Effect and mechanism of Astragalus polysaccharide on peritoneal fibrosis and angiogenesis in peritoneal dialysis rats / 中国药房

OBJECTIVE To investigate the effect and mechanism of Astragalus polysaccharide （APS） on peritoneal fibrosis and angiogenesis in rats with peritoneal dialysis （PD）. METHODS Rats were randomly divided into normal control group （Control group）， model group （PD group）， 70 mg/kg APS group （APS-L group）， 140 mg/kg APS group （APS-H group）， and 140 mg/kg APS+40 mg/kg hypoxia-inducible factor-1α （HIF-1α） agonist DMOG group （APS-H+DMOG group）， with 12 rats in each group. PD rat models were constructed in the last four groups of rats. Administration groups were given APS intragastrically and DMOG intraperitoneally. Control group and PD group were given constant volume of normal saline intragastrically， once a day， for 4 consecutive weeks. After the last medication， the peritoneal ultrafiltration （UF）， mass transfer of glucose （MTG）， the levels of serum creatinine （Scr） and blood urea nitrogen （BUN） were detected in rats； peritoneal histomorphology and peritoneal fibrosis （peritoneal thickness and proportion of collagen fiber deposition） were observed； the microvascular density and the expression levels of α-smooth muscle actin （α-SMA）， laminin （LN）， HIF-1α and vascular endothelial growth factor （VEGF） proteins were detected in peritoneal tissue of rats. RESULTS Compared with Control group， the mesothelium of rats in the PD group was loosely arranged and shed， inflammatory cells infiltrated， the peritoneal thickness and proportion of collagen fiber deposition were increased significantly （P＜0.05）. The levels of MTG， Scr and BUN in serum， microvascular density and the expressions of α-SMA， LN， HIF-1α and VEGF proteins were significantly increased， while the level of UF was significantly decreased （P＜ 0.05）； compared with PD group， the levels of above indexes were significantly reversed in APS-L and APS-H groups （P＜0.05）， and the improvement of APS-H group was better than APS-L group （P＜0.05）. Compared with APS-H group， the levels of above indexes in APS-H+DMOG group were all reversed （P＜0.05）. CONCLUSIONS APS inhibits peritoneal fibrosis and angioge-nesis in PD rats by inhibiting HIF-1α/VEGF signaling pathway.

Effects of echinacoside on renal injury in uremia rats and its mechanism / 中国药房

OBJECTIVE To investigate the effects of echinacoside （ECH） on renal injury in uremia （URE） rats and its mechanism. METHODS URE model of the rat was established by 5/6 nephrectomy. Successfully modeled rats were grouped into uremia group （URE group）， ECH low-dose [10 mg/（kg·d）] group， ECH medium-dose [20 mg/（kg·d）] group， ECH high-dose [40 mg/（kg·d）] group， ECH high-dose+anisomycin [p38 mitogen-activated protein kinase （p38 MAPK） pathway activator] group [ECH-H+Ani group， 40 mg/（kg·d） ECH +2 mg/（kg·d） anisomycin]， with a sham operation group， 12 mice in each group. Each drug group was given corresponding ECH intragastrically， while ECH-H+Ani group was further injected with anisomycin via the tail vein， once a day， for 8 consecutive weeks. The serum levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， IL-6， blood urea nitrogen （BUN）， β2-microglobulin （β2-MG）， serum creatinine （Scr）， neutrophil gelatinase-associated lipocalin （NGAL）， kidney injury molecule-1 （KIM-1）， cystatin C （Cys-C） and 24 h urine protein （24 h UP） as well as the levels of malondialdehyde （MDA） and superoxide dismutase （SOD） activity in renal tissue were all detected； pathological changes of renal tissue were observed； the rate of positive expression of α-smooth muscle protein （α-SMA） and E-cadherin， and the phosphorylation of p38 MAPK and nuclear factor-κB （NF-κB） p65 were determined in renal tissue of rats. RESULTS Compared with URE group， glomerular swelling， damage and necrosis of renal tubular epithelial cells and inflammatory cell infiltration were relieved significantly in ECH groups. The renal injury score， levels of TNF-α， IL-1β， IL-6， BUN， Scr， β2-MG， 24 h UP， NGAL， KIM- 1， Cys-C and MDA， the positive expression rate of α-SMA in renal tissue， the phosphorylation of p38 MAPK and NF-κB p65 were decreased in dose-dependent manner， while SOD activity and the positive expression rate of E-cadherin were obviously increased in dose-dependent manner （P＜0.05）. Anisomycin significantly attenuated the improvement effect of high-dose ECH on renal injury in URE rats （P＜0.05）. CONCLUSIONS ECH may inhibit inflammation and oxidative stress， enhance renal function， and improve renal injury in uremic rats by inhibiting the activation of p38 MAPK/NF-κB signaling pathway.

