1.Bioequivalence study of ezetimibe tablets in Chinese healthy subjects
Pei-Yue ZHAO ; Tian-Cai ZHANG ; Yu-Ning ZHANG ; Ya-Fei LI ; Shou-Ren ZHAO ; Jian-Chang HE ; Li-Chun DONG ; Min SUN ; Yan-Jun HU ; Jing LAN ; Wen-Zhong LIANG
The Chinese Journal of Clinical Pharmacology 2024;40(16):2378-2382
		                        		
		                        			
		                        			Objective To evaluate the bioequivalence and safety of ezetimibe tablets in healthy Chinese subjects.Methods The study was designed as a single-center,randomized,open-label,two-period,two-way crossover,single-dose trail.Subjects who met the enrollment criteria were randomized into fasting administration group and postprandial administration group and received a single oral dose of 10 mg of the subject presparation of ezetimibe tablets or the reference presparation per cycle.The blood concentrations of ezetimibe and ezetimibe-glucuronide conjugate were measured by high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS),and the bioequivalence of the 2 preparations was evaluated using the WinNonlin 7.0 software.Pharmacokinetic parameters were calculated to evaluate the bioequivalence of the 2 preparations.The occurrence of all adverse events was also recorded to evaluate the safety.Results The main pharmacokinetic parameters of total ezetimibe in the plasma of the test and the reference after a single fasted administration:Cmax were(118.79±35.30)and(180.79±51.78)nmol·mL-1;tmax were 1.40 and 1.04 h;t1/2 were(15.33±5.57)and(17.38±7.24)h;AUC0-t were(1 523.90±371.21)and(1 690.99±553.40)nmol·mL-1·h;AUC0-∞ were(1 608.70±441.28),(1 807.15±630.00)nmol·mL-1·h.The main pharmacokinetic parameters of total ezetimibe in plasma of test and reference after a single meal:Cmax were(269.18±82.94)and(273.93±87.78)nmol·mL-1;Tmax were 1.15 and 1.08 h;t1/2 were(22.53±16.33)and(16.02±5.84)h;AUC0_twere(1 463.37±366.03),(1 263.96±271.01)nmol·mL-1·h;AUC0-∞ were(1 639.01±466.53),(1 349.97±281.39)nmol·mL-1·h.The main pharmacokinetic parameters Cmax,AUC0-tand AUC0-∞ of the two preparations were analyzed by variance analysis after logarithmic transformation.In the fasting administration group,the 90%CI of the log-transformed geometric mean ratios were within the bioequivalent range for the remaining parameters in the fasting dosing group,except for the Cmax of ezetimibe and total ezetimibe,which were below the lower bioequivalent range.The Cmax of ezetimibe,ezetimibe-glucuronide,and total ezetimibe in the postprandial dosing group was within the equivalence range,and the 90%CI of the remaining parameters were not within the equivalence range for bioequivalence.Conclusion This test can not determine whether the test preparation and the reference preparation of ezetimibe tablets have bioequivalence,and further clinical trials are needed to verify it.
		                        		
		                        		
		                        		
		                        	
2.Establishment of HPLC fingerprints and content determination of eight constituents for freeze-dried powder of Yinhuo Decoction
Jing HU ; Ya-Ming DING ; Shuang LIU ; Yue QIAO ; Yue ZHANG ; Hong-Dan XU ; Ning ZHANG ; Ji-Hui ZHAO
Chinese Traditional Patent Medicine 2024;46(8):2499-2505
		                        		
		                        			
		                        			AIM To establish the HPLC fingerprints for freeze-dried powder of Yinhuo Decoction,and to determine the contents of rehmannitin D,methylophiopogonanone A,verbascoside,protocatechuic acid,catalpol,schisandrol A,schisandrin B,schisandrin A.METHODS The fingerprint esablishment was performed on a 30℃thermostatic Supersil AQ18 column(4.6 mm×250 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1%phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelength was set at 230 nm.The UPLC-MS/MS content determination was performed on a 30℃thermostatic Alphasil VC-C18 column(2.1 mm×100 mm,2.5 μm),with the mobile phase comprising of acetonitrile-0.1%formic acid flowing at 0.3 mL/min in a gradient elution manner,and electron spray ionization source was adopted in positive and negative ion scanning with multiple reaction monitoring mode.RESULTS There were 17 common peaks in the fingerprints for 10 batches of freeze-dried powder with the similarities of more than 0.90.and piloside,crystal blue glycoside,deacetylated caryoside schisandrin A were identified.Eight constituents showed good linear relationships within their own ranges(R2>0.990 6),whose average recoveries were 98.7%-101.1%with the RSDs of 2.0%-5.2%.CONCLUSION The combination of fingerprints and content determination can completely characterize the quality of Yinhuo Decoction reference sample,thus provide a reference for the quality evaluation of its key chemical properties.
		                        		
