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

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

Study on the correlation between meibomian gland dysfunction and sleep quality / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To study the correlation between meibomian gland dysfunction(MGD)patients and their sleep quality.METHODS: Retrospective case-control study. A total of 150 MGD patients treated in our hospital from January 2021 to October 2022 were selected and divided into sleep disorder group(75 cases, PSQI&#x003E;10 points)and control group(75 cases, PSQI≤10 points)according to the Pittsburgh sleep quality index(PSQI). Both groups were scored using the ocular surface disease index(OSDI), underwent meibomian gland-related examinations(eyelid margin morphology, meibomian gland secretion ability, meibomian gland secretion quality score), corneal fluorescein staining(FL)score, Schirmer Ⅰ test(SⅠt), tear film break-up time(BUT)was measured, and sleep indicators(sleep quality, sleep latency, subjective sleep quality, sleep time)were evaluated.RESULTS: There were significant differences in OSDI score, FL score, SⅠt, BUT, eyelid margin morphology score, meibomian gland secretion ability score, and meibomian gland secretion quality score between the two groups(P&#x003C;0.05). In the sleep disorder group, PSQI score, sleep latency score, subjective sleep quality score, and sleep time score were significantly positively correlated with OSDI score, FL score, meibomian gland secretion ability score, and meibomian gland secretion quality score(P&#x003C;0.05); PSQI score, subjective sleep quality score, and sleep time score were significantly positively correlated with eyelid margin morphology score(P&#x003C;0.05); PSQI score, sleep latency score, and subjective sleep quality score were significantly negatively correlated with BUT and SⅠt(P&#x003C;0.05); sleep time score was significantly negatively correlated with BUT(P&#x003C;0.05); sleep latency score was not significantly correlated with eyelid margin morphology score(P&#x003E;0.05); sleep time score was not significantly correlated with SⅠt(P&#x003E;0.05).CONCLUSION:The ocular surface condition of MGD patients is correlated with multiple sleep quality indicators, and a decline in sleep quality may increase the risk of MGD.

Projection-Specific Heterogeneity of the Axon Initial Segment of Pyramidal Neurons in the Prelimbic Cortex / 神经科学通报·英文版

The axon initial segment (AIS) is a highly specialized axonal compartment where the action potential is initiated. The heterogeneity of AISs has been suggested to occur between interneurons and pyramidal neurons (PyNs), which likely contributes to their unique spiking properties. However, whether the various characteristics of AISs can be linked to specific PyN subtypes remains unknown. Here, we report that in the prelimbic cortex (PL) of the mouse, two types of PyNs with axon projections either to the contralateral PL or to the ipsilateral basal lateral amygdala, possess distinct AIS properties reflected by morphology, ion channel expression, action potential initiation, and axo-axonic synaptic inputs from chandelier cells. Furthermore, projection-specific AIS diversity is more prominent in the superficial layer than in the deep layer. Thus, our study reveals the cortical layer- and axon projection-specific heterogeneity of PyN AISs, which may endow the spiking of various PyN types with exquisite modulation.

Application of back-forward Bending CT localization image in the prediction of proximal junctional kyphosis after spinal deformity surgery in adults / 中国修复重建外科杂志