Value of different scoring models in predicting the survival of patients with liver cirrhosis after transjugular intrahepatic portosystemic shunt / 临床肝胆病杂志

Objective To compare the value of Child-Pugh score, Model for End-Stage Liver Disease (MELD) score, MELD combined with serum sodium concentration (MELD-Na) score, CLIF Consortium Acute Decompensation (CLIF-C AD) score, and Freiburg index of post-transjugular intrahepatic portosystemic shunt (TIPS) survival (FIPS) score in predicting the survival of patients undergoing TIPS. Methods A retrospective analysis was performed for the clinical data of 447 patients with liver cirrhosis who underwent TIPS in several hospitals in southwest China, among whom there were 306 patients in the survival group and 62 in the death group. The scores of the above five models were calculated, and a survival analysis was performed based on these models. The independent samples t -test was used for comparison of normally distributed continuous data between groups, and the non-parametric Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the Pearson chi-square test was used for comparison of categorical data between groups; a multivariate Cox regression analysis was used for correction analysis of known influencing factors with statistical significance which were not included in the scoring models; the Kaplan-Meier method was used to evaluate the discriminatory ability of each model in identifying risks in the surgical population, and the log-rank test was used for analysis. The area under the receiver operating characteristic curve (AUC), C-index at different time points, and calibration curve were used to evaluate the predictive ability of each scoring model. Results Compared with the death group, the survival group had significantly lower age ( Z =2.884, P < 0.05), higher albumin ( t =3.577, P < 0.05), and Na + ( Z =-3.756, P < 0.05) and significantly lower proportion of patients with alcoholic cirrhosis ( χ 2 =22.674, P < 0.05), aspartate aminotransferase ( Z =2.141, P < 0.05), prothrombin time ( Z =2.486, P < 0.05), international normalized ratio ( Z =2.429, P < 0.05), total bilirubin ( Z =3.754, P < 0.05), severity of ascites ( χ 2 =14.186, P < 0.05), and scores of the five models (all P < 0.05). Survival analysis showed that all scoring models effectively stratified the prognostic risk of the patients undergoing TIPS. Comparison of the C-index of each scoring model at different time points showed that Child-Pugh score had the strongest ability in predicting postoperative survival, followed by MELD-Na score, MELD score, and CLIF-C AD score, and FIPS score had a relatively poor predictive ability; in addition, the prediction efficiency of each score gradually decreased over time. Child-Pugh score had the largest AUC of 0.832 in predicting 1-year survival rate after surgery, and MELD-Na score had the largest AUC of 0.726 in predicting 3-year survival rate after surgery, but FIPS score had a poor ability in predicting 1- and 3-year survival rates. Conclusion All five scoring models can predict the survival of patients with liver cirrhosis after TIPS and can provide effective stratification of prognostic risk for such patients. Child-Pugh score has a better ability in predicting short-term survival, while MELD-Na score has a better ability in predicting long-term survival, but FIPS score has a relatively poor predictive ability in predicting both short-term and long-term survival.