		                        		
		                        		
		                        	
3.HbA1c comparison and diagnostic efficacy analysis of multi center different glycosylated hemoglobin detection systems.
Ping LI ; Ying WU ; Yan XIE ; Feng CHEN ; Shao qiang CHEN ; Yun Hao LI ; Qing Qing LU ; Jing LI ; Yong Wei LI ; Dong Xu PEI ; Ya Jun CHEN ; Hui CHEN ; Yan LI ; Wei WANG ; Hai WANG ; He Tao YU ; Zhu BA ; De CHENG ; Le Ping NING ; Chang Liang LUO ; Xiao Song QIN ; Jin ZHANG ; Ning WU ; Hui Jun XIE ; Jina Hua PAN ; Jian SHUI ; Jian WANG ; Jun Ping YANG ; Xing Hui LIU ; Feng Xia XU ; Lei YANG ; Li Yi HU ; Qun ZHANG ; Biao LI ; Qing Lin LIU ; Man ZHANG ; Shou Jun SHEN ; Min Min JIANG ; Yong WU ; Jin Wei HU ; Shuang Quan LIU ; Da Yong GU ; Xiao Bing XIE
Chinese Journal of Preventive Medicine 2023;57(7):1047-1058
		                        		
		                        			
		                        			Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R2 of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.
		                        		
		                        		
		                        		
		                        			Pregnancy
		                        			;
		                        		
		                        			Child
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Glycated Hemoglobin
		                        			;
		                        		
		                        			Cohort Studies
		                        			;
		                        		
		                        			Diabetes Mellitus/diagnosis*
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		                        			Sensitivity and Specificity
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		                        			ROC Curve
		                        			
		                        		
		                        	
4.Comparison of the effects and safety of dydrogesterone and medroxyprogesterone acetate on endometrial hyperplasia without atypia: a randomized controlled non-inferior phase Ⅲ clinical study.
Yao Chen LOU ; Shuang ZHOU ; Jiong Bo LIAO ; Wen Yu SHAO ; Ying Ying HU ; Cheng Cheng NING ; Qian WANG ; Yierfulati GULINAZI ; Bing Yi YANG ; Ya Li CHENG ; Peng Fei WU ; Qin ZHU ; Xian Rong ZHOU ; Wei Wei SHAN ; Xiao Jun CHEN
Chinese Journal of Obstetrics and Gynecology 2023;58(7):526-535
		                        		
