1. MW-9, a chalcones derivative bearing heterocyclic moieties, ameliorates ulcerative colitis via regulating MAPK signaling pathway
Zhao WU ; Nan-Ting ZOU ; Chun-Fei ZHANG ; Hao-Hong ZHANG ; Qing-Yan MO ; Ze-Wei MAO ; Chun-Ping WAN ; Ming-Qian JU ; Chun-Ping WAN ; Xing-Cai XU
Chinese Pharmacological Bulletin 2024;40(3):514-520
		                        		
		                        			
		                        			 Aim To investigate the therapeutic effect of the MW-9 on ulcerative colitis(UC)and reveal the underlying mechanism, so as to provide a scientific guidance for the MW-9 treatment of UC. Methods The model of lipopolysaccharide(LPS)-stimulated RAW264.7 macrophage cells was established. The effect of MW-9 on RAW264.7 cells viability was detected by MTT assay. The levels of nitric oxide(NO)in RAW264.7 macrophages were measured by Griess assay. Cell supernatants and serum levels of inflammatory cytokines containing IL-6, TNF-α and IL-1β were determined by ELISA kits. Dextran sulfate sodium(DSS)-induced UC model in mice was established and body weight of mice in each group was measured. The histopathological damage degree of colonic tissue was assessed by HE staining. The protein expression of p-p38, p-ERK1/2 and p-JNK was detected by Western blot. Results MW-9 intervention significantly inhibited NO release in RAW264.7 macrophages with IC50 of 20.47 mg·L-1 and decreased the overproduction of inflammatory factors IL-6, IL-1β and TNF-α(P<0.05). MW-9 had no cytotoxicity at the concentrations below 6 mg·L-1. After MW-9 treatment, mouse body weight was gradually reduced, and the serum IL-6, IL-1β and TNF-α levels were significantly down-regulated. Compared with the model group, MW-9 significantly decreased the expression of p-p38 and p-ERK1/2 protein. Conclusions MW-9 has significant anti-inflammatory activities both in vitro and in vivo, and its underlying mechanism for the treatment of UC may be associated with the inhibition of MAPK signaling pathway. 
		                        		
		                        		
		                        		
		                        	
2.A Real-World Single-Center Study of Adult Hodgkin's Lymphoma
Ling-Li WANG ; Lei TIAN ; Fei DONG ; Ping YANG ; Wei WAN ; Qi-Hui LI ; Lan MA ; Jin-Jie GAO ; Ji-Jun WANG ; Wei ZHAO ; Hong-Mei JING
Journal of Experimental Hematology 2024;32(2):428-433
		                        		
		                        			
		                        			Objective:To summarize the clinical characteristics,therapeutic effect and prognostic factors of patients with Hodgkin's lymphoma(HL).Methods:A total of 129 patients with HL diagnosed in Peking University Third Hospital from January 2010 to March 2021 who were given at least one efficacy assessment after treatment were enrolled,and their clinical data,including sex,age,pathological type,Ann Arbor stage,ECOG score,blood test,β2-microglobulin,lactate dehydrogenase level,albumin level were collected.The clinical characteristics,therapeutic effect and long-term prognosis of the patients were summarized and analyzed.Results:In classical HL,nodular sclerosis HL accounted for the highest proportion of 51.6%,followed by mixed cellularity HL(36.5%),lymphocyte-rich classical HL(3.2%),and lymphocyte depletion HL(0.7%),while nodular lymphocyte predominant HL accounted for 4.8%.The 3-year overall survival(OS)rate of HL patients was 89.8%,and 5-year OS was 85.0%.The 3-year progression-free survival(PFS)rate was 73.4%,and 5-year PFS was 63.1%.Multivariate regression analysis indicated that IPI score was an independent negative factor,while hemoglobin(Hb)level was an independent positive factor for OS in HL patients.When the mediastinal mass size was 9.2 cm,it was most significant to judge the survival status of HL patients.5-year OS and 5-year PFS were 97.4%and 76.0%in early-stage HL patients without large mass,respectively,while in patients with advanced-stage HL was 83.4%and 55.9%(both P<0.05).After 2-4 courses of treatment,the overall response rate(ORR)of patients who received chemotherapy combined with radiotherapy was 95.0%,while that was 89.6%in those with chemotherapy alone.Conclusions:The overall prognosis of patients with HL is satisfactory,especially those in early-stage without large mass.IPI score and Hb level are independent risk factors for the prognosis of HL patients.A 9.2 cm mediastinal mass can be used as the cut-off value for the prognosis of Chinese HL patients.
		                        		