Expression of CD24 gene in human malignant pleural mesothelioma and its relationship with prognosis / 中华劳动卫生职业病杂志

Objective: To investigate the expression of CD24 gene in human malignant pleural mesothelioma (MPM) cells and tissues, and evaluate its relationship with clinicopathological characteristics and clinical prognosis of MPM patients. Methods: In February 2021, UALCAN database was used to analyze the correlation between CD24 gene expression and clinicopathological characteristics in 87 cases of MPM patients. The TIMER 2.0 platform was used to explore the relationship between the expression of CD24 in MPM and tumor immune infiltrating cells. cBioportal online tool was used to analyze the correlation between CD24 and MPM tumor marker gene expression. RT-qPCR was used to analyze the expressions of CD24 gene in human normal pleural mesothelial cell lines LP9 and MPM cell lines NCI-H28 (epithelial type), NCI-H2052 (sarcoma type), and NCI-H2452 (biphasic mixed type). RT-qPCR was performed to detect the expressions of CD24 gene in 18 cases of MPM tissues and matched normal pleural tissues. The expression difference of CD24 protein in normal mesothelial tissue and MPM tissue was analyzed by immunohistochemistry. A Kaplan-Meier model was constructed to explore the influence of CD24 gene expression on the prognosis of MPM patients, and Cox regression analysis of prognostic factors in MPM patients was performed. Results: The CD24 gene expression without TP53 mutation MPM patients was significantly higher than that of patients in TP53 mutation (P<0.05). The expression of CD24 gene in MPM was positively correlated with B cells (r(s)=0.37, P<0.001). The expression of CD24 gene had a positive correlation with the expressions of thrombospondin 2 (THBS2) (r(s)=0.26, P<0.05), and had a negative correlation with the expression of epidermal growth factor containing fibulin like extracellular matrix protein 1 (EFEMP1), mesothelin (MSLN) and calbindin 2 (CALB2) (r(s)=-0.31, -0.52, -0.43, P<0.05). RT-qPCR showed that the expression level of CD24 gene in MPM cells (NCI-H28, NCI-H2052 and NCI-H2452) was significantly higher than that in normal pleural mesothelial LP9 cells. The expression level of CD24 gene in MPM tissues was significantly higher than that in matched normal pleural tissues (P<0.05). Immunohistochemistry showed that the expressions of CD24 protein in epithelial and sarcoma MPM tissues were higher than those of matched normal pleural tissues. Compared with low expression of CD24 gene, MPM patients with high expression of CD24 gene had lower overall survival (HR=2.100, 95%CI: 1.336-3.424, P<0.05) and disease-free survival (HR=1.800, 95%CI: 1.026-2.625, P<0.05). Cox multivariate analysis showed that compared with the biphasic mixed type, the epithelial type was a protective factor for the prognosis of MPM patients (HR=0.321, 95%CI: 0.172-0.623, P<0.001). Compared with low expression of CD24 gene, high expression of CD24 gene was an independent risk factor for the prognosis of MPM patients (HR=2.412, 95%CI: 1.291-4.492, P=0.006) . Conclusion: CD24 gene and protein are highly expressed in MPM tissues, and the high expression of CD24 gene suggests poor prognosis in MPM patients.

Research Progress and Application Prospect of Facial Micro-Expression Analysis in Forensic Psychiatry / 法医学杂志

Research on facial micro-expression analysis has been going on for decades. Micro-expression can reflect the true emotions of individuals, and it has important application value in assisting auxiliary diagnosis and disease monitoring of mental disorders. In recent years, the development of artificial intelligence and big data technology has made the automatic recognition of micro-expressions possible, which will make micro-expression analysis more convenient and more widely used. This paper reviews the development of facial micro-expression analysis and its application in forensic psychiatry, to look into further application prospects and development direction.

