ZHENG
Chinese Journal of Primary Medicine and Pharmacy 2017;24(15):2272-2276
Objective To study the application of contrast-enhanced ultrasonography (CEUS) in the evaluation of the stability of carotid atherosclerotic plaque (CAP).Methods 162 patients with CAP were selected as study group.Meanwhile,34 patients with carotid artery strong echo plaques were selected as control group.The color doppler ultrasound was used to observe the CAP.Results The proportions of lipid type,fiber type,calcification and ulcer plaque in the study group were 21.60%,33.33%,34.57% and 10.37%,which were higher than those of the control group (5.88%,2.94%,2.94% and 2.94%),the differences were statistically significant (χ2=4.537,12.859,13.629 and 3.855,all P<0.05).There were 75 patients of soft plaques,36 patients with mixed plaques,51 patients with hard plaque in 162 patients.The new blood vessels classification in soft plaque group (36.00%,45.33% and 10.33%) were higher than the mixed plaque (30.56%,41.67% and 8.33%) and hard plaque group (31.37%,13.72% and 7.84%).The peak intensity (-86.41±7.81) %,tmax (8.34±1.62)s,mean transit time (24.18±8.67)s in the soft plaque group were significantly lower than the mixed plaque [(-100.73±6.52)%,(9.79±2.14)s and (28.93±9.11)s] and hard plaque patients [(-104.14±6.15)%,(10.23±2.33)s and (30.07±9.48)s],the differences were statistically significant (t=9.518,6.966,2.658,13.592,5.374 and 3.064,all P<0.05),but there were no statistically significant differences between mixed plaque and hard plaque (all P>0.05).The plaque diameter (4.13±0.75)mm diagnosed by CEUS was significantly larger than that of conventional ultrasound [(3.62±1.14)mm],the difference was statistically significant (t=4.757,P=0.000).Conclusion The CEUS can qualitatively detect the atherosclerotic plaque angiogenesis,can quantitatively assess plaque,evaluate the stability of the plaques,and the sensitivity is high.
10.Effect of nimodipine combined with 7.5% hypertonic saline on postoperative cognitive function in aged rats
Qi ZHANG ; Yanan LI ; Shuping HUO ; Chunping YIN ; Yangyang GUO ; Xi XIN ; Fang GAO ; Xiuli WANG ; Qiujun WANG
Chinese Journal of Anesthesiology 2017;37(5):573-576
Objective To evaluate the effect of nimodipine combined with 7.5% hypertonic saline (HS) on postoperative cognitive function in aged rats.Methods Ninety-six healthy male Wistar rats,aged 18 months,weighing 450-500 g,were assigned into 4 groups (n=24 each) using a random number table:splenectomy group (group S),nimodipine group (group N),group HS and nimodipine plus HS group (group N+HS).Nimodipine 1 mg/kg was intraperitoneally injected in group N.In group HS,7.5% HS 4 ml/kg was injected via the caudal vein.The equal volume of normal saline was injected intraperitoneally or via the caudal vein in group S.Splenectomy was performed under sevoflurane anesthesia at 30 min after the end of administration.On 1 day before operation and 3 and 7 days after operation,Morris water maze test was performed,and blood sainples from the caudal vein were simultaneously collected for determination of the concentrations of serum S100β protein and neuron-specific enolase (NSE) by enzyme-linked immunosorbent assay.Results Compared with group S,the frequency of crossing the original platform was significantly increased,the escape latency was shortened,and the concentrations of serum S100β protein and NSE were decreased at each time point after operation in N,HS and N+HS groups (P<0.05).Compared with group N or group HS,the frequency of crossing the original platform was significantly increased,the escape latency was shortened,and the concentrations of serum S100β protein and NSE were decreased at each time point after operation in group N+HS (P<0.05).Conclusion Nimodipine combined with 7.5% HS exerts better efficacy than either alone in improving postoperative cognitive function in aged rats.

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