Recent advances in drug screening methods of SARS-CoV-2 spike protein / 药学学报

The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a serious impact on global public health and the economy. SARS-CoV-2 infiltrates host cells via its surface spike protein, which binds to angiotensin-converting enzyme 2 on the host cell membrane. As a result, small molecules targeting spike protein have emerged as a hotspot in anti-SARS-CoV-2 drug research. Activity screening is an important step in seeking small molecule drugs. Therefore, this article aims to review the biological activity evaluation methods of small molecule inhibitors targeting SARS-CoV-2 spike protein, with the goal of laying the foundation for the discovery of new anti-SARS-CoV-2 drugs.

The preliminary therapeutic effect of endoscopic ultrasound-guided tissue adhesive injection with the assistance of metal clips in treatment of cirrhotic patients with gastric varices and gastric-renal shunt / 临床肝胆病杂志

ObjectiveTo investigate the safety and efficacy of endoscopic ultrasound-guided tissue adhesive injection with the assistance of metal clips in the treatment of cirrhotic patients with gastric varices and gastric-renal shunt （GRS）. MethodsThe patients who attended Beijing Ditan Hospital， Capital Medical University， due to liver cirrhosis and gastric varices from February to June 2023 were enrolled， and all patients were confirmed to have GRS and received endoscopic ultrasound-guided tissue adhesive injection with the assistance of metal clips. The primary evaluation index was alleviation or disappearance of varicose veins after surgery， and the secondary evaluation indices were surgical completion and complications. ResultsA total of 11 patients were enrolled in this study， among whom there were 7 male patients and 4 female patients， with a median age of 55 years. Of all patients， 1 had Child class A liver function， 7 had Child class B liver function， and 3 had Child class C liver function. The maximum （median） diameter of the shunt was 8 mm， and the minimum （median） diameter of the shunt was 4 mm. The median blood flow velocity of the target vessel was 11 cm/s before treatment and 5 cm/s after occlusion with metal clips. The median amount of tissue adhesive injected was 2 mL， and the amount of lauromacrogol used was 1 mL. Disappearance of blood flow signals was observed in all patients after surgery （100%）， and the success rate of surgery was 100%. No patient experienced rebleeding after follow-up for 6 weeks. Gastroscopy at 1 month after surgery showed that gastric varices were eradicated or almost disappeared in 9 patients and were alleviated in 2 patients. ConclusionEndoscopic ultrasound-guided tissue adhesive injection with the assistance of metal clips is a feasible， safe， and effective treatment method for cirrhotic patients with gastric varices and GRS.

Risk Assessment of the Onset of Sleep-related Painful Erection / 中山大学学报(医学科学版)

ObjectiveSleep-related painful erections （SRPE） is a rare sleep disorder characterized by repeated awakening due to painful interruptions of penile erections during nighttime sleep， and its etiology is currently unclear. The purpose of this study is to explore the impact of potential risk factors on the incidence of SRPE. MethodsInformation was collected through questionnaires administered to patients who presented at the urology department and suffered from SRPE or did not suffer from SRPE. A total of 290 participants completed the study， including 145 controls and 145 cases. Logistic regression analysis was used to assess the impact of age， occupation， sleep initiation time per night， frequency of sexual intercourse per week， psychological status， erectile dysfunction， chronic prostatitis， prostate enlargement， lumbar spine disease， central nervous system disease， hypertension， diabetes and family history on the onset of SRPE. ResultsSingle-factor logistic regression analysis found that a history of chronic prostatitis， intellectual labor occupation， central nervous system disease， late sleep onset， frequency of sexual activity， and anxiety status might be related to the onset of SRPE. After incorporating these factors into a multivariate regression analysis model， it was found that having sexual activity ≥2 times/week （OR 95%CI = 0.326（0.179，0.592） and late sleep onset （after 24：00） （OR 95%CI = 0.494（0.265，0.918）might be protective factors for SRPE， while a history of chronic prostatitis（OR 95%CI = 3.779（2.082，6.859） might be a risk factor for SRPE. However， there was no significant statistical difference in the impact of central nervous system diseases and occupation on multivariate analysis. ConclusionChronic prostatitis and anxiety status may be independent risk factors for SRPE； having sexual activity ≥2 times/week and delaying sleep time appropriately may be independent protective factors.

