1.Relationship between Phenotypic Changes of Dendritic Cell Subsets and the Onset of Plateau Phase during Intermittent Interferon Therapy in Patients with CHB
Liu YANG ; Yu Shi WANG ; Ting Ting JIANG ; Wen DENG ; Min CHANG ; Ling Shu WU ; Hua Wei CAO ; Yao LU ; Ge SHEN ; Yu Ru LIU ; Jiao Yuan GAO ; Jiao Meng XU ; Ping Lei HU ; Lu ZHANG ; Yao XIE ; Hui Ming LI
Biomedical and Environmental Sciences 2024;37(3):303-314
		                        		
		                        			
		                        			Objective This study aimed to evaluate whether the onset of the plateau phase of slow hepatitis B surface antigen decline in patients with chronic hepatitis B treated with intermittent interferon therapy is related to the frequency of dendritic cell subsets and expression of the costimulatory molecules CD40,CD80,CD83,and CD86. Method This was a cross-sectional study in which patients were divided into a natural history group(namely NH group),a long-term oral nucleoside analogs treatment group(namely NA group),and a plateau-arriving group(namely P group).The percentage of plasmacytoid dendritic cell and myeloid dendritic cell subsets in peripheral blood lymphocytes and monocytes and the mean fluorescence intensity of their surface costimulatory molecules were detected using a flow cytometer. Results In total,143 patients were enrolled(NH group,n = 49;NA group,n = 47;P group,n = 47).The results demonstrated that CD141/CD1c double negative myeloid dendritic cell(DNmDC)/lymphocytes and monocytes(%)in P group(0.041[0.024,0.069])was significantly lower than that in NH group(0.270[0.135,0.407])and NA group(0.273[0.150,0.443]),and CD86 mean fluorescence intensity of DNmDCs in P group(1832.0[1484.0,2793.0])was significantly lower than that in NH group(4316.0[2958.0,5169.0])and NA group(3299.0[2534.0,4371.0]),Adjusted P all<0.001. Conclusion Reduced DNmDCs and impaired maturation may be associated with the onset of the plateau phase during intermittent interferon therapy in patients with chronic hepatitis B.
		                        		
		                        		
		                        		
		                        	
2.Association of Cytokines with Clinical Indicators in Patients with Drug-Induced Liver Injury
Hua Wei CAO ; Ting Ting JIANG ; Ge SHEN ; Wen DENG ; Yu Shi WANG ; Yu Zi ZHANG ; Xin Xin LI ; Yao LU ; Lu ZHANG ; Yu Ru LIU ; Min CHANG ; Ling Shu WU ; Jiao Yuan GAO ; Xiao Hong HAO ; Xue Xiao CHEN ; Ping Lei HU ; Jiao Meng XU ; Wei YI ; Yao XIE ; Hui Ming LI
Biomedical and Environmental Sciences 2024;37(5):494-502
		                        		
		                        			
		                        			Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators. Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),anti-infective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group. Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-α and IL-6 may partake the inflammatory process of DILI.
		                        		
		                        		
		                        		
		                        	
3.Bioequivalence study of sidenafil citrate tablets in Chinese healthy subjects
Xiao-Bin LI ; Lu CHEN ; Xiu-Jun WU ; Yu-Xin GE ; Wen-Chao LU ; Ting XIAO ; He XIE ; Hua-Wei WANG ; Wen-Ping WANG
The Chinese Journal of Clinical Pharmacology 2024;40(3):430-434
		                        		
		                        			
		                        			Objective To evaluate the bioequivalence of oral sidenafil citrate tablets manufactured(100 mg)test preparations and reference preparations in healthy subjects under fasting and fed conditions.Methods Using a single-dose,randomized,open-lable,two-period,two-way crossover design,36 healthy subjects respectively for fasting and fed study were enrolled,and randomized into two groups to receive a single dose of test 100 mg with 7-day washout period.Plasma concentration of sidenafil and N-demethylsildenafil was determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS)method.The pharmacokinetic parameters were calculated by Analyst 1.6.3(AB Scie)using non-compartmental model,and bioequivalence evaluation was performed for the two preparations.Relevant safety evaluations were performed during the trial.Results The main pharmacokinetic parameters of sidenafil after a single oral dose of sidenafil citrate tablets under fasting condition for test and reference were as follows:Cmax were(494.69±230.94)and(558.78±289.83)ng·mL-1,AUC0-t were(1 336.21±509.78)and(1 410.82±625.99)h·ng·mL-1,AUC0-were(1 366.49±512.16)and(1 441.84±628.04)h·ng·mL-1,respectively.The main pharmacokinetic parameters of sidenafil under fed condition for T and R were as follows:Cmax were(381.89±126.53)and(432.47±175.91)ng·mL-1,AUC0-t were(1 366.34±366.99)and(1 412.76±420.37)h·ng·mL-1,AUC0-were(1 403.28±375.32)and(1 454.13±429.87)h·ng·mL-1,respectively.The results demonstrated the bioequivalence of sidenafil citrate tablets between T and R.The incidence of adverse events in fasting and fed tests were 33.33%and 25.00%,respectively.No serious adverse event was reported.Conclusion The test and reference formulation of sidenafil citrate tablets were equivalent and was safe.
		                        		
