NME3 is a gatekeeper for DRP1-dependent mitophagy in hypoxia.

NME3 is a member of the nucleoside diphosphate kinase (NDPK) family localized on the mitochondrial outer membrane (MOM). Here, we report a role of NME3 in hypoxia-induced mitophagy dependent on its active site phosphohistidine but not the NDPK function. Mice carrying a knock-in mutation in the Nme3 gene disrupting NME3 active site histidine phosphorylation are vulnerable to ischemia/reperfusion-induced infarction and develop abnormalities in cerebellar function. Our mechanistic analysis reveals that hypoxia-induced phosphatidic acid (PA) on mitochondria is essential for mitophagy and the interaction of DRP1 with NME3. The PA binding function of MOM-localized NME3 is required for hypoxia-induced mitophagy. Further investigation demonstrates that the interaction with active NME3 prevents DRP1 susceptibility to MUL1-mediated ubiquitination, thereby allowing a sufficient amount of active DRP1 to mediate mitophagy. Furthermore, MUL1 overexpression suppresses hypoxia-induced mitophagy, which is reversed by co-expression of ubiquitin-resistant DRP1 mutant or histidine phosphorylatable NME3. Thus, the site-specific interaction with active NME3 provides DRP1 a microenvironment for stabilization to proceed the segregation process in mitophagy.

Bushen Yugu Formula （补肾愈骨方） for Postoperative Functional Rehabilitation of Patients with Chronic Lateral Ankle Instability with Syndrome of Liver-Kidney Insufficiency and Sinews-Vessels Deprived of Nourishment：A Retrospective Cohort Study / 中医杂志

ObjectiveTo investigate the effectiveness and safety of Bushen Yugu Formula （补肾愈骨方） promoting postoperative functional rehabilitation of patients with chronic lateral ankle instability （CLAI） with syndrome of liver-kidney insufficiency and sinews-vessels deprived of nourishment. MethodsClinical data were retrospectively collected from 40 patients with CLAI with syndrome of liver-kidney insufficiency and sinews-vessels deprived of nou-rishment who underwent external ankle ligament repair surgery. They were divided into 20 cases each in the treatment group and control group according to whether or not they took Bushen Yugu Formula； patients in the control group underwent postoperative functional rehabilitation， while patients in the treatment group took Bushen Yugu Formula in the 3rd and 4th postoperative weeks combined with the rehabilitation. The American Orthopaedic Foot and Ankle Society （AOFAS） scores， the flexion/extension and internal/external rotation， the imaging scores of the ankle joint on the operated side and the traditional Chinese medicine （TCM） syndrome scores were recorded in the preoperative and 3-month postoperative， respectively. The patients' liver and kidney functions were tested in the preoperative and 4-month postoperative， and adverse events during treatment were recorded. ResultsCompared with the preoperative period， the AOFAS scores were higher and the TCM syndrome scores were lower in both groups 3 months after surgery （P＜0.01）， and the ankle internal and external rotation mobility and imaging scores were higher in the treatment group （P＜0.05 or P＜0.01）， and ankle flexion/extension mobility was lower in the control group （P＜0.05）. At 3 months after surgery， the AOFAS score was higher in the treatment group than in the control group， and the TCM syndrome score was lower than in the control group （P＜0.05 or P＜0.01）. Two cases of gastrointestinal reactions were reported in the treatment group， which relieved on their own after stopping the formula， and no abnormality was observed in liver and kidney function indexes. ConclusionBushen Yugu Formula can promote functional rehabilitation of ankle joint and improve clinical symptoms in CLAI patients with syndrome of liver-kidney insufficiency and sinews-vessels deprived of nourishment， and it shows a good safety.

Analysis of Cardiac Events and the Subsequent Impact for Geriatric Patients Undergoing Hip Fracture Surgeries.

Perioperative complications, particularly cardiac events, compromised surgical outcomes for geriatric patients. This retrospective study intended to investigate the occurrence and subsequent impact of cardiac events for geriatric patients undergoing hip fracture surgeries. We collected 607 patients undergoing hip fracture surgeries from January 2017 to December 2022 that received transthoracic echocardiography (TTE) pre-operatively to screen for cardiac abnormalities. Except for demographic characteristics, the researchers recorded fracture type, surgical method, American Society of Anesthesiologists (ASA) class, anesthesia type, perioperative cardiac events, and in-hospital mortality. Statistical analysis was performed using SPSS 22.0 statistics software. Throughout the whole course of the study, 16 postoperative cardiac events occurred. The cardiac events included ten arrhythmias, three acute myocardial infarctions, two heart failures, and one sudden death. Notably, 12 of 16 patients with cardiac events presented with abnormal findings on TTE, except 15 of them had a history of cardiac disease. This study disclosed 93.7% of cardiac events developed in patients with a history of cardiovascular disease. Among patients that experienced cardiac events, 75% of patients had abnormal echocardiographic findings. Pre-operative transthoracic echocardiography deserves a recommendation for geriatric patients with histories of cardiac diseases undergoing hip fracture surgeries to detect the risk of developing cardiac events earlier.