Analysis of HPV infection and subtypes in 60 354 patients in Changsha / 中华检验医学杂志

Objective:Analysis of subtype distribution characteristics of human papillomavirus (HPV) infection, pathological findings of HPV-positive patients operated colposcopy and cervical histopathological examination in Changsha from 2020 to 2022.Methods:Retrospective analysis of HPV infection status of 60 354 patients was treated in the First Affiliated Hospital of Hunan University of Chinese Medicine from Jan. 2020 to Oct. 2022. They were divided into<25 years old group (3 250 cases), 25-34 years old group (19 406 cases), 35-44 years old group (17 297 cases), 45-54 years old group (13 104 cases), 55-64 years old group (4 793 cases) and≥65 years old group (2 504 cases). Cervical exfoliated cells were collected from women and specimen of lesion site were collected from men. HPV genotyping detection used polymerase chain reaction (PCR) and flow fluorescence hybridization, which could detect 27 HPV genotypes. Analyze the distribution of HPV subtypes in patients of different age groups and different treatment departments. Analyze the relationship between the infection of HPV subtypes and the outcome of 224 patients with HPV positive who also underwent colposcopy and cervical histopathology. Pearson correlation test was used for correlation analysis, and two-tailed P<0.05 was statistically significant; Pearson chi-square test or continuous correction chi-square test was used to compare the rates between groups, and two-tailed P<0.05 was statistically significant; Chi-square split test was used to compare multiple sample rates. The standard test was corrected according to the number of groups and then compared. The difference was statistically significant when the two-tailed P value was less than the corrected standard test. Results:The overall positive rate of HPV was 16.4% (9 909/60 354). Among all HPV positive patients, affection of single type HPV accounted for 75.5% (7 479/9 909) and affection of multi-type HPV accounted for 24.5% (2 430/9 909). The top six HPV types with infection rates from high to low were: HPV52 22.8% (2 256/9 909), HPV58 11.1% (1 097/9 909), HPV53 10.5% (1 045/9 909), HPV16 9.0% (890/9 909), HPV61 7.8% (774/9 909) and HPV6 7.6% (750/9 909). The difference of overall infection rate between different age groups was statistically significant (χ 2=536.90, P<0.001). The HPV infection rate was the highest in the<25 years old group, 30.1% (978/3 250), and it is higher than the age groups of 25-34 years old, 15.6% (3 035/19 406), group of 35-44 years old, 14.2% (2 464/17 297), group of 45-54 years old, 16.1% (2 115/13 104), group of 55-64 years old, 19.1% (915/4 793) and group of≥65 years old, 16.1% (402/2 504), with statistical significance( P<0.001 respectively). The most common types of HPV infection were type 6, 16.7% (378/2 266) and type 11, 10.5% (239/2 266) in dermatology clinics. The positive rate of HPV16 accounted for 12/17 in cervical intraepithelial neoplasia (CIN) 3 and cervical cancer cases, it was significantly higher than that in the inflammatory cases, 25.0% (35/140) and CIN1 cases, 23.0% (11/48), the statistical values were χ 2=15.02, P<0.001 and χ 2=12.48, P<0.001, respectively, all of which were statistically significant. Conclusions:HPV infection rate is highest in young people under 25 years old. Low-risk HPV6 and 11 are the main types of skin and venereal diseases. Among the total cases, high-risk HPV52, 58 and 53 are the most common types of infection with women in Changsha. However, high-grade cervical intraepithelial neoplasia and cervical cancer are more closely related to HPV16 infection.

Advances in the establishment and evaluation of animal models of secondary lymphedema / 中华显微外科杂志

Secondary lymphedema is a chronic progressive disease caused by the obstruction of lymphatic reflux, which leads to a series of secondary affection. There is no cure at present. Exploring the pathogenesis and treatment of lymphedema is based on animal models that mimic the pathophysiology of chronic lymphedema in humans. Currently, there are many known animal models of lymphedema, such as the limb lymphedema model of mice, dogs and other animals, and the rabbit ear lymphedema model. But most of them cannot induce the persistent and stable lymphedema temporarily, which lead to a deadlock in the related research progress. Therefore, it is necessary to improve and even create new animal models of lymphedema. This paper summarises the progress of relevant literature and provides references for further improving the establishment of a lymphedema animal model. It also summarise existing methods for evaluating lymphedema or lymphatic vessel function to provide an evaluation tool for modified or new animal models.