		                        		
		                        		
		                        	
4.Distinguishing between Artemisia stolonifera and A. argyi by specific PCR of leaves and non-glandular trichomes.
Ya-Chen ZHAO ; Shuang-Ge LI ; Hui LI ; Yi-Mei LIU ; Ting-Ting ZHAO ; Yu-Huan MIAO ; Da-Hui LIU ; Lu-Qi HUANG
China Journal of Chinese Materia Medica 2023;48(14):3730-3735
		                        		
		                        			
		                        			Artemisia stolonifera is a relative of A. argyi. The two species are difficult to be distinguished due to the similarity in leaf shape and have even less distinctive features after processing. This study aims to establish a method to quickly distinguish between them. At the same time, we examined the reasonability and applicability of the specific polymerase chain reaction(PCR) method. The C/T single nucleotide polymorphism was detected at the position 202 of the sequence, based on which specific primers were designed to identify these two species. The PCR with the specific primer JNC-F and the universal primer ITS3R produced a specific band at 218 bp for A. argyi and no band for A. stolonifera, which can be used to detect at least 3% of A. argyi samples mixed in A. stolonifera samples. The PCR with the specific primer KY-F and the universal primer ITS3R produced a specific band at 218 bp for A. stolonifera and no band for A. argyi, which can be used to detect at least 5% of A. stolonifera samples mixed with A. argyi. The limit of detection of the established method was 5 ng DNA. The established PCR method can accurately distinguish between A. stolonifera and A. argyi, which provides an experimental basis for the quality control of A. stolonifera and determines whether the herbs are adulterated.
		                        		
		                        		
		                        		
		                        			Artemisia/genetics*
		                        			;
		                        		
		                        			Trichomes
		                        			;
		                        		
		                        			Polymerase Chain Reaction
		                        			;
		                        		
		                        			Nucleic Acid Amplification Techniques
		                        			;
		                        		
		                        			Plant Leaves/genetics*
		                        			
		                        		
		                        	
5.Performance of screening of contacts of COVID-19 cases in same flight.
Dan LI ; Ying QIN ; Si Meng FAN ; Zhi Bin PENG ; Hui GE ; Zhao Rui CHANG ; Rui ZHANG ; Xiao Kun YANG ; Hong Ting ZHAO ; Jian Dong ZHENG ; Shi Cheng YU ; Hui WANG ; Jun YAN ; Zhong Jie LI
Chinese Journal of Epidemiology 2023;44(5):713-719
		                        		
		                        			
		                        			Objective: To understand the performance of 2019-nCoV nucleic acid detection in screening of contacts of COVID-19 cases in same flights and provide evidence for the effective screening of persons at high risk for the infection in domestic flights. Methods: The information of passengers who took same domestic flights with COVID-19 cases in China from April 1, 2020 to April 30, 2022 were retrospectively collected,and χ2 test was used to analyze positive nucleic acid detection rates in the passengers in different times before the onsets of the index cases, in different seat rows and in epidemic periods of different 2019-nCoV variants. Results: During the study period, a total of 433 index cases were identified among 23 548 passengers in 370 flights. Subsequently, 72 positive cases of 2019-nCoV nucleic acid were detected in the passengers, in whom 57 were accompanying persons of the index cases. Further analysis of the another 15 passengers who tested positive for the nucleic acid showed that 86.67% of them had onsets or positive detections within 3 days after the diagnosis of the index cases, and the boarding times were all within 4 days before the onsets of the index cases. The positive detection rate in the passengers who seated in first three rows before and after the index cases was 0.15% (95%CI: 0.08%-0.27%), significantly higher than in the passengers in other rows (0.04%, 95%CI: 0.02%-0.10%, P=0.007),and there was no significant difference in the positive detection rate among the passengers in each of the 3 rows before and after the index cases (P=0.577). No significant differences were found in the positive detection rate in the passengers, except the accompanying persons, among the epidemics caused by different 2019-nCoV variants (P=0.565). During the Omicron epidemic period, all the positive detections in the passengers, except the accompanying persons, were within 3 days before the onset of the index cases. Conclusions: The screening test of 2019-nCoV nucleic acid can be conducted in the passengers took the same flights within 4 days before the onsets of the index cases on board. Passengers who seated within 3 rows from the index cases can considered as the close contacts at high risk for 2019-nCoV, for whom screening should be conducted first and special managements are needed. The passengers in other rows can be classified as general risk persons for screening and management.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			COVID-19
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			SARS-CoV-2
		                        			;
		                        		