Antioxidant, anti-inflammatory, and anticancer function of Engleromyces goetzei Henn aqueous extract on human intestinal Caco-2 cells treated with t-BHP.

High body mass index (high BMI, obesity) is a serious public health problem, and "obesity-induced oxidative stress, inflammation, and cancer" have become modern epidemic diseases. We carried out this study to explore a functional beverage that may protect against obesity-induced diseases. The Engleromyces goetzei Henn herbal tea is such a candidate. For this study, we carried out LC-MS analysis of E. goetzei Henn aqueous extract (EgH-AE); then used the Caco-2 cell line for the model cells and treated the cells with t-BHP to form an oxidative stress system. An MTT assay was used for testing the biocompatibility and cytoprotective effects; reactive oxygen species and malondialdehyde determination was used for evaluating the antioxidative stress effect; TNF-α and IL-1ß were used for observing the anti-inflammatory effect, and 8-OHdG for monitoring anticancer activity. The results of this study demonstrate that the EgH-AE has very good biocompatibility with the Caco-2 cell line and has good cytoprotective, antioxidant, anti-inflammatory, and anticancer properties. It is clear that EgH-AE, a kind of ancient herbal tea, may be used to develop a functional beverage that can be given to people with a high BMI to protect against obesity-induced diseases.

Immobilizing engineered Escherichia coli cells into zeolitic imidazolate framework 8 for efficient biosynthesis of Ala-Gln / 生物工程学报

The α-amino acid ester acyltransferase (SAET) from Sphingobacterium siyangensis is one of the enzymes with the highest catalytic ability for the biosynthesis of l-alanyl-l-glutamine (Ala-Gln) with unprotected l-alanine methylester and l-glutamine. To improve the catalytic performance of SAET, a one-step method was used to rapidly prepare the immobilized cells (SAET@ZIF-8) in the aqueous system. The engineered Escherichia coli (E. coli) expressing SAET was encapsulated into the imidazole framework structure of metal organic zeolite (ZIF-8). Subsequently, the obtained SAET@ZIF-8 was characterized, and the catalytic activity, reusability and storage stability were also investigated. Results showed that the morphology of the prepared SAET@ZIF-8 nanoparticles was basically the same as that of the standard ZIF-8 materials reported in literature, and the introduction of cells did not significantly change the morphology of ZIF-8. After repeated use for 7 times, SAET@ZIF-8 could still retain 67% of the initial catalytic activity. Maintained at room temperature for 4 days, 50% of the original catalytic activity of SAET@ZIF-8 could be retained, indicating that SAET@ZIF-8 has good stability for reuse and storage. When used in the biosynthesis of Ala-Gln, the final concentration of Ala-Gln reached 62.83 mmol/L (13.65 g/L) after 30 min, the yield reached 0.455 g/(L·min), and the conversion rate relative to glutamine was 62.83%. All these results suggested that the preparation of SAET@ZIF-8 is an efficient strategy for the biosynthesis of Ala-Gln.

Baicalin Ameliorates Corticosterone-Induced Depression by Promoting Neurodevelopment of Hippocampal via mTOR/GSK3β Pathway / 中国结合医学杂志

OBJECTIVE@#To investigate the role of hippocampal neurodevelopment in the antidepressant effect of baicalin.@*METHODS@#Forty male Institute of Cancer Research mice were divided into control, corticosterone (CORT, 40 mg/kg), CORT+baicalin-L (25 mg/kg), CORT+baicalin-H (50 mg/kg), and CORT+fluoxetine (10 mg/kg) groups according to a random number table. An animal model of depression was established by chronic CORT exposure. Behavioral tests were used to assess the reliability of depression model and the antidepressant effect of baicalin. In addition, Nissl staining and immunofluorescence were used to evaluate the effect of baicalin on hippocampal neurodevelopment in mice. The protein and mRNA expression levels of neurodevelopment-related factors were detected by Western blot analysis and real-time polymerase chain reaction, respectively.@*RESULTS@#Baicalin significantly ameliorated the depressive-like behavior of mice resulting from CORT exposure and promoted the development of dentate gyrus in hippocampus, thereby reversing the depressive-like pathological changes in hippocampal neurons caused by CORT neurotoxicity. Moreover, baicalin significantly decreased the protein and mRNA expression levels of glycogen synthase kinase 3β (GSK3β), and upregulated the expression levels of cell cycle protein D1, p-mammalian target of rapamycin (mTOR), doublecortin, and brain-derived neurotrophic factor (all P<0.01). There were no significant differences between baicalin and fluoxetine groups (P>0.05).@*CONCLUSION@#Baicalin can promote the development of hippocampal neurons via mTOR/GSK3β signaling pathway, thus protect mice against CORT-induced neurotoxicity and play an antidepressant role.