		                        			
		                        			Objective: To compare the effects and safety of dydrogesterone (DG) and medroxyprogesterone acetate (MPA) on the treatment in patients with endometrial hyperplasia without atypia (EH). Methods: This was a single-center, open-label, prospective non-inferior randomized controlled phase Ⅲ trial. From February 2019 to November 2021, patients with EH admitted to the Obstetrics and Gynecology Hospital of Fudan University were recruited. Enrolled patients were stratified according to the pathological types of simple hyperplasia (SH) or complex hyperplasia (CH), and were randomised to receive MPA or DG. Untill May 14, 2022, the median follow-up time after complete response (CR) was 9.3 months (1.1-17.2 months). The primary endpoint was the 6-month CR rate (6m-CR rate). The secondary endpoints included the 3-month CR rate (3m-CR rate), adverse events rate, recurrence rate, and pregnancy rate in one year after CR. Results: (1) A total of 292 patients with EH were enrolled in the study with the median age of 39 years (31-45 years). A total of 135 SH patients were randomly assigned to MPA group (n=67) and DG group (n=68), and 157 CH patients were randomly assigned to MPA group (n=79) and DG group (n=78). (2) Among 292 patients, 205 patients enrolled into the primary endpoint analysis, including 92 SH patients and 113 CH patients, with 100 patients in MPA group and 105 in DG group, respectively. The 6m-CR rate of MPA group and DG group were 90.0% (90/100) and 88.6% (93/105) respectively, and there were no statistical significance (χ2=0.11, P=0.741), with the rate difference (RD) was -1.4% (95%CI:-9.9%-7.0%). Stratified by the pathology types, the 6m-CR rate of SH patients was 93.5% (86/92), and MPA group and DG group were respectively 91.1% (41/45) and 95.7% (45/47); and the 6m-CR rate of CH patients was 85.8% (97/113), and MPA group and DG group were 89.1% (49/55) and 82.8% (48/58) respectively. The 6m-CR rates of the two treatments had no statistical significance either (all P>0.05). A total of 194 EH patients enrolled into the secondary endpoint analysis, including 88 SH patients and 106 CH patients, and 96 patients in MPA group and 98 in DG group, respectively. The 3m-CR rate of SH patients were 87.5% (77/88), while the 3m-CR rates of MPA group and DG group were 90.7% (39/43) and 84.4% (38/45), respectively; the 3m-CR rate of CH patients was 66.0% (70/106), and MPA group and DG group had the same 3m-CR rate of 66.0% (35/53). No statistical significance was found between the two treatments both in SH and CH patients (all P>0.05). (3) The incidence of adverse events between MPA group and DG group had no statistical significance (P>0.05). (4) A total of 93 SH patients achieved CR, and the cumulative recurrence rate in one year after CR were 5.9% and 0 in MPA group and DG group, respectively. While 112 CH patients achieved CR, and the cumulative recurrence rate in one year after CR were 8.8% and 6.5% in MPA group and DG group, respectively. There were no statistical significance between two treatment groups (all P>0.05). Among the 93 SH patients, 10 patients had family planning but no pregnancy happened during the follow-up period. Among the 112 CH patients, 21 were actively preparing for pregnancy, and the pregnancy rate and live-birth rate in one year after CR in MPA group were 7/9 and 2/7, while in DG group were respectively 4/12 and 2/4, and there were no statistical significance in pregnancy rate and live-birth rate between the two treatment groups (all P>0.05). Conclusions: Compared with MPA, DG is of good efficacy and safety in treating EH. DG is a favorable alternative treatment for EH patients.
		                        		
		                        		
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Adult
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		                        			Medroxyprogesterone Acetate/adverse effects*
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		                        			Endometrial Hyperplasia/pathology*
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		                        			Dydrogesterone/adverse effects*
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		                        			Hyperplasia
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		                        			Prospective Studies
		                        			
		                        		
		                        	
5.Progress in research of etiology of childhood obesity based on interaction between genes and environment.
Bo Rui LIU ; Jia Jin HU ; Ning Yu WAN ; Yang YU ; Yang LIU ; Ya Nan MA ; De Liang WEN
Chinese Journal of Epidemiology 2023;44(3):511-515
		                        		
		                        			
		                        			Childhood obesity is a global public health problem, which can not only endangers children's health, but also might be an important cause of chronic diseases in adulthood. In recent years, with the in-depth development of precision medicine research, more and more research evidences have shown that there are interactions between environmental factors, such as early intrauterine environment, children's diet, physical activity and children's gene factor on the incidence of childhood obesity, which can result in or inhibit the incidence and development of childhood obesity. This paper summarizes the progress in research in this field to reveal the effects and potential mechanisms of genetic factors and environmental factors on the incidence of childhood obesity in order to provide reference for the precise prevention and control of childhood obesity under different genetic backgrounds.
		                        		
