Single-cell transcriptome analysis reveals the regulatory effects of artesunate on splenic immune cells in polymicrobial sepsis / 药物分析学报

Sepsis is characterized by a severe and life-threatening host immune response to polymicrobial infection accompanied by organ dysfunction.Studies on the therapeutic effect and mechanism of immunomod-ulatory drugs on the sepsis-induced hyperinflammatory or immunosuppression states of various im-mune cells remain limited.This study aimed to investigate the protective effects and underlying mechanism of artesunate(ART)on the splenic microenvironment of cecal ligation and puncture-induced sepsis model mice using single-cell RNA sequencing(scRNA-seq)and experimental validations.The scRNA-seq analysis revealed that ART inhibited the activation of pro-inflammatory macrophages recruited during sepsis.ART could restore neutrophils'chemotaxis and immune function in the septic spleen.It inhibited the activation of T regulatory cells but promoted the cytotoxic function of natural killer cells during sepsis.ART also promoted the differentiation and activity of splenic B cells in mice with sepsis.These results indicated that ART could alleviate the inflammatory and/or immunosuppressive states of various immune cells involved in sepsis to balance the immune homeostasis within the host.Overall,this study provided a comprehensive investigation of the regulatory effect of ART on the splenic microenvironment in sepsis,thus contributing to the application of ART as adjunctive therapy for the clinical treatment of sepsis.

A single-cell landscape of triptolide-associated testicular toxicity in mice / 药物分析学报

Triptolide is a key active component of the widely used traditional Chinese herb medicine Tripterygium wilfordii Hook.F.Although triptolide exerts multiple biological activities and shows promising efficacy in treating inflammatory-related diseases,its well-known safety issues,especially reproductive toxicity has aroused concerns.However,a comprehensive dissection of triptolide-associated testicular toxicity at single cell resolution is still lacking.Here,we observed testicular toxicity after 14 days of triptolide exposure,and then constructed a single-cell transcriptome map of 59,127 cells in mouse testes upon triptolide-treatment.We identified triptolide-associated shared and cell-type specific differentially expressed genes,enriched pathways,and ligand-receptor pairs in different cell types of mouse testes.In addition to the loss of germ cells,our results revealed increased macrophages and the inflammatory response in triptolide-treated mouse testes,suggesting a critical role of inflammation in triptolide-induced testicular injury.We also found increased reactive oxygen species(ROS)signaling and down-regulated pathways associated with spermatid development in somatic cells,especially Leydig and Sertoli cells,in triptolide-treated mice,indicating that dysregulation of these signaling pathways may contribute to triptolide-induced testicular toxicity.Overall,our high-resolution single-cell landscape offers comprehensive information regarding triptolide-associated gene expression profiles in major cell types of mouse testes at single cell resolution,providing an invaluable resource for understanding the underlying mechanism of triptolide-associated testicular injury and additional discoveries of therapeutic targets of triptolide-induced male reproductive toxicity.

Single-cell transcriptome analysis uncovers underlying mechanisms of acute liver injury induced by tripterygium glycosides tablet in mice / 药物分析学报

Tripterygium glycosides tablet(TGT),the classical commercial drug of Tripterygium wilfordii Hook.F.has been effectively used in the treatment of rheumatoid arthritis,nephrotic syndrome,leprosy,Behcet's syndrome,leprosy reaction and autoimmune hepatitis.However,due to its narrow and limited treatment window,TGT-induced organ toxicity(among which liver injury accounts for about 40％of clinical reports)has gained increasing attention.The present study aimed to clarify the cellular and molecular events underlying TGT-induced acute liver injury using single-cell RNA sequencing(scRNA-seq)technology.The TGT-induced acute liver injury mouse model was constructed through short-term TGT exposure and further verified by hematoxylin-eosin staining and liver function-related serum indicators,including alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase and total bilirubin.Using the mouse model,we identified 15 specific subtypes of cells in the liver tissue,including endothelial cells,hepatocytes,cholangiocytes,and hepatic stellate cells.Further analysis indicated that TGT caused a significant inflammatory response in liver endothelial cells at different spatial locations;led to marked inflammatory response,apoptosis and fatty acid metabolism dysfunction in hepatocytes;activated he-patic stellate cells;brought about the activation,inflammation,and phagocytosis of liver capsular macrophages cells;resulted in immune dysfunction of liver lymphocytes;disturbed the intercellular crosstalk in liver microenvironment by regulating various signaling pathways.Thus,these findings elaborate the mechanism underlying TGT-induced acute liver injury,provide new insights into the safe and rational applications in the clinic,and complement the identification of new biomarkers and ther-apeutic targets for liver protection.

