1.A unicenter real-world study of the correlation factors for complete clinical response in idiopathic inflammatory myopathies
Zhanhong LAI ; Jiachen LI ; Zelin YUN ; Yonggang ZHANG ; Hao ZHANG ; Xiaoyan XING ; Miao SHAO ; Yue-Bo JIN ; Naidi WANG ; Yimin LI ; Yuhui LI ; Zhanguo LI
Journal of Peking University(Health Sciences) 2024;56(2):284-292
		                        		
		                        			
		                        			Objective:To investigate the correlation factors of complete clinical response in idiopathic inflammatory myopathies(IIMs)patients receiving conventional treatment.Methods:Patients diagnosed with IIMs hospitalized in Peking University People's Hospital from January 2000 to June 2023 were in-cluded.The correlation factors of complete clinical response to conventional treatment were identified by analyzing the clinical characteristics,laboratory features,peripheral blood lymphocytes,immunological indicators,and therapeutic drugs.Results:Among the 635 patients included,518 patients finished the follow-up,with an average time of 36.8 months.The total complete clinical response rate of IIMs was 50.0%(259/518).The complete clinical response rate of dermatomyositis(DM),anti-synthetase syn-drome(ASS)and immune-mediated necrotizing myopathy(IMNM)were 53.5%,48.9%and 39.0%,respectively.Fever(P=0.002)and rapid progressive interstitial lung disease(RP-ILD)(P=0.014)were observed much more frequently in non-complete clinical response group than in complete clinical re-sponse group.The aspartate transaminase(AST),lactate dehydrogenase(LDH),D-dimer,erythrocyte sedimentation rate(ESR),C-reaction protein(CRP)and serum ferritin were significantly higher in non-complete clinical response group as compared with complete clinical response group.As for the treat-ment,the percentage of glucocorticoid received and intravenous immunoglobin(IVIG)were significantly higher in non-complete clinical response group than in complete clinical response group.Risk factor analysis showed that IMNM subtype(P=0.007),interstitial lung disease(ILD)(P=0.001),eleva-ted AST(P=0.012),elevated serum ferritin(P=0.016)and decreased count of CD4+T cells in peripheral blood(P=0.004)might be the risk factors for IIMs non-complete clinical response.Conclu-sion:The total complete clinical response rate of IIMs is low,especially for IMNM subtype.More effec-tive intervention should be administered to patients with ILD,elevated AST,elevated serum ferritin or decreased count of CD4+T cells at disease onset.
		                        		
		                        		
		                        		
		                        	
2.Protective effects and mechanisms of berberine hydrochloride on intestinal mucosal barrier injury in rats with sepsis
Ying LING ; Qi SHEN ; Jian WANG ; Yufan YUAN ; Peng WANG ; Zelin LI ; Jinlan JIN
Chinese Critical Care Medicine 2024;36(6):597-603
		                        		