		                        		
		                        		
		                        	
3.A multicenter study of neonatal stroke in Shenzhen,China
Li-Xiu SHI ; Jin-Xing FENG ; Yan-Fang WEI ; Xin-Ru LU ; Yu-Xi ZHANG ; Lin-Ying YANG ; Sheng-Nan HE ; Pei-Juan CHEN ; Jing HAN ; Cheng CHEN ; Hui-Ying TU ; Zhang-Bin YU ; Jin-Jie HUANG ; Shu-Juan ZENG ; Wan-Ling CHEN ; Ying LIU ; Yan-Ping GUO ; Jiao-Yu MAO ; Xiao-Dong LI ; Qian-Shen ZHANG ; Zhi-Li XIE ; Mei-Ying HUANG ; Kun-Shan YAN ; Er-Ya YING ; Jun CHEN ; Yan-Rong WANG ; Ya-Ping LIU ; Bo SONG ; Hua-Yan LIU ; Xiao-Dong XIAO ; Hong TANG ; Yu-Na WANG ; Yin-Sha CAI ; Qi LONG ; Han-Qiang XU ; Hui-Zhan WANG ; Qian SUN ; Fang HAN ; Rui-Biao ZHANG ; Chuan-Zhong YANG ; Lei DOU ; Hui-Ju SHI ; Rui WANG ; Ping JIANG ; Shenzhen Neonatal Data Network
Chinese Journal of Contemporary Pediatrics 2024;26(5):450-455
		                        		
		                        			
		                        			Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75%(27/36);boys accounted for 64%(23/36).Among the 36 neonates,31(86%)had disease onset within 3 days after birth,and 19(53%)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61%)had left cerebral infarction and 13(36%)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75%)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72%)and seizures in 10 neonates(34%).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33%,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44%(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.
		                        		
		                        		
		                        		
		                        	
4.Pharmacokinetics study of single and multiple doses of azvudine in healthy young and elderly subjects
Yu ZHANG ; Xiao-Jian LIU ; Hao-Shuang JU ; Bin-Yuan HE ; Yuan-Hao WAN ; Li-Wei CHAI ; Le-Yang REN ; Min LÜ ; Ya-Qiang JIA ; Wei ZHANG ; Ping XU
The Chinese Journal of Clinical Pharmacology 2024;40(9):1316-1320
		                        		
