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.

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.

Clinical application and research progress of angle Kappa in ophthalmic surgery / 国际眼科杂志(Guoji Yanke Zazhi)

The human eye has various axes and angles, of which the angle Kappa is an important indicator of the centrality of the human eye and is widely used in ophthalmic surgery. Proper preoperative evaluation and application of the angle Kappa facilitated the achievement of optimal postoperative visual quality. Chord mu is a new term that has emerged recently to better express the angle Kappa. The two concepts are not well understood clinically, limiting their usefulness. Therefore, to better understand the angle Kappa and chord mu, the definitions and connections between them are presented separately in this paper. Meanwhile, the application of angle Kappa in strabismus surgery was summarized, the method for compensating large angle Kappa in corneal refractive surgery and the clinical significance of angle Kappa in predicting postoperative centrality of multifocal intraocular lens(MIOL)in phacoemulsification combined with MIOL implantation were discussed, with a view to providing references for clinical work.

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.

Analysis of biochemical and genetic screening results for neonatal methylmalonic acidemia / 中华实用儿科临床杂志

Objective:To investigate the incidence rate and gene variation of methylmalonic academia (MMA) in Ji′nan city by analyzing biochemical and genetic screening results, and to explore the carrier frequency of MMA-related pathogenic genes in the population in Ji′nan.Methods:The children diagnosed with MMA by tandem mass spectrometry screening in Ji′nan Neonatal Disease Screening Centre from May 2011 to May 2022 were enrolled in this study.Their genetic test results were retrospectively analyzed and summarized.The dried heel blood tablets collected from 6 800 newborns were tested for neonatal gene screening. MMAA, MMAB, MMACHC and MMUT genes in 4 800 cases were detected by high-throughput sequencing+ target area capture technology.Ultra-multiplex polymerase chain reaction+ target gene locus capture technology was used to detect 174 target loci of 8 genes related to MMA in 2 000 cases.The hotspot mutation and related gene carrier rate of MMA were analyzed. Results:A total of 367 452 newborns were screened by tandem mass spectrometry, and 103 cases (56 males and 47 females) were diagnosed with MMA by screening.The estimated incidence of MMA was 1∶3 567.Among the 103 MMA cases, 76 were genetically diagnosed, and 4 gene variants of MMA ( MMAHC, MMUT, MMAA, MMADHC) were identified.A total of 6 800 neonates underwent neonatal genetic screening.Three of them were diagnosed with MMA.About 318 infants carried pathogenic variants of MMA, with a total carrier rate of 4.68%.Specifically, the carrier rates of MMACHC and MMUT gene variants were 3.09%(210/6 800) and 1.43% (97/6 800), respectively. Conclusions:MMA is the most common organic acid metabolism disorder in our country.The incidence and carrier rate of this disease are high in Jinan city.Neonatal genetic screening is an important supplement to neonatal biochemical screening.Carrier screening for MMA-related pathogenic genes is recommended for couples of childbearing age in Jinan.

Effect of Fugan Huaxian Decoction （扶肝化纤汤） on Th17/Treg Balance and Related Transcription Factors in Hepatic Fibrosis with Healthy Qi Deficiency and Toxin Accumulation Pattern Model Rats / 中医杂志