Analysis of the death characteristics of inpatients in a provincial tertiary hospital over a decade / 中国中西医结合急救杂志

Objective To collect the data of hospitalized death cases in a provincial grade A tertiary general hospital,analysis the characteristics,changing trends,rescue conditions and related influencing factors of inpatient death cases,and provide a reference for the hospital's death case management and improvement of medical quality.Methods The gender,age,inpatient department,length of hospitalization,cause of death,rescue measures,sequential organ failure assessment(SOFA)score,and the date of death cases in a grade A tertiary general hospital from January 1,2012,to December 31,2022,were collected from the hospital medical record database.The characteristics of death cases were then statistically summarized through data aggregation.Spearman's rank correlation coefficient was used to analyze the relationship between the two research variables,while multivariate Logistic regression analysis was employed to explore the relevant factors affecting the implementation of rescue measures when death events occur in hospitalized patients,and draw the receiver operator characteristic curve(ROC curve)to analyze the relevant factors affecting the implementation of cardiopulmonary resuscitation in the event of death in hospitalized patients.Results ① The in-hospital mortality rate of inpatients in this hospital in the past 10 years was 0.26％,the mortality rate of males was significantly higher than that of females[0.32％(1 959/607 170)vs.0.19％(1 021/549 802),χ2 = 210.615,P<0.01],the mortality rate of hospitalized patients increased with age(r = 0.860,P = 0.037),and elderly patients>65 years old were the main group of hospital deaths;②The top 5 main causes of death among patients in this hospital were tumors,circulatory system diseases,respiratory system diseases,digestive system diseases and the symptoms,signs,clinical and laboratory abnormal findings,and those who died due to these 5 types of diseases accounted for 82.05％(2 445/2 980)of the total number of deaths;③Before the death event,the electrocardiogram(ECG)monitoring rate of inpatients in this hospital was 77.99％,the epinephrine usage rate was 83.46％,the endotracheal intubation rate was 57.55％,the cardiopulmonary resuscitation implementation rate was 44.93％,and the defibrillation rate was 12.85％.The epinephrine usage rate[86.17％(1 688/1 959)vs.78.26％(799/1 021)],the endotracheal intubation rate[59.37％(1 163/1 959)vs.54.06％(552/1 021)]and the cardiopulmonary resuscitation implementation rate[46.30％(907/1 959)vs.42.31％(432/1 021)]of male patients was significantly higher than that of female patients(all P<0.05);the cardiopulmonary resuscitation implementation rate for patients who died over 65 years old was significantly lower than those in other age groups[43.25％(734/1 697)vs.47.16％(605/1 283),P<0.05],before the death of inpatients in the surgical department,the ECG monitoring rate[68.63％(641/934)vs.82.26％(1 679/2 041)],the epinephrine usage rate[75.48％(705/934)vs.87.21％(1 780/2 041)]and the cardiopulmonary resuscitation implementation rate[31.16％(291/934)vs.51.34％(1 048/2 041)]were significantly lower than those in other department(all P<0.05).Patients who died from tumors had the lowest implementation rate of rescue measures when the death event occurred.Except for tumor patients,the ECG monitoring rate[68.33％(233/341)vs.93.07％(1 356/1 457)],the epinephrine usage rate[86.22％(294/341)vs.95.47％(1 391/1 457)],the endotracheal intubation rate[60.12％(205/341)vs.71.31％(1 039/1 457)],the cardiopulmonary resuscitation rate[40.18％(137/341)vs.55.66％(811/1 457)]and the defibrillation rate[7.92％(27/341)vs.19.42％(283/1 457)]of patients who died due to digestive system diseases were significantly lower than those who died due to circulatory diseases,respiratory diseases,and symptoms,signs,clinical and laboratory abnormalities(all P<0.05);④Multivariate Logistic regression analysis showed that urban household registration and SOFA score≥14 points before death were independent factors influencing the likelihood of cardiopulmonary resuscitation being performed in patients with severe death[odds ratio(OR)and 95％confidence interval(95％ CI)were 6.731(1.891-23.958)and 10.023(3.169-31.704),P values are 0.003 and<0.001 respectively];⑤ROC curve analysis shows that urban household registration,SOFA score≥14 points before death and their combination had a certain predictive value for cardiopulmonary resuscitation in hospitalized patients with digestive diseases(all P<0.05),and the combined value was higher,the area under ROC curve(AUC)= 0.840,95％ CI was 0.742-0.934.sensitivity was 82.76％,specificity was 75.51％,positive predictive value was 78.18％,and negative predictive value was 73.91％.Conclusions Hospitals should specifically strengthen the medical quality management of inpatient death cases,enhance the early warning system for high-risk patients,and consistently standardize the rescue measures and procedures for inpatients.Additionally,hospitals should prioritize the care of elderly and male patients with circulatory and respiratory-related critical illnesses,they should also strive to improve their ability to identify and treat critically ill surgical patients,as well as enhance their expertise in managing severe digestive system diseases.