		                        			
		                        			Objective To evaluate the pharmacokinetic characteristics and safety of single and multiple oral azvudine tablets in healthy young and elderly Chinese subjects.Methods This was a open-label and parallel-group study.The trial consisted of two groups:healthy young subjects group and healthy elderly subjects group,with 12 subjects in each group.Enrolled subjects were first given a single dose,fasting oral azvudine tablet 5 mg,after a 3-day cleansing period entered the multiple dose phase,fasting oral azvudine tablet 5 mg·d-1 for 7 days.Results After a single dose of azvudine 5 mg,Cmax and AUC0-∞ were(4.76±2.12)ng·mL-1,(6.53±2.20)ng·mL-1·h,and Tmax,t1/2 were 0.75,1.87 h in young subjects;Cmax and AUC0-∞ were(6.40±3.25)ng·mL-1,(9.50±3.70)ng·mL-1·h,and Tmax,t1/2 were 0.63,2.66 h in elderly subjects.After a multiple dose of azvudine 5 mg·d-1 for 7 d,Cmax and AUC0-∞ were(3.26±1.61)ng·mL-1,(5.38±2.19)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.88,2.13 h in young subjects;Cmax,ss and AUC0-∞,ss were(3.97±2.09)ng·mL-1,(6.71±3.26)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.75,2.56 h in elderly subjects.Elderly/young geometric mean ratios and 90%CIs were 128.37%(88.23%-186.76%),139.93%(105.42%-185.72%),140.03%(106.33%-184.41%)for azvudine Cmax,AUC0-t,AUC0-∞ after a single dose,and were 118.66%(80.83%-174.20%),118.41%(83.60%-167.69%),118.95%(84.78%-166.89%)for azvudine Cmax,AUC0-t,AUC0_∞ after a multiple dose of azvudine 5 mg·d-1 for 7 d.Conclusion After single and multiple oral administration of azvudine tablets,systemic exposure to azvudine was higher in healthy elderly subjects compared with healthy young subjects.After taking azvudine tablets,the types,severity and incidence of adverse events and adverse drug reactions in healthy elderly people were not significantly different from those in healthy young subjects.Azvudine was found to be safe and well tolerated in healthy elderly subjects.
		                        		
		                        		
		                        		
		                        	
5.Relationship Between Mindfulness and Affiliate Stigma in Parents of Children with Autism Spectrum Disorder in China: The Mediating Role of Coping Styles
Ya-Nan WANG ; Qi-Heng LIN ; Dan MENG ; Jing WANG ; Hai-Ping XU ; Wan-Hong WEI ; Jin-Yan ZHANG
Asian Nursing Research 2024;18(2):89-96
		                        		
		                        			 Purpose:
		                        			This study aims to investigate the current status of affiliate stigma among parents of autistic children, analyze the influencing factors, explore the relationship among mindfulness, coping styles, and affiliate stigma, and verify the mediating role of coping styles between mindfulness and affiliate stigma in parents of children with autism in China.MethodBetween February and April 2023, the Child Development Behaviour Centre of a public hospital in China recruited 345 parents of children with autism. These parents completed the general information questionnaire, the Mindful Attention Awareness Scale, the Affiliate Stigma Scale, and the Simple Coping Style Questionnaire. We then adapted the Hayes Process Macro and Bootstrap methods to examine the mediating effects of coping styles between mindfulness and affiliate stigma. 
		                        		
		                        			Results:
		                        			(1) The total affiliate stigma score of parents of children with autism was 48.53 (standard deviation:: 10.74). Parents' age, monthly family income, duration of care, mindfulness, and coping styles were the influencing factors of parental affiliate stigma. (2) Mindfulness was positively correlated with positive coping style (r = 0.33, p < .01) and negatively correlated with negative coping style, affiliate stigma (r = −0.38, −0.39, p < .01), whereas affiliate stigma was negatively correlated with positive coping style (r = −0.34, p < .01) and positively correlated with negative coping style (r = 0.41, p < .01). (3) Positive coping style and negative coping style play a parallel mediating role between mindfulness and affiliate stigma of parents of autistic children. 
		                        		
		                        			Conclusions
		                        			Parents of children with autism experience significant levels of affiliate stigma. Mindfulness has a direct impact on associated stigma in parents of children with autism and also indirectly predicts associated stigma through the intermediary influence of positive and negative coping styles. Healthcare professionals could perform mindfulness interventions from an optimistic psychology viewpoint to boost parents' mindfulness and coping abilities, thereby accomplishing the objective of mitigating affiliate stigma. 
		                        		