ObjectiveTo investigate the possible mechanism of Fugan Huaxian Decoction （扶肝化纤汤， FHD） against hepatic fibrosis （HF） from the perspective of immunity. MethodsForty-eight SD rats were randomly divided into blank group， model group， colchicine group， FHD high-， medium- and low-dose group， with eight rats in each group. Except for the blank group， the disease-syndrome combined model of HF with healthy qi deficiency and toxin accumulation pattern was established during six weeks in the other five groups. After successful modeling， the high-， medium- and low-dose FHD groups were respectively given 37.5， 18.75 and 9.38 g/（kg·d） of FHD granules by gavage， while the colchicine group received 2 mg/ （kg·d） of colchicine tablets by gavage， and the blank group and the model group were given 10 ml/（kg·d） of purified water， all for 3 weeks. The general condition of the rats was recorded. After the treatment， the histopathological morphology of the liver was observed by HE staining， and the levels of interleukin 10 （IL-10） and interleukin 17 （IL-17） in serum were determined by enzyme-linked immunosorbent assay （ELISA）. The expression of helper T cells 17 （Th17） and regulatory T cells （Treg） in peripheral blood were detected by flow cytometry， and the Th17/Treg value was calculated. The mRNA expression of retinoic acid-related nuclear orphan receptor γ （RORγt） and fork-head/wing-like helix transcription factor （FoxP3） in liver tissue were detected by qRT-PCR. ResultsCompared to the general condition of rats in the blank group， those in the model group were listless， less active， stretched and pushed， arched and prone， having no resistance to gavage， significantly reduced food intake， loose stools， dirty anus， slow weight gain， dry and dull hair， purple and darkening skin of the limbs with ecchymoses， purple and black spots with varying degrees of the skin of the tail； hepatic fibrosis and hyperplasia of rats in model group were more obvious； serum IL-17， peripheral blood Th17 expression and Th17/Treg value， RORγt mRNA expression in the liver tissue significantly increased in the model group， while expression of IL-10， Treg and FoxP3 mRNA significantly decreased （P＜0.05 or P＜0.01）. Compared to those in the model group， the general condition of the rats and the liver fibrosis of HE stained liver tissue were improved in all the medication groups； the expression of IL-17 and Th17， Th17/Treg， and RORγt mRNA expression significantly decreased， while expression of IL-10， Treg， and FoxP3 mRNA increased in the high- and medium-dose FHD groups and the colchicine group； the expression of IL-17， Th17， and RORγt mRNA decreased， while the expression of IL-10 and FoxP3 mRNA increased in the low-dose FHD group （P＜0.05 or P＜0.01）. And more improvements were found in the FHD high-dose group than FHD medium- and low-dose groups and colchicine group （P＜0.05 or P＜0.01）. ConclusionFHD can may regulate immune balance and act against fibrosis by regulating the expression of specific transcription factors FoxP3 and RORγt， affecting the differentiation of Th17 and Treg cells and Th17/Treg balance， and regulating the secretion of IL-10 and IL-17.

Study of prefrontal cortex activation characteristics of patients with psychiatric disorders in verbal fluency task using functional near-infrared spectroscopy / 四川精神卫生

BackgroundFunctional near-infrared spectroscopy （fNIRS） is a new generation of imaging tool that can be used to assist the diagnosis of psychiatric disorders. However， whether the patterns of prefrontal cortex activation observed by fNIRS are specific for different psychiatric disorders remains to be explored. ObjectiveTo investigate the characteristics of prefrontal cortex activation in patients with depression， anxiety disorder， bipolar disorder and schizophrenia in verbal fluency task （VFT） using fNIRS. MethodsFrom September to December 2021， 39 patients with schizophrenia， 205 patients with depressive disorder， 212 patients with anxiety disorder and 77 patients with bipolar disorder meeting the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） were recruited in the outpatient and inpatient department of West China Hospital， Sichuan University. fNIRS was used to monitor the prefrontal cortex hemodynamic changes of patients under VFT， and the clinical symptoms of patients were assessed by Symptom Checklist 90 （SCL-90） and Hypomania Checklist-32 items（HCL-32）. Differences in mean oxyhemoglobin （HbO2） concentration and the initial slope from 2 to 7 second during VFT were compared among patients with different diseases， and the correlation between mean HbO2 concentration/initial slope and clinical symptoms was analyzed by partial correlation analysis. ResultsThe concentration of HbO2 in channel 4 （Z=2.828， P=0.028） and channel 6 （Z=2.912， P=0.022） in patients with depression were significantly higher than those in patients with schizophrenia. Patients with anxiety had significantly higher changes in mean HbO2 concentration in channel 4 （Z=3.154， P=0.010）， channel 5 （Z=3.021， P=0.015）， channel 6 （Z=2.980， P=0.017） and of all channels （Z=2.881， P=0.024） than those of schizophrenia patients. There was a statistically significant difference in the initial slope of channel 3 between patients with depressive disorder and those with bipolar disorder （Z=2.691， P=0.039）. Among patients with bipolar disorder， the anger-hostility scores of SCL-90 were negatively correlated with the mean HbO2 concentration changes in channel 4 （r=-0.505， P=0.004）， channel 6 （r=-0.390， P=0.004）， channel 15 （r=-0.546， P=0.002）， channel 16 （r=-0.550， P=0.002） and the mean HbO2 concentration changes of all channels （r=-0.491， P=0.006）. ConclusionPatients with schizophrenia had lower activation in frontopolar and orbitofrontal region than patients with depression and anxiety disorder， and the initial slope of the right frontopolar， inferior frontal and orbitofrontal region in patients with depression is higher than patients with bipolar disorder. In addition， patients with bipolar disorder had less activation in the frontopolar and orbitofrontal lobe， the insular cover of Broca's area and the upper outer frontal cortex， and were more irritable and hostile. ［Funded by 1·3·5 Project for Disciplines of Excellence-Clinical Research Incubation Project， West China Hospital， Sichuan University （number， ZYJC21083）］