		                        		
		                        		
		                        			Child
		                        			;
		                        		
		                        			Humans
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		                        			Pediatric Obesity/genetics*
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		                        			Diet
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		                        			Causality
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		                        			Exercise
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		                        			Public Health
		                        			
		                        		
		                        	
6.Discovery of human pancreatic lipase inhibitors from root of Rhodiola crenulata via integrating bioactivity-guided fractionation,chemical profiling and biochemical assay
Ma LI-JUAN ; Hou XU-DONG ; Qin XIAO-YA ; He RONG-JING ; Yu HAO-NAN ; Hu QING ; Guan XIAO-QING ; Jia SHOU-NING ; Hou JIE ; Lei TAO ; Ge GUANG-BO
Journal of Pharmaceutical Analysis 2022;12(4):683-691
		                        		
		                        			
		                        			Although herbal medicines(HMs)are widely used in the prevention and treatment of obesity and obesity-associated disorders,the key constituents exhibiting anti-obesity activity and their molecular mechanisms are poorly understood.Recently,we assessed the inhibitory potentials of several HMs against human pancreatic lipase(hPL,a key therapeutic target for human obesity),among which the root-extract of Rhodiola crenulata(ERC)showed the most potent anti-hPL activity.In this study,we adopted an integrated strategy,involving bioactivity-guided fractionation techniques,chemical profiling,and biochemical assays,to identify the key anti-hPL constituents in ERC.Nine ERC fractions(retention time=12.5-35 min),obtained using reverse-phase liquid chromatography,showed strong anti-hPL activity,while the major constituents in these bioactive fractions were subsequently identified using liquid chromatography-quadrupole time-of-flight mass spectrometry(LC-Q-TOF-MS/MS).Among the identified ERC constituents,1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose(PGG)and catechin gallate(CG)showed the most potent anti-hPL activity,with pIC50 values of 7.59±0.03 and 7.68±0.23,respectively.Further investigations revealed that PGG and CG potently inhibited hPL in a non-competitive manner,with inhibition constant(Ki)values of 0.012 and 0.082 μM,respectively.Collectively,our integrative analyses enabled us to efficiently identify and characterize the key anti-obesity constituents in ERC,as well as to elucidate their anti-hPL mechanisms.These findings provide convincing evidence in support of the anti-obesity and lipid-lowering properties of ERC.
		                        		
		                        		
		                        		
		                        	
7.Dihydromyricetin mediates epithelial mesenchymal transformation and regulates the proliferation and apoptosis of esophageal squamous cell carcinoma cells.
Ya Ping TIAN ; Yi Shuang CUI ; Xuan ZHENG ; Bao Lin LIU ; Yong Pan ZHANG ; Kun Peng WEI ; Zhi ZHANG ; Wan Ning HU ; Xue Mei ZHANG ; Guo Gui SUN
Chinese Journal of Oncology 2022;44(4):326-333
		                        		