		                        			China
		                        			;
		                        		
		                        			Nucleic Acids
		                        			
		                        		
		                        	
6.Platelet Removal Efficiency by Leukocyte Filter in Red Blood Cell Units at Different Storage Periods
Hao-qiang LIU ; Lin PENG ; Yu-ting LIN ; Bao-ying FENG ; Sang BA ; Ge-lie GAMA ; Ying LU
Journal of Sun Yat-sen University(Medical Sciences) 2023;44(5):835-839
		                        		
		                        			
		                        			ObjectiveThe aim of this study is to investigate change of platelet count in red blood cell (RBC) units at different storage periods and explore the efficiency of platelet removal by leukocyte filter. MethodsA total of 58 RBC units were divided into four groups according to different storage periods: 1 week Group (16), 2 weeks Group (16), 3 weeks Group (14) and 4 weeks Group (12). RBC units in the four groups were filtered through leukocyte filter. The RBC samples before and after filtration were obtained. The platelet count was detected by automatic blood cell counter and the efficiency of platelet removal was calculated. RBC samples before filtration were made into blood cell smears. The blood cell smears were dyed with Wright-Giemsa stain, and the morphology of platelets was observed through a microscope. ResultsThe platelet count in RBC units stored for 1, 2, 3 and 4 weeks was (286.5±62.34)×109/L, (238.0±57.37)×109/L, (193.6±56.21)×109/L and (167.8±24.76)×109/L, respectively. Platelet count in blood stored for 3 weeks (P<0.01) and 4 weeks (P <0.000 1) were significantly lower than those stored for 1 weeks. When observed in the blood smears of RBC units at different storage periods, platelets with normal morphology were distributed in clump and scattered style. The platelet removal rates of the four groups were (80.13±9.06) %, (76.41±10.13) %, (77.78±9.30) % and (70.63±9.39) %, respectively, with no significant difference (P >0.05). ConclusionsPlatelet count in RBC units decreases gradually as the storage period increases, but most platelets still remain in RBC units of late storage periods (3 weeks and 4 weeks). The leukocyte filter is able to remove most of the platelets, and the removal efficiency is similar among the groups. 
		                        		
		                        		
		                        		
		                        	
7.Study on the correlation between ceramic and chronic obstructive pulmonary disease in Foshan City.
Li Xian ZHENG ; Wen Guang YOU ; Yu Huan ZHAO ; Ai Hua ZHU ; Li Hua LIANG ; Ge Ting CHEN
Chinese Journal of Industrial Hygiene and Occupational Diseases 2023;41(2):126-129
		                        		
		                        			
		                        			Objective: To study the correlation between ceramic and chronic obstructive pulmonary disease (COPD), and explore its related risk factors. Methods: In January 2021, five representative ceramic enterprises were selected from Chancheng District, Nanhai District, Gaoming District and Sanshui District of Foshan City. The ceramic workers who came to Chancheng Hospital of Foshan First People's Hospital for physical examination from January to October 2021 were selected as the research objects, and 525 people were included. Conduct questionnaire survey and pulmonary function test. Logistic regresion was performed to analyze the influencing facters of COPD among ceramic workers. Results: The subjects were (38.51±1.25) years old, 328 males and 197 females, and the detection rate of COPD was 9.52% (50/525). The incidence of respiratory symptoms such as dyspnea, chronic cough, wheezing and chest tightness, the detection rates of abnormal lung age, abnormal lung function and COPD in males were higher than those in females (P<0.05). The logistic regression analysis showed that male, age, working years, smoking status and family history of COPD were the risk factors for COPD among ceramic workers (P<0.05) . Conclusion: The ceramic workers are the high risk population of COPD. We should do a good job in health education, and do a regular physical examination to find the changes of lung function in time, and prevent the occurrence of COPD as soon as possible.
		                        		