Preparation of berberine-naringin dual drug-loaded composite microspheres and evaluation of their antibacterial-osteogenic properties / 中国修复重建外科杂志

OBJECTIVE@#To develop a drug-loaded composite microsphere that can simultaneously release the berberine (BBR) and naringin (NG) to repair infectious bone defects.@*METHODS@#The NG was loaded on mesoporous microspheres (MBG) to obtain the drug-loaded microspheres (NG-MBG). Then the dual drug-loaded compound microspheres (NG-MBG@PDA-BBR) were obtained by wrapping NG-MBG with polydopamine (PDA) and modifying the coated PDA with BBR. The composite microspheres were characterized by scanning electron microscopy, X-ray diffraction, specific surface area and pore volume analyzer, and Fourier transform infrared spectroscopy; the drug loading rate and release of NG and BBR were measured; the colony number was counted and the bacterial inhibition rate was calculated after co-culture with Staphylococcus aureus and Escherichia coli for 12 hours to observe the antibacterial effect; the biocompatibility was evaluated by live/dead cell fluorescence staining and cell counting kit 8 assay after co-culture with rat's BMSCs for 24 and 72 hours, respectively, and the osteogenic property was evaluated by alkaline phosphatase (ALP) staining and alizarin red staining after 7 and 14 days, respectively.@*RESULTS@#NG-MBG@PDA-BBR and three control microspheres (MBG, MBG@PDA, and NG-MBG@PDA) were successfully constructed. Scanning electron microscopy showed that NG-MBG@PDA-BBR had a rough lamellar structure, while MBG had a smooth surface, and MBG@PDA and NG-MBG@PDA had a wrapped agglomeration structure. Specific surface area analysis showed that MBG had a mesoporous structure and had drug-loading potential. Low angle X-ray diffraction showed that NG was successfully loaded on MBG. The X-ray diffraction pattern contrast showed that all groups of microspheres were amorphous. Fourier transform infrared spectroscopy showed that NG and BBR peaks existed in NG-MBG@PDA-BBR. NG-MBG@PDA-BBR had good sustained drug release ability, and NG and BBR had early burst release and late sustained release. NG-MBG@PDA-BBR could inhibit the growth of Staphylococcus aureus and Escherichia coli, and the antibacterial ability was significantly higher than that of MBG, MBG@PDA, and NG-MBG@PDA ( P<0.05). But there was a significant difference in biocompatibility at 72 hours among microspheres ( P<0.05). ALP and alizarin red staining showed that the ALP positive area and the number of calcium nodules in NG-MBG@PDA-BBR were significantly higher than those of MBG and NG-MBG ( P<0.05), and there was no significant difference between NG-MBG@PDA and NG-MBG@PDA ( P>0.05).@*CONCLUSION@#NG-MBG@PDA-BBR have sustained release effects on NG and BBR, indicating that it has ideal dual performance of osteogenesis and antibacterial property.

Single-cell analysis reveals an Angpt4-initiated EPDC-EC-CM cellular coordination cascade during heart regeneration

Mammals exhibit limited heart regeneration ability, which can lead to heart failure after myocardial infarction. In contrast, zebrafish exhibit remarkable cardiac regeneration capacity. Several cell types and signaling pathways have been reported to participate in this process. However, a comprehensive analysis of how different cells and signals interact and coordinate to regulate cardiac regeneration is unavailable. We collected major cardiac cell types from zebrafish and performed high-precision single-cell transcriptome analyses during both development and post-injury regeneration. We revealed the cellular heterogeneity as well as the molecular progress of cardiomyocytes during these processes, and identified a subtype of atrial cardiomyocyte exhibiting a stem-like state which may transdifferentiate into ventricular cardiomyocytes during regeneration. Furthermore, we identified a regeneration-induced cell (RIC) population in the epicardium-derived cells (EPDC), and demonstrated Angiopoietin 4 (Angpt4) as a specific regulator of heart regeneration. angpt4 expression is specifically and transiently activated in RIC, which initiates a signaling cascade from EPDC to endocardium through the Tie2-MAPK pathway, and further induces activation of cathepsin K in cardiomyocytes through RA signaling. Loss of angpt4 leads to defects in scar tissue resolution and cardiomyocyte proliferation, while overexpression of angpt4 accelerates regeneration. Furthermore, we found that ANGPT4 could enhance proliferation of neonatal rat cardiomyocytes, and promote cardiac repair in mice after myocardial infarction, indicating that the function of Angpt4 is conserved in mammals. Our study provides a mechanistic understanding of heart regeneration at single-cell precision, identifies Angpt4 as a key regulator of cardiomyocyte proliferation and regeneration, and offers a novel therapeutic target for improved recovery after human heart injuries.