The relationship between gut microbiota characteristics and peripheral blood lymphocytes in patients with primary Sj?gren′s syndrome / 中华风湿病学杂志

Objective:By detecting the species and distribution of fecal flora in patients with pSS, we investigated the relationship between the alterations of the gut microbiome and its metabolic characteristics with peripheral lymphocyte subsets, and their potential role in the occurrence and development of pSS.Methods:A total of 101 pSS patients who were hospitalized in the department of rheumatology of the Second Hospital of Shanxi Medical University, and 101 age and sex-matched healthy control (HC) in the health check-up center of Shanxi Provincial People′s Hospital from January 2019 to January 2020 were enrolled for 16s rDNA-Amplicon sequencing. The statistical analysis was performed in R software 4.0.3. The Alpha diversity were compared by Wilcoxon test, and Beta diversity were compared by ANOSIM analysis between pSS patients and HC. The difference flora was analyzed by t test. The levels of peripheral lymphocyte subsets pSS patients were detected by flow cytometry. Then the relationship between characteristic flora and clinical indicators such as lymphocyte subsets, erythrocyte sedimentation rate, C-reactive protein, unstimulated whole saliva and stimulated whole saliva were analyzed using Pearson′s correlation analysis. Results:Patients with pSS exhibited a significant reduction in the richness (Chao1, ACE) and diversity (Shannon,Simpson) of gut microbiota compared with those of HC, and there was statistical significant difference in gut microbiota composition (ANOSIM, r=0.09, P=0.001). At the phylum level, the relative abundance of Firmicutes decreased and the relative abundance of Proteobacteria increased in pSS patients. At the genus level, the proportion of Escherichia-shigella ( P<0.001), Lactobacillus ( P<0.001), Bifidobacterium ( P<0.001), Subdoligranulum ( P<0.001), Alistipes ( P<0.001) and [ Eubacterium]_ coprostanoligenes (P=0.002) were increased. The proportion of Faecalibacterium ( P<0.001), Prevotella ( P<0.001), Roseburia ( P<0.001), Megamonas ( P<0.001), Agathobacter ( P<0.001), Lachnospira ( P<0.001), Lachnospira_NK4A136 ( P=0.006), [ Eubacterium] _eligens ( P<0.001) were significantly reduced. PICRUST analysis showed significant enrichment of amino acid metabolism taurine and hypotaurine metabolism ( P<0.001), fatty acid metabolism such as propanoate metabolism ( P<0.001), glutathione metabolism ( P=0.002), lipoic acid metabolism ( P=0.003), lipopolysaccharide biosynthesis and biosynthesis of siderophore group nonribosomal peptides ( P=0.005) and Aminobenzoate degradation ( P=0.002) in patients with pSS. The Pearson correlation results showed that there were significant different in the abundances of the key gut microbiota between the HC and pSS groups, and they were closely related to unstimulated whole saliva, the absolute number of Treg cells and Th17 cells. Conclusion:The dysbiosis and metabolism changes of the pSS intestinal microbiota may contribute to immune homeostasis imbalance, and may be involved in the occurrence and development of pSS.

Effect of family management intervention on disease management ability of parents and family function with coronary artery lesions in Kawasaki disease / 中国实用护理杂志

Objective:To investigate the intervention effects and influencing factors of family management intervention on parents' disease management ability, family function of children with coronary artery lesions in Kawasaki disease.Methods:This was a quasi experimental study. Conveniently, 88 parents of children with Kawasaki disease coronary artery lesions from the Children's Hospital of Chongqing Medical University from March 2020 to June 2021 were selected for the study, and they were divided into the control group and the intervention group according to the order of the first consultation with 44 cases in each group. In the control group, conventional care and health education were used, while in the intervention group, a 6-month family management intervention was implemented on the basis of the control group. Family Management Measure (FaMM), Family Assessment Device (FAD) were used to assess the parents' disease management ability, family function before and after the intervention, respectively.Results:A total of 88 study subjects completed the pre-intervention survey in this study, and a total of 79 study subjects were surveyed when they returned to the hospital for review at the end of 6 months of intervention, including 40 in the intervention group and 39 in the control group, with a missed rate of 10.23% (9/88). There was no significant difference in the score of FAD, FaMM, Kawasaki disease knowledge questionnaire before the intervention between the two groups ( P>0.05). The scores of FAD in the intervention group was (21.58 ± 4.60) points, which was lower than that in the control group (24.62 ± 5.28) points, and the difference was statistically significant ( t=2.73, P <0.05). The scores of FaMM in the intervention group was (46.83 ± 6.02) points, which was higher than that in the control group (42.72 ± 6.09) points, and the differences was statistically significant ( t=-3.01, P <0.05). The age of the child, and whether the child was an only child were the influencing factors of the difference in disease management ability, and the difference in the family function of the parents of the child, respectively (all P<0.05). Conclusions:Family management intervention can improve the disease management ability of the parents of children with coronary artery lesion, improve family function. In the future, targeted interventions can be conducted according to different ages of children, and different family members' composition in order to obtain better intervention effects.