		                        		
		                        		
		                        	
6.Rapid characterization and identification of non-volatile constituents in Pogostemonis Herba by UPLC-Q-TOF-MS combined with UNIFI and an in-house library.
Chao-Fa WEI ; Li-Wan ZHU ; Xiao-Yan LAN ; Li ZHOU ; Xiang LI ; Qing-Xiu HAO ; Zi-Dong QIU ; Li-Ping KANG
China Journal of Chinese Materia Medica 2023;48(14):3826-3838
		                        		
		                        			
		                        			This study aimed to characterize and identify the non-volatile components in Pogostemonis Herba by using ultra-perfor-mance liquid chromatography-quadrupole-time of flight-mass spectrometry(UPLC-Q-TOF-MS) combined with UNIFI and an in-house library. The chemical components in 50% methanol extract of Pogostemonis Herba were detected by UPLC-Q-TOF-MS in both positive and negative MS~E continuum modes. Then, the MS data were processed in UNIFI combined with an in-house library to automatically characterize the metabolites. Based on the multiple adduct ions, exact mass, diagnostic fragment ions, and peak intensity of compounds and the fragmentation pathways and retention behaviors of reference substances, the structures identified by UNIFI were further verified and those of the unidentified compounds were tentatively elucidated. A total of 120 compound structures were identified or tentatively identified, including flavonoids, phenylpropanoids, phenolic acids, terpenes, fatty acids, alkaloids, and phenylethanoid glycosides. Sixteen of them were accurately identified by comparison with reference substances, and 53 compounds were reported the first time for Pogostemonis Herba. This study systematically characterized and identified the non-volatile compounds in Pogostemonis Herba for the first time. The findings provide a scientific basis for revealing the pharmacodynamic material basis, establishing a quality control system, and developing products of Pogostemonis Herba.
		                        		
		                        		
		                        		
		                        	
7.Analysis of the Prognostic Value and Risk Factors of Early Relapse for Newly Diagnosed Multiple Myeloma Patients in the Era of Novel Agents.
Qi-Hui LI ; Yan LIU ; Jing WANG ; Ji-Jun WANG ; Fei DONG ; Ping YANG ; Wei WAN ; Xiao-Yan KE ; Hong-Mei JING
Journal of Experimental Hematology 2023;31(1):148-153
		                        		
		                        			OBJECTIVE:
		                        			To investigate the influece of early relapse in the era of novel drugs on the prognosis of the patients with newly diagnosed multiple myeloma(NDMM) and risk factors, and to provide the basis for the early identification of the high-risk patients and guiding the treatment.
		                        		
		                        			METHODS:
		                        			The clinical data of the patients with NDMM admitted to our hospital from November 2011 to May 2022 were retrospectively analyzed. According to whether the progression free survival(PFS) was more than 12 months, they were divided into early relapse group(≤12 months) and late relapse group(>12 months). The high-risk factors of the patients in two groups were analyzed, including age, anemia, renal insufficiency, hypercalcemia, increasing of lactate dehydrogenase(LDH) level, Extramedullary disease (EMD), International Staging System(ISS) stage, Revised International Staging System (R-ISS) stage, cytogenetic abnormalities(CA) detected by fluorescence in situ hybridization(FISH), and treatment efficacy. The meaningful clinical indicators were screened, and multivariate analysis was used to explore the high-risk factors of early relapse.
		                        		
		                        			RESULTS:
		                        			170 patients with NDMM were collected, including 25 cases in early relapse group and 145 cases in late relapse group. The median OS time of the patients in early death group was 20 months, and 140 months in late relapse group by the end of follow-up, there was significant difference in OS of the patients between two groups(P<0.001). Fifteen patients(56.0%)in early relapse group obtained ≥VGPR, and 113(77.9%) patients in late relapse group, the difference was statistically significant(P=0.011). Survival outcomes remained poor among early relapse patients irrespective of depth of response to initial therapy. Multivariate analysis showed that the EMD and high-risk CA predicted early relapse.
		                        		