OBJECTIVE@#To investigate the feasibility of predicting proximal junctional kyphosis (PJK) in adults after spinal deformity surgery based on back-forward Bending CT localization images and related predictive indicators.@*METHODS@#A retrospective analysis was performed for 31 adult patients with spinal deformity who underwent posterior osteotomy and long-segment fusion fixation between March 2017 and March 2020. There were 5 males and 26 females with an average age of 62.5 years (range, 30-77 years). The upper instrumented vertebrae (UIV) located at T 5 in 1 case, T 6 in 1 case, T 9 in 13 cases, T 10 in 12 cases, and T 11 in 4 cases. The lowest instrumented vertebrae (LIV) located at L 1 in 3 cases, L 2 in 3 cases, L 3 in 10 cases, L 4 in 7 cases, L 5 in 5 cases, and S 1 in 3 cases. Based on the full-length lateral X-ray film of the spine in the standing position before and after operation and back-forward Bending CT localization images before operation, the sagittal sequence of the spine was obtained, and the relevant indexes were measured, including thoracic kyphosis (TK), lumbar lordosis (LL), local kyphosis Cobb angle (LKCA) [the difference between the different positions before operation (recovery value) was calculated], kyphosis flexibility, hyperextension sagittal vertical axis (hSVA), T 2-L 5 hyperextension C 7-vertebral sagittal offset (hC 7-VSO), and pre- and post-operative proximal junctional angle (PJA). At last follow-up, the patients were divided into PJK and non-PJK groups based on PJA to determine whether they had PJK. The gender, age, body mass index (BMI), number of fusion segments, number of cases with coronal plane deformity, bone mineral density (T value), UIV position, LIV position, operation time, intraoperative blood loss, osteotomy grading, and related imaging indicators were compared between the two groups. The hC 7-VSO of the vertebral body with significant differences between groups was taken, and the receiver operating characteristic curve (ROC) was used to evaluate its accuracy in predicting the occurrence of PJK.@*RESULTS@#All 31 patients were followed up 13-52 months, with an average of 30.0 months. The patient's PJA was 1.4°-29.0° at last follow-up, with an average of 10.4°; PJK occurred in 8 cases (25.8%). There was no significant difference in gender, age, BMI, number of fusion segments, number of cases with coronal plane deformity, bone mineral density (T value), UIV position, LIV position, operation time, intraoperative blood loss, and osteotomy grading between the two groups ( P>0.05). Imaging measurements showed that the LL recovery value and T 8-L 3 vertebral hC 7-VSO in the PJK group were significantly higher than those in the non-PJK group ( P>0.05). There was no significant difference in hyperextension TK, hyperextension LL, hyperextension LKCA, TK recovery value, LL recovery value, kyphosis flexibility, hSVA, and T 2-T 7, L 4, L 5 vertebral hC 7-VSO ( P>0.05). T 8-L 3 vertebral hC 7-VSO was analyzed for ROC curve, and combined with the area under curve and the comprehensive evaluation of sensitivity and specificity, the best predictive index was hC 7-L 2, the cut-off value was 2.54 cm, the sensitivity was 100%, and the specificity was 60.9%.@*CONCLUSION@#Preoperative back-forward Bending CT localization image can be used to predict the occurrence of PJK after posterior osteotomy and long-segment fusion fixation in adult spinal deformity. If the patient's T 8-L 2 vertebral hC 7-VSO is too large, it indicates a higher risk of postoperative PJK. The best predictive index is hC 7-L 2, and the cut-off value is 2.54 cm.

Efficacy of autologous peripheral blood nucleated cell therapy on periocular wrinkles / 中华医学美学美容杂志

Objective:To explore the clinical effect of dermal and subcutaneous injection of autologous peripheral blood nucleated cells in improving periocular wrinkles.Methods:Eighteen cases of beauty seekers who planned to improve periocular wrinkles were selected as the research objects of this study. Autologous nucleated cells and blood active components were isolated and purified by negative collection mixed method and evenly injected into the periocular skin of patients. VISIA image analysis system, and satisfactory score were used to detect and evaluate the related characteristics of periocular skin at different stages before and after treatment. The scores were compared and analyzed, and the complications after treatment were recorded.Results:The 18 patients were followed up. The score of VISIA periorbital static wrinkles decreased from (22.09±8.21) before treatment to (18.31±7.84) one month after treatment, and the difference was statistically significant ( t=-7.495, P<0.05). 17 patients were satisfied; After 3 months of follow-up, 15 cases were satisfied. The texture, consistency and pore state of periorbital skin were improved in some patients (10 cases). Conclusions:Autologous peripheral blood nucleated cell therapy can improve periorbital wrinkles, especially skin fine lines, and geta high satisfactory rate. There are almost no adverse reactions after the treatment, which is worthy of clinical application.

Changes of corneal nerve fiber and the correlation analysis with visual acuity in demyelinating optical neuritis patients / 中华眼底病杂志