Effects of RNA M6A demethylase ALKBH5 gene deficiency on morphology and function of cerebellum in aged mice / 中华病理学杂志

Objective: To investigate the effects of RNA m6A demethylase ALKBH5 gene deficiency on cerebellar morphology and function in the aged mice, and to explore the role of ALKBH5 in cerebellar degeneration. Methods: Western blot was performed to detect the protein level of ALKBH5 in the cerebellum of wild-type mice of various ages. The expression of NeuN, Calbindin-D28K, MAP2, GFAP and other proteins in the cerebella of middle-aged (12-month-old) and aged (18-month-old) wild-type mice and ALKBH5-/- mice was examined using immunohistochemistry. The balance beam test and gait analysis were performed to test the balance ability and motor coordination of the mice. Results: With aging of the mice, the expression of ALKBH5 in the cerebellum increased gradually in an age-dependent manner. In the aged mice, but not middle-aged mice, the body weight, whole brain weight and cerebellum weight of ALKBH5-/- mice decreased by 15%, 10% and 21%, respectively (P<0.05). The expression of ALKBH5 in the Purkinje cells was much higher than that in other types of neural cells. Correspondingly, ALKBH5-deficiency caused 40% reduction in the number of Purkinje cells, as well as the length and density of neuronal dendrites in the aged mice (P<0.01). In addition, the time for the aged ALKBH5-/- mice to pass the balance beam was 70% longer than that of the wild type mice of the same age, with unstable gaits (P<0.01). Conclusions: Gene deficiency of RNA m6A demethylase ALKBH5 causes cerebellar atrophy, Purkinje neuron loss and damage in the aged mice. These changes eventually affect mice's motor coordination and balance ability. These results suggest that imbalanced RNA m6A methylation may lead to neurodegenerative lesions in the cerebellum of mice.

Signal transducer and activator of transcription 3 and cancer associated fibroblasts jointly generate chemo-resistance and affect prognosis in epithelial ovarian cancer / 中华妇产科杂志