Effect of wheat-grain moxibustion on Wnt/β-catenin signaling pathway in bone marrow cell in mice with bone marrow inhibition / 中国针灸

OBJECTIVE@#To observe the effect of wheat-grain moxibustion at "Dazhui" (GV 14), "Zusanli" (ST 36) and "Sanyinjiao" (SP 6) on Wnt/β-catenin signaling pathway in bone marrow cell in mice with bone marrow inhibition, and to explore the possible mechanism of wheat-grain moxibustion in treating bone marrow inhibition.@*METHODS@#Forty-five SPF male CD1(ICR) mice were randomly divided into a blank group, a model group and a wheat-grain moxibustion group, 15 mice in each group. The bone marrow inhibition model was established by intraperitoneal injection of 80 mg/kg of cyclophosphamide (CTX). The mice in the wheat-grain moxibustion group were treated with wheat-grain moxibustion at "Dazhui" (GV 14), "Zusanli" (ST 36) and "Sanyinjiao" (SP 6), 3 moxa cones per acupoint, 30 s per moxa cone, once a day, for 7 consecutive days. The white blood cell count (WBC) was measured before modeling, before intervention and 3, 5 d and 7 d into intervention. After intervention, the general situation of mice was observed; the number of nucleated cells in bone marrow was detected; the serum levels of interleukin-3 (IL-3), interleukin-6 (IL-6) and granulocyte macrophage colony stimulating factor (GM-CSF) were measured by ELISA; the protein and mRNA expression of β-catenin, cyclinD1 and C-Myc in bone marrow cells was measured by Western blot and real-time PCR method.@*RESULTS@#Compared with the blank group, the mice in the model group showed sluggish reaction, unstable gait, decreased body weight, and the WBC, number of nucleated cells in bone marrow as well as serum levels of IL-3, IL-6, GM-CSF were decreased (P<0.01), and the protein and mRNA expression of β-catenin, cyclinD1 and C-Myc was decreased (P<0.01). Compared with the model group, the mice in the wheat-grain moxibustion group showed better general condition, and WBC, the number of nucleated cells in bone marrow as well as serum levels of IL-3, IL-6, GM-CSF were increased (P<0.01, P<0.05), and the protein and mRNA expression of β-catenin, cyclinD1 and C-Myc was increased (P<0.05).@*CONCLUSION@#Wheat-grain moxibustion shows therapeutic effect on bone marrow inhibition, and its mechanism may be related to activating Wnt/β-catenin signaling pathway in bone marrow cells, improving bone medullary hematopoiesis microenvironment and promoting bone marrow cell proliferation.

A prospective cohort study of long-term fasting blood glucose variability and risk of mortality in patients with type 2 diabetes / 中华流行病学杂志

Objective: To investigate the association between long-term fasting blood glucose (FPG) variability and all-cause mortality in patients with type 2 diabetes. Methods: A total of 7 174 type 2 diabetic patients included in National Basic Public Health Service Program in Changshu of Jiangsu Province were recruited as participants. Long-term glucose variability was assessed using standard deviation (SD), coefficient of variation (CV), average real variability (ARV), and variability independent of the mean (VIM) across FPG measurements at the more than three visits. Death information were mainly obtained from the death registry system in Jiangsu. Then Cox proportional hazards regression models were used to estimate the associations of four variability indicators and all-cause mortality's hazard ratios (HRs) and their 95%CIs. Results: Among 55 058.50 person-years of the follow-up, the mean follow-up time was 7.67 years, and 898 deaths occurred during the follow-up period. After adjustment, compared with T1 group, the Cox regression model showed that HRs of T3 group in SD, CV, ARV and VIM were 1.24 (95%CI: 1.03-1.49), 1.20 (95%CI: 1.01-1.43), 1.28 (95%CI: 1.07-1.55) and 1.20 (95%CI:1.01-1.41), respectively. HRs of per 1 SD higher SD, CV, ARV and VIM were 1.13 (95%CI: 1.06-1.21), 1.08 (95%CI: 1.01-1.15), 1.05 (95%CI: 1.00-1.12) and 1.09 (95%CI: 1.02-1.16) for all-cause mortality, respectively. In the stratified analysis, age, gender, hypoglycemic agent and insulin uses had no effect on the above associations (all P for interaction >0.05). Conclusion: Long-term FPG glycemic variability was positively associated with the risk of all-cause mortality in type 2 diabetes patients.

Cyclopentadiene as a Multifunctional Reagent for Normal- and Inverse-Electron Demand Diels-Alder Bioconjugation.