Surveys on management of neonatal respiratory distress syndrome in ten hospitals in Northwest China in 2016 and 2021 / 中华围产医学杂志

Objective:To analyze the status of neonatal respiratory distress syndrome (RDS) management in 10 hospitals in Northwest China over the past five years and to investigate the strategies for improving the prevention and treatment of RDS.Methods:This retrospective study involved premature infants with RDS who were admitted to the neonatal intensive care units (NICU) of 10 hospitals (six in Shaanxi Province, three in Gansu Province, and one in Xinjiang Uygur Autonomous Region) of the Northwest China Neonatal Collaborative Group within 3 d after birth from January 1 to December 31, 2016, and from January 1 to December 31, 2021. Basic information, perinatal condition, treatment approaches, complications, and prognosis of the patients were compared. T-test, rank sum, and Chi-square tests were used for statistical analysis. Result:(1) This study enrolled 322 premature infants with RDS in 2016 and 349 in 2021. Premature infants at the gestational age of 30 to 33 weeks were mainly affected, and the majority were male [64.3% (207/322) and 57.3% (200/349)]. The average maternal age in 2021 was older than that in 2016 [(30.6±4.8) years vs (28.6±5.4) years, t=24.02, P<0.001], and the proportion of women at advanced maternal age was also higher in 2021 [19.2% (67/349) vs 12.4% (40/322), χ2=4.18, P<0.05]. (2) The proportions of pregnancies conceived with assisted reproductive technologies [11.7% (41/349) vs 1.9% (6/322), χ2=25.12], underwent routine prenatal examinations [58.5% (204/349) vs 30.4% (98/322), χ2=53.33], exposed to steroids [62.2% (217/349) vs 28.6% (92/322), χ2=82.58] and delivered by cesarean section or elective cesarean section [73.6% (257/349) vs 51.6% (166/322), χ2=35.06; 24.1% (84/349) vs 6.5% (21/322), χ2=39.07], as well as the ratio of cesarean scar pregnancy [7.4% (26/349) vs 3.4% (11/322), χ2=5.23] were all higher in 2021 than those in 2016 (all P<0.05). Moreover, the incidence of fetal distress [30.1% (105/349) vs 20.2% (65/322), χ2=8.68], gestational hypertension [24.6% (86/349) vs 13.0% (42/322), χ2=14.59], premature rupture of membranes [16.0% (56/349) vs 10.2% (33/322), χ2=4.89], meconium-stained amniotic fluid [12.6% (44/349) vs 5.6% (18/322), χ2=9.83], placental abruption [10.3% (36/349) vs 5.3% (17/322), χ2=5.84], gestational diabetes mellitus [10.3% (36/349) vs 1.6%(5/322), χ2=22.41], chorioamnionitis [4.6%(16/349) vs 0.9% (3/322), χ2=8.12], thyroid dysfunction [4.3% (15/349) vs 0.6% (2/322), χ2=7.88] and heart disease [4.3% (15/349) vs 0.3% (1/322), χ2=9.17] were higher in 2021 than in 2016 (all P<0.05). (3) In 2021, the rate of pulmonary surfactant (PS) usage, the dosage of porcine PS, and the proportion of bovine PS usage were all significantly higher than those in 2016 [73.6% (257/349) vs 67.1% (216/322), χ2=11.62; (178.5±38.0) mg/kg vs (165.2±42.8) mg/kg, t=7.85; 47.9% (123/257) vs 19.4% (42/216), χ2=41.72; all P<0.01]. No significant difference in the incidence of intubation-surfactant-extubation (INSURE), early PS administration (≤2 h after birth), or the arterial blood gas values before and after PS treatment was found between the cases enrolled in 2021 and 2016. The duration of antibiotic treatment [7.0 d (5.0-14.0 d) vs 5.0 d (1.0-8.0 d), Z=7.55] and assisted ventilation [144 h (81-264 h) vs 73 h (47-134 h), Z=8.20] and the median hospital stay [24 d(14-42 d) vs 16 d (10-25 d), Z=6.74] were significantly longer in 2021 than in 2016 (all P<0.01). More patients required nasal intermittent positive pressure ventilation [29.6% (100/338) vs 1.0% (3/306), χ2=97.81] and conventional ventilation [42.6% (144/338) vs 30.1% (92/306), χ2=10.87] in 2021 as compared with those five years ago (both P<0.01). (4) In 2021, the incidence of patent ductus arteriosus [15.5% (54/349) vs 6.2% (20/322), χ2=63.40], bronchopulmonary dysplasia [9.2% (32/349) vs 2.8% (9/322), χ2=12.88], persistent pulmonary hypertension [5.4% (19/349) vs 0.6% (2/322), χ2=12.85], periventricular leukomalacia [4.3% (15/349) vs 1.2% (4/322), χ2=7.52] and pneumothorax [3.4% (12/349) vs 0.3% (1/322), χ2=9.68] increased as compared with those in 2016 (all P<0.05), while the incidence of nosocomial infection decreased significantly [7.4% (26/349) vs 19.6% (63/322), χ2=21.37, P<0.001]. (5) The cure rate of premature infants with RDS was 70.8% (247/349) in 2021, which was significantly higher than that in 2016 [56.2% (181/322), χ2=15.37, P<0.001]. Moreover, the rate of withdrawing treatment and the total mortality rate was lower in 2021 than in 2016 [7.7% (27/349) vs 14.3% (46/322), χ2=7.41; in-hospital: 1.4% (5/349) vs 5.6% (18/322), χ2=8.74; out of hospital: 8.3% (29/349) vs 13.7% (44/322), χ2=4.96; all P<0.05]. Conclusions:The clinical management of RDS in premature infants in the involved hospitals has been improved. However, there is room for improvement in prenatal examinations.