Objective: To investigate the mechanism of signal transducer and activator of transcription 3 (STAT3) and cancer associated fibroblasts (CAF) jointly generate chemo-resistance in epithelial-ovarian cancer and their effect on prognosis. Methods: A total of 119 patients with high-grade ovarian serous cancer who received surgery in Cancer Hospital of Chinese Academy of Medical Sciences from September 2009 to October 2017 were collected. The clinico-pathological data and follow-up data were complete. Multivariate Cox regression model was used to analyze the prognostic factors. Ovarian cancer tissue chips of patients in our hospital were prepared. EnVision two-step method immunohistochemistry was used to detect the protein expression levels of STAT3, the specific markers of CAF activation, fibroblast activating protein (FAP), and type Ⅰ collagen (COL1A1) secreted by CAF. The relationship between the expression of STAT3, FAP, COL1A1 protein and drug resistance and prognosis of ovarian cancer patients was analyzed, and the correlation between the expression of three proteins was analyzed. These results were verified through the gene expression and prognostic information of human ovarian cancer tissues collected in the GSE26712 dataset of gene expression omnibus (GEO) database. Results: (1) Multivariate Cox regression model analysis showed that chemotherapy resistance was an independent risk factor for overall survival (OS) of ovarian cancer (P<0.001). (2) The expression levels of STAT3, FAP, and COL1A1 proteins in chemotherapy resistant patients were significantly higher than those in chemotherapy sensitive patients (all P<0.05). Patients with high expression of STAT3, FAP, and COL1A1 had significantly shorter OS than those with low expression (all P<0.05). According to the human ovarian cancer GSE26712 dataset of GEO database, patients with high expression of STAT3, FAP, and COL1A1 also showed shorter OS than patients with low expression (all P<0.05), the verification results were consistent with the detection results of ovarian cancer patients in our hospital. (3) Correlation analysis showed that the protein level of STAT3 was positively correlated with FAP and COL1A1 in our hospital's ovarian cancer tissue chips (r=0.47, P<0.001; r=0.30, P=0.006), the analysis of GEO database GSE26712 dataset showed that the expression of STAT3 gene and FAP, COL1A1 gene were also significantly positively correlated (r=0.31, P<0.001; r=0.52, P<0.001). Conclusion: STAT3 and CAF could promote chemotherapy resistance of ovarian cancer and lead to poor prognosis.

Association between gestational diabetes mellitus and preterm birth subtypes / 中华流行病学杂志

Objective: To investigate the association between gestational diabetes mellitus (GDM) and preterm birth subtypes. Methods: Based on the cohort of pregnant women in Anqing Prefectural Hospital, the pregnant women who received prenatal screening in the first or second trimesters were recruited into baseline cohorts; and followed up for them was conducted until delivery, and the information about their pregnancy status and outcomes were obtained through electronic medical record system and questionnaire surveys. The log-binomial regression model was used to explore the association between GDM and preterm birth [iatrogenic preterm birth, spontaneous preterm birth (preterm premature rupture of membranes and preterm labor)]. For multiple confounding factors, the propensity score correction model was used to compute the adjusted association. Results: Among the 2 031 pregnant women with a singleton delivery, the incidence of GDM and preterm birth were 10.0% (204 cases) and 4.4% (90 cases) respectively. The proportions of iatrogenic preterm birth and spontaneous preterm birth in the GDM group (n=204) were 1.5% and 5.9% respectively, while the proportions in non-GDM group (n=1 827) were 0.9% and 3.2% respectively, and the difference in the proportion of spontaneous preterm birth between the two groups was significant (P=0.048). Subtypes of spontaneous preterm were further analyzed, and the results showed that the proportions of preterm premature rupture of membranes and preterm labor in the GDM group were 4.9% and 1.0% respectively, while the proportions in the non-GDM group were 2.1% and 1.1% respectively. It showed that the risk of preterm premature rupture of membranes in GDM pregnant women was 2.34 times (aRR=2.34, 95%CI: 1.16-4.69) higher than that in non-GDM pregnant women. Conclusions: Our results showed that GDM might increase the risk of preterm premature rupture of membranes. No significant increase in the proportion of preterm labor in pregnant women with GDM was found.

Preliminary study of PPARA regulate the ferroptosis of hepatocellular carcinoma to prevent disease deterioration / 中华预防医学杂志