Objective:To investigate the changes in the nerve fiber layer of the cornea in patients with demyelinating optic neuritis (DON) and its correlation with visual acuity.Methods:A cross-sectional study. From March 2021 to July 2022, 27 cases (39 eyes) of DON patients diagnosed in the Department of Neurology and Ophthalmology of Beijing Tongren Hospital Affiliated to Capital Medical University were enrolled in this study. According to the serological test results, the patients were divided into aquaporin 4 antibody associated optic neuritis (AQP4-ON group) and myelin oligodendrocyte glycoprotein antibody associated optic neuritis (MOG-ON group), with 15 cases (19 eyes) and 12 cases (20 eyes) respectively. According to previous history of glucocorticoid treatment, the patients were divided into glucocorticoid treated group and non-glucocorticoid treated group, with 17 cases (27 eyes) and 10 cases (12 eyes) respectively. Twenty healthy volunteers (20 eyes) with age- and gender-matched were selected as the control group. All eyes underwent best corrected visual acuity (BCVA) and in vivo confocal microscopy (IVCM) examinations. BCVA was performed using Snellen's standard logarithmic visual acuity chart, which was converted into logarithmic minimum angle resolution (logMAR) visual acuity during statistics. The corneal nerve fiber length (CNFL), corneal nerve fiber density (CNFD), corneal nerve fiber branch length (CNBL), corneal nerve fiber branch density (CNBD) and the density of corneal dendritic cells (DC) were detected by IVCM examination. Parameter comparison between groups by t-test and Kruskal-Wallis rank sum test. The correlation between logMAR BCVA and pamameters of corneal nerve fibers were analyzed using Spearman analysis. Results:The CNFL, CNFD, and CNBL of the DON group and the control group were (10.67±2.55) mm/mm 2, (57.78±12.35) root/mm 2, (3.27±1.34) mm/mm 2, and (13.74±3.05) mm/mm 2, (70.95±13.14) root/mm 2, and (4.22±1.03) mm/mm 2, respectively; the difference in CNFL, CNFD, and CNBL between the two groups were statistically significant ( t=4.089, 3.795, 2.773; P<0.05). The CNFL, CNBL, and CNBD of the affected eyes in the MOG-ON group and AQP4-ON group were (12.02±2.13) mm/mm 2, (3.80±1.19) mm/mm 2, (47.97±8.86) fibers/mm 2, and (9.25±2.19) mm/mm 2, (2.72±1.19) mm/mm 2, (39.43±13.86) fibers/mm 2, respectively; the differences in CNFL, CNBL, and CNBD between the two groups were statistically significant ( t=-4.002, -2.706, -2.306; P<0.05). The corneal DC density of the patients in the hormone treated group and the non-hormone treated group was (24.43±8.32) and (41.22±9.86) cells/mm 2, respectively. The difference in corneal DC density between the two subgroups was statistically significant ( P<0.001). Correlation analysis showed that there was a significant negative correlation between logMAR BCVA and CNBL and CNFL in patients with DON ( r=-0.422, -0.456; P<0.05). Conclusions:There are different degrees of corneal nerve fiber damage in patients with different types of DON. There was a negative correlation between BCVA and the length of corneal nerve fibers.

Difference and its clinical significance of peripheral blood lymphocyte subsets between elderly and non-elderly patients with rheumatoid arthritis / 中华老年医学杂志

Objective:To investigate the difference of lymphocyte subsets between elderly patients with rheumatoid arthritis and non-elderly patients and its clinical significance.Methods:A total of 124 patients with rheumatoid arthritis in Affiliated Hospital of Nantong University from January, 2017 to December, 2019 were enrolled.The patients were divided into elderly group(≥60 years old, 34 cases)and non-elderly group(<60 years old, 90 cases). Rheumatoid arthritis activity(DAS-28)scoring was performed for each patient.Peripheral blood mononuclear cells(PBMCs)were extracted by Ficoll density centrifugation.Lymphocytes were labeled and detected by 18-color flowcytometry with more than 30 fluorescent antibodies.Results:DAS-28 scoring showed that the disease activity score of the elderly group(4.56±1.89)was higher than that of the non-elderly group(3.37±1.49)( t=3.633, P<0.001). Flow cytometry showed that MAIL%T(mucus-associated lymphoid tissue T cell subset)( Z=-2.798, P=0.005), Tn%CD8 T cells(initial CD8 T cells)( Z=-2.179, P=0.029), VD2% T(Vδ2+ T, γδT cell subtype)( Z=-2.806, P=0.005), PD1-CD28-%Th( Z=-2.050, P=0.040)and IGM+ D-%B( Z=-2.376, P=0.017)were lower in the elderly group than in the non-elderly group.While, CD45+ CD27+ %CD8 T cells( Z=-3.069, P=0.002), abT%T cell(αβT cells)( Z=-2.103, P=0.035), CD27-CD28+ %T cells( Z=-2.341, P=0.019), ASC%PBMC( Z=-2.341, P=0.019)and ASC%CD19+ ( Z=-2.000, P=0.046)subgroup expression were higher in the elderly group than in the non-elderly group. Conclusions:The disease activity of elderly patients with rheumatoid arthritis is significantly higher than that of younger patients.The expressions of abT%T and CD4% abT in effector T cells of elderly patients with rheumatoid arthritis are higher than those of younger patients, while the expression of VD2% T is lower.The expression level of CD45RA+ CD27+ %CD8 T with cytotoxic effect is higher; However, the expression level of Tn%CD8 T in naive cells is lower.