Risk factors affecting coagulation function in premature infants at birth / 中国新生儿科杂志

Objective To study the coagulation function of premature infants at birth and the associated risk factors.Method From January 2014 to January 2018,a prospective study was conducted on preterm infants born in obstetrics department of our hospital.According to the gestational age,these infants are assigned into early preterm group,moderate preterm group and late preterm group.The prothrombin time (PT),activated partial thromboplastin time (APTF),fibrinogen (FIB) and thrombin time (TT) were measured using automatic coagulation analyzer.The possible risk factors affecting the coagulation function in each group were analyzed.Result A total of 795 preterm infants were studied including 93 in the early preterm group,151 in the moderate preterm group and 551 in the late preterm group.In the early preterm group,infants with premature rupture of membranes (PROM) had increased FIB,shortened TT,and infants with severe asphyxia had prolonged PT,and the differences were statistically significant (P ＜ 0.05).In the moderate preterm group,infants with PROM had significantly prolonged APTT (P ＜ 0.05).In the late preterm group,PT and TT were prolonged and FIB was decreased in male infants.Infants with PROM have increased FIB;PT was prolonged among infants with severe asphyxia (P ＜ 0.05).Multivariate linear regression analysis showed that neonatal asphyxia,weight and gender were the main factors affecting PT (P ＜ 0.05),gestational age was the main risk factor affecting APTT (P ＜ 0.05),PROM,gestational age,weight and gender were the main factors affecting FIB (P ＜ 0.05),and neonatal asphyxia was the main factor affecting TT (P ＜ 0.05).Conclusion The coagulation function of premature infants is affected by many factors including gender,gestational age,weight,asphyxia,PROM,and maternal complications.Coagulation function should be monitored in preterm infants with severe asphyxia.