Current Status of Off-label Use of Denosumab in Bone Tumor and Bone Diseases / 肿瘤防治研究

Denosumab is a monoclonal antibody against the receptor activator of nuclear factor-κB (RANK) ligand (RANKL) that significantly inhibits osteoclast activity and has been approved to treat osteoporosis, giant cell tumor of bone, and prophylactic as well as therapeutic entities for bone metastasis. However, the imbalance of RANKL/RANK/OPG has also been implicated in the pathogenesis of several other rare bone diseases and tumor-like disorders, including aneurysmal bone cyst, fibrous dysplasia of bone, and Langerhans cell histiocytosis. Nevertheless, there have been various clinical reports although these diseases have not been approved for indications. The review aims to summarize the available evidence for the off-label use of denosumab in metabolic bone diseases and tumor-like disorders and provide a reference for clinical diagnosis and treatment.

Bile duct ligation differently regulates protein expressions of organic cation transporters in intestine, liver and kidney of rats through activation of farnesoid X receptor by cholate and bilirubin

Body is equipped with organic cation transporters (OCTs). These OCTs mediate drug transport and are also involved in some disease process. We aimed to investigate whether liver failure alters intestinal, hepatic and renal Oct expressions using bile duct ligation (BDL) rats. Pharmacokinetic analysis demonstrates that BDL decreases plasma metformin exposure, associated with decreased intestinal absorption and increased urinary excretion. Western blot shows that BDL significantly downregulates intestinal Oct2 and hepatic Oct1 but upregulates renal and hepatic Oct2. In vitro cell experiments show that chenodeoxycholic acid (CDCA), bilirubin and farnesoid X receptor (FXR) agonist GW4064 increase OCT2/Oct2 but decrease OCT1/Oct1, which are remarkably attenuated by glycine-β-muricholic acid and silencing FXR. Significantly lowered intestinal CDCA and increased plasma bilirubin levels contribute to different Octs regulation by BDL, which are confirmed using CDCA-treated and bilirubin-treated rats. A disease-based physiologically based pharmacokinetic model characterizing intestinal, hepatic and renal Octs was successfully developed to predict metformin pharmacokinetics in rats. In conclusion, BDL remarkably downregulates expressions of intestinal Oct2 and hepatic Oct1 protein while upregulates expressions of renal and hepatic Oct2 protein in rats, finally, decreasing plasma exposure and impairing hypoglycemic effects of metformin. BDL differently regulates Oct expressions via Fxr activation by CDCA and bilirubin.

Dihydrotanshinone I preconditions myocardium against ischemic injury via PKM2 glutathionylation sensitive to ROS

Ischemic preconditioning (IPC) is a potential intervention known to protect the heart against ischemia/reperfusion injury, but its role in the no-reflow phenomenon that follows reperfusion is unclear. Dihydrotanshinone I (DT) is a natural compound and this study illustrates its role in cardiac ischemic injury from the aspect of IPC. Pretreatment with DT induced modest ROS production and protected cardiomyocytes against oxygen and glucose deprivation (OGD), but the protection was prevented by a ROS scavenger. In addition, DT administration protected the heart against isoprenaline challenge. Mechanistically, PKM2 reacted to transient ROS via oxidization at Cys423/Cys424, leading to glutathionylation and nuclear translocation in dimer form. In the nucleus, PKM2 served as a co-factor to promote HIF-1α-dependent gene induction, contributing to adaptive responses. In mice subjected to permanent coronary ligation, cardiac-specific knockdown of Pkm2 blocked DT-mediated preconditioning protection, which was rescued by overexpression of wild-type Pkm2, rather than Cys423/424-mutated Pkm2. In conclusion, PKM2 is sensitive to oxidation, and subsequent glutathionylation promotes its nuclear translocation. Although IPC has been viewed as a protective means against reperfusion injury, our study reveals its potential role in protection of the heart from no-reflow ischemia.