		                        			
		                        			Objective:To investigate the protective effect of berberine hydrochloride on intestinal mucosal barrier damage in sepsis rats and its mechanism.Methods:Forty-eight male SD rats were divided into a control group (Sham group, 6 cases), a sepsis model group (LPS group, 14 cases), a berberine hydrochloride intervention group (Ber group, 14 cases), and a Notch signaling pathway inhibition group (DAPT group, 14 cases) according to random number table method. The DAPT group was intraperitoneally injected with 5 mg/kg Notch signaling pathway inhibition DAPT 2 hours before modeling. The sepsis model was established by intraperitoneal injection of 10 mg/kg lipopolysaccharide (LPS); Sham group was injected with an equal amount of saline (2 mL). The Ber group and DAPT group were treated with gavage of 50 mg/kg berberine hydrochloride 2 hours after modeling; Sham group and LPS group were treated with gavage of an equal amount of saline (2 mL). The temperature, weight, behavior and survival rate of rats were observed at 0, 6, 12 and 24 hours of modeling. After 24 hours of modeling, abdominal aortic blood was collected under anesthesia, and intestinal tissues were obtained after euthanasia. The pathological changes of ileum were observed under light microscope. The ultrastructure of ileum was observed under transmission electron microscope. Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of serum diamine oxidase (DAO), intestinal fatty acid binding protein (iFABP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Real time-polymerase chain reaction (RT-PCR) and Western blotting were used to detect the mRNA and protein expressions of tight junction proteins (Occludin and Claudin1), Notch1 and their downstream target signals in the ileum tissue.Results:After 24 hours of modeling, compared with the Sham group, the LPS group, Ber group, and DAPT group showed a decrease in weight and an increase in temperature. Among them, the LPS group showed the most significant changes, followed by the DAPT group, and the Ber group showed the least significant changes. The survival rates of the LPS group, Ber group, and DAPT group were all lower than those of the Sham group [42.9% (6/14), 57.1% (8/14), 57.1% (8/14) vs. 100% (6/6)], and six rats were taken from each group for subsequent testing. Macroscopic observation of the intestine showed that the LPS group had the most severe edema in the ileum tissue and abdominal bleeding, with significant improvement in the Ber group and followed by the DAPT group. Under the light microscope, the LPS group showed disordered arrangement of glandular tissue in the ileum mucosa, significantly reduced goblet cells, and extensive infiltration of inflammatory cells, which were significantly improved in the Ber group but less improved in the DAPT group. Under electron microscopy, the LPS group showed extensive shedding of ileal microvilli and severe damage to the tight junction complex structure of intestinal epithelial cells, which was significantly improved in the Ber group but less improved in the DAPT group. The levels of serum DAO, iFABP, TNF-α, IL-6 in the LPS group were significantly higher than those in the Sham group, while the above indicators in the Ber group were significantly lower than those in the LPS group [DAO (μg/L): 4.94±0.44 vs. 6.53±0.49, iFABP (ng/L): 709.67±176.97 vs. 1 417.71±431.44, TNF-α (ng/L): 74.70±8.15 vs. 110.36±3.51, IL-6 (ng/L): 77.34±9.80 vs. 101.65±6.92, all P < 0.01], while the above indicators in the DAPT group were significantly higher than those in the Ber group. The results of RT-PCR and Western blotting showed that the mRNA and protein expressions of Occludin, Claudin1, Notch1, and Hes1 in the ileum tissue of LPS group rats were decreased compared to the Sham group, which were significantly increased in the Ber group compared with the LPS group [mRNA expression: Occludin mRNA (2 -ΔΔCt): 1.61±0.74 vs. 0.30±0.12, Claudin1 mRNA (2 -ΔΔCt): 1.97±0.37 vs. 0.58±0.14, Notch1 mRNA (2 -ΔΔCt): 1.29±0.29 vs. 0.36±0.10, Hes1 mRNA (2 -ΔΔCt): 1.22±0.39 vs. 0.27±0.04; protein expression: Occludin/GAPDH: 1.17±0.14 vs. 0.74±0.04, Claudin1/GAPDH: 1.14±0.06 vs. 0.58±0.10, Notch1/GAPDH: 0.87±0.11 vs. 0.56±0.09, Hes1/GAPDH: 1.02±0.13 vs. 0.62±0.01; all P < 0.05], while those in the DAPT group were significantly lower than those in the Ber group. Conclusion:Early use of berberine hydrochloride can significantly improve intestinal mucosal barrier damage in sepsis rats, and its mechanism may be related to inhibiting inflammatory response and regulating the expression of intestinal mechanical barrier tight junction protein through Notch1 signal.
		                        		
		                        		
		                        		
		                        	
3.Molluscicidal effect of spraying different formulations of niclosamide ethanolamine salt with drones against Oncomelania hupensis in ditches
Zelin ZHU ; Xia ZHANG ; Junyi HE ; Ying CHEN ; Weisi WANG ; Hehua HU ; Chunli CAO ; Ziping BAO ; Suying GUO ; Liping DUAN ; Yi YUAN ; Jing XU ; Shizhu LI ; Xiaonong ZHOU
Chinese Journal of Schistosomiasis Control 2024;36(5):527-530
		                        		