		                        			
		                        			Objective: To study the effects of dihydromyricetin (DMY) on the proliferation, apoptosis and epithelial mesenchymal transition (EMT) of esophageal squamous cell carcinoma (ESCC) cell KYSE150 and KYSE410. Methods: KYSE150 and KYSE410 cells were treated with different concentrations of DMY (0, 25, 50, 100, 150, 200 μmol/L) for 24 hours. The median inhibition concentration (IC50) values of KYSE150 and KYSE410 were detected by cell counting kit-8 (CCK-8) method. Then 0.5‰ dimethyl sulfoxide (DMSO) was used as control group, dihydromyricetin (DMY), dihydromyricetin and transforming growth factor-β1 (DMY+ TGF-β1), transforming growth factor-β1 (TGF-β1) were used as experimental group. Cell proliferation and apoptosis rates were measured by clonal formation and flow cytometry. Transwell invasion and wound healing assay were used to detect cell invasion and migration. The protein expression levels of Caspase-3, Caspase-9, Bcl-2, Bax, Smad2/3, phosphorylation-Smad2/3 (p-Smad2/3) and Vimentin were detected by western blot. Results: The IC50 values of DMY on KYSE410 and KYSE150 cells were 100.51 and 101.27 μmol/L. The clone formation numbers of KYSE150 and KYSE410 in DMY group [(0.53±0.03) and (0.31±0.03)] were lower than those in DMSO group [(1.00±0.10) and (1.00±0.05), P<0.05]. The apoptosis rates of KYSE150 and KYSE410 cells in DMY group [(1.84±0.22)% and (2.80±0.07)%] were higher than those in DMSO group [(1.00±0.18)% and (1.00±0.07)%, P<0.05]. The invasion numbers of KYSE150 and KYSE410 cells in DMY group [(0.42±0.03) and (0.29±0.05)] were lower than those in DMSO group [(1.00±0.08) and (1.00±0.05), P<0.05]. The migration rates of KYSE150 and KYSE410 cells in DMY group [(0.65±0.14)% and (0.40±0.17)%] were lower than those in DMSO group [(1.00±0.10)% and (1.00±0.08)%, P<0.05]. The clone formation numbers of KYSE150 and KYSE410 in TGF-β1 group [(1.01±0.08) and (0.99±0.25)] were higher than those in DMY+ TGF-β1 group [(0.73±0.10) and (0.58±0.05), P<0.05]. The apoptosis rates of KYSE150 and KYSE410 cells in TGF-β1 group [(0.81±0.14)% and (1.18±0.10)%] were lower than those in DMY+ TGF-β1 group [(1.38±0.22)% and (1.85±0.04)%, P<0.05]. The invasion numbers of KYSE150 and KYSE410 cells in TGF-β1 group [(1.19±0.11) and (1.39±0.11)] were higher than those in DMY+ TGF-β1 group [(0.93±0.09) and (0.93±0.05), P<0.05]. The migration rates of KYSE150 and KYSE410 cells in TGF-β1 group [(1.87±0.19)% and (1.32±0.04)%] were higher than those in DMY+ TGF-β1 group [(0.86±0.16)% and (0.77±0.12)%, P<0.05]. The protein expression levels of Bax, Caspase-3 and Caspase-9 in KYSE150 and KYSE410 cells in DMY group were higher than those in DMSO group, while the protein expression level of Bcl-2 was lower than that in DMSO group (P<0.05). The protein expression levels of p-Smad2/3, Smad2/3 and Vimentin in KYSE150 and KYSE410 cells in DMY group were lower than those in DMSO group (P<0.05). The protein expression levels of Bax, Caspase-3 and Caspase-9 in KYSE150 and KYSE410 cells in TGF-β1 group were lower than those in DMY+ TGF-β1 group, and the protein expression level of Bcl-2 was higher than that in DMY+ TGF-β1 group (P<0.05). The protein expression levels of Bax, Caspase-3 and Caspase-9 in KYSE150 and KYSE410 cells in DMY+ TGF-β1 group were lower than those in DMY group, and the protein expression level of Bcl-2 was higher than that in DMY group (P<0.05). The protein expression levels of p-Smad2/3, Smad2/3 and Vimentin in KYSE150 and KYSE410 cells in TGF-β1 group were higher than those in DMY+ TGF-β1 group (P<0.05). Conclusion: DMY can inhibit the proliferation and EMT of ESCC mediated by TGF-β1 and promote cell apoptosis.
		                        		
		                        		
		                        		
		                        			Apoptosis
		                        			;
		                        		
		                        			Caspase 3/metabolism*
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		                        			Caspase 9/metabolism*
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		                        			Cell Line, Tumor
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		                        			Cell Movement
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		                        			Cell Proliferation
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		                        			Dimethyl Sulfoxide/pharmacology*
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		                        			Epithelial-Mesenchymal Transition
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		                        			Esophageal Neoplasms/metabolism*
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		                        			Esophageal Squamous Cell Carcinoma
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		                        			Flavonols
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		                        			Humans
		                        			;
		                        		
		                        			Signal Transduction
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		                        			Transforming Growth Factor beta1/pharmacology*
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		                        			Vimentin/metabolism*
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		                        			bcl-2-Associated X Protein/pharmacology*
		                        			
		                        		
		                        	
8.Pathological Mechanism of HSOS in Rats Induced by Different Doses of Monocrotaline
Si-qi GAO ; Zhun XIAO ; Ya-dong FU ; Yong-hong HU ; Gao-feng CHEN ; Xiao-ning WANG ; Wei LIU ; Jia-mei CHEN ; Ping LIU
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(12):48-60
		                        		