The single nucleotide polymorphism rs1814521 in long non-coding RNA ADGRG3 associates with the susceptibility to silicosis: a multi-stage study

BACKGROUND@#This study aimed to evaluate the correlation between long non-coding RNA (lncRNA)-related single nucleotide polymorphisms (SNPs) and susceptibility to silicosis.@*METHODS@#First, RNA-sequencing (RNA-seq) data were comprehensively analyzed in the peripheral blood lymphocytes of eight participants (four silicosis cases and four healthy controls) exposed to silica dust to identify differentially expressed lncRNAs (DE-lncRNAs). The functional SNPs in the identified DE-lncRNAs were then identified using several databases. Finally, the association between functional SNPs and susceptibility to silicosis was evaluated by a two-stage case-control study. The SNPs of 155 silicosis cases and 141 healthy silica-exposed controls were screened by genome-wide association study (GWAS), and the candidate SNPs of 194 silicosis cases and 235 healthy silica-exposed controls were validated by genotyping using the improved Mutiligase Detection Reaction (iMLDR) system.@*RESULTS@#A total of 76 DE-lncRNAs were identified by RNA-seq data analysis (cut-offs: fold change > 2 or fold change < 0.5, P < 0.05), while 127 functional SNPs among those 76 DE-lncRNAs were identified through multiple public databases. Furthermore, five SNPs were found to be significantly correlated with the risk of silicosis by GWAS screening (P < 0.05), while the results of GWAS and iMLDR validation indicated that the variant A allele of rs1814521 was associated with a reduced risk of silicosis (OR = 0.76, 95% CI = 0.62-0.94, P = 0.011).@*CONCLUSION@#The presence of the SNP rs1814521 in the lncRNA ADGRG3 is associated with susceptibility to silicosis. Moreover, ADGRG3 was found to be lowly expressed in silicosis cases. The underlying biological mechanisms by which lncRNA ADGRG3 and rs1814521 regulate the development of silicosis need further study.

Effects of Postmortem Hemolysis and Ultrafiltration on Creatinine Detection Results / 法医学杂志

OBJECTIVES@#To investigate the interference of postmortem hemolysis on the detection of creatinine and whether ultrafiltration can reduce the interference.@*METHODS@#A total of 33 non-hemolyzed whole blood samples from the left heart were collected. Hemolyzed samples with 4 hemoglobin mass concentration gradients H1-H4 were artificially prepared. Ultrafiltration was performed on each hemolyzed sample. Creatinine concentrations in non-hemolyzed serum (baseline serum), hemolyzed samples and ultrafiltrate were detected. Bias (B), Pearson correlation and receiver operator characteristic (ROC) of baseline creatinine concentration between before and after ultrafiltration were analyzed.@*RESULTS@#As the hemoglobin mass concentration increased, B of the hemolyzed samples in the H1-H4 groups gradually increased, the |B| was 2.41(0.82, 8.25)-51.31(41.79, 188.25), reaching a maximum of 589.06%, and there was no statistically significant between the creatinine concentration and the baseline creatinine concentration (P=0.472 7, r=0.129 5). After ultrafiltration of hemolyzed samples, the interference of creatinine concentration in ultrafiltrate was significantly reduced, the |B| was 5.32(2.26, 9.22)-21.74(20.06, 25.58), reaching a maximum of 32.14%, and there was a positive correlation with baseline creatinine concentration (P<0.05, r=0.918 2). In the hemolyzed samples of H3 and H4 groups, there were 7 false-positive samples and 1 false-negative sample; in the ultrafiltrate samples, there were no false-positive sample and 1 false-negative sample. ROC analysis results showed the hemolyzed samples were lack of diagnostic value (P=0.117 5).@*CONCLUSIONS@#The postmortem hemolysis significantly interferes creatinine detection results of blood samples, ultrafiltration can reduce hemolysis-induced interference in postmortem creatinine detection.

Application Prospect of Integrative Omics in Forensic Identification of Methamphetamine-Associated Psychosis / 法医学杂志

The clinical symptoms and signs of methamphetamine-associated psychosis (MAP) and schizophrenia are highly similar, but the situation is completely different when MAP and schizophrenia patients need to be assessed for criminal responsibility after they comitted a harmful behavior. Therefore, the distinction between the two psychoses is very important in forensic psychiatry. At present, the identification of these two psychoses is mainly dependent on the corresponding criteria such as the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and the Chinese Classification of Mental Disorders Version 3 (CCMD-3). It's challenging to diagnose and distinguish between the two in practical cases due to their similar clinical symptoms and the lack of effective objective indexes. Different from the limitations of single omics, integrative omics intergrates data from multiple dimensions and has been extensively studied in the field of schizophrenia and has achieved some preliminary results. In view of the correlation between MAP and schizophrenia and the potential application value of integrative omics, this paper proposes an integrative omics strategy for MAP pathogenesis and forensic identification, aiming to improve the further understanding of the relationship between the two psychoses and the corresponding pathogenesis. It also provides references for the future exploration of integrative omics in forensic precise identification and effective monitoring and early warning methods.