Effects and mechanism of ginsenoside Rh2 on the proliferation and apoptosis of human glioma cells / 中国药房

ABSTRACT OBJECTIVE To investigate the effects and mechanism of ginsenoside Rh2 on the proliferation and apoptosis in human glioma U87 and U251 cells. METHODS Using human glioma U87 and U251 cells as subjects， the proliferation and apoptosis， as well as the expression of histone deacetylase 1（HDAC1） protein and apoptosis-related proteins [B cell lymphoma-2（Bcl-2）， Bcl-2-associated X protein （Bax） and cleaved caspase-3] were detected after being treated with different concentrations of ginsenoside Rh2. RESULTS The concentrations of 10，20，30，40，50，60，70，80 μmol/L ginsenoside Rh2 could generally significantly increase the proliferation inhibition rate of U87 and U251 cells （P＜0.05 or P＜0.01）， and the half inhibitory concentrations of this component after 48 hours of action were 51.34 and 55.84 μmol/L， respectively；30，50 μmol/L ginsenoside Rh2 could increase the total apoptotic rate of both types of cells， reduced the protein expressions of HDAC1 and Bcl-2， and increased the protein expressions of Bax and cleaved caspase-3 significantly （P＜0.05 or P＜0.01）. CONCLUSIONS Ginsenoside Rh2 has a significant inhibitory effect on the proliferation of glioma cells and promotes the apoptosis of cells， which may be through reducing the expression of HDAC1 protein and activating the Bcl-2 family protein-mediated apoptosis pathway.

Comparative study of endoscopic spine surgery with and without assistance of an electromagnetic navigation surgical robot in the treatment of lumbar disc herniation / 中华显微外科杂志

Objective:To compair the clinical effect of endoscopic spine surgery with and without assistance of an electromagnetic navigation surgical robot(ENSR) system in the treatment of lumbar disc herniations(LDH).Methods:From March 2021 to December 2021, 73 patients with LDH underwent endoscopic minimally invasive treatment in the Department of Spine Surgery, Limin Hospital of Weihai High District. Thirty-eight patients were treated with endoscopic spine surgery assisted by domestic ENSR system(ENSR group), and 35 patients were treated with endoscopic spine surgery alone(endoscopic group). The patients received follow up regularly by telephone or Wechat. The intraoperative fluoroscopy times, puncture times, upper facet arthroplasty times, operation time, preoperative and postoperative Visual Analogue Scale(VAS), Japanese Orthopaedic Association Scores(JOA), and the MOS item short from health survey(SF-36)were compared between the 2 groups. The early postoperative efficacy was evaluated by modified MacNab criteria at 1 week after surgery. SPSS 26.0 was used to analyse the data. P<0.05 was considered that the difference was statistically significant. Results:The age, gender, body mass index(BMI) and other general data of the 2 groups were basically the same, and there was no statistically significant difference( P>0.05). There was no significant difference in the excellent and good rate of postoperative treatment between ENSR group(97.37%) and endoscopic group(94.29%)( Z=0.90, P>0.05). In terms of operation time, intraoperative fluoroscopy times, puncture times, and plasty times, ENSR group[(67.00±17.00) min, (4±2) times, 1 time, 1 time, respectively] was compared with the endoscopic group[(82.00±16.00] min, (17±6) times, (9±5) times, (5±2) times], and the difference was statistically significant( t=3.87,12.62, 9.87, respectively, P<0.05). There were significant differences in VAS, JOA and SF-36 scores between the 2 groups between before and after surgery( F=106.42, 112.14, 26.88, respectively, P<0.05). There was no significant difference in VAS, JOA and SF-36 scores before and after surgery between the 2 groups( F=0.95, 3.54, 0.97, respectively, P>0.05). Conclusion:The endoscopic spine surgery assisted by the ENSR can achieve satisfactory clinical results and is a safe and effective surgical assistance system. For the endoscopic surgery, assisted by the ENSR has obvious advantages in reducing the times of fluoroscopy, puncture, and facet arthroplasty, and shortening the operation time.