Monoterpenes from an aqueous extract of the Angelica sinensis root head / 药学学报

Eleven monoterpenes including seven new chemical structures or new natural products covering two pairs of scalemic enantiomers, together with four known analogues, were isolated from an aqueous extract of the Angelica sinensis root head (Guitou) by separation techniques of column chromatography over macroporous adsorbent resin, MCI resin, silica gel, Sephadex LH-20, and Toyopearl HW-40C, together with preparative thin-layer chromatography as well as reversed phase and chiral HPLC. Their structures were determined by spectroscopic data analysis, combined with theoretic calculation of electronic circular dichroism (ECD) spectra and single crystal X-ray diffraction. The new structures or new natural products named (+)-/(-)-angelinones A and B [(+)-/(-)-1 and (+)-/(-)-2], angelinones C and D (3 and 4), and angelinol A (5), respectively, while the known analogues were 6β,9-dihydroxy-(+)-α-pinene (6), 1,1,5-trimethyl-2-hydroxymethyl-cyclohexa-2,5-dien-4-one (7), jasminol E (8), and (+)-trans-sobrerol (9). All the isolates were reported in this plant for the first time, except for the previously reported 6 from an ethanol extract of the aerial parts of A. sinensis, of which the structure was confirmed by X-ray crystallography in this study.

Searching for potential biomarkers reflecting early injury and progressive of podocytes in nephropathy based on cellular metabolomics combined with ROC analysis / 药学学报

The pathogenesis of the nephrotic syndrome is complex and the pathological types are diverse, so the minor symptoms in its early phases are difficult to detect. Renal biopsy is the gold indicator for the diagnosis of renal pathology and progression, but poor patient compliance shows, and the optimal treatment time is often delayed. Therefore, the discovery of biomarkers for early diagnosis and disease progression monitoring is of great clinical significance. In this study, doxorubicin-injured podocyte models were used to simulate human kidney disease at different stages of progression. LC-MS-based metabolomic technology combined with statistical methods was used to screen and identify the potential biomarkers associated with early injury or progression of podocytes. The results of cell viability, apoptosis tests and podocyte structural protein analysis showed that the model was successfully constructed, and the degree of podocyte injury was significantly different between the two modeling methods. According to VIP > 1 and P < 0.05 based on the orthogonal partial least squares discriminant analysis (OPLS-DA) model, nine differential metabolites reflecting early podocyte injury and twelve differential metabolites reflecting the injury progression were screened, respectively. ROC analysis was adopted to focus on the potential biomarkers that can reflecting the early podocyte injury including L-tryptophan, guanosine triphosphate (GTP), 5′-thymidylic acid (dTMP) and thymidine, and the biomarkers reflecting the injury progression of podocytes composed of L-phenylalanine, L-tyrosine acid, uridine 5′-diphosphate (UDP) and guanosine 5′-diphosphate (GDP) AUC > 0.85. It indicated that these eight metabolites may have high sensitivity and diagnostic ability. This study provides a reference for the research on biomarkers of progressive diseases.

Characterization of the anti-fatigue effect of Astragali Radix from the Shanxi Hengshan area and its association with taurine metabolism based on 1H NMR metabolomic technology combined with network pharmacology / 药学学报

The objective of this work was to evaluate the anti-fatigue efficacy of Astragali Radix (AR) from the Shanxi Hengshan area and to reveal possible mechanisms by which it relieves fatigue. Efficacy differences between Guangling (GL) and Hunyuan (HY) AR preparations were compared and evaluated, and an 1H NMR metabolomic technique combined with statistical methods was used to identify the metabolites in different groups of mouse gastrocnemius muscle tissues. The differential metabolites after AR treatments were identified according to VIP and P values and the upstream targets were predicted with the help of Metscape. Cytoscape software was utilized to construct a network map of AR potential anti-fatigue targets. Key differential metabolites were identified based on shared targets and entered into the Metaboanalyst website for pathway enrichment analysis, which led to the preliminary elucidation of the molecular mechanisms. The results showed that intervention with AR can significantly improve the swimming-to-exhaustion time, increase liver glycogen, and reduce urea-nitrogen levels in mice. The difference between GL and HY ARs was relatively small, indicating that the quality of AR produced in the Hengshan area is consistent and stable. The metabolic fingerprints of mouse gastrocnemius muscle tissue extracts were composed of 34 metabolites, and the statistical results showed that 19 differential metabolites were significantly reversed after the Hengshan AR intervention. We found that the anti-fatigue effects of AR in the Shanxi Hengshan area were mainly associated with taurine and hypotaurine metabolism through regulation of GAD1, based on network pharmacological analysis. In conclusion, 1H NMR metabolomic techniques were combined with network pharmacology to compare and evaluate the quality of Hengshan ARs, and further associate the fatigue relieve with the regulation of taurine metabolism. This provides a theoretical basis for the resource utilization of Hengshan ARs and the development of anti-fatigue-related products. The animal experiments in this study followed the regulations of the Animal Ethics Committee of Shanxi University and passed the ethical review of animal experiments (Approval No. SXULL2021028).

