Genome-wide analysis of AP2/ERF superfamily in Isatis indigotica / 中西医结合学报

OBJECTIVE@#AP2/ERF (APETALA2/ethylene-responsive factor) superfamily is one of the largest gene families in plants and has been reported to participate in various biological processes, such as the regulation of biosynthesis of active lignan. However, few studies have investigated the genome-wide role of the AP2/ERF superfamily in Isatis indigotica. This study establishes a complete picture of the AP2/ERF superfamily in I. indigotica and contributes valuable information for further functional characterization of IiAP2/ERF genes and supports further metabolic engineering.@*METHODS@#To identify the IiAP2/ERF superfamily genes, the AP2/ERF sequences from Arabidopsis thaliana and Brassica rapa were used as query sequences in the basic local alignment search tool. Bioinformatic analyses were conducted to investigate the protein structure, motif composition, chromosome location, phylogenetic relationship, and interaction network of the IiAP2/ERF superfamily genes. The accuracy of omics data was verified by quantitative polymerase chain reaction and heatmap analyses.@*RESULTS@#One hundred and twenty-six putative IiAP2/ERF genes in total were identified from the I. indigotica genome database in this study. By sequence alignment and phylogenetic analysis, the IiAP2/ERF genes were classified into 5 groups including AP2, ERF, DREB (dehydration-responsive element-binding factor), Soloist and RAV (related to abscisic acid insensitive 3/viviparous 1) subfamilies. Among which, 122 members were unevenly distributed across seven chromosomes. Sequence alignment showed that I. indigotica and A. thaliana had 30 pairs of orthologous genes, and we constructed their interaction network. The comprehensive analysis of gene expression pattern in different tissues suggested that these genes may play a significant role in organ growth and development of I. indigotica. Members that may regulate lignan biosynthesis in roots were also preliminarily identified. Ribonucleic acid sequencing analysis revealed that the expression of 76 IiAP2/ERF genes were up- or down-regulated under salt or drought treatment, among which, 33 IiAP2/ERF genes were regulated by both stresses.@*CONCLUSION@#This study undertook a genome-wide characterization of the AP2/ERF superfamily in I. indigotica, providing valuable information for further functional characterization of IiAP2/ERF genes and discovery of genetic targets for metabolic engineering.

LOX-1 Regulation in Anti-atherosclerosis of Active Compounds of Herbal Medicine: Current Knowledge and the New Insight / 中国结合医学杂志

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) have recently been identified to be closely related to the occurrence and development of atherosclerosis (AS). A growing body of evidence has suggested Chinese medicine takes unique advantages in preventing and treating AS. In this review, the related research progress of AS and LOX-1 has been summarized. And the anti-AS effects of 10 active components of herbal medicine through LOX-1 regulation have been further reviewed. As a potential biomarker and target for intervention in AS, LOX-1 targeted therapy might provide a promising and novel approach to atherosclerotic prevention and treatment.

Targeting microRNA-125b inhibited the metastasis of Alisertib resistance cells through mediating p53 pathway / 中华肿瘤杂志

Objective: To clarify the mechanisms involvement in Alisertib-resistant colorectal cells and explore a potential target to overcome Alisertib-resistance. Methods: Drug-resistant colon cancer cell line (named as HCT-8-7T cells) was established and transplanted into immunodeficient mice. The metastasis in vivo were observed. Proliferation and migration of HCT-8-7T cells and their parental cells were assessed by colony formation and Transwell assay, respectively. Glycolytic capacity and glutamine metabolism of cells were analyzed by metabolism assays. The protein and mRNA levels of critical factors which are involved in mediating glycolysis and epithelial-mesenchymal transition (EMT) were examined by western blot and reverse transcription-quantitative real-time polymerase chain reaction(RT-qPCR), respectively. Results: In comparison with the mice transplanted with HCT-8 cells, which were survival with limited metastatic tumor cells in organs, aggressive metastases were observed in liver, lung, kidney and ovary of HCT-8-7T transplanted mice (P<0.05). The levels of ATP [(0.10±0.01) mmol/L], glycolysis [(81.77±8.21) mpH/min] and the capacity of glycolysis [(55.50±3.48) mpH/min] in HCT-8-7T cells were higher than those of HCT-8 cells [(0.04±0.01) mmol/L, (27.77±2.55) mpH/min and(14.00±1.19) mpH/min, respectively, P<0.05]. Meanwhile, the levels of p53 protein and mRNA in HCT-8-7T cells were potently decreased as compared to that in HCT-8 cells (P<0.05). However, the level of miRNA-125b (2.21±0.12) in HCT-8-7T cells was significantly elevated as compared to that in HCT-8 cells (1.00±0.00, P<0.001). In HCT-8-7T cells, forced-expression of p53 reduced the colon number (162.00±24.00) and the migration [(18.53±5.67)%] as compared with those in cells transfected with control vector [274.70±40.50 and (100.00±29.06)%, P<0.05, respectively]. Similarly, miR-125b mimic decreased the glycolysis [(25.28±9.51) mpH/min] in HCT-8-7T cells as compared with that [(54.38±12.70)mpH/min, P=0.003] in HCT-8-7T cells transfected with control. Meanwhile, in comparison with control transfected HCT-8-7T cells, miR-125b mimic also significantly led to an increase in the levels of p53 and β-catenin, in parallel with a decrease in the levels of PFK1 and HK1 in HCT-8-7T cells (P<0.05). Conclusions: Silencing of p53 by miR-125b could be one of the mechanisms that contributes to Alisertib resistance. Targeting miR-125b could be a strategy to overcome Alisertib resistance.