Expression profiling of cell-derived exosomal lncRNAs resistant to concurrent chemoradiotherapy in nasopharyngeal carcinoma / 中华放射肿瘤学杂志

Objective:To screen the key exosomal long non-coding RNAs (lncRNAs) molecules that cause nasopharyngeal carcinoma cells to develop chemoradiotherapy resistance.Methods:In vitro, a model of concurrent chemoradiotherapy for human nasopharyngeal carcinoma cells was constructed, and the continuous shock method of high-dose concurrent chemoradiotherapy was used to induce the establishment of chemoradiotherapy-resistant nasopharyngeal carcinoma cell lines, and its resistance formation was verified. Exosomes produced by chemoradiotherapy-resistant cell lines and respective mother cell lines for nasopharyngeal carcinoma were extracted and identified. Finally, biochip technology was used to detect the differential expression levels of exosomal lncRNAs. Results:After 10 repeated treatments of concurrent chemoradiotherapy, CNE-1 CRR and CNE-2 CRR were successfully obtained. Compared with the mother cell lines, CNE-1 CRR and CNE-2 CRR had a tendency to transform from epithelial to interstitial morphology, and the number of cell clones was higher, and the values of average lethal dose (D 0), quasi-threshould dose (D q), survival fraction after 2 Gy irradiation (SF 2) and cell survival rate were higher. Nasopharyngeal carcinoma cells were detected by PCR chip of exosomal lncRNAs. Compared with their respective mother cell lines, 18 lncRNAs in CNE-1 CRR exosomes were significantly up-regulated and 31 lncRNAs were significantly down-regulated, and 15 lncRNAs were significantly up-regulated and 38 lncRNAs were significantly down-regulated in CNE-2 CRR exosomes. CNE-1 CRR also had similar expression profiles to CNE-2 CRR. Conclusion:There are significantly up-regulated and down-regulated lncRNAs in the exosomes of CNE-1 CRR and CNE-2 CRR.

Evaluation of neonatal resuscitation simulation exercise for perinatal medical personnel / 中国新生儿科杂志

Objective:To evaluate the efficacy of neonatal resuscitation simulation exercise for perinatal medical personnel.Methods:From August 2020 to July 2021, perinatal medical personnel receiving simulated training of neonatal resuscitation in our hospital were prospectively enrolled. The professional backgrounds of the trainees were collected and their performances on both knowledge skills and behavioral skills were scored. The knowledge skills included pre-resuscitation preparation, initial resuscitation, positive pressure ventilation, tracheal intubation, chest compression and umbilical vein catheterization. The behavioral skills included situational awareness, problem solving, resource utilization, communication and leadership. SPSS 26.0 was used for data analysis.Results:Among the 200 participants, 127(63.5%) were neonatal/pediatric doctors and nurses, 65(32.5%) were obstetricians and midwives, 8(4.0%) were anesthesiologists and the ratio of doctors to nurses was 1.74∶1. The score of knowledge skills was (19.52±2.92) at the beginning of the simulation exercise and (27.02±2.72) at the end. The scores on preparation before resuscitation, initial resuscitation and positive pressure ventilation were significantly improved ( P<0.05). The score of behavioral skills was (16.60±2.34) at the beginning and (20.58±1.77) at the end. The scores of resource utilization, communication and leadership were significantly improved ( P<0.05). Conclusions:The simulation exercise provides multidisciplinary teamwork training for perinatal medical personnel, may significantly improve neonatal resuscitation skills and is worth promoting.