Optimizing the Diels-Alder (DA) reaction for aqueous coupling has resulted in practical methods to link molecules such as drugs and diagnostic agents to proteins. Both normal electron demand (NED) and inverse electron demand (IED) DA coupling schemes have been employed, but neither mechanism entails a common multipurpose reactive group. This report focuses on expanding the bioconjugation toolbox for cyclopentadiene through the identification of reactive groups that couple through NED or IED mechanisms in aqueous solution. Dienophiles and tetrazine derivatives were screened for reactivity and selectivity toward antibodies bearing cyclopentadiene amino acids to yield bioconjugates. Twelve NED dienophiles and four tetrazine-based IED substrates were identified as capable of practical biocoupling. Furthermore, tetrazine ligation to cyclopentadiene occurred at a rate of 3.3 ± 0.5 M-1 s-1 and was capable of bioorthogonal transformations, as evidenced by the selective protein labeling in serum. Finally, an antibody-drug conjugate (ADC)-bearing monomethyl auristatin E was prepared via tetrazine conjugation to cyclopentadiene. The resulting ADC was stable and demonstrated potent activity in vitro. These findings expand the utility of cyclopentadiene as a tool to couple entities to proteins via dual DA addition mechanisms.

Does ultrasound education improve anatomy learning? Effects of the Parallel Ultrasound Hands-on (PUSH) undergraduate medicine course.

BACKGROUND: As ultrasound has become increasingly prominent in medicine, portable ultrasound is perceived as the visual stethoscope of the twenty-first century. Many studies have shown that exposing preclinical students to ultrasound training can increase their motivation and ultrasound competency. However, few studies have discussed the effect of ultrasound training on anatomy learning. METHOD: The Parallel Ultrasound Hands-on (PUSH) course was designed to investigate whether or not ultrasonography training affects anatomy knowledge acquisition. The PUSH course included anatomical structures located in the chest and abdomen (target anatomy) and was conducted in parallel to the compulsory gross anatomy course. Learners (n = 140) voluntarily participated in this elective course (learners in the course before the midterm examination (Group 1, n = 69), or after the midterm examination (Group 2, n = 71)). Anatomy examination scores (written and laboratory tests) were utilized to compare the effects of the PUSH course. RESULT: Group 1 obtained significantly higher written test scores on the midterm examination (mean difference [MD] = 1.5(7.6%), P = 0.014, Cohen's d = 0.43). There was no significant difference in the final examination scores between the two groups (Written Test: MD = 0.3(1.6%), P = 0.472). In Laboratory test, both mid-term (MD:0.7(2.8%), P = 0.308) and final examination (MD:0.3(1.5%), P = 0.592) showed no significant difference between two groups. Students provided positive feedback in overall learning self-efficacy after the PUSH course (Mean = 3.68, SD = ±0.56 on a 5-point Likert scale). Learning self-efficacy in the cognitive domain was significantly higher than that in the affective domain (MD = 0.58; P < 0.001) and psychomotor domain (MD = 0.12; P = 0.011). CONCLUSION: The PUSH course featured a hands-on learning design that empowered medical students to improve their anatomy learning.

The expression changes of lncRNA in patients with systemic lupus erythematosus and its correlation with regulatory T cells / 中华风湿病学杂志

Objective:To explore the link between the differentially expressed long non-coding RNAs (lncRNAs) and the number of regulatory T cells (Tregs) by detecting the lncRNAs expression profiles in patients with systemic lupus erythematosus (SLE), then analyze the correlation between Tregs and lncRNAs and the clinical features of SLE patients. We also predict the mechanism by which lncRNAs regulate the differentiation and development of Tregs, and provid new approach for the treatment of SLE.Methods:Peripheral blood of 9 active SLE patients was collected and mononuclear cells (PBMCs) were extracted. The lncRNAs expression profiles of PBMCs was analyzed by whole transcriptome sequencing. Nine healthy people served as controls to screen the differentially expressed lncRNAs, and to analyze the correlation between lncRNAs and Tregs number. Pearson test was used to analyze the correlation between lncRNA and the number of Tregs, and the correlation between Treg-associated lncRNAs and systemic lupus erythematosus disease activity index(SLEDAI) score, erythrocyte sedimentation rate (ESR), C3, C4 in SLE patients. The targeted genes of Treg asso-ciated lncRNAs were predicted with miRcode and Targetscan databases and co-expression network.Results:There were 240 differentially expressed lncRNAs in SLE patients compared with healthy controls, including 134 highly expressed lncRNAs ( P<0.05) and 106 low expressed lncRNAs ( P<0.05). The expression of ANKRD44-AS1 ( r=0.74, P=0.022), LINC00200 ( r=0.70, P=0.037), AP001363.2 ( r=0.78, P=0.014) and LINC02824 (r=0.79, P=0.011) were positively correlated with the number of Tregs, and the expression of AP000640.1 ( r=-0.72, P=0.028), AC124248.1 ( r=-0.77, P=0.016), LINC00482 ( r=-0.83, P=0.005) and MIR503HG ( r=-0.96, P<0.001) were negatively correlated with the number of Tregs. Among these eight Tregs associated lncRNAs, the expression of LINC00482 ( r=-0.73, P<0.001) and MIR503HG ( r=-0.76, P<0.001) were negatively correlated with C3. LINC00200, ANKRD44-AS1 and AP000640.1 related to Tregs regulated the expression of STAT5, PLD1, HOPX and RUNX3 through competitively binding of miRNA or transregulatory mechanism, thereby regulating the differentiation and development of Tregs. Conclusion:The lncRNAs expression profiles are changed in SLE patients, the differentially expressed lncRNAs are associated with abnormal number and function of Tregs in SLE patients, and Treg associated lncRNAs are associated with SLE disease activity, which may affect the expression of STAT5, PLD1, HOPX, RUNX3 and regulate Tregs function and participate in the pathogenesis and progression of SLE by competitively binding to miRNAs or trans-regulatory mechanism.