Assessment of the diagnostic value and prognosis of different detection markers in endocervical adenocarcinoma / 中华肿瘤杂志

Objective: To study the diagnostic value of different detection markers in histological categories of endocervical adenocarcinoma (ECA), and their assessment of patient prognosis. Methods: A retrospective study of 54 patients with ECA in the Cancer Hospital, Chinese Academy of Medical Sciences from 2005-2010 were performed. The cases of ECA were classified into two categories, namely human papillomavirus-associated adenocarcinoma (HPVA) and non-human papillomavirus-associated adenocarcinoma (NHPVA), based on the 2018 international endocervical adenocarcinoma criteria and classification (IECC). To detect HR-HPV DNA and HR-HPV E6/E7 mRNA in all patients, we used whole tissue section PCR (WTS-PCR) and HPV E6/E7 mRNA in situ hybridization (ISH) techniques, respectively. Additionally, we performed Laser microdissection PCR (LCM-PCR) on 15 randomly selected HR-HPV DNA-positive cases to confirm the accuracy of the above two assays in identifying ECA lesions. Receiver operating characteristic (ROC) curves were used to analyze the efficacy of markers to identify HPVA and NHPVA. Univariate and multifactorial Cox proportional risk model regression analyses were performed for factors influencing ECA patients' prognoses. Results: Of the 54 patients with ECA, 30 were HPVA and 24 were NHPVA. A total of 96.7% (29/30) of HPVA patients were positive for HR-HPV DNA and 63.3% (19/30) for HR-HPV E6/E7 mRNA, and 33.3% (8/24) of NHPVA patients were positive for HR-HPV DNA and HR-HPV E6/E7 mRNA was not detected (0/24), and the differences were statistically significant (P<0.001). LCM-PCR showed that five patients were positive for HR-HPV DNA in the area of glandular epithelial lesions and others were negative, which was in good agreement with the E6/E7 mRNA ISH assay (Kappa=0.842, P=0.001). Analysis of the ROC results showed that the AUC of HR-HPV DNA, HR-HPV E6/E7 mRNA, and p16 to identify HPVA and NHPVA were 0.817, 0.817, and 0.692, respectively, with sensitivities of 96.7%, 63.3%, and 80.0% and specificities of 66.7%, 100.0%, and 58.3%, respectively. HR-HPV DNA identified HPVA and NHPVA with higher AUC than p16 (P=0.044). The difference in survival rates between HR-HPV DNA (WTS-PCR assay) positive and negative patients was not statistically significant (P=0.156), while the difference in survival rates between HR-HPV E6/E7 mRNA positive and negative patients, and p16 positive and negative patients were statistically significant (both P<0.05). Multifactorial Cox regression analysis showed that International Federation of Obstetrics and Gynecology (FIGO) staging (HR=19.875, 95% CI: 1.526-258.833) and parametrial involvement (HR=14.032, 95% CI: 1.281-153.761) were independent factors influencing the prognosis of patients with ECA. Conclusions: HR-HPV E6/E7 mRNA is more reflective of HPV infection in ECA tissue. The efficacy of HR-HPV E6/E7 mRNA and HR-HPV DNA (WTS-PCR assay) in identifying HPVA and NHPVA is similar, with higher sensitivity of HR-HPV DNA and higher specificity of HR-HPV E6/E7 mRNA. HR-HPV DNA is more effective than p16 in identifying HPVA and NHPVA. HPV E6/E7 mRNA and p16 positive ECA patients have better survival rates than negative.

Anticoagulation status and adherence in patients with atrial fibrillation hospitalized for ACS and the impact on 1-year prognosis: a multicenter cohort study / 中华心血管病杂志