		                        			
		                        			 Objective To evaluate the molluscicidal effect of spraying different formulations of niclosamide ethanolamine salt with drones against Oncomelania hupensis in ditches. Methods A semi-dry and semi-wet ditch with O. hupensis snails was selected in the second branch field of Jiangbei Farm, Jiangling County, Hubei Province in May 2023, and divided into 4 experimental areas, named groups A1, A2, B1 and B2. Environmental cleaning was performed in groups A1 and B2, and was not conducted in groups A2 or B2. Then, 50% wettable powder of niclosamide ethanolamine salt was sprayed with drones at an effective dose of 2 g/m2 in groups A1 and A2, and 5% niclosamide ethanolamine salt granule was sprayed with drones at an effective dose of 2 g/m2 in groups B1 and B2. O. hupensis snails were surveyed using the systematic sampling method 1, 3, 5, 7, 14 days after spraying, and the natural mortality and corrected mortality of O. hupensis snails were calculated. Results The occurrence of frames with living snails, mean density of living snails and natural mortality of snails were 97.50% (117/120), 6.30 snails/0.1 m2 and 1.18% (9/765) in the test ditch before spraying, respectively. There were significant differences in the mortality of snails among four groups 1, 3, 5, 7 and 14 days after spraying niclosamide formulations with drones (χ2 = 17.230, 51.707, 65.184, 204.050 and 34.435, all P values < 0.01). The overall mortality rates of snails were 94.51% (1 051/1 112), 79.44% (908/1 143), 96.54% (977/1 012) and 88.55% (1 021/1 153) in groups A1, A2, B1 and B2 (χ2 = 207.773, P < 0.05), respectively. In addition, there was no significant difference in the overall snail mortality between groups A1 and B1 (P > 0.05), and the snail mortality in groups A1 and B1 were both statistically different from that in groups A2 and B2 (all P values < 0.05). Conclusion Both 50% wettlable powder of niclosamide ethanolamine salt and 5% niclosamide ethanolamine salt granule sprayed with drones are active against O. hupensis snails in ditches, and environmental cleaning may improve the molluscicidal effect. 
		                        		
		                        		
		                        		
		                        	
4.Causal relationship between sleep phenotype and idiopathic normal pressure hydrocephalus:a two-sample bidirectional Mendelian randomization study
Weitao ZHONG ; Weisong LI ; Zelin LI ; Qiang WANG ; Wangming ZHANG
Journal of Southern Medical University 2024;44(8):1612-1619
		                        		
		                        			
		                        			Objective To explore the causal relationship between sleep phenotype and idiopathic normal pressure hydrocephalus(iNPH)using two-sample bidirectional Mendelian randomization.Methods The exposure data including 8 sleep phenotypes used in this study were obtained from GWAS catalog,FinnGenR10 and MRCIEU GWAS.The outcome data for idiopathic normal-pressure hydrocephalus were obtained from FinnGen R10.We used the inverse-variance weighted(IVW)method to perform the principal analyses.Cochrane Q-statistics test was used to assess the heterogeneity and MR Egger-intercept test performed to evaluate the pleiotropy for sensitivity analyses.Results IVW result showed that frequent daytime nap was associated with higher odds of iNPH(OR=3.3393,95 CI%:1.0646-10.4742,P=0.0270).Cochrane Q-statistics test and MR Egger-intercept test showed that the MR analysis had no pleiotropy or heterogeneity(P>0.05).The external validation reproduced this result(OR=2.5660,95 CI%:1.1680-5.6373,P=0.0189;OR=4.0424,95 CI%:1.5709-10.4024,P=0.0038).Reverse Mendelian randomization suggested that iNPH did not have significant impact on sleep phenotype.Conclusion The frequency of daytime naps is causally associated with iNPH,and reducing the frequency of weekly daytime naps can reduce the risk of iNPH in the elderly population.
		                        		
		                        		
		                        		
		                        	
5.Treatment status of tyrosine kinase inhibitor for newly-diagnosed chronic myeloid leukemia: a domestic multi-centre retrospective real-world study
Xiaoshuai ZHANG ; Bingcheng LIU ; Xin DU ; Yanli ZHANG ; Na XU ; Xiaoli LIU ; Weiming LI ; Hai LIN ; Rong LIANG ; Chunyan CHEN ; Jian HUANG ; Yunfan YANG ; Huanling ZHU ; Ling PAN ; Xiaodong WANG ; Guohui LI ; Zhuogang LIU ; Yanqing ZHANG ; Zhenfang LIU ; Jianda HU ; Chunshui LIU ; Fei LI ; Wei YANG ; Li MENG ; Yanqiu HAN ; Li'e LIN ; Zhenyu ZHAO ; Chuanqing TU ; Caifeng ZHENG ; Yanliang BAI ; Zeping ZHOU ; Suning CHEN ; Huiying QIU ; Lijie YANG ; Xiuli SUN ; Hui SUN ; Li ZHOU ; Zelin LIU ; Danyu WANG ; Jianxin GUO ; Liping PANG ; Qingshu ZENG ; Xiaohui SUO ; Weihua ZHANG ; Yuanjun ZHENG ; Qian JIANG
Chinese Journal of Hematology 2024;45(3):215-224
		                        		
		                        			
		                        			Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.
		                        		