		                        			
		                        			ObjectiveTo observe the pathological changes of hepatic sinusoidal obstruction syndrome (HSOS) induced by different doses of monocrotaline (MCT) in rats, investigate the dose and duration of modeling, and elucidate the mechanism. MethodA total of 72 male SD rats were randomized into normal group (n=12), and low-, medium-, and high-dose MCT groups (n=20 per group, 80,120,160 mg·kg-1, respecctively). In the model groups, different doses of MCT were intragastrically administered to induce the HSOS in rats. After 48 h and 120 h separately, rats in each group were sacrificed and sampling was performed. The survival rate of rats in each group was calculated, and the body weight, liver weight, and and serum liver function indexes of the rats were examined. The histopathological changes of the liver were observed based on scanning electron microscopy, hematoxylin and eosin (HE) staining, and Sirius red (SR) staining. Glutathione S-transferase (GST) activity, total superoxide dismutase (T-SOD) activity, and malondialdehyde (MDA) content of liver tissue homogenate were measured with microplate method. The expression of liver tissue-related indexes was detected by real-time polymerase chain reaction (PCR), Western blot, and immunohistochemistry. ResultThe activity of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in MCT groups rose with the increase in MCT dose (P<0.05, P<0.01) compared with that in the normal group. With the extension of modeling time, the activity of serum ALT and AST in the low-dose group decreased (P<0.01), while the activity of them in the medium-dose and high-dose groups increased (P<0.01). HE staining showed that hepatocyte necrosis, inflammatory cell infiltration, and erythrocyte accumulation in MCT groups. Electron microscopy demonstrated that fenestrae of liver sinusoidal endothelial cells widened and the sieve plates disappeared. Morever, the injury was worsened with the increase in MCT dose. In addition, the expression of CD44 in MCT groups was significantly reduced compared with that in the normal group (P<0.05, P<0.01). SR staining showed that no positive staining was found in model groups after 48 h, while collagen deposition in portal areas and liver sinusoids could be seen in model groups after 120 h. MCT groups showed increase in MDA content and GST activity and decrease in T-SOD activity compared with the normal group, particularly the medium-dose and high-dose groups (P<0.01), and the changes were dose-dependent after 120 h (P<0.01). The protein expression of CD68 (pro-inflammatory macrophage marker) was raised with the increase in dosage, which was consistent with the results of immunohistochemistry (P<0.01), while CD163 (anti-inflammatory macrophage marker) protein and mRNA expression was significantly decreased with the increase in dosage (P<0.01). Western blot results showed that the expression of phosphorylated nuclear factor-κB/nuclear factor-κB (p-NF-κB/NF-κB) and phosphorylated protein kinase B/protein kinase B (p-Akt/t-Akt) was significantly increased in medium-dose and high-dose MCT groups (P<0.05,P<0.01). The protein expression of α-smooth muscle actin (α-SMA) in liver tissues in MCT groups was significantly increased over time and with the increase in dose, and the mRNA expression of α-SMA, collagen type I α1 (Col1a1), and collagen type Ⅳ α1 (Col4a1) showed the same trend (P<0.05, P<0.01). The results of TUNEL staining showed that apoptotic cells were increased with the rise of MCT dose, while B-cell lymphoma-2(Bcl-2) /Bcl-2 associated X protein (Bax) was remarkably decreased (P<0.01). ConclusionHSOS in rats induced by intragastric administration of different doses of MCT was aggravated with the increase of dosage. In the low-dose (80 mg·kg-1) MCT group, the liver healed spontaneously over time. However, liver damage caused by MCT of 120 mg·kg-1 and 160 mg·kg-1 aggravated over time, and even fibrosis and death occurred. The pathological mechanism of MCT-induced HSOS in rats may be that MCT triggered intense oxidative stress in liver tissue, thus activated pro-inflammatory macrophages to secrete large amounts of inflammatory factors, and further activated the NF-κB/Akt signalling pathway, leading to severe cell damage and death. 
		                        		
		                        		
		                        		
		                        	
9.Clinical Characteristics and Risk Factors of Invasive Fungal Infections in Acute Leukemia Patients in Tropical Regions.
Wen-Shuai ZHENG ; Li-Xun GUAN ; Shen-Yu WANG ; Ya-Lei HU ; Bo PENG ; Jian BO ; Quan-Shun WANG ; Xiao-Ning GAO
Journal of Experimental Hematology 2022;30(1):99-106
		                        		
		                        			OBJECTIVE:
		                        			To analyze the clinical characteristics and risk factors of invasive fungal infection (IFI) occurenced in patients with acute leukemia (AL) during treatment in tropical regions.
		                        		