Objective: For patients with atrial fibrillation (AF) complicated with acute coronary syndrome (ACS), both anticoagulant and antiplatelet therapy should be applied, but the use of anticoagulation therapy is still poor in these patients in China. The purpose of this study was to explore the status and adherence of antithrombotic therapy in AF patients with ACS and the impact on 1 year clinical outcomes. Methods: Patients with AF hospitalized for ACS were retrospectively included from 6 tertiary hospitals in China between July 2015 and December 2020. According to the use of anticoagulant drugs at discharge, patients were divided into two groups: anticoagulant treatment group and non-anticoagulant treatment group. Logistic regression model was used to analyze the main factors influencing the use of anticoagulant drugs in patients with atrial fibrillation complicated with ACS. Major adverse cardiac events (MACEs) were defined as all-cause death, non-fatal myocardial infarction or coronary revascularization, and ischemic stroke and Bleeding Academic Research Consortium (BARC) 3 bleeding events were also collected at 1 year after discharge. After propensity score matching, Cox proportional hazards models and Kaplan-Meier analysis were used to evaluate the effect of anticoagulant treatment and non-anticoagulant treatment on 1-year prognosis. The patients were divided into different groups according to whether anticoagulation was performed at discharge and follow-up, and the sensitivity of the results was analyzed. Results: A total of 664 patients were enrolled, and 273 (41.1%) were treated with anticoagulant therapy, of whom 84 (30.8%) received triple antithrombotic therapy, 91 (33.3%) received double antithrombotic therapy (single antiplatelet combined with anticoagulant), and 98 (35.9%) received single anticoagulant therapy. Three hundred and ninety-one (58.9%) patients were treated with antiplatelet therapy, including 253 (64.7%) with dual antiplatelet therapy and 138 (35.3%) with single antiplatelet therapy. After 1∶1 propensity score matching between the anticoagulant group and the non-anticoagulant group, a total of 218 pairs were matched. Multivariate logistic regression analysis showed that history of diabetes, HAS-BLED score≥3, and percutaneous coronary intervention were predictors of the absence of anticoagulant therapy, while history of ischemic stroke and persistent atrial fibrillation were predictors of anticoagulant therapy. At 1-year follow-up, 218 patients (79.9%) in the anticoagulant group continued to receive anticoagulant therapy, and 333 patients (85.2%) in the antiplatelet group continued to receive antiplatelet therapy. At 1-year follow-up, 36 MACEs events (13.2%) occurred in the anticoagulant group, and 81 MACEs events (20.7%) in the non-anticoagulant group. HR values and confidence intervals were calculated by Cox proportional risk model. Patients in the non-anticoagulant group faced a higher risk of MACEs (HR=1.802, 95%CI 1.112-2.921, P=0.017), and the risk of bleeding events was similar between the two group (HR=0.825,95%CI 0.397-1.715, P=0.607). Conclusions: History of diabetes, HAS-BLED score≥3, and percutaneous coronary intervention are independent factors for the absence of anticoagulant therapy in patients with AF complicated with ACS. The incidence of MACEs, death and myocardial infarction is lower in the anticoagulant group, and the incidence of bleeding events is similar between the two groups. The risk of bleeding and ischemia/thrombosis should be dynamically assessed during follow-up and antithrombotic regiments should be adjusted accordingly.

Application of Mini-Clinical Evaluation Exercise combined with direct observation of procedural skills in standardized training of emergency medicine guided by professional physician qualification examination / 中华医学教育探索杂志

Objective:To investigate the application effect of Mini-Clinical Evaluation Exercise (Mini-CEX) combined with direct observation of procedural skills (DOPS) in standardized training of emergency medicine guided by professional physician qualification examination.Methods:Based on the time of emergency medicine teaching reform in Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, 32 standardized training residents in Emergency Department before September 2020 were included as control group and were given traditional teaching, and 32 standardized training residents after September 2020 were included as observation group and were given Mini-CEX combined with DOPS teaching under the guidance of professional physician qualification examination. The two groups were compared in terms of Mini-CEX score, DOPS score, assessment score of comprehensive emergency skills, pass rate of professional physician qualification examination, and comprehensive teaching quality. SPSS 25.00 was used to perform the t-test and the chi-square test. Results:Compared with the control group after training, the observation group had significantly higher scores of Mini-CEX, DOPS, and comprehensive emergency skill assessment ( P<0.05). There were no significant differences between the two groups in the pass rates of theoretical and practical examinations in professional physician qualification examination, and the observation group had a significantly higher total pass rate than the control group ( P<0.05). The observation group had significantly higher comprehensive teaching quality scores than the control group ( P<0.05). Conclusion:Mini-CEX combined with DOPS guided by professional physician qualification examination can help to improve the teaching effectiveness of standardized training residents in emergency, enhance their comprehensive skills and emergency professional skills, achieve a relatively high pass rate of professional physician qualification examination, and improve their post competency, and thus it holds promise for clinical application.