Inferring Postmortem Submersion Interval in Rats Found in Water Based on Vitreous Humor Metabolites / 法医学杂志

OBJECTIVES@#The metabolomics technique of LC-MS/MS combined with data analysis was used to detect changes and differences in metabolic profiles in the vitreous humor of early rat carcasses found in water, and to explore the feasibility of its use for early postmortem submersion interval (PMSI) estimation and the cause of death determination.@*METHODS@#The experimental model was established in natural lake water with 100 SD rats were randomly divided into a drowning group (n=50) and a postmortem (CO2 suffocation) immediately submersion group (n=50). Vitreous humor was extracted from 10 rats in each group at 0, 6, 12, 18 and 24 h postmortem for metabolomics analyses, of which 8 were used as the training set to build the model, and 2 were used as test set. PCA and PLS multivariate statistical analysis were performed to explore the differences in metabolic profiles among PMSI and causes of death in the training set samples. Then random forest (RF) algorithm was used to screen several biomarkers to establish a model.@*RESULTS@#PCA and PLS analysis showed that the metabolic profiles had time regularity, but no differences were found among different causes of death. Thirteen small molecule biomarkers with good temporal correlation were selected by RF algorithm. A simple PMSI estimation model was constructed based on this indicator set, and the data of the test samples showed the mean absolute error (MAE) of the model was 0.847 h.@*CONCLUSIONS@#The 13 metabolic markers screened in the vitreous humor of rat corpses in water had good correlations with the early PMSI. The simplified PMSI estimation model constructed by RF can be used to estimate the PMSI. Additionally, the metabolic profiles of vitreous humor cannot be used for early identification of cause of death in water carcasses.

Study on mechanisms of Th17/Treg imbalance in patients with cystic echinococcosis based on miRNA expression profiles / 中国血吸虫病防治杂志

OBJECTIVE@#To investigate the serum microRNA (miRNA) expression and examine the impact of miRNA expression profiles on T helper type 17 (Th17)/regulatory T cells (Treg) imbalance among patients with cystic echinococcosis, so as to provide insights into the illustration of the mechanisms underlying chronic Echinococcus granulosus infections, and long-term pathogenesis.@*METHODS@#Total RNA was extracted from the sera of cystic echinococcosis patients and healthy controls, and subjected to high-throughput sequencing with the Illumina sequencing platform. Known miRNAs were annotated and new miRNAs were predicted using the miRBase database and the miRDeep2 tool, and differentially expressed miRNAs were identified. The target genes of differentially expressed miRNAs were predicted using the software miRanda and TargetScan, and the intersection was selected for Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Among the differentially expressed miRNAs with the 20 highest fold changes, miRNAs that targeted genes relating to key transcription factors RORC and FOXP3 that determine the production of Th17 and Treg cells or their important regulatory pathways (PI3K-Akt and mTOR pathways) were matched.@*RESULTS@#A total of 53 differentially expressed miRNAs were screened in sera of cystic echinococcosis patients and healthy controls, including 47 up-regulated miRNAs and 6 down-regulated miRNAs. GO enrichment analysis showed that these differentially expressed miRNA were involved DNA transcription and translation, cell components, cell morphology, neurodevelopment and metabolic decomposition, and KEGG pathway analysis showed that the differentially expressed miRNA were mainly involved in MAPK, PI3K-Akt and mTOR signaling pathways. Among the differentially expressed miRNAs with the 20 highest fold changes, there were 3 miRNAs that had a potential for target regulation of RORC, and 15 miRNAs that had a potential to target the PI3K-Akt and mTOR signaling pathways.@*CONCLUSIONS@#Significant changes are found in serum miRNA expression profiles among patients with E. granulosus infections, and differentially expressed miRNAs may lead to Th17/Treg imbalance through targeting the key transcription factors of Th17/Treg or PI3K-Akt and mTOR pathways, which facilitates the long-term parasitism of E. granulosus in hosts and causes a chronic disease.