Effect of comprehensive intervention on the incidence of lactation galactostasis during breasefeeding of pregnant and delivery women / 上海预防医学

ObjectiveTo observe the effect of comprehensive intervention on the incidence of lactation galactostasis in communities from the perspective of preventive medicine， so as to prevent the occurrence of the mammary ducts obstruction disease. MethodsA total of 400 women in the early stage of pregnancy were selected from four communities. Those in two communities were set up as the intervention group. Comprehensive intervention for the prevention and treatment of mammary ducts obstruction disease during pregnancy and "Six-step recanalization manual therapy" practical guidance were conducted on the intervention group. The pregnant women from the other two communities were the control group， who received no intervention or guidance training. The two groups were followed up at 1 month， 3 months and 5 months postpartum， and the occurrence of mammary ducts obstruction disease was investigated and interventions were carried out. ResultsThe incidence of galactostasis in the intervention group was 26.0%， 10.6% and 5.1%， respectively at 1， 3 and 5 months after delivery， and the incidence of galactostasis in the control group was 38.0%， 22.2% and 8.3%， respectively. The incidence of galactostasis at 1 month and3 months after delivery was statistically different （P<0.05）， while the incidence of galactostasis 5 months after delivery was not statistically different （P>0.05）. The protection rates of comprehensive intervention on galactostasis were 31.58%， 52.25% and 38.55%， respectively. ConclusionPublicity and education work of prevention and control of the mammary ducts obstruction disease and "Six-step recanalization manual therapy" practical guidance can effectively reduce the occurrence of plugged mammary ducts， and therefore should be promoted.

Visual trephine arthroplasty assisted percutaneous transforaminal endoscopic discectomy for lumbar disc herniation / 中国骨伤

OBJECTIVE@#To compare the clinical efficacy between visual trephine arthroplasty assisted percutaneous transforaminal endoscopic discectomy (VPTED) and traditional percutaneous transforaminal endoscopic discectomy(PTED) in the treatment of lumbar disc herniation.@*METHODS@#The clinical data of 60 patients with lumbar disc herniation admitted from June 2019 to December, 2020 was retrospectively analyzed. There were 38 males and 22 females, aged from 26 to 58 years old with an average of (43.63±8.48) years, 47 cases were on L4,5 segment and 13 cases were on L5S1 segment. Among them, 32 were treated with VPTED (group A) and 28 were treated with traditional PTED (group B). The general conditions of all the patients were recorded, including intraoperative fluoroscopy times, operation time, hospital stay and surgical complications during follow-up. The arthroplasty area ratio was observed by sagittal CT at the middle level of the intervertebral foramen. Visual analogue scale (VAS) and Japanese Orthopaedic Association (JOA) score of low back pain, Oswestry disability index (ODI) were used to evaluate the clinical efficacy between two groups.@*RESULTS@#All patients were followed up from 9 to 15 months with an average of (12.10±1.16) months. There was no statistical difference of preoperative general data between two groups. The operation time, fluoroscopy times and hospital stay were (70.47±5.87) min, (13.66±1.34) times and (6.31±0.69) d in group A, and (90.71±7.66) min, (22.82±2.48) times and (6.54±0.92) d in group B. The operation time and intraoperative fluoroscopy times in group A were lower than those in group B(P<0.05). There was no significant difference in hospital stay between two groups (P>0.05). No obvious surgical complications were found during the follow-up in both groups. The arthroplasty area ratio in group A was (29.72±2.84)% and (29.57±2.20)% in group B, respectively, with no significant difference (P>0.05). There was no significant difference in VAS, ODI and JOA score between two groups before operation and at the final follow-up(P>0.05), but the final follow-up was significantly improved(P<0.05).@*CONCLUSION@#The two surgical methods have definite clinical efficacy in the treatment of lumbar disc herniation. Visual trephine arthroplasty assisted percutaneous transforaminal endoscopic discectomy has the advantages of high efficiency and rapidity when establishing the channel, and can significantly reduce the operation time and intraoperative fluoroscopy times.