Occupational Burnout and Turnover Intention of Social Workers under the Context of Epidemic Prevention and Control: The Moderating Effect of Professional Self-care / 中国医学伦理学

To understand the current situation of occupational burnout, turnover intention, and professional self-care among social workers under the context of epidemic prevention and control, and the role of professional self-care in the relationship between occupational burnout and turnover intention, this study investigated 1 066 social workers in Fujian Province with Professional Self-Care Practice Scale, and the Burnout Scale. SPSS 26.0 and its PROCESS plug-in analysis were used, the results showed that the proportion of social workers with moderate and severe occupational burnout accounted for 44.22% and 29.99% respectively, the proportion with turnover intention in the past year accounted for 25.67%, and the average score of professional self-care was (22.57±5.98) points. There was a significant positive correlation between occupational burnout and turnover intention (r=0.29, P<0.01). Professional self-care of social workers was significant negatively correlated with occupational burnout (r=-0.46, P<0.01) and turnover intention (r=-0.16, P<0.01). Professional self-care played a moderating role in the relationship between occupational burnout and turnover intention (β=-0.01, P<0.05). This paper indicated that social workers had a high degree of occupational burnout and turnover intention, low level of professional self-care under the context of epidemic prevention and control, and the attention should be paid to the protective role of professional self-care.

Computer Vision in Medical Imaging and its Impact on the Rare Musculoskeletal Diseases / 罕见病研究

There are over 6000 rare diseases in the world, affecting more than 300 million people. Early and precise diagnosis of rare diseases has always been the goal in clinical medicine. Emerging computer vision technology now greatly enhance medicine and healthcare and shows the potential in assisting the diagnosis and treatment for rare diseases. The technology can be a useful tool for extracting disease-relevant patterns from medical imaging. However, the effectiveness of its application depends on the complexity of the medical cases. In this paper, we summarize the challenges and emerging solution for the application of computer vision in diagnosis, rehabilitation as well as management of rare musculoskeletal diseases.

Establishment and evaluation of predictive models of platelet transfusion effect in multi-center tumor patients / 中国输血杂志

【Objective】 To study the platelet transfusion predictive models in tumor patients and evaluate its application effect. 【Methods】 A retrospective study was conducted on 944 tumor patients, including 533 males and 411 females who received platelet transfusion in the Affiliated Hospital of Traditional Chinese Medicine of Xinjiang Medical University, the Affiliated Cancer Hospital of Xinjiang Medical University and Kailuan General Hospital from August 2022 to January 2023. Multivariate Logistic regression analysis was used to establish the platelet transfusion predictive models, and Medcalc15.8 software was used to draw the receiver operating curve (ROC) to evaluate the application effect of the prediction model. The actual application effect of models was verified through 162 female clinical cases and 172 male clinical cases. 【Results】 The incidence of platelet transfusion refractoriness in tumor patients was 28.9% (273/944), with 33.2% (177/533) in males, significantly higher than that in females [23.4% (96/411)] (P<0.05). Platelet transfusion predictive models: Y1 (female) =-8.546+ (0.581×number of pregnancies) + (0.964×number of inpatient transfusion bags) + number of previous platelet transfusion bags (5-9 bags: 1.259, ≥20 bags: 1.959) + clinical diagnosis (lymphoma: 2.562, leukemia: 3.214); Y2 (male) =-7.600+ (1.150×inpatient transfusion bags) + previous platelet transfusion bags (10-19 bags: 1.015, ≥20 bags: 0.979) + clinical diagnosis (lymphoma: 1.81, leukemia: 3.208, liver cancer: 1.714). Application effect evaluation: The AUC (area under the curve), cut-off point, corresponding sensitivity and specificity of female and male platelet transfusion effect prediction models were 0.868, -0.354, 68.75%, 89.84% and 0.854, -0.942, 81.36%, 77.53%, respectively. Actual application results showed that the sensitivity, specificity, and accuracy of female and male model were 89.47%, 92.74%, 91.98% and 83.72%, 91.47%, 89.53%, respectively. 【Conclusion】 There is high incidence of platelet transfusion refractoriness in tumor patients, and the predictive model has good prediction effect on platelet transfusion refractoriness in tumor patients, which can provide reliable basis for accurate platelet transfusion in tumor patients.

Application of CT pulmonary angiography in acute pulmonary embolism and right heart function / 中国康复理论与实践

ObjectiveTo explore the application value of CT pulmonary angiography (CTPA) in assessing the severity of acute pulmonary embolism (APE) and right heart function in rehabilitation patients. MethodsFrom January, 2013 to January, 2020, 133 inpatients (94 positive and 39 negative) who underwent CTPA examination in Beijing Bo'ai Hospital were involved. Positive patients were further divided into mild, moderate and severe groups based on the pulmonary artery obstruction index (PAOI). The clinical parameters and right heart function indicators were compared. Spearman correlation analysis was used to analyze the correlation between PAOI, and clinical parameters and right heart function indicators, and Logistic regression analysis was used to predict the risk factors of APE. ResultsThere was significant difference in lower extremity venous thrombosis, D-dimer, oxygen partial pressure, PAOI and left process of interventricular septum among four groups (H ≥ 12.350, P < 0.01). PAOI was moderately positively correlated with D-dimer (r = 0.443, P < 0.001) and left process of interventricular septum (r = 0.520, P < 0.001), and was weakly positively correlated with lower extremity venous thrombosis (r = 0.399, P < 0.001), left pulmonary artery diameter (r = 0.213, P = 0.014) and inferior vena cava regurgitation (r = 0.229, P = 0.008). Lower extremity venous thrombosis (OR = 7.708, P < 0.001) and left process of interventricular septum (OR = 3.641, P = 0.008) were independent risk factors for the onset of APE. The combination of the two indicators was effective for diagnosis of APE, and AUC was 0.795 (95% CI 0.715 to 0.874). ConclusionCTPA may be applied to evaluate the severity of APE and right heart function in rehabilitation patients.