To explore whether PPARA is involved in the process of ferroptosis in hepatoma cells, peroxisome proliferator activated receptor (PPARA) was comprehensively analyzed in hepatocellular carcinoma (HCC) through public database and experimental data, including the expression, the functions and the potential roles of tumor progression. The research design is experimental research,data analysis based on bioinformatics and cell experiment. From January 2022 to August 2022, relevant cell experiments were conducted in the Basic Medical Laboratory of the General Hospital of the Southern Theatre of the Chinese People's Liberation Army. The expression and the correlation with clinicopathologic features of PPARA in HCC were analyzed by The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. To study the protein expression of PPARA in HCC and normal tissues through the Human Protein Atlas (HPA). The protein-protein interaction (PPI) network between PPARA and the core factor of ferroptosis was constructed based on Search Tool for the Retrival of Interacting Genes/Protein (STRING) database, then, the correlation between PPARA and the core gene Glutamate-cysteine Ligase Catalytic Subunit (GCLC) was analyzed by Gene Expression Profiling Interactive Analysis (GEPIA). Assessed the expression of PPARA in HCC cell lines SK-HEP-1, SMMC-7721, MHCC-97H, BEL-7402 and normal liver cell L02 by Western Blot (WB) and the changes of PPARA expression after 48h treatment with ferroptosis inducer Erastin were observed. Single factor analysis of variance was used to compare the expression of PPARA between groups in GEPIA database. The expression of PPARA in GSE25097 and GSE112790 data was compared by rank sum test. Survival analysis was performed using time series test method. The difference of PPARA expression between clinical and pathological features was compared using the Kruskal-Wallis test. The correlation between the expression of GCLC and PPARA was compared by the method of Spearman correlation. The expression of PPARA in cell lines was compared by paired T test. The results showed that the RNA and protein expression of PPARA in HCC was lower than that in normal tissues (P<0.05). PPARA alterations were correlated with patient clinicopathological features and prognosis (P<0.05). The PPI constructed by STRING database suggests that PPARA interact with the key factors of ferroptosis, such as NFE2 like bZIP transcription factor 2 (NFE2L2), Heme Oxygenase 1 (HMOX1), Tumor Protein P53 (TP53), GCLC, Dipeptidyl Peptidase 4 (DPP4), Citrate Synthase (CS), Arachidonate 15-Lipoxygenase (ALOX15) and Acyl-CoA Synthetase Long Chain Family Member 4 (ACSL4). Furthermore, the PPARA was significantly associated with GCLC validated via GEPIA database(R=0.6, P<0.05). The expression of PPARA increased after treatment with ferroptosis inducer Erastin for 48 h by WB. In conclusion, the expression of PPARA is lower in HCC with a poor prognosis. PPARA interacts with GCLC in regulating ferroptosis in HCC.

Xingnao Kaiqiao acupuncture on promoting wake-up of consciousness disorder in children with early severe traumatic brain injury / 中国针灸

OBJECTIVE@#To observe the awakening effect and safety of Xingnao Kaiqiao (regaining consciousness and opening orifices) acupuncture on consciousness disorder in children with early severe traumatic brain injury (STBI) based on western medicine treatment.@*METHODS@#A total of 62 children with STBI were randomly divided into an observation group (31 cases,1 case dropped off) and a control group (31 cases, 1 case dropped off). The control group was treated with routine rehabilitation therapy (6 times a week for 30 days), and intravenous drip of cattle encephalon glycoside and ignotin injection (once a day for 28 days). On the basis of the treatment in the control group, the observation group was treated with Xingnao Kaiqiao acupuncture at Neiguan (PC 6), Shuigou (GV 26), Yintang (GV 24+), Baihui (GV 20), Sanyinjiao (SP 6), Zusanli (ST 36), etc., and supplementary acupoints according to clinical symptoms, once a day, 6 times a week for 30 days. The scores of Glasgow coma scale (GCS), coma recovery scale-revised (CRS-R) and modified Barthel index (MBI) were observed before treatment and 10, 20 and 30 d into treatment. Electroencephalogram (EEG) grading before and after treatment was observed in the two groups, and safety was evaluated.@*RESULTS@#After 10, 20 and 30 days of treatment, the scores of GCS, CRS-R and MBI in the two groups were increased compared before treatment (P<0.05), and those in the observation group were higher than the control group (P<0.05). After treatment, EEG grading of both groups was improved compared with that before treatment (P<0.05), and the observation group was better than the control group (P<0.05). There were no adverse events or adverse reactions in the two groups during treatment.@*CONCLUSION@#On the basis of western medicine treatment, Xingnao Kaiqiao acupuncture plays a remarkable role in wakening the early STBI children, can improve the level of consciousness disorder and daily living ability, and it is safe and effective.