Development and reflection of revisional bariatric surgery / 中华消化外科杂志

Obesity is one of the most challenging global public health issues, and more than half of adults in Chia are overweight or obese. Obesity has been shown to be a risk factor for type 2 diabetes, cardiovascular disease, colon cancer and other specific cancers, and has become a serious threat and even a danger to the health and quality of life of the nation. With the mature development of bariatric surgery in the last 20 years, it is now widely recognized for its effectiveness and safety in the treatment of obesity and related metabolic diseases, as well as improving patients′ life expectancy and quality of life. However, previous data from the literatures suggest that some patients require revisional surgery after bariatric surgery, with the incidence of revisional bariatric surgery as 5% to 50%. The main reasons for revisional bariatric surgery are poor post-operative outcomes, including the lack of significant weight loss, weight regain and no significant improvement or even recurrence of associated metabolic disease, and other reasons include the development of anaemia, malnutrition and long-term chronic pain. Currently, there is only the East Asian expert consensus on revised bariatric surgery proposed by Chinese Society for Metabolic & Bariatric Surgery in 2018. However, there are still no uniform standards regarding the indications, contraindications and surgical modalities of revisional bariatric surgery in clinical practice. The authors summarize the latest researches of revisional bariatric surgery, in order to provide the guidance value for clinical practice.

Research on implementation status and key issues of function fulfillment in China national medical centers and national regional medical centers / 中华医院管理杂志

China national medical centers and national regional medical centers are the key entities to expand the availability of quality medical resources and ensure they are better distributed among regions. It is of great significance for the centers′ high-quality development to understand the key issues in the construction and progression of centers by evaluating the performance of their function fulfillment. The evaluation framework of this study was based on the " structure-process-outcome" model. The study was divided into three stages, including centers′ self-evaluation, data reporting, and on-site investigation and evaluation. The team conducted the evaluation on 15 entity hospitals supporting 6 national medical centers and 5 national regional medical centers that had been approved by October 2020. As the results showed, the funding and policy support for these centers from governments at all levels were increased, the internal and external management mechanism of the centers were preliminarily set up, the functions of the centers were executed properly, and the " radiation effect" of the centers was in place gradually. The key problems hindering the fulfillment of functions concern the mechanisms that were not sound and need to be further refined, which included the field of financial investment and policy guarantee for the entity hospitals, internal and external management of centers, introduction and cultivaton of the talented, and the innovation and transformation of scientific achievements which facilitates breakthroughs in core technologies. To promote the efficient implementation of functional tasks of the centers, the authors proposed four suggestions. First, the " commission and province co-construction" mechanism should be further improved to augment investment and policy guarantee from the government. Second, the internal organization and management mechanism of each centers should be optimized. Third, the reform and innovation in the training and management system of the talented medical personnel should be accelerated. Last, the health needs oriented mechanism for scientific research innovation and achievements transformation should be established.

Ferroptosis in laryngeal squamous cell carcinoma and its regulation by M2 macrophage-derived exosomes / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate ferroptosis in laryngeal squamous cell carcinoma (LSCC) and its regulation by M2 macrophage-derived exosomes. Methods: LSCC and adjacent noncancerous tissue samples were collected from 32 patients treated in the Department of Otorhinolaryngology, Head and Neck Surgery of the Second Affiliated Hospital of Harbin between September 2018 and April 2021, including 26 males and 6 females, aged 43-79 years. The expressions of ferroptosis marker glutathione peroxidase 4(GPX4) in LSCC and adjacent noncancerous tissues were detected by immunohistochemistry and reverse transcriptase-polymerase chain reaction(RT-PCR). The correlations between GPX4 expression and clinicopathological factors in LSCC were analyzed. Biological changes of TU212 cells after treated with ferroptosis-induced agent erastin were detected by transmission electron microscope, cell counting kit-8(CCK-8), clone test, reactive oxygen species(ROS), malondialdehyde(MDA), glutathione(GSH), JC-1, RT-PCR and western blot. Exosomes were isolated from the supernatant of M0/M2 macrophages (M0-exos/M2-exos) and co-incubated with erastin-treated TU212 cells to detect the change of ferroptosis in cells of each group. The data were analyzed by SPSS software of version19.0. Results: GPX4 expression in LSCC tissues was significantly higher than that in adjacent noncancerous tissues (2.04±0.65 vs. 0.99±0.09, F=30.36, P<0.001), and was closely related to T stage and clinical stage (Ⅰ-Ⅱvs.Ⅲ-Ⅳ: 1.75±0.39 vs. 2.18±0.71, F=2.25, P<0.05; T1-2 vs. T3-4: 1.71±0.42 vs. 2.20±0.69, F=2.06, P<0.05). In TU212 cells treated with erastin, mitochondrial crest became smaller, membrane density increased, proliferation rate decreased, intracellular ROS level increased, mitochondrial membrane potential depolarized, GSH content decreased, intracellular MDA level increased and expressions of GPX4 mRNA and protein decreased. Change of M0 into M2 macrophages was induced by IL-4 stimulation. When erastin-treated TU212 cells were incubated with M2-exos, cell proliferation was partially restored and GPX4 expression was enhanced, and also with the recoveries of levels of ROS, MDA and GSH (all P<0.05). Conclusions: Ferroptosis is one of the cell death ways of LSCC. M2-exos may inhibit ferroptosis of LSCC cells.