Construction of predictive ceRNA network and identification of the patterns of immune cells infiltrated in Graves ' ophthalmopathy / 中南大学学报(医学版)

OBJECTIVES@#Graves' ophthalmopathy (GO) is a multifactorial disease, and the mechanism of non coding RNA interactions and inflammatory cell infiltration patterns are not fully understood. This study aims to construct a competing endogenous RNA (ceRNA) network for this disease and clarify the infiltration patterns of inflammatory cells in orbital tissue to further explore the pathogenesis of GO.@*METHODS@#The differentially expressed genes were identified using the GEO2R analysis tool. The Kyoto encyclopedia of genes and genomes (KEGG) and gene ontology analysis were used to analyze differential genes. RNA interaction relationships were extracted from the RNA interactome database. Protein-protein interactions were identified using the STRING database and were visualized using Cytoscape. StarBase, miRcode, and DIANA-LncBase Experimental v.2 were used to construct ceRNA networks together with their interacted non-coding RNA. The CIBERSORT algorithm was used to detect the patterns of infiltrating immune cells in GO using R software.@*RESULTS@#A total of 114 differentially expressed genes for GO and 121 pathways were detected using both the KEGG and gene ontology enrichment analysis. Four hub genes (SRSF6, DDX5, HNRNPC,and HNRNPM) were extracted from protein-protein interaction using cytoHubba in Cytoscape, 104 nodes and 142 edges were extracted, and a ceRNA network was identified (MALAT1-MIR21-DDX5). The results of immune cell analysis showed that in GO, the proportions of CD8+ T cells and CD4+ memory resting T cells were upregulated and downregulated, respectively. The proportion of CD4 memory resting T cells was positively correlated with the expression of MALAT1, MIR21, and DDX5.@*CONCLUSIONS@#This study has constructed a ceRNA regulatory network (MALAT1-MIR21-DDX5) in GO orbital tissue, clarifying the downregulation of the proportion of CD4+ stationary memory T cells and their positive regulatory relationship with ceRNA components, further revealing the pathogenesis of GO.

Research progress in targeting autophagy of traditional Chinese medicine and natural compounds to regulate atherosclerosis / 中国中药杂志

Atherosclerosis(AS) is the common pathological basis of many ischemic cardiovascular diseases, and its formation process involves various aspects such as vascular endothelial injury and platelet activation. Vascular endothelial injury is the initiating factor of AS plaque. Monocytes are recruited to differentiate into macrophages at the damaged endothelial cells, which absorb oxidized low-density lipoprotein(ox-LDL) and slowly transform into foam cells. Smooth muscle cells(SMCs) proliferate and migrate continuously. As the only cell producing interstitial collagen fibers in the fibrous cap, SMCs largely determine whether the plaque ruptured or not. The amplifying inflammatory response during the formation of AS recruits platelets to adhere to the damaged area of vascular endothelium and stimulates excessive platelet aggregation. Autophagy activity is associated with vascular lesions and abnormal platelet activation, and excessive autophagy is considered to be a negative factor for plaque stability. Therefore, precise regulation of different types of vascular autophagy and platelet autophagy to treat AS may provide a new therapeutic perspective for the prevention and treatment of atherosclerotic ischemic cardiovascular disease. Currently, treatment strategies for AS still focus on lowering lipid levels with high-intensity statins, which often cause significant side effects. Therefore, the development of safer and more effective drugs and treatment modes is the focus of current research. Traditional Chinese medicine and natural compounds have the potential to treat AS by targeted autophagy, and have been playing an increasingly important role in the prevention and treatment of cardiovascular diseases in China. This paper summarizes the experimental studies on different vascular cell types and platelet autophagy in AS, and sums up the published research results on targeted autophagy of traditional Chinese medicine and natural plant compounds to regulate AS, providing new ideas for further research.