		                        			METHODS:
		                        			The clinical data of 68 AL patients admitted to the Hainan Hospital of PLA General Hospital from April 2012 to April 2019 was retrospectively analyzed. Logistic regression analysis was used to analyze the factors affecting the occurrence of IFI in AL patients.
		                        		
		                        			RESULTS:
		                        			Among the 68 patients, 44 were acute myeloid leukemia, 24 were acute lymphoblastic leukemia, 39 were male, 29 were female and the median age was 41(13-75) years old. The 68 patients received 242 times of chemotherapy or hematopoietic stem cell transplantation(HSCT), including 73 times of initial chemotherapy or inducting chemotherapy after recurrence, 14 times of HSCT, 155 times of consolidating chemotherapy. Patients received 152 times of anti-fungal prophylaxis, including 77 times of primary anti-fungal prophylaxis and 75 times of secondary anti-fungal prophylaxis. Finally, the incidence of IFI was 31 times, including 24 times of probable diagnosis, 7 times of proven diagnosis, and the total incidence of IFI was 12.8%(31/242), the incidence of IFI in inducting chemotherapy was 24.66%(18/73), the incidence of IFI in HSCT patients was 28.57% (4/14), the incidence of IFI in consolidating chemotherapy was 5.80% (9/155). Multivariate analysis showed that inducting chemotherapy or HSCT, the time of agranulocytosis ≥7 days, risk stratification of high risk were the independent risk factors for IFI in AL patients during treatment in tropical regions.
		                        		
		                        			CONCLUSION
		                        			The incidence of IFI in patients with AL in the tropics regions is significantly higher than that in other regions at homeland and abroad. Anti-fungal prophylaxis should be given to the patients with AL who have the high risk factors of inducting chemotherapy or HSCT, time of agranulocytosis ≥7 days and risk stratification of high risk.
		                        		
		                        		
		                        		
		                        			Adult
		                        			;
		                        		
		                        			Aged
		                        			;
		                        		
		                        			Antifungal Agents/therapeutic use*
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Hematopoietic Stem Cell Transplantation
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Invasive Fungal Infections/epidemiology*
		                        			;
		                        		
		                        			Leukemia, Myeloid, Acute/drug therapy*
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Risk Factors
		                        			
		                        		
		                        	
10.Prevention and control of HIV/AIDS in China: lessons from the past three decades.
Jun-Jie XU ; Meng-Jie HAN ; Yong-Jun JIANG ; Hai-Bo DING ; Xi LI ; Xiao-Xu HAN ; Fan LV ; Qing-Feng CHEN ; Zi-Ning ZHANG ; Hua-Lu CUI ; Wen-Qing GENG ; Jing ZHANG ; Qi WANG ; Jing KANG ; Xiao-Lin LI ; Hong SUN ; Ya-Jing FU ; Ming-Hui AN ; Qing-Hai HU ; Zhen-Xing CHU ; Ying-Jie LIU ; Hong SHANG
Chinese Medical Journal 2021;134(23):2799-2809
		                        		
		                        			
		                        			In the past 37 years, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has undergone various major transmission routes in China, with the world most complex co-circulating HIV-1 subtypes, even the prevalence is still low. In response to the first epidemic outbreak of HIV in injecting drug users and the second one by illegal commercial blood collection, China issued the Anti-Drug Law and launched the Blood Donation Act and nationwide nucleic acid testing, which has avoided 98,232 to 211,200 estimated infections and almost ended the blood product-related infection. China has been providing free antiretroviral therapy (ART) since 2003, which covered >80% of the identified patients and achieved a viral suppression rate of 91%. To bend the curve of increasing the disease burden of HIV and finally end the epidemic, China should consider constraining HIV spread through sexual transmission, narrowing the gaps in identifying HIV cases, and the long-term effectiveness and safety of ART in the future.
		                        		
		                        		
		                        		
		                        			Acquired Immunodeficiency Syndrome/prevention & control*
		                        			;
		                        		
		                        			China/epidemiology*
		                        			;
		                        		
		                        			Disease Outbreaks
		                        			;
		                        		
		                        			HIV Infections/prevention & control*
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Prevalence
		                        			
		                        		
		                        	
            
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