		                        			CONCLUSION
		                        			The prognosis of patients with early relapse in NDMM is poor. EMD and high-risk CA is an independent prognostic factor of early relapse.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Multiple Myeloma/diagnosis*
		                        			;
		                        		
		                        			Prognosis
		                        			;
		                        		
		                        			In Situ Hybridization, Fluorescence
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Neoplasm Recurrence, Local
		                        			;
		                        		
		                        			Risk Factors
		                        			
		                        		
		                        	
8.Response characteristics of tislelizumab combined with chemotherapy in first-line treatment of locally advanced or metastatic non-squamous non-small cell lung cancer.
Shun LU ; Xin Min YU ; Yan Ping HU ; Zhi Yong MA ; Xing Ya LI ; Wei Dong LI ; Yun Peng LIU ; Dong WANG ; Xiu Wen WANG ; Zhe Hai WANG ; Jing Xun WU ; Dian Sheng ZHONG ; Gao Feng LI ; Wan Yu HE ; Yuan Yuan BAO ; Yuan YUAN ; Jing Hui FAN
Chinese Journal of Oncology 2023;45(4):358-367
		                        		
		                        			
		                        			Objective: To investigate the response characteristics of patients with locally advanced/metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) treated with tislelizumab in combination with chemotherapy in the first line. Methods: Patients with nsq-NSCLC who achieved complete or partial remission after treatment with tislelizumab in combination with chemotherapy or chemotherapy alone in the RATIONALE 304 study, as assessed by an independent review board, were selected to analyze the response characteristics and safety profile of the responders. Time to response (TTR) was defined as the time from randomization to the achievement of first objective response. Depth of response (DpR) was defined as the maximum percentage of tumor shrinkage compared with the sum of the baseline target lesion length diameters. Results: As of January 23, 2020, 128 patients treated with tislelizumab in combination with chemotherapy achieved objective tumor response (responders), representing 57.4%(128/223) of the intention-to-treat population, with a TTR of 5.1 to 33.3 weeks and a median TTR of 7.9 weeks. Of the responders (128), 50.8%(65) achieved first remission at the first efficacy assessment (week 6), 31.3%(40) at the second efficacy assessment (week 12), and 18.0%(23) at the third and subsequent tumor assessments. The percentages of responders who achieved a depth of tumor response of 30% to <50%, 50% to <70% and 70% to 100% were 45.3%(58/128), 28.1%(36/128) and 26.6%(34/128), respectively, with median progression-free survival (PFS) of 9.0 months (95% CI: 7.7 to 9.9 months), 11.5 months (95% CI: 7.7 months to not reached) and not reached (95% CI: 11.8 months to not estimable), respectively. Tislelizumab plus chemotherapy were generally well tolerated in responders with similar safety profile to the overall safety population. Conclusion: Among responders to tislelizumab in combination with chemotherapy for nsq-NSCLC, 82.0%(105/128) achieves response within the first two tumor assessments (12 weeks) and 18.0%(23/128) achieves response at later (18 to 33 weeks) assessments, and there is a trend toward prolonged PFS in responders with deeper tumor response.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Antibodies, Monoclonal, Humanized/therapeutic use*
		                        			;
		                        		
		                        			Antineoplastic Combined Chemotherapy Protocols/adverse effects*
		                        			;
		                        		
		                        			Carcinoma, Non-Small-Cell Lung/pathology*
		                        			;
		                        		
		                        			Lung Neoplasms/pathology*
		                        			;
		                        		
		                        			Treatment Outcome
		                        			
		                        		
		                        	
9.Changes of renin-angiotensin-aldosterone system in workers exposed to noise
WU Qi feng LI Qi ping LI Cong LIANG Wei hui LI Bin LI Wan li DENG Xiao feng
China Occupational Medicine 2022;49(06):640-644
		                        		