Research progress on the role of gut microbiota alterations in the pathogenesis of neuromyelitis optica spectrum disorders / 中华眼底病杂志

Neuromyelitis optica spectrum disorders (NMOSDs) are a class of immune-mediated inflammatory demyelinating diseases of the central nervous system that mainly involve the optic nerve and spinal cord. As an important environmental factor, the gut microbiota may play an important role in the occurrence and development of NMOSDs. Previous studies have shown that the structure and number of intestinal flora in NMOSDs patients are different from those of normal healthy people. The altered intestinal flora may cross-react with central nervous system autoantigens, induce T cell differentiation, and affect short-chain fatty acids, etc. The metabolite secretion pathway triggers the occurrence of NMOSDs. The summary of the changes of gut microbiota in patients with NMOSDs and the possible underlying mechanisms by summarizing the literature, aim to provide more effective treatments for the prevention and treatment of NMOSDs in the future.

Short-and mid-term results after adventitial inversion technique for root repair in acute type A aortic dissection / 中华胸心血管外科杂志

Objective:To evaluate the safety and effectiveness of adventitial inversion technique for root repair in patients with acute type A aortic dissection(ATAAD).Methods:Between 2015 and 2018, ATAAD patients with dissected root and underwent open surgery were included. The exclusion criteria were as follows: previous root intervention, traumatic dissection and patient underwent root replacement(Bentall or David procedure). 490 ATAAD patients were included, 366(74.69%) male and 124(25.31%) female, aged(51.28±10.99) years(range 24-77 years). The clinical data were retrospectively analyzed with ANOVA/ nonparametric test and Chi- square test. Follow-up mortality and reoperation were displayed with Kaplan- Meier curve. Results:All patients were technically divided into three groups: adventitial inversion(A), direct suture(B) and Cabrol-shunt(C). The mean age in group A was(53.05±11.09) years, whereas worse cardiac and renal function occurred in group C. The mean duration of HCA, CPB and ACC were shortest, with a highest average of minimum rectal temperature during surgical interval in group A. Postoperative complications and early mortality were similar among groups. There were no significant differences of mid-term mortality and reoperation among these three techniques. Though no late reintervention for aortic root was found in both group A and B, the root diameter was more stable in group A during follow-up period[(33.14±3.74)mm vs.(34.51±3.83)mm vs.(33.89±3.89)mm, P=0.008]. Conclusion:Adventitial inversion technique is safe and effective for root repair in patients with ATAAD, achieving satisfactory short- and mid-term effects.

Latest research progress in effects of exercise and nutritional interventions on sarcopenia / 中华老年医学杂志

Sarcopenia etiology is diverse and the pathogenesis is complex.It is closely related to limited activity, malnutrition and a variety of clinical diseases, which seriously affects the quality of life in the elderly and has become a global common health problem.This review focuses on the literature of non-drug interventions for sarcopenia in the past five years, focusing on the relationship of multimodal exercise, intestinal flora, parenteral nutrition and comprehensive intervention with sarcopenia, in order to provide a new basis for formulating scientific and effective non-drug intervention for sarcopenia.