Autophagy-regulated strategies in pre-clinical studies of inflammatory bowel disease / 药学学报

Inflammatory bowel disease (IBD) is a group of chronic idiopathic colorectal inflammatory diseases with a progressive and unpredictable course, including ulcerative colitis (UC) and Crohn's disease (CD). Abnormal intestinal inflammation and immune response contribute to the pathogenesis of IBD. Autophagy as an essential catabolic process in cells, has been demonstrated to have associations with a variety of inflammatory diseases including IBD. Here, we review the relationship between autophagy dysfunction and the process of IBD. The progress of several autophagy regulators for intestinal epithelial cells and macrophages is highlighted (inflammasome inhibitors, intestinal flora regulators, and other signal regulators) in the current studies on IBD.

Establishment and evaluation of in vitro galectin-3 inhibitor screening model / 药学学报

Galectin-3 (Gal-3) belongs to the galectin family and is specific in binding β-galactoside. Through its C-terminal domain, Gal-3 binds to the galactoside group of the glycosylated insulin receptor (IR) and inhibits IR signaling pathway, which leads to the insulin resistance. Thus, Gal-3 is a potential therapeutic target for the treatment of insulin resistance and type 2 diabetes. Here we report a simple Gal-3 screening model based on the property that Gal-3 binds to the galactoside. We expressed and purified human Gal-3 in Escherichia coli (E.coli), and labeled it with fluorescein isothiocyanate (FITC) in vitro. After incubating FITC labeled Gal-3 (Gal-3-FITC) with PANC-1 cells, which express glycosylated membrane protein, PANC-1 cells started to show green fluorescent signal due to the Gal-3-FITC binding to the glycosylated membrane protein. Gal-3 inhibitor disrupts the binding of Gal-3-FITC and PANC1 cells, subsequently leads to the decrease of the fluorescent signal in PANC-1 cells. We can evaluate the inhibitory efficiency of Gal-3 inhibitors through measurement of the fluorescent signal. Further studies show this model is simple, stable, and repeatable with a Z' factor between 0.7 and 0.85. In sum, we have successfully established an in vitro high-throughput screening model for Gal-3 inhibitors.

Spatial language understanding and expression in children with autism: a study of “(go/come) to” sentence in Chinese / 中国康复理论与实践

Objective To investigate the characteristics of spatial orientation language comprehension and expression behavior ofchildren with autism. MethodsA three-ladder test was designed to test the comprehension and expression of "(go/come) to" sentences, including general subject-predicate sentences, conjunctive-predicate sentences with displacement purposes, and conjunctive-predicate sentences with displacement modes. March to June, 2022, the test was conducted on 17 children with autism from a special education school and 17 healthy children matched the scores of Peabody Picture Vocabulary Test-Chinese revised from a kindergarten. The typical errors were analyzed for children with autism. ResultsThe main effects of sentence ladders (F > 3.718, P < 0.05) and children groups (F > 8.782, P < 0.001) were significant on comprehension and expression of sentences, while the performance was poor for the complex sentences and for the children with autism. The common types of errors in expression were missing components, mixed sentences, autonomous sentences, inaccurate wording, inconsistent content, blending errors and non-response. The numbers and the distribution of error types were quite different from the children with autism to the healthy children. ConclusionChildren with autism are more difficult to understand and express "(go/come) to" sentences, mainly manifested in a higher error frequency and more kinds of error.