		                        		
		                        		
		                        	
6.Causal relationship between sleep phenotype and idiopathic normal pressure hydrocephalus:a two-sample bidirectional Mendelian randomization study
Weitao ZHONG ; Weisong LI ; Zelin LI ; Qiang WANG ; Wangming ZHANG
Journal of Southern Medical University 2024;44(8):1612-1619
		                        		
		                        			
		                        			Objective To explore the causal relationship between sleep phenotype and idiopathic normal pressure hydrocephalus(iNPH)using two-sample bidirectional Mendelian randomization.Methods The exposure data including 8 sleep phenotypes used in this study were obtained from GWAS catalog,FinnGenR10 and MRCIEU GWAS.The outcome data for idiopathic normal-pressure hydrocephalus were obtained from FinnGen R10.We used the inverse-variance weighted(IVW)method to perform the principal analyses.Cochrane Q-statistics test was used to assess the heterogeneity and MR Egger-intercept test performed to evaluate the pleiotropy for sensitivity analyses.Results IVW result showed that frequent daytime nap was associated with higher odds of iNPH(OR=3.3393,95 CI%:1.0646-10.4742,P=0.0270).Cochrane Q-statistics test and MR Egger-intercept test showed that the MR analysis had no pleiotropy or heterogeneity(P>0.05).The external validation reproduced this result(OR=2.5660,95 CI%:1.1680-5.6373,P=0.0189;OR=4.0424,95 CI%:1.5709-10.4024,P=0.0038).Reverse Mendelian randomization suggested that iNPH did not have significant impact on sleep phenotype.Conclusion The frequency of daytime naps is causally associated with iNPH,and reducing the frequency of weekly daytime naps can reduce the risk of iNPH in the elderly population.
		                        		
		                        		
		                        		
		                        	
7.Stratified Treatment in Pediatric Anaplastic Large Cell Lymphoma: Result of a Prospective Open-Label Multiple-Institution Study
Tingting CHEN ; Chenggong ZENG ; Juan WANG ; Feifei SUN ; Junting HUANG ; Jia ZHU ; Suying LU ; Ning LIAO ; Xiaohong ZHANG ; Zaisheng CHEN ; Xiuli YUAN ; Zhen YANG ; Haixia GUO ; Liangchun YANG ; Chuan WEN ; Wenlin ZHANG ; Yang LI ; Xuequn LUO ; Zelin WU ; Lihua YANG ; Riyang LIU ; Mincui ZHENG ; Xiangling HE ; Xiaofei SUN ; Zijun ZHEN
Cancer Research and Treatment 2024;56(4):1252-1261
		                        		
		                        			 Purpose:
		                        			The risk stratification of pediatric anaplastic large cell lymphoma (ALCL) has not been standardized. In this study, new risk factors were included to establish a new risk stratification system for ALCL, and its feasibility in clinical practice was explored. 
		                        		
		                        			Materials and Methods:
		                        			On the basis of the non-Hodgkin’s lymphoma Berlin–Frankfurt–Munster 95 (NHL-BFM-95) protocol, patients with minimal disseminated disease (MDD), high-risk tumor site (multiple bone, skin, liver, and lung involvement), and small cell/lymphohistiocytic (SC/LH) pathological subtype were enrolled in risk stratification. Patients were treated with a modified NHL-BFM-95 protocol combined with an anaplastic lymphoma kinase inhibitor or vinblastine (VBL). 
		                        		
		                        			Results:
		                        			A total of 136 patients were enrolled in this study. The median age was 8.8 years. The 3-year event-free survival (EFS) and overall survival of the entire cohort were 77.7% (95% confidence interval [CI], 69.0% to 83.9%) and 92.3% (95% CI, 86.1% to 95.8%), respectively. The 3-year EFS rates of low-risk group (R1), intermediate-risk group (R2), and high-risk group (R3) patients were 100%, 89.5% (95% CI, 76.5% to 95.5%), and 67.9% (95% CI, 55.4% to 77.6%), respectively. The prognosis of patients with MDD (+), stage IV cancer, SC/LH lymphoma, and high-risk sites was poor, and the 3-year EFS rates were 45.3% (95% CI, 68.6% to 19.0%), 65.7% (95% CI, 47.6% to 78.9%), 55.7% (95% CI, 26.2% to 77.5%), and 70.7% (95% CI, 48.6% to 84.6%), respectively. At the end of follow-up, one of the five patients who received maintenance therapy with VBL relapsed, and seven patients receiving anaplastic lymphoma kinase inhibitor maintenance therapy did not experience relapse. 
		                        		