Anesthetic Management and Outcomes of Endovascular Treatment of Basilar Artery Occlusion: Results From the ATTENTION Registry / 대한뇌졸중학회지

Background@#and Purpose To examine the clinical and safety outcomes after endovascular treatment (EVT) for acute basilar artery occlusion (BAO) with different anesthetic modalities. @*Methods@#This was a retrospective analysis using data from the Endovascular Treatment for Acute Basilar Artery Occlusion (ATTENTION) registry. Patients were divided into two groups defined by anesthetic modality performed during EVT: general anesthesia (GA) or non-general anesthesia (non-GA). The association between anesthetic management and clinical outcomes was evaluated in a propensity score matched (PSM) cohort and an inverse probability of treatment weighting (IPTW) cohort to adjust for imbalances between the two groups. @*Results@#Our analytic sample included 1,672 patients from 48 centers. The anesthetic modality was GA in 769 (46.0%) and non-GA in 903 (54.0%) patients. In our primary analysis with the PSM-based cohort, non-GA was comparable to GA concerning the primary outcome (adjusted common odds ratio [acOR], 1.01; 95% confidence interval [CI], 0.82 to 1.25; P=0.91). Mortality at 90 days was 38.4% in the GA group and 35.8% in the non-GA group (adjusted risk ratio, 0.95; 95% CI, 0.83 to 1.08; P=0.44). In our secondary analysis with the IPTW-based cohort, the anesthetic modality was significantly associated with the distribution of modified Rankin Scale at 90 days (acOR: 1.45 [95% CI: 1.20 to 1.75]). @*Conclusion@#In this nationally-representative observational study, acute ischemic stroke patients due to BAO undergoing EVT without GA had similar clinical and safety outcomes compared with patients treated with GA. These findings provide the basis for large-scale randomized controlled trials to test whether anesthetic management provides meaningful clinical effects for patients undergoing EVT.

Effects of different moxibustion time on knee cartilage morphology and the expression of TNF-α and IL-10 in rats with knee osteoarthritis / 针灸推拿医学（英文版）

Objective:To observe the effects of different moxibustion time on cartilage morphology,tumor necrosis factor(TNF)-α and interleukin(IL)-10 of the knee joint in rats with knee osteoarthritis(KOA),and to explore the best treatment time of moxibustion for KOA.Methods:Healthy male Wistar rats were randomly divided into a blank group,a model group,a 15-minute-moxibustion group,a 30-minute-moxibustion group,and a 60-minute-moxibustion group,with 10 rats in each group.Except for the blank group,the KOA model was established in all groups by injecting sodium iodoacetate solution into the knee joint cavity of rats.Rats in the 15-minute-moxibustion group,the 30-minute-moxibustion group,and the 60-minute-moxibustion group were all treated with mild moxibustion intervention for 15 min,30 min,and 60 min,respectively at Neixiyan(EX-LE4)and Dubi(ST35)points near the patella,3 times a week for 4 weeks,12 times in total.Rats in the blank group and the model group were fixed for 30 min without moxibustion intervention.Macroscopic observation for the smoothness of knee cartilage surface was performed after the intervention.Hematoxylin-eosin staining,toluidine blue staining,and Mankin score were used to evaluate the pathological changes in the cartilage.The expression levels of TNF-α and IL-10 in the serum were detected by enzyme-linked immunosorbent assay.Results:Compared with the blank group,the articular cartilage surface in the model group was rough,the chondrocyte arrangement was irregular,the Mankin score and the serum TNF-α expression were significantly increased(P＜0.05),while the expression of serum IL-10 was significantly decreased(P＜0.05).Compared with the model group,the articular cartilage surface was smoother,the chondrocytes were arranged neatly,the Mankin score and serum TNF-α expression level were significantly lower in the three moxibustion intervention groups(P＜0.05);the serum IL-10 level in the 30-minute-moxibustion group and the 60-minute-moxibustion group was increased significantly(P＜0.05).Compared with the 15-minute-moxibustion group,the articular cartilage surface in the 30-minute-moxibustion group and the 60-minute-moxibustion group was smoother,the chondrocyte arrangement was more regular,the Mankin score and the serum TNF-α level were decreased significantly(P＜0.05),and the serum IL-10 level was increased(P＜0.05).There was no significant difference in the serum TNF-α or IL-10 level between the 30-minute-moxibustion group and the 60-minute-moxibustion group(P＞0.05).Conclusion:Moxibustion can obviously improve the morphology and structure of KOA articular cartilage,protect articular cartilage,inhibit cartilage inflammation,and delay KOA cartilage degeneration.Moxibustion's effect is closely related to moxibustion time;the therapeutic effect of the 30-minute-moxibustion and the 60-minute-moxibustion is better than that of the 15-minute-moxibustion.