Thirty-day outcomes of in-hospital multi-vessel versus culprit-only revascularization strategy for ST-segment elevation myocardial infarction with multivessel coronary disease / 老年心脏病学杂志（英文版）

BACKGROUND@#Many studies have demonstrated the benefit of complete multivessel revascularization versus culprit-only intervention in patients of ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease. However, only a few single-center retrospective studies were performed on small Chinese cohorts. Our study aims to demonstrate the advantage of multivessel percutaneous intervention (PCI) strategy on 30-day in-hospital outcomes to patients with STEMI and multivessel disease in larger Chinese population.@*METHODS@#From the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome (CCC-ACS) project, 5935 patients with STEMI and multivessel disease undergoing PCI and hospitalized for fewer than 30 days were analyzed. After 5: 1 propensity score matching, 3577 patients with culprit-only PCI and 877 with in-hospital multivessel PCI were included. The primary outcome was major adverse cardiovascular and cerebrovascular event (MACCE), defined as a composite of myocardial infarction, all-cause death, stent thrombosis, heart failure, and stroke.@*RESULTS@#Multivariable logistic regression analysis revealed that in-hospital multivessel PCI was associated with lower risk of 30-day MACCE (adjusted OR = 0.75, 95% CI: 0.57-0.98, P = 0.032) than culprit-only PCI and conferred no increased risk of all-cause death, myocardial infarction, stent thrombosis, stroke, or bleeding. Subgroup analysis showed that MACCE reduction was observed more often from patients with trans-femoral access (OR = 0.34, 95% CI: 0.15-0.74) than with trans-radial access (OR = 0.87, 95% CI: 0.66-1.16, P for interaction = 0.017).@*CONCLUSIONS@#The in-hospital multivessel PCI strategy was associated with a lower risk of 30-day MACCE than culprit-only PCI in patients with STEMI and multivessel coronary artery disease.

Cross-sectional study on the sleep status and risk factors for sleep problems in infants and young children in Jilin Province / 中国当代儿科杂志

OBJECTIVES@#To explore the sleep status and risk factors for sleep problems in infants and young children in Jilin Province.@*METHODS@#A total of 1 080 healthy infants and young children aged 0-3 years from eight prefecture-level cities and one autonomous prefecture in Jilin Province were selected as subjects. A self-designed questionnaire was used to collect the general information of the subjects, and the Brief Infant Sleep Questionnaire was used to understand the sleep status of the subjects. Multivariate logistic regression analysis was used to analyze the risk factors for sleep problems.@*RESULTS@#The total detection rate of sleep problems in the infants and young children was 38.24% (413/1 080). The total sleep time in the 4-11 month, 12-24 month, and 25-36 month age groups was higher than the recommended total sleep time (P<0.05). Multivariate logistic regression analysis showed that full-term birth, higher educational level of the main caregiver, and higher daytime activity intensity were protective factors for sleep problems in the infants and young children (P<0.05), while lower frequency of vitamin D supplementation, frequent night feeding, and maternal snoring were risk factors for sleep problems (P<0.05).@*CONCLUSIONS@#The total sleep time of infants and young children over 4 months old in Jilin Province is higher than the recommended total sleep time, but the prevalence rate of sleep problems is higher. The occurrence of sleep problems is related to various factors. Strengthening follow-up on preterm infants, providing education on infant sleep knowledge to primary caregivers, and regularly supplementing with vitamin D can be beneficial in reducing sleep problems in infants and young children.

Danhong Injection Up-regulates miR-125b in Endothelial Exosomes and Attenuates Apoptosis in Post-Infarction Myocardium / 中国结合医学杂志