Clinical research progress of Traditional Chinese Medicine treating precancerous lesions of gastric cancer with syndrome differentiation / 国际中医中药杂志

Traditional Chinese Medicine (TCM) has certain advantages in the treatment of precancerous lesions of gastric cancer (PLGC) based on the holistic concept and the thought of syndrome differentiation. Currently, it is generally divided into 6 kinds of syndromes: liver and stomach qi stagnation syndrome, liver and stomach heat stagnation syndrome, spleen and stomach weakness syndrome (including spleen and stomach qi deficiency syndrome with coldness), spleen and stomach damp heat syndrome, stomach yin deficiency syndrome and blood stasis in stomach collateral syndrome. Clinically, the doctor should treat PLGC patients according to different syndrome types by using Chinese medicine prescription, which could improve the gastric mucosal pathological state, gastroscopy and clinical symptoms, to rehibit the development of precancerous lesions, reduce the incidence rate of gastric cancer. In the future, the doctors shouldreach the consensus of treating PLGC with TCM diagnosis, and focus on the research of TCM compounds or monomers with obvious curative effect, increase the times of follow-up, and evaluate the long-term curative effect.

Advanced progress of ex vivo biosensor assay in toxicological evaluation / 中华预防医学杂志

The ex vivo biosensor assay is developed to assess the health effects and toxicological mechanism of environmental pollutants with internal environment homeostasis changes by integrating the in vivo exposure evaluation, in vitro outcomes analysis, and systematic environment component screening. This toxicology testing model combines the real-world exposure of people in the field and the study of molecular mechanism exploration in lab experiments to overcome the shortcomings of a single toxicology method. It provides a new technique and perspective for toxicity testing and risk assessment in mesoscale between macroscopic population study and microscopic mechanism exploration.

Anti-tumor Effect and Mechanism of Lycopus lucidus Polysaccharide on Non-small Cell Lung Cancer A549 Cells / 中国实验方剂学杂志

ObjectiveTo study the anti-tumor activity and mechanism of Lycopus lucidus polysaccharide （LLP） in vitro. MethodCell counting kit-8 （CCK-8） assay was used to detect the inhibitory effect of LLP （0， 5， 10， 15， 20 g·L-1） on the proliferation of A549 cells at different time points （24，48，72 h）. The migration and invasion abilities of A549 cells were detected by wound healing assay and transwell assay after LLP （10， 20 g·L-1） treatment for 24，48 h. Propidium iodide （PI） single staining was applied to determine the effect of LLP of different concentrations （10，20 g·L-1） on the cell cycle of A549. The apoptosis of A549 cells induced by LLP （10， 20 g·L-1） was detected by Annexin V-FITC/PI kit. Real-time fluorescence-based quantitative polymerase chain reaction （Real-time PCR） was adopted to measure effect of LLP （10， 20 g·L-1） on gene expression of cysteine aspartate protease-3 （Caspase-3），cysteine aspartate protease-8 （Caspase-8），cysteine aspartate protease-9 （Caspase-9），cyclin-dependent kinase-1 （CDK-1）， and Cyclin B1 in A549 cells. Western blot was used to detect the effect of LLP on protein expression of Caspase-3，Caspase-8，Caspase-9，B-cell lymphoma 2 （Bcl-2）-associated X protein （Bax），CDK-1，cyclin-dependent kinase-4 （CDK-4），cyclin-dependent kinase-6 （CDK-6），Cyclin B1，and Cyclin D1 in A549 cells. ResultCompared with the blank group， the LLP group showed decreased proliferation， migration， and invasion of A549 cells （P<0.05， P<0.01）， increased proportion of G0/G1 phase （P<0.05）， enhanced apoptosis rate （P<0.05， P<0.01）， elevated mRNA expression of Caspase-3，Caspase-8，and Caspase-9 （P<0.05，P<0.01）， reduced mRNA expression of CDK-1 and Cyclin B1 （P<0.05，P<0.01）， up-regulated protein expression of Caspase-3，Caspase-8，Caspase-9， and Bax （P<0.05， P<0.01）， and down-regulated protein expression of Bcl-2， CDK-1， CDK-4， CDK-6， Cyclin B1， and Cyclin D1 （P<0.05， P<0.01）. ConclusionLLP can inhibit the proliferation of A549 cells， block the cell cycle in the G0/G1 phase （also G2/M phase）， and induce cell apoptosis via the mitochondrial apoptosis pathway and death receptor pathway.