Characteristics of vaginal microbiota in pregnant women with premature rupture of membranes and establishment of prediction model / 中华微生物学和免疫学杂志

Objective:To study the characteristics of vaginal microbiota in pregnant women with premature rupture of membranes (PROM) and to establish prediction models for PROM.Methods:This study involved 35 women with preterm premature rupture of membranes (PPROM), 180 with term premature rupture of membranes (TPROM) and 255 term birth cases without premature rupture of membranes (TBWPROM, control group). The V3-V4 hypervariable region sequences in the vaginal samples collected at 16-28 weeks of gestation were detected by 16S rRNA gene next-generation sequencing. The differences in Alpha and Beta diversity, and the attributes and metabolic function prediction of each recognized species among the three groups were analyzed. Subsequently, a random forest model was used to establish the prediction models for PROM using vaginal microbiota species and environmental risk factors.Results:Compared with the control group, the Alpha diversity of the PPROM group was higher (Observed features, P=0.022; Faith_pd index, P=0.024) and Beta diversity was also significantly different (Unweighted UniFrac, P=0.010; Jaccard index, P=0.008). In PPROM cases, Megasphaera genomosp. typeⅠ was significantly increased ( P=0.017) and Lactobacillus mulieris was significantly decreased ( P=0.003). In the patients with TPROM, Megasphaera was significantly increased ( P=0.009) and Lactobacillus mulieris was significantly decreased ( P=0.002). In terms of functional pathways, sulfur oxidation ( P=0.021), methanogenesis from acetate ( P=0.036), L-histidine biosynthesis ( P=0.009), adenosylcobalamin biosynthesis ( P=0.041) and fucose degradation ( P=0.001) were significantly increased in patients with PPROM; L-histidine biosynthesis ( P<0.001) and fucose degradation ( P=0.030) were significantly increased in patients with TPROM. The prediction models were established using the random forest model with vaginal microbiota species and environmental risk factors and the prediction model for PPROM performed well [AUC: 0.739 (95%CI: 0.609-0.869), sensitivity: 0.928, specificity: 0.659, positive predictive value: 0.750, negative predictive value: 0.906], which had a certain reference value. Conclusions:Vaginal microbiota might be related to the development and progression of PROM. Studying the differences in vaginal microbiota might provide a new idea for the prevention and treatment of PROM. Functional prediction provided a direction for further research on the mechanism of PROM. The established prediction model could prevent the occurrence of PPROM and promote maternal and infant health.

Role of S1PR1 in dorsal root ganglion in remifentanil-induced hyperalgesia in rats with incisional pain / 中华麻醉学杂志

Objective:To evaluate the role of sphingosine-1-phospho-1 receptor(S1PR1)in the dorsal root ganglion in remifentanil-induced hyperalgesia in rats with incisional pain.Methods:Forty-eight male Sprague-Dawley rats with successful intrathecal and caudal vein catheterization, weighing 260-280 g, aged 2-3 months, were divided into 6 groups ( n= 8 each) using a random number table method: control group (group C), S1PR1 antagonist (FTY720) group (group F), remifentanil group (group R), remifentanil + S1PR1 antagonist (FTY720) group (group R+ F), remifentanil + incisional pain group (group R+ I), and remifentanil + incisional pain + S1PR1 antagonist (FTY720) group (group R+ I+ F). In C group, normal saline 0.1 μg·kg -1·min -1 was intravenously infused for 60 min. In R group, remifentanil 1.0 μg· kg -1·min -1 was infused for 60 min through the caudal vein. In F group, FTY720 3 nmol was intrathecally injected, and 10 min later normal saline 1.0 μg· kg -1·min -1 was infused for 60 min via the caudal vein. In R+ F group, FTY720 3 nmol was intrathecally injected, and 10 min later remifentanil 1.0 μg· kg -1·min -1 was infused for 60 min through the caudal vein. In R+ I group, remifentanil 1.0 μg·kg -1·min -1 was infused for 60 min through the caudal vein while the model of incisional pain was developed. In R+ I+ F group, FTY720 3 nmol was intrathecally injected, 10 min later the incisional pain model was prepared, and remifentanil 1.0 μg·kg -1·min -1 was injected for 60 min through the caudal vein at the same time. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 24 h before remifentanil or normal saline infusion (T 0) and 2, 6, 24 and 48 h after stopping remifentanil or normal saline infusion (T 1-4). Rats were sacrificed after the last measurement of pain threshold, and the L 4-6 segments of dorsal root ganglion were taken for determination of the expression of S1PR1, NOD-like receptor thermal protein domain-associated protein 3 (NLRP3), interleukin-1β (IL-1β) and glutamate transporter-1 (GLT-1) protein and mRNA (by Western blot and quantitative polymerase chain reaction). Results:Compared with C group, the MWT was significantly decreased and TWL was shortened at T 1-4, the expression of S1PR1, NLRP3 and IL-1β protein and mRNA in dorsal root ganglion was up-regulated, and the expression of GLT-1 protein and mRNA in dorsal root ganglion was down-regulated in R group ( P<0.05), and no significant change was found in the parameters mentioned above in group F ( P>0.05). Compared with R group, MWT was significantly decreased and TWL was shortened at T 1-4, the expression of S1PR1, NLRP3 and IL-1β protein and mRNA in dorsal root ganglion was up-regulated, and GLT-1 protein and mRNA expression in dorsal root ganglion was down-regulated in R+ I group, and MWT was significantly increased and TWL was prolonged at T 1-4, the expression of S1PR1, NLRP3 and IL-1β protein and mRNA in the dorsal root ganglion was down-regulated, and GLT-1 protein and mRNA expression in the dorsal root ganglion was up-regulated in R+ F group ( P<0.05). Compared with R+ I group, MWT was significantly increased and TWL was prolonged at T 1-4, the expression of S1PR1, NLRP3 and IL-1β protein and mRNA in the dorsal root ganglion was down-regulated, and the expression of GLT-1 protein and mRNA in the dorsal root ganglion was up-regulated in R+ I+ F group( P<0.05). Conclusions:The mechanism by which remifentanil induces hyperalgesia is associated with up-regulation of S1PR1 expression, activation of inflammatory factors, and down-regulation of GLT-1 expression in the rats with incisional pain.