OBJECTIVE@#To investigate the involvement of endothelial cells (ECs)-derived exosomes in the anti-apoptotic effect of Danhong Injection (DHI) and the mechanism of DHI-induced exosomal protection against postinfarction myocardial apoptosis.@*METHODS@#A mouse permanent myocardial infarction (MI) model was established, followed by a 14-day daily treatment with DHI, DHI plus GW4869 (an exosomal inhibitor), or saline. Phosphate-buffered saline (PBS)-induced ECs-derived exosomes were isolated, analyzed by miRNA microarray and validated by droplet digital polymerase chain reaction (ddPCR). The exosomes induced by DHI (DHI-exo), PBS (PBS-exo), or DHI+GW4869 (GW-exo) were isolated and injected into the peri-infarct zone following MI. The protective effects of DHI and DHI-exo on MI hearts were measured by echocardiography, Masson's trichrome staining, and TUNEL apoptosis assay. The Western blotting and quantitative reverse transcription PCR (qRT-PCR) were used to evaluate the expression levels of miR-125b/p53-mediated pathway components, including miR-125b, p53, Bak, Bax, and caspase-3 activities.@*RESULTS@#DHI significantly improved cardiac function and reduced infarct size in MI mice (P<0.01), which was abolished by the GW4869 intervention. DHI promoted the exosomal secretion in ECs (P<0.01). According to the results of exosomal miRNA microarray assay, 30 differentially expressed miRNAs in the DHI-exo were identified (28 up-regulated miRNAs and 2 down-regulated miRNAs). Among them, DHI significantly elevated miR-125b level in DHI-exo and DHI-treated ECs, a recognized apoptotic inhibitor impeding p53 signaling (P<0.05). Remarkably, treatment with DHI and DHI-exo attenuated apoptosis, elevated miR-125b expression level, inhibited capsase-3 activity, and down-regulated the expression levels of proapoptotic effectors (p53, Bak, and Bax) in post-MI hearts, whereas these effects were blocked by GW4869 (P<0.05 or P<0.01).@*CONCLUSION@#DHI and DHI-induced exosomes inhibited apoptosis, promoted the miR-125b expression level, and regulated the p53 apoptotic pathway in post-infarction myocardium.

Bloodletting Acupuncture at Jing-Well Points on Hand Induced Autophagy to Alleviate Brain Injury in Acute Altitude Hypoxic Rats by Activating PINK1/Parkin Pathway / 中国结合医学杂志

OBJECTIVE@#To explore the protective effect of bloodletting acupuncture at twelve Jing-well points on hand (BAJP) on acute hypobaric hypoxia (AHH)-induced brain injury in rats and its possible mechanisms.@*METHODS@#Seventy-five Sprague Dawley rats were divided into 5 groups by a random number table (n=15), including control, model, BAJP, BAJP+3-methyladenine (3-MA), and bloodletting acupuncture at non-acupoint (BANA, tail tip blooding) groups. After 7-day pre-treatment, AHH models were established using hypobaric oxygen chambers. The levels of S100B, glial fibrillary acidic protein (GFAP), superoxide dismutase (SOD), and malondialdehyde (MDA) in serum were measured by enzyme-linked immunosorbent assay. Hematoxylin-eosin staining and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling method were used to assess hippocampal histopathology and apoptosis. Transmission electron microscopy assay was used to observe mitochondrial damage and autophagosomes in hippocampal tissues. Flow cytometry was used to detect mitochondrial membrane potential (MMP). The mitochondrial respiratory chain complexes I, III and IV activities and ATPase in hippocampal tissue were evaluated, respectively. Western blot analysis was used to detect the protein expressions of Beclin1, autophagy protein 5 (ATG5), microtubule-associated protein 1 light chain 3 beta (LC3B), phosphatase and tensin homolog induced kinase 1 (PINK1), and Parkin in hippocampal tissues. The mRNA expressions of Beclin1, ATG5 and LC3-II were analyzed by quantitative real-time polymerase chain reaction.@*RESULTS@#BAJP treatment reduced hippocampal tissue injury and inhibited hippocampal cell apoptosis in AHH rats. BAJP reduced oxidative stress by decreasing S100B, GFAP and MDA levels and increasing SOD level in the serum of AHH rats (P<0.05 or P<0.01). Then, BAJP increased MMP, the mitochondrial respiratory chain complexes I, III and IV activities, and the mitochondrial ATPase activity in AHH rats (all P<0.01). BAJP improved mitochondrial swelling and increased the autophagosome number in hippocampal tissue of AHH rats. Moreover, BAJP treatment increased the protein and mRNA expressions of Beclin1 and ATG5 and LC3-II/LC3-I ratio in AHH rats (all P<0.01) and activated the PINK1/Parkin pathway (P<0.01). Finally, 3-MA attenuated the therapeutic effect of BAJP on AHH rats (P<0.05 or P<0.01).@*CONCLUSION@#BAJP was an effective treatment for AHH-induced brain injury, and the mechanism might be through reducing hippocampal tissue injury via increasing the PINK1/Parkin pathway and enhancement of mitochondrial autophagy.