CHINA PH ARMACY Volume 33，Number 12，June 30，2022 Semimonthly Table of Contents Construction of total q uality managemen t system of clinica l comprehens ive evaluation of drugs in China / 中国药房

OBJECTIVE To provide reference for scientifi c and standardized development of clinical comprehensive evaluation of drugs in China. METHODS Guided by the theory of total quality management （TQM），drawing lessons from the successful experience of the British and German conducting evaluation ，combining with plan-do-check-act cycle and other quality management methods and tools ，drug clinical comprehensive evaluation of total quality management system was constructed in accordance with the requirements for our country related policy and local practice. RESULTS & CONCLUSIONS To construct total quality management system of clinical comprehensive evaluation of drugs in China from 5 aspects of organization system ，management process，assessment system ，evaluation and supervision platform ，support and guarantee mechanism. The organization system included national ，provincial and medical institutions ；management process should focus on the key links in the 3 stages of theme selection，evaluation and implementation ，and result transformation and application ；assessment system ，evaluation and supervision platform，support and guarantee mechanism should be established together so as to further improve the scientificity ，rationality， practicality and standardization of total quality management of clinical comprehensive evaluation of drugs. The development of total quality management is an effective starting point to promote the continual improvement of the drug clinical comprehensive evaluation；relevant government departments and the implementation of evaluation of medical institutions should further set up quality management consciousness ，establish report quality feedback mechanism and the results co-constructing and sharing mechanism and strengthen professional personnel training and innovation synergy regulation mode to ensure that the authenticity and reliability of evaluation results.

Analysis of influencing factors related to the prognosis of visual acuity on myelin oligodendrocyte glycoprotein antibody positive optic neuritis after methylprednisolone pulse / 中华眼底病杂志

Objective:To analyze the prognostic factors of vision of myelin oligodendrocyte glycoprotein (MOG) antibody positive associated optic neuritis (ON) after methylprednisolone pulse therapy.Methods:A clinical observational study. A total of 32 patients (47 eyes) with MOG antibody positive ON were observed and followed up in the ophthalmology department of Beijing Tongren Hospital Affiliated to Capital Medical University and Beijing Puren Hospital from March 2019 to January 2022. Clinical data including the best corrected visual acuity (BCVA) and orbital magnetic resonance imaging were recorded. The BCVA was examined by Snellen visual acuity chart, which was finally converted into the logarithm of the minimal angle of resolution (logMAR) for statistical analysis. There were 22 case (38 eyes) with complete image data. All patients were treated with intravenous methylprednisolone pulse (IVMP) for 3-5 days. According to the intervention time (from onset to glucocorticoid treatment), the patients were divided into three groups: <7 d group, 7-14 d and> 14 d group, with 16, 13, 11 eyes, respectively. The median follow-up time was 28 months. After 1 week, 1, 3 and 6 months treatment, the same equipment and methods were used for relevant examinations to observe the changes of visual acuity and the factors influencing the prognosis of visual acuity after IVMP treatment. Logistic regression and linear regression were used to analyze the prognostic correlation factors. Receiver operating characteristic (ROC) curve was used to determine the critical cut-off point of intervention timing.Results:Among the patients, 16 were male and 16 were female. The median onset age was 26 years. The onset duration time was 5-60 days. There were 18 cases (56.3%, 18/32) with abnormal serum immune indexes. The initial symptom was decreased vision with unilateral or bilateral ON. Seventeen (53.1%, 17/32) cases had unilateral ON and 15 (46.9%, 15/32) cases with bilateral ON. Thirty-six eyes (76.6%, 36/47) got optic disc edema, 37 eyes (78.7%, 37/47) accompanied by pain of ocular movement. The nadir logMAR BCVA was mean 1.69±0.13. Long T2WI signals with segmental thickening in the orbital segment of the optic nerve were obtained in 27 eyes (71.1%, 27/38) and in 24 eyes (63.2%, 24/38) with optic nerve and sheath enhancement. During the follow-up period, there were 10 cases of relapse (31.3%, 10/32). The logMAR BCVA of attacked eyes were 0.52±0.09, 0.22±0.06, 0.12±0.06, 0.10±0.06 at 1 week and 1, 3 and 6 months after IVMP treatment, respectively. The rate of BCVA improvement was the fastest at 1 week after treatment, and BCVA returned to stability at 3 months. Logistic regression analysis showed that the timing of intervention was significantly correlated with the prognosis of vision in primary onset patients (odds ratio=12.17, P=0.006), with a negative linear regression relationship ( r=-0.48, 95% confidence interval -0.71--0.17, P=0.008). Comparing the logMAR BCVA between the intervention time >14 group with the <7 group and the 7-14 group, there were statistically significant difference ( P=0.017, 0.037), respectively. The cut-off point of ROC curve to predict the optimal intervention time was 13.5 days. Other factors such as: gender, age, predisposing factor, pain of eye motion, edema of optic disc, bilateral ON, imaging changes, abnormal autoimmune indicators were not associated with the prognosis of visual acuity. Conclusion:The timing of hormone intervention in primary onset patients is an important factor affecting the prognosis of vision and the optimal intervention time window of IVMP is two weeks.