		                        		
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Adult
		                        			;
		                        		
		                        			Pulmonary Disease, Chronic Obstructive/epidemiology*
		                        			;
		                        		
		                        			Ceramics
		                        			;
		                        		
		                        			Health Education
		                        			;
		                        		
		                        			Hospitals
		                        			;
		                        		
		                        			Physical Examination
		                        			
		                        		
		                        	
8. Development of a method for determination of osmotic pump controlled-release tablets of lorcaserin hydrochloride in beagle dog plasma and its application to pharmacokinetic study
Miao-Miao ZHANG ; Cheng-Jun JIANG ; Chong-Yang WANG ; Ting-Yu GE ; Qi-Qi SONG ; Zhen-Bao LI ; Dian-Lei WANG
Chinese Pharmacological Bulletin 2023;39(5):993-997
		                        		
		                        			
		                        			 Aim To develop an UPLC-MS/MS method to determine the concentration of lorcaserin hydrochloride in beagle plasma, and study the pharmacokinetics of osmotic pump controlled-release tablets of lorcaserin hydrochloride. Methods A randomized crossover design was used, carbamazepine as the internal standard(IS), and plasma protein precipitation with acetonitrile. The chromatographic was Phenomenex Polar C18 column(100 mm×2. 1 mm, 3 μm), and acetonitrile - water(containing 10 mmol·L-1 ammonium acetate and 0.1% formic acid)(40:60, V/V)was mobile phase. Multiple reaction monitoring mode and electrospray positive ionization were used to detect lorcaserin hydrochloride. The MS/MS ion transitions were monitored at m/z 196.2→129.2 for lorcaserin hydrochloride and m/z 237→194.1 for carbamazepine, respectively. Results The linear range was 1 to 500 μg·L-1(r=0.999 2), the extraction recovery rate ranged from 87.70% to 89.70%, the precision RSD was 9.7%. The accuracy and matrix effect met the requirements, and the stability of lorcaserin hydrochloride was good in -20 ℃ refrigerator for 45 d, repeated freezing and thawing for three times, placed at room temperature for 24 h, and the disposed samples placed in automatsampler for 6 h were stable. The main pharmacokinetic parameters of the controlled-release tablet and immediate-release tablet were as follows:Tmax was(8.00±1.27)h and(1.00±0.13)h, Cmax was(70.56±3.73)μg·L-1 and(176.33±16.73)μg·L-1, and AUC0-t was(966.33±7.56)μg·h·L-1 and(973.05±69.09)μg·h·L-1, respectively. Conclusions The established UPLC-MS/MS method can be used to study the pharmacokinetics of lorcaserin hydrochloride in the plasma of beagle dogs, and osmotic pump controlled-release tablets has sustained release effect. 
		                        		
		                        		
		                        		
		                        	
9.Research progress in quality control of Bufonis Venenum in preparations.
Yu-Xiu WANG ; Peng-Fei WANG ; Yun-Ge FANG ; Ya-Ting LIU ; Liang-Mian CHEN ; Zhi-Min WANG ; Hui-Min GAO
China Journal of Chinese Materia Medica 2023;48(17):4552-4568
		                        		
		                        			
		                        			Bufonis Venenum, an animal medicinal material, is widely used for treating cardiovascular diseases and pain induced by rheumatics or malignant tumors. In view of the high activity and high toxicity, it is of great significance to pay attention to the quality control of Bufonis Venenum to ensure the safety and effectiveness of its preparations. China's drug standards involve 102 preparations(474 batch numbers) containing Bufonis Venenum approved for sale, including 14 preparations in the Chinese Pharmacopoeia(2020 edition) and 68 preparations in the standards issued by the Ministry of Health Drug Standard of the People's Republic of China. Bufonis Venenum is mostly used in pill and powder preparations in the form of raw powder, with the main functions of clearing heat, removing toxin, relieving swelling and pain, replenishing qi, activating blood, opening orifice, and awakening brain. Except the high level of quality control for Bufonis Venenum in the preparations in the Chinese Pharmacopoeia(2020 edition), the quality control standards of Bufonis Venenum in other preparations are low or even absent. Therefore, it is urgent to conduct research on the improvement of quality standards for the preparations containing Bufonis Venenum. This study retrieved the reports focusing on the quality evaluation and quality control of the preparations containing Bufonis Venenum from CNKI, PubMed, and Web of Science. Qualitative and quantitative analysis methods for 64 preparations containing Bufonis Venenum have been reported, mainly including thin-layer chromatography, HPLC fingerprint, and multi-component content determination. The index components mainly involved bufadienolides, such as gamabufalin, arenobufagin, bufotalin, bufalin, cinobufagin, and resibufogenin. According to the literature information, this paper suggests that attention should be paid to the correlations between the analysis methods and detection indexes of medicinal materials, decoction pieces and preparations, the monitoring of indole alkaloids, and the content uniformity inspection for further improving the quality standards for the preparations containing Bufonis Venenum.
		                        		