Association of bone lesions distribution with prognosis in renal cell carcinoma bone metastasis / 中华泌尿外科杂志

Objective:To investigate the association between bone lesions distribution and survival outcome and prognostic risk stratification in renal cell carcinoma bone metastasis (RCC-BM).Methods:The data of 122 RCC-BM patients admitted to Peking University People's Hospital between January 2009 and December 2019 were retrospectively reviewed. There were 100 males and 22 females, with a baseline age of (59.87±11.33) years old. According to the Memorial Sloan-Kettering Cancer Center (MSKCC)/Motzer score, patients were stratified into different risk groups using profiles at first bone metastasis diagnosis, with 20 (16.4%), 74 (60.6%) and 28 (23.0%) patients in favorable, intermediate and poor group, respectively. The spatial distribution of bone metastasis was investigated at the first bone metastasis diagnosis. The overall distribution patterns were as follows: locoregional group (lesions only involved thoracic and/or lumbar vertebrates) in 26 cases (21.3%), stochastic group (bone lesions randomly distributed) in 69 cases (56.6%), extensive group (with concomitant visceral metastasis) in 27 cases (22.1%). Metastatic site involvement was as follows: spine in 48 cases(39.3%), pelvis in 43 cases (35.2%), upper extremities in 22 cases (18.0%), and lower extremities in 20 cases (16.4%). Half (61 cases) of the enrolled patients had synchronous bone metastasis as their first bone metastases were diagnosed simultaneously with their renal tumors. Of all the patients, 99 (81.1%) accepted radical nephrectomy, 6 (4.9%) accepted partial nephrectomy, and the other 17 patients (13.9%) accepted the treatment of ablation or embolization. Eighty-two patients (67.2%) received definitive treatment for bone metastatic lesions, respectively. Forty patients (32.8%) accepted the palliative tumor reduction therapy. Thirty-two patients (26.2%) received tyrosine kinase inhibitor (TKI) or immune checkpoint inhibitor (ICI) medication, and 12 patients (9.8%) received local radiotherapy. Distribution variation and therapeutic strategies throughout the disease course until the last follow-up were recorded. Univariate analysis (chi-squared test, Mantel-Haenszel test), Kaplan-Meier survival analysis, and multivariate ordinal logistic regression were performed for the possible association.Results:Patients from the locoregional group (30.8%, 8/26) were prone to have higher risk stratification at first diagnosis than patients in the stochastic and extensive groups ( 20.8%, 20/96, P=0.107) as the marginal difference was found. At first bone metastasis diagnosis, RCC-BM patients with spinal involvement were more likely to have higher MSKCC risk stratification than those without spinal involvement [20.3%(15/48) vs. 17.6%(13/74), P<0.05]. Multivariate ordinal logistic regression showed that after adjusting for general data, bone metastasis sites, and concomitant visceral metastasis, RCC-BM patients with spinal involvement at first bone metastasis diagnosis were 3.3 times (95% CI 1.195-9.091, P<0.05)more likely to fall into the higher MSKCC risk group than those without spinal involvement.In those 93 cases with follow-up records, 20 (21.5%), 53 (57.0%), and 20 (21.5%) cases were in the locoregional group, stochastic group, and extensive group, respectively. The median overall survival time (mOS) of patients with pelvic involvement (36 cases) throughout the disease course was 32.0 months (95% CI 6.0-58.0), which was shorter than that of patients without pelvic involvement (57 cases, mOS 49.0 months, 95% CI 20.4-77.5, P<0.05). Conclusions:Spinal involvement (especially limited to thoracic and/or lumbar vertebrates) at first bone metastasis diagnosis and pelvic involvement throughout the disease course were associated with poor prognosis.