Clinical effect of Yiqi-Huoxue decoctions combined with exercise rehabilitation training for the patients with chronic heart failure / 国际中医中药杂志

Objective To study the clinical effect of Yiqi-Huoxue decoctions combined with exercise rehabilitation training for patients with chronic heart failure and its effect on serum MMP-1, TIMP-1. Methods A total of 120 patients with chronic heart failure in our hospital from February 2016 to January 2017 were enrolled in this study. The subjects were randomly divided into the control group (n=60) and the treatment group (n=60). The control group were treated with conventional treatment, and the treatment group were treated with Yiqi-Huoxue decoctions combined with exercise training. The two groups were treated for 30 days. The clinical effects of the two groups after treatment were compared. The SBP, DBP, LVESD, LVEDD and LVEF of the two groups before and after treatment were compared. The serum MMP-1, TIMP-1 of the two groups before and after treatment were compared. The adverse reaction rates of the two groups during treatment were compared. Results The total effect rate of the treatment group was 93.3％ (56/60), significantly higher than 73.3％ (44/60)of the control group (χ2=8.640, P=0.003). After treatment, the SBP (125.17 ± 13.51 mmHg vs. 140.82 ± 14.63 mmHg, t=6.087), DBP (74.36 ± 10.31 mmHg vs. 86.29 ± 11.17 mmHg, t=6.079), LVESD (41.11 ± 3.23 mm vs. 49.69 ± 4.99 mm, t=11.181) and LVEDD (57.36 ± 3.28 mm vs. 64.16 ± 4.05 mm, t=10.107) of the treatment group were significantly lower than those of the control group (P<0.05). The LVEF (69.82％ ± 5.05％ vs. 51.40％ ± 4.11％, t=21.913) of the treatment group was significantly higher than the control group (P<0.05). After treatment, the serum MMP-1 (141.52 ± 15.22 μg/L vs. 164.10 ± 16.18 μg/L, t=7.874) of the treatment group were significantly lower than those of the control group (P<0.05), and the serum TIMP-1 (3.98 ± 0.22 μg/L vs. 3.51 ± 0.16 μg/L, t=13.383) of the treatment group were significantly higher than those of the control group (P<0.05). There was no significant differences of the adverse reaction rates of the two groups during treatment (χ2=0.152, P=0.697). Conclusions The Yiqi-Huoxue decoctions combined with exercise rehabilitation training for patients with chronic heart failure showed good efficacy and low incidence of adverse reactions, can significantly improve cardiac function and the cardiac remodeling.

A comparative study on the coagulation indices of newborns of different gestational ages on the first day of birth / 中国新生儿科杂志

Objective To study the differences of coagulation indices on the first day of birth in newborns with different gestational ages.Method Premature infants born in our hospital between January 2014 and December 2015 were enrolled in this study as the observational group,and they were divided into early preterm group,moderate preterm group,and late preterm group according to their gestational ages.Healthy full-term infants born during the same period were selected as the control group by 3:1 The clinicaldata and coagulation indices of the infants and their mothers in each group were compared.Result There were 44,50,71,and 52 cases in the early preterm,moderate preterm,late preterm,and control group,respectively.The prothrombin time (PT),activated partial thromboplastin time (APTT),and thrombin time (TT) of the premature infants in the early preterm group,moderate preterm group,and late preterm group were all longer than those of the control group [PT:(16.1 ±4.3) s,(16.8 ±4.9) s,(15.8 ±4.8) s,vs.(13.0±1.3)s;APTT:(88.3±38.1) s,(93.5±37.7) s,(91.0±32.3) s,vs.(66.0±17.8) s;TT:(25.4 ±4.6) s,(25.1 ±5.5) s,(25.0 ±3.3) s,vs.(24.0 ±3.3) s;all P＜0.05].The fibrinogen level of the premature newborns in three groups were all lower than that of the full-term infants in the control group [(1.11 ± 0.46) g/L,(1.12 ± 0.44) g/L,(1.12 ± 0.45) g/L vs.(1.28 ± 0.37) g/L,P ＜ 0.05].The differences of all the indices among the three groups of premature infants were all not statistically significant (P ＞ 0.05).The comparison of the coagulation indices of the mothers of the newborns from all four groups showed no significant differences (P ＞ 0.05).Conclusion Compared with full-term infants,preterm infants showed significantly poorer coagulation function on the first day of birth.However,there were no significant differences in coagulation indices among preterm infants of different gestational ages.