Fangji Huangqi Detumescence Prescription Treats Synovitis in Rats with Knee Osteoarthritis by Modulating Polarization of Synovial Macrophages / 中国实验方剂学杂志

ObjectiveTo assess the curative effects of Fangji Huangqi detumescence prescription （FHDP） on synovitis and polarization of synovial macrophages of knee osteoarthritis （KOA） model in rats induced by Hulth method. MethodThirty-six rats were randomly divided into sham operation group， model group， high-dose， medium-dose， and low-dose （29.16， 14.58， and 7.29 g·kg-1） FHDP groups， and loxoprofen sodium （16.2 mg·kg-1） group. KOA model in rats was induced by modified Hulth method. Six weeks after the operation， rats were given high， medium， and low concentrations of FHDP， normal saline （NS）， and loxoprofen sodium according to the group to intervene， and sacrificed after 2-week administration. Synovium and cartilage histopathological changes were observed after hematoxylin-eosin （HE） staining. Flow cytometry （FCM） and immunofluorescence （IF） test were used to evaluate the polarization of M1/M2 macrophages. Immunohistochemistry （IMC） and enzyme-linked immunosorbent assay （ELISA） were used to detect the related protein expression levels of macrophage polarization， such as interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， interleukin-10 （IL-10）， and matrix metalloproteinase-13 （MMP-13） in joint tissues and serum. ResultCompared with the sham operation group， Krenn and Mankin scores in the model group were significantly increased （P<0.01）. Compared with the model group， Krenn score was decreased in all administration groups （P<0.05， P<0.01）， but there was no significant difference in Mankin score in any administration groups. Compared with the sham operation group， M1/mø （CD38+） ratio in the model group was significantly increased （P<0.01）， and M2/mø （CD206+） ratio in the model group was decreased （P<0.05）. Compared with the model group， M1/mø ratio in the high， medium， and low-dose FHDP groups was decreased （P<0.05， P<0.01）， but M2/mø ratio was increased in all administration groups （the difference had no statistical significance）. Compared with the sham operation group， M1/M2 ratio in the model group was significantly increased （P<0.01）. Compared with the model group， M1/M2 ratio in all FHDP groups was significantly decreased （P<0.01）， and M1/M2 ratio in the high and medium-dose FHDP groups was lower than that in the loxoprofen sodium group （P<0.05）. Compared with the sham operation group， the levels of TNF-α， IL-1β， and MMP-13 in synovium and cartilage of the model group were significantly increased （P<0.01）， the level of IL-10 was significantly decreased （P<0.01）. Compared with the model group， the levels of TNF-α and IL-1β in synovium were decreased in all administration groups （P<0.05）， but the difference of the levels of MMP-13 and IL-10 in synovium had no statistical significance. The level of inflammatory mediators in cartilage was not affected in all administration groups. Compared with the sham operation group， the levels of TNF-α and IL-β in serum of the model group were significantly increased （P<0.01）， the level of IL-10 was decreased （P<0.05）. Compared with the model group， the level of TNF-α in the high-dose FHDP group was decreased （P<0.05）， and the level of IL-10 was increased in all administration groups （P<0.05， P<0.01）. The difference of the level of IL-β in all administration groups had no statistical significance. ConclusionFHDP attenuated the synovitis of KOA rats. FHDP exert the effect on the releasing of proinflammatory cytokines and MMP by inhibiting the polarization of M1 macrophages in synovium， and had no significant effect on the polarization of M2 macrophages. Modulating the imbalanced polarization of synovial macrophages was a possible mechanism of FHDP on attenuating synovitis and treating KOA.

Efficacy of doxycycline versus azithromycin for the treatment of rectal chlamydia: a systematic review and meta-analysis.

BACKGROUND: Chlamydia trachomatis infection is the most common sexually transmitted infectious disease and carries a risk of complications. However, the optimal treatment for rectal chlamydial infection remains unclear. OBJECTIVES: To compare the efficacy of doxycycline and azithromycin for the treatment of rectal chlamydia by undertaking a systematic review and meta-analysis of published data. METHODS: We searched PubMed, EMBASE, Cochrane Library, Web of Science and clinicaltrials.gov databases from inception to 7 July 2021 for randomized controlled trials (RCTs) and observational studies that compared the efficacy of doxycycline and single-dose azithromycin on rectal chlamydia cure rates. Data were synthesized using a random-effects model, and subgroup analysis was conducted. RESULTS: All included studies were conducted in developed countries. Two RCTs and nine observational studies, with a total of 2457 patients, were analysed. Doxycycline had a higher microbiological cure rate than azithromycin (risk ratio = 1.21; 95% CI = 1.15-1.28; P < 0.05). Pooled results from two RCTs also revealed a higher microbiological cure rate for doxycycline than azithromycin (risk ratio = 1.27; 95% CI = 1.20-1.35; P < 0.05). The results remained consistent in subgroups of different study designs, countries and sexes. CONCLUSIONS: On the basis of our findings, we recommend doxycycline rather than azithromycin as a first-line treatment for rectal chlamydia in developed countries. More RCTs from developing countries are warranted.