"Shapeshifter of the mycobacterial world" : Discuss the mechanism of morphological transformation of Mycobacterium abscesses / 中华临床感染病杂志

Mycobacterium abscessesus (MAB) is the most common species of rapidly growing pathogenic nontuberculous mycobacteria (NTM). MAB is also an opportunistic pathogen with high drug resistance. The unique structure of cell wall enables it to exist in different forms and to undergo morphological transformation, making it the "shapeshifter of the mycobacterial world" , which facilitates its survival in natural environment in a saprophytic manner; and also facilitates its invasion into the host with long-term survival and being pathogenic. This article reviews research progress on the specific deformability of MAB and the mechanism associated with its phenotypic transformation; discusses the evolutionary characteristics of MAB to adapt environmental changes to provide reference for better understanding the biological characteristics and pathogenicity of MAB.

Characteristics of acupuncture and moxibustion therapy in Tibetan medicine based on Medical Canon in Four Sections / 中国针灸

By tracing to the origin of Tibetan medicine, it is known that Tibetan medicine absorbs a variety of medical ideas such as traditional Chinese medicine, Vedic medicine, Persian medicine and Byzantine medicine, and forms a unique theoretical system. The meridian-acupoint system and the characteristics and application of external therapies such as bloodletting and moxibustion in Tibetan medicine are analyzed by elaborating the relevant aspects of acupuncture and moxibustion involved in treatment of diseases listed in Medical Canon in Four Sections. The paper emphasizes the introduction of ironing moxibustion and huo'er moxibustion of fire moxibustion and the application of separation-action decoction and ghee therapy in bloodletting, as well as alternative therapy. Besides, by taking the external treatment of cirrhotic ascites and head trauma as an example, the idea of acupuncture and moxibustion therapy in Tibetan medicine embodied in the Medical Canon in Four Sections is explained so as to benefit the development of acupuncture and moxibustion therapy in Tibetan medicine.

PANoptosis： Molecular Mechanism of Action and Effects on Blinding Eye Diseases / 中山大学学报(医学科学版)

Previous studies focused on the unique regulatory mechanisms of different cell death pathways. However， recent studies highlight crosstalk and co-ordination between these pathways and initiate a new cell death process called PANoptosis （pyroptosis， apoptosis， necroptosis）. PANoptosis is an inflammatory programmed cell death pathway regulated by the PANoptosome complex with critical features of pyroptosis， and/or necroptosis but cannot be characterized by any of the death modes of pyroptosis， apoptosis or necroptosis alone. By activating the PANoptosis pathway， some triggers like bacterial， viral， and fungal infections can cause death of the host. This review explains the PANoptosis-related routes， regulators and their potential effects on blinding eye diseases.

Interpretation of guidance on non-clinical safety evaluation for nanomedicines / 药学学报

With the rapid development of nanotechnology, the research and development of nanomedicines have become one of the development directions of drug innovation. Nanomedicines have special physical and chemical properties, such as nanoscale effects and nanostructure effects, so they have special biological properties, which may change the pharmacokinetic profiles such as absorption and tissue distribution of drug molecules, and thus affect their safety and effectiveness. There are many special concerns on the non-clinical safety evaluation of nanomedicines at the basis of ordinary drug because of the particularity of nanomedicines. On August 25, 2021, China issued Guidance on Non-clinical Safety Evaluation for Nanomedicines(interim). This article interprets comprehensively the guidance, focuses on the key points of non-clinical safety evaluation for nanomedicines, and expounds combined with some cases, aiming to provide reference for drug researchers.

Non clinical pharmacodynamic evaluation system of high-altitude hypoxic brain injury / 药学学报

The air at high altitude is thin and belongs to the environment of low temperature, low oxygen and low pressure. The human brain is the most sensitive to hypoxia. Hypoxia will cause dysfunction of the central nervous system, resulting in high-altitude hypoxic brain injury, including mild high altitude headache and more destructive high altitude cerebral edema (HACE). Recently, with more and more people work and live in high altitude areas, the development of high-altitude hypoxic brain injury drugs would produce great economic value and social significance. Non clinical pharmacodynamic evaluation is the basic of drug development, which plays a key role in improving the success rate of clinical transformation and reducing the risk of clinical research. This review summarizes the cell models and animal models, and the evaluation indicators usually used to explore the candidates of high-altitude hypoxic brain injury. We aim at establishing a standardized non clinical efficacy evaluation system for high altitude hypoxic encephalopathy, and provide a standardized reference for drug development in hypoxic encephalopathy at high altitude at nonclinical stage.