Pathological features and immune microenvironment in HER-2 intratumoral heterogeneous breast cancers / 中华肿瘤杂志

Objective: To observe the clinical pathology features, and immune microenvironment of HER-2 intratumoral heterogeneity breast cancer. Methods: Thirty cases of HER-2 intratumoral heterogeneous breast cancer were retrospectively analyzed in Tianjin Medical University Cancer Institute and Hospital from November 2017 to June 2020. HER-2 expression was detected by immunohistochemistry and verified by dual color silver-enhanced in-situ hybridization (D-SISH). HER-2 intratumoral positive and negative regions were divided. The pathological characteristics, subtype, and the level of tumor infiltrating lymphocytes (TILs) and the expression of programmed cell death-ligand 1 (PD-L1) were evaluated respectively. Results: The proportion of HER-2 positive cells of the breast cancer ranged from 10% to 90%. The pathological type was mainly invasive non-special typecarcinoma. Six cases presented different pathological types between HER-2 positive and negative regions. The HER-2-positive areas included 2 cases of carcinoma with apocrine differentiation, and the negative areas included 2 cases of invasive micropapillary carcinoma, 1 case of invasive papillary carcinoma, and 1 case of carcinoma with apocrine differentiation. In HER-2 positive regions, 17 cases were Luminal B and 13 cases were HER-2 overexpressed types. There were 22 cases of Luminal B and 8 cases of triple negative tumors in the HER-2 negative areas. The levels of TILs in HER-2 positive and negative areas accounted for 53.3% (16/30) and 26.7% (8/30), respectively, with a statistically significant difference (P=0.035). The positive expression of PD-L1 in HER-2 positive area and HER-2 negative area were 6 cases and 9 cases, respectively. Among 8 cases with HER-2 negative regions containing triple negative components, 4 cases were positive for PD-L1 expression. Conclusions: In the case of HER-2 intratumoral heterogeneity, it is necessary to pay attention to both HER-2 positive and negative regions, and evaluate subtype separately as far as possible. For HER-2 intratumoral heterogeneous breast cancer containing triple negative components, the treatment mode can be optimized by refining the intratumoral expression of PD-L1.

Satisfaction of Patients with Above-the-knee Amputation following Periprosthetic Joint Infection / 中山大学学报(医学科学版)

ObjectiveThe purpose of this study was to evaluate the functional outcomes and satisfaction in periprosthetic knee infection patients after above-the-knee amputation （AKA）. MethodsA review was performed in 13 patients who underwent AKA due to periprosthetic knee infection from October 2010 to August 2022， there were 7 females and 6 males with the median age of 69 （45~ 73） years. The mean number of surgical procedures between primary total knee arthroplasty and AKA was 2.9 times （range： 1 ~ 6）. Patients were segregated into non-elderly group （including patients <65 years old） and elderly group （involving patients ≥65 years old）. Functional outcomes were evaluated by SF-12 and Barthel activities daily living index （Barthel ADL index）. Patient satisfaction was accomplished through a questionnaire. ResultsFour patients died within 6 months after the amputation. Three patients received surgical procedures for recurrent infections after AKA. In the remaining 9 patients，the median time from AKA to the final follow-up was 4.2 （1.9~8.2） years， three patients received surgical procedures for recurrent infections after AKA. Patients in non-elderly group showed better functional outcomes than elderly patients after AKA （both P<0.05）. All patients in non-elderly group were fitted with a prosthesis. Whereas， elderly patients reported a better satisfaction after AKA than young patients. ConclusionYoung PJI patients seemed to have better function and ambulatory ability with high expectation and demand， which made them feel less satisfied about AKA. Meanwhile，despite poor function outcomes due to the less healthy physical condition， the alleviation of financial and psychological burdens resulting from reinfections and multiple surgeries and the less demand in function and daily activities made elderly patients have a good satisfaction after AKA.