Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

AIM:To investigate the effects of ginkgetin on neurological deficit and angiogenesis induced by cerebral ischemia/reperfusion(I/R)and its underlying mechanism.METHODS:Sixty SD rats were randomly allocated into three groups:sham group,I/R model group,and ginkgetin(40 mg/kg)treatment(I/R+ginkgetin)group,with twenty rats in each group.The middle cerebral artery occlusion/reperfusion(MCAO/R)rat model was employed to simulate cere-bral I/R,and ginkgetin was administered continuously for 7 days following reperfusion.The cerebral infarction volume was quantified using TTC staining.Neuronal density in the ischemic penumbra was assessed through Nissl staining and immu-nohistochemistry for neuron-specific nuclear protein(NeuN).Microvessel density and angiogenesis in the ischemic pen-umbra of each group were analyzed using CD31 labeling and BrdU/von willebrand factor(vWF)double labeling immuno-fluorescence staining.Western blot analysis was performed to determine the levels of heat shock protein 70(HSP70),vas-cular endothelial growth factor(VEGF),and hypoxia inducible factor-1α(HIF-1α)in the ischemic penumbra.RE-SULTS:Compared with the I/R model group,the cerebral infarction volume was significantly reduced in ginkgetin treat-ment group(P<0.01),the number of neurons,the microvessel density,angiogenesis and the expression levels of HIF-1α,VEGF,and HSP70 in the ischemic penumbra were significantly increased(P<0.01).CONCLUSION:Ginkgetin exhibits the potential to augment angiogenesis and facilitate neurological function recovery in MCAO rats,while concur-rently upregulating the expression of HSP70,VEGF,and HIF-1α within the ischemic penumbra.

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.

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.

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.

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.

Objective:To observe any effect of intermittent theta burst stimulation (iTBS) on the spatially-delayed responses of working memory using cynomolgus macaques.Methods:The working memory of six male cynomolgus macaques (8-9 years old) was trained using a spatially-delayed response task. They were then randomly divided into an iTBS group and a control group, each of 3. The iTBS group was given iTBS at an intensity of 35% of the maximum output, with 2 seconds of stimulation followed by 8 seconds of rest with trains of 50Hz bursts repeated at a frequency of 5Hz over a period of 192 seconds once daily for 5 days, while the control group was given sham iTBS. Before and after the 5 days, the body weight and working memory of each animal were evaluated. The total number of effective feeding episodes, and of effective feeding episodes with short and long delay periods were recorded.Results:There was no significant change in the average body weight of either group before and after the modeling and iTBS intervention. After the intervention the number of total effective feeding cases and those with a short delay period were both significantly higher in the iTBS group than in the control group. However, no significant inter-group differences in the effective feeding cases with a long delay period were observed.Conclusions:iTBS is effective in improving the spatially-delayed responses of working memory, at least in cynomolgus macaques.

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.

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.

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.