		                        			Conclusion
		                        			This study has confirmed the poor prognostic of MDD (+), high-risk site and SC/LH, but patients with SC/LH lymphoma and MDD (+) at diagnosis still need to receive better treatment (ClinicalTrials.gov number, NCT03971305). 
		                        		
		                        		
		                        		
		                        	
8.Research progress in antenna technology for microwave imaging of stroke
Haisheng ZHANG ; Xu NING ; Lin XU ; Wei ZHUANG ; Zelin BAI ; Lilong ZHOU ; Jia XU ; Feng WANG ; Mingsheng CHEN
International Journal of Biomedical Engineering 2023;46(3):231-239
		                        		
		                        			
		                        			The diagnostic technology of acute stroke by microwave imaging has the advantages of being non-ionizing, fast, small, and low-cost. Therefore, this technology is expected to become an auxiliary or alternative means to CT and MRI technology. As the signal transmitting and receiving device of the microwave imaging system, the antenna has an important influence on the performance of the imaging system. At present, there are many antennas with different performances used in imaging systems, but there is a lack of clear evaluation criteria for them. In this paper, several typical antennas were introduced, their advantages and disadvantages from the perspective of bandwidth and near-field were analyzed, and the common requirements of imaging systems for antennas and the performance indicators of various types of imaging systems were summarized. Moreover, the development trend of antenna technology for microwave imaging was pointed out to provide a reference for the study of stroke microwave imaging technology.
		                        		
		                        		
		                        		
		                        	
9.Prokaryotic expression and biological activities of the hemolysin BL subunit of a pathogenic Bacillus cereus of cattle origin.
Yunjiao CHEN ; Yunjiang HE ; Qinglei MENG ; Zhilin LIU ; Xin ZHANG ; Zelin JIA ; Jiayu CUI ; Xueli WANG
Chinese Journal of Biotechnology 2023;39(12):4939-4949
		                        		
		                        			
		                        			Bacillus cereus belongs to Gram-positive bacteria, which is widely distributed in nature and shows certain pathogenicity. Different B. cereus strains carry different subsets of virulence factors, which directly determine the difference in their pathogenicity. It is therefore important to study the distribution of virulence factors and the biological activity of specific toxins for precise prevention and control of B. cereus infection. In this study, the hemolysin BL triayl was expressed, purified, and characterized. The results showed that the bovine pathogenic B. cereus hemolysin BL could be expressed and purified in the prokaryotic expression system, and the bovine pathogenic B. cereus hemolysin BL showed hemolysis, cytotoxicity, good immunogenicity and certain immune protection in mice. In this study, the recombinant expression of hemolysin BL triayl was achieved, and the biological activity of hemolysin BL of bovine pathogenic ceroid spore was investigated. This study may facilitate further investigating the pathogenic mechanism of B. cereus hemolysin BL and developing a detection method for bovine pathogenic B. cereus disease.
		                        		
		                        		
		                        		
		                        			Cattle
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		                        			Animals
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		                        			Mice
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		                        			Bacterial Proteins/metabolism*
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		                        			Bacillus cereus/metabolism*
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		                        			Hemolysin Proteins/metabolism*
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		                        			Virulence Factors/metabolism*
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		                        			Enterotoxins/metabolism*
		                        			
		                        		
		                        	
10.Analysis of clinical guidelines for oro-maxillofacial cone-beam CT
Zelin YE ; Yuanyuan LIU ; Hu WANG ; Meng YOU
Chinese Journal of Stomatology 2023;58(9):964-970
		                        		
		                        			
		                        			Oro-maxillofacial cone-beam CT (CBCT) is the most widely used three-dimensional imaging method in the field of oral and maxillofacial radiology. It has been widely used in China, while radiation safety, examination indications and other issues still lack comprehensive regulations and standards. Over the years, clinical guidelines and position statements for the rational use of CBCT examinations have been issued in the world, providing standardized instructions for local practitioners. This paper reviewed these guidelines to provide reference for the formulation of relevant guidelines in China.
		                        		
		                        		
		                        		
		                        	
            
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