Daidzein affects proliferation and apoptosis in non-small cell lung cancer cells:role of p53 signaling pathway / 中国药理学通报

Aim To investigate the effects of daidzeinDD on the proliferation and apoptosis of non-small cell lung cancer cells,with a focus on the possible role of the p53 signaling pathway in this regard. Methods CCK-8 method and flow cytometry were used to detect the effects of soy isoflavone crude extract and DD on the viability and apoptosis of HELF and H1299 cells. Gene microarray was used to detect the changes in gene expression after treatment of H1299 cells with DD. GSEA and differential analysis were used to screen the major pathways and key genes. RT-qPCR and Western blot were performed to verify the differences in mRNA and protein expression of key genesp53 and CASP9 in the major pathways. After p53 inhibitor Pifithrin-α inhibited the expression of p53,the effect of DD on p53 mRNA and protein expression levels was examined,and the proliferative effect on H1299 cells was observed. Results Soy isoflavone crude extract and DD promoted proliferation and inhibited apoptosis of normal lung cells and inhibited proliferation and promoted apoptosis of lung cancer cells. p53 signaling pathway was significantly enriched in the DD-treated groupNES=1.78,P=0.000,and the expressions of p53 and CASP9 genes were found to be significantly up-regulated in the treated group. Compared with the control group,mRNA expression of CASP9 and p53 significantly increased in both HELF and H1299 cells treated with DDP<0.05,and p53 protein expression also increased in HELF cellsP<0.05. After inhibition of p53 expression,DD significantly increased the mRNA expression of p53 in H1299 and HELF cellsP<0.05 and also markedly increased the expression of p53 protein in H1299 cellsP<0.05,and it was observed that DD inhibited the proliferation of lung cancer cells. Conclusions DD inhibits the proliferation and promotes the apoptosis of lung cancer H1299 cells,and the mechanism mainly involves the p53 signaling pathway.

Long-term follow-up of humanized and murine CD19 CAR-T-cell therapy for B-cell acute lymphoblastic leukemia / 中华血液学杂志

Objective: Murine CD19 chimeric antigen receptor T-cell (CAR-T) products have been approved for the treatment of refractory/relapsed (R/R) B-cell acute lymphocytic leukemia (B-ALL) ; moreover, humanized products are also undergoing clinical trials. This study aimed to explore the differences in safety and short- and long-term follow-up efficacy between humanized and murine CD19 CAR-T-cells for treating relapsed and refractory B-ALL. Methods: Clinical data of 80 patients with R/R B-ALL treated with CD19-targeted CAR-T-cells at the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology between May 2016 and March 2023 were analyzed, which included 31 patients with murine CAR-T and 49 with humanized products. Results: The proportion of patients with cytokine-release syndrome (CRS) in the murine and humanized groups was 63.1% and 65.3%, respectively. Moreover, a higher proportion of patients suffered from severe CRS in the murine group than in the humanized CAR-T group (19.4% vs 8.2%, P=0.174). Furthermore, one patient per group died of grade 5 CRS. The incidence of grade 1-2 immune effector cell-associated neurotoxicity syndrome (ICANS) was 12.9% and 6.1%, respectively; severe ICANS were not observed. Among patients receiving murine CAR-T-cells, an overall response (OR) was observed in 74.2%. Conversely, the OR rate of patients receiving humanized CAR-T-cells was 87.8%. During the median follow-up time of 10.5 months, the median recurrence-free survival (RFS) of patients with murine CAR-T-cells was 12 months, which was as long as that of patients with humanized CAR-T-cells. The median overall survival (OS) were not reached in both groups. Of the 45 patients with a bone marrow burden over 20% at baseline, humanized CAR-T therapy was associated with a significantly improved RFS (43.25% vs 33.33%, P=0.027). Bridging transplantation was an independent factor in prolonging OS (χ(2)