		                        		
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Bufonidae
		                        			;
		                        		
		                        			Powders
		                        			;
		                        		
		                        			Bufanolides/pharmacology*
		                        			;
		                        		
		                        			Quality Control
		                        			;
		                        		
		                        			Chromatography, High Pressure Liquid
		                        			;
		                        		
		                        			Pain/drug therapy*
		                        			
		                        		
		                        	
10.The efficacy of chemotherapy re-challenge in third-line setting for metastatic colorectal cancer patients: a real-world study.
Jing Jing DUAN ; Tao NING ; Ming BAI ; Le ZHANG ; Hong Li LI ; Rui LIU ; Shao Hua GE ; Xia WANG ; Yu Chong YANG ; Zhi JI ; Fei Xue WANG ; Yan Sha SUN ; Yi BA ; Ting DENG
Chinese Journal of Oncology 2023;45(11):967-972
		                        		
		                        			
		                        			Objective: To explore the efficacy of chemotherapy re-challenge in the third-line setting for patients with metastatic colorectal cancer (mCRC) in the real world. Methods: The clinicopathological data, treatment information, recent treatment efficacy, adverse events and survival data of mCRC patients who had disease progression after treatment with oxaliplatin-based and/or irinotecan-based chemotherapy and received third-line chemotherapy re-challenge from January 2013 to December 2020 at Tianjin Medical University Cancer Institute and Hospital were retrospectively collected. Survival curves were plotted with the Kaplan-Meier method, and the Cox proportional hazard model was used to analyze the prognostic factors. Results: A total of 95 mCRC patients were included. Among them, 32 patients (33.7%) received chemotherapy alone and 63 patients (66.3%) received chemotherapy combined with targeted drugs. Eighty-three patients were treated with dual-drug chemotherapy (87.4%), including oxaliplatin re-challenge in 35 patients and irinotecan re-challenge in 48 patients. The remaining 12 patients were treated with triplet chemotherapy regimens (12.6%). Among them, as 5 patients had sequential application of oxaliplatin and irinotecan in front-line treatments, their third-line therapy re-challenged both oxaliplatin and irinotecan; 7 patients only had oxaliplatin prescription before, and these patients re-challenged oxaliplatin in the third-line treatment. The overall response rate (ORR) and disease control rate (DCR) reached 8.6% (8/93) and 61.3% (57/93), respectively. The median progression free survival (mPFS) and median overall survival (mOS) were 4.9 months and 13.0 months, respectively. The most common adverse events were leukopenia (34.7%) and neutropenia (34.7%), followed by gastrointestinal adverse reactions such as nausea (32.6%) and vomiting (31.6%). Grade 3-4 adverse events were mostly hematological toxicity. Cox multivariate analysis showed that gender (HR=1.609, 95% CI: 1.016-2.548) and the PFS of front-line treatments (HR=0.598, 95% CI: 0.378-0.947) were independent prognostic factors. Conclusion: The results suggested that it is safe and effective for mCRC patients to choose third-line chemotherapy re-challenge, especially for patients with a PFS of more than one year in front-line treatments.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Irinotecan/therapeutic use*
		                        			;
		                        		
		                        			Oxaliplatin/therapeutic use*
		                        			;
		                        		
		                        			Colorectal Neoplasms/pathology*
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Fluorouracil
		                        			;
		                        		
		                        			Colonic Neoplasms/chemically induced*
		                        			;
		                        		
		                        			Rectal Neoplasms/drug therapy*
		                        			;
		                        		
		                        			Antineoplastic Combined Chemotherapy Protocols/adverse effects*
		                        			;
		                        		
		                        			Camptothecin/adverse effects*
		                        			
		                        		
		                        	
            
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