Clinical effects of Huayutongmai decoction in treating patients with carotid atherosclerotic plaques / 中国基层医药

Objective To investigate the clinical effects of Huayutongmai decoction in treating patients with carotid atherosclerotic plaques .Methods Prospectively analyzed 102 cases with carotid atherosclerotic plaques were divided into the control group and observation group according to random number table method ,51 cases were in each group.The patients in the control group were given the Simvastatin Tablet only ,and the patients in the observation group were given the treatment of Huayutongmai decoction .The CAD,IMT,volume of plaque,PI and lipid levels were detected.The clinical efficacy and adverse reaction were observed after treatment of three months .Results After treatment of three months,the CAD,IMT,volume of plaque,PI(t=0.97,1.83,0.65,1.43) and levels of lipid(TG, TC,HDL-C,LDL-C and AI,t=1.86,1.88,1.42,1.85,1.14) of the observation group were better than those of the control group,but with no significant(all P>0.05).Conclusion Huayutongmai decoction in treating patients with carotid atherosclerotic plaques has better clinical efficacy ,can improve lipid metabolism ,eliminate and stabilize CAS to some extent ,which is worthy of clinical application .

Effects of Shouwu-Yizhi capsule on learning and memory and the expressions of presenilin 1,β-amyloid precursor protein mRNAs in the hippocampus following cerebral ischemia reperfusion in rats / 国际中医中药杂志

Objective To investigate the effects of Shouwu-Yizhi capsule on learning and memory, and the expressions of presenilin 1(PS1),β-amyloid precursor protein (APP) mRNAs in the hippocampus following cerebral ischemia reperfusion in rats. Methods Sprague–Dawley rats were randomly divided into a Shouwu-Yizhi group, a piracetam group, a model group, and a sham operation group with 20 rats in each group. Focal cerebral ischemia reperfusion model was induced by middle cerebral artery occlusion for 2 hours. Seven days after ischemia reperfusion, the rats in the Shouwu-Yizhi and piracetam groups were administered intragastrically Shouwu-Yizhi solution (52 mg/ml) and piracetam solution (28 mg/ml) for 28 days, both in dose of 1 ml/(100 g?d) for 28 days;and the rats in the model and sham operation groups were given intragastrically equivalent volumes of normal saline. Learning and memory were tested using the Morris water maze, and the expressions of PS1 and APP mRNAs were measured using real-time quantitative fluorescent PCR. Results Water maze test showed that the escape latency (12.98±0.70s vs. 9.43±0.78s) was significantly shorter, and the frequency of crossing platform (5.08±0.39 vs. 7.62±0.43) significantly lower in the model groupthan those in the sham operation group; the escape latency (9.77±0.58s vs. 12.98±0.70s) was significantly shorter and the frequency of crossing platform (7.40±0.44 vs. 5.08±0.39) significantly lower in the Shouwu-Yizhi group than those in the model group(all P<0.01). The expressions of PS1 (0.99±0.01 vs. 1.08± 0.03)and APP (1.06±0.03 vs. 1.12±0.04) mRNAs in the hippocampus in the Shouwu-Yizhi group were significantly decreased than those in the model group (P<0.05 or 0.01). Conclusion Shouwu-Yizhi capsule may inhibit the expressions of PS1 and APP mRNAs in the hippocampus, and improve the learning and memory following cerebral ischemia reperfusion in rats.

Clinical Study on Unstable Angina Pectoris Treated by Wenxintang / 中国中医药信息杂志

Objective To observe the clinical therapeutic effect of Wenxintang in treating unstable angina pectoris. Methods Sixty patients of Yangqikuixu, Tanyuzuluo type suffered with unstable angina pectoris were randomly divided into two groups. 30 patients in the control group were treated with IsMo-20, Metoprolol and Aspirin, while another 30 patients in the treated group were treated with Wenxintang include the three medicines above. Each group was observed for 4 weeks respectively. Results The total effective rate in relieving angina in the treated group and the control group was 86.67% and 66.67% respectively, that in improving ECG changes was 69.23% and 47.82% respectively, the difference of the two parameters between the two groups was significant (P