		                        			
		                        			Objective - ( )- ( )
To observe the effects of renin angiotensin Ang aldosterone system RAAS in workers exposed to
Methods - -
occupational noise. Forty five workers with suspected occupational noise induced deafness were selected as noise
, ,
exposure group using convenient sampling method. According to their tinnitus symptom noise exposure intensity and work age
- , ,
they were divided into no tinnitus and tinnitus subgroups <90 dB and ≥90 dB subgroups work years <10 years and ≥10 years
subgroups. Another 45 workers with no occupational noise exposure history were selected as control group. The levels of plasma
( ), , ,
renin activity PRA AngⅠ AngⅡ and aldosterone of the two groups were detected and the aldosterone to renin activity
Results
ratio was calculated. The diastolic blood pressure of the noise exposure group was higher than that of the control group
[( )vs( ) ,P ] ,
80±7 76±8 mmHg <0.05 . However there was no significant difference in systolic blood pressure between the two
(P ) ( :
groups >0.05 . The level of plasma AngⅡ in the noise exposure group was higher than that in the control group median
vs ,P ) ( P )
100.98 65.43 μg/L <0.05 . There was no statistical significance in other indexes between the two groups all >0.05 . The
( :
plasma AngⅡ level in < 90 dB subgroup in the noise exposure group was higher than that of the control group median 123.16
vs ,P )
65.43 μg/L <0.05 . There was no statistical significance in other indexes among the two subgroups of tinnitus symptom or
( P )
work age in the noise exposure group and the control group all >0.05 . There were no significant differences in the abnormal
, ( P )
rates of PRA AngⅡ and aldosterone in plasma between the noise exposure group and the control group all >0.05 .
Conclusion
Occupational noise exposure may affect RAAS and lead to increased plasma AngⅡ levels in the workers.
-
Tinnitus and work age may not affect RAAS in occupational noise exposure workers.
		                        		
		                        		
		                        		
		                        	
10.Changes of renin-angiotensin-aldosterone system in workers exposed to noise
WU Qi feng LI Qi ping LI Cong LIANG Wei hui LI Bin LI Wan li DENG Xiao feng
China Occupational Medicine 2022;49(06):640-644
		                        		
		                        			
		                        			Objective - ( )- ( )
To observe the effects of renin angiotensin Ang aldosterone system RAAS in workers exposed to
Methods - -
occupational noise. Forty five workers with suspected occupational noise induced deafness were selected as noise
, ,
exposure group using convenient sampling method. According to their tinnitus symptom noise exposure intensity and work age
- , ,
they were divided into no tinnitus and tinnitus subgroups <90 dB and ≥90 dB subgroups work years <10 years and ≥10 years
subgroups. Another 45 workers with no occupational noise exposure history were selected as control group. The levels of plasma
( ), , ,
renin activity PRA AngⅠ AngⅡ and aldosterone of the two groups were detected and the aldosterone to renin activity
Results
ratio was calculated. The diastolic blood pressure of the noise exposure group was higher than that of the control group
[( )vs( ) ,P ] ,
80±7 76±8 mmHg <0.05 . However there was no significant difference in systolic blood pressure between the two
(P ) ( :
groups >0.05 . The level of plasma AngⅡ in the noise exposure group was higher than that in the control group median
vs ,P ) ( P )
100.98 65.43 μg/L <0.05 . There was no statistical significance in other indexes between the two groups all >0.05 . The
( :
plasma AngⅡ level in < 90 dB subgroup in the noise exposure group was higher than that of the control group median 123.16
vs ,P )
65.43 μg/L <0.05 . There was no statistical significance in other indexes among the two subgroups of tinnitus symptom or
( P )
work age in the noise exposure group and the control group all >0.05 . There were no significant differences in the abnormal
, ( P )
rates of PRA AngⅡ and aldosterone in plasma between the noise exposure group and the control group all >0.05 .
Conclusion
Occupational noise exposure may affect RAAS and lead to increased plasma AngⅡ levels in the workers.
-
Tinnitus and work age may not affect RAAS in occupational noise exposure workers.
		                        		
		                        		
		                        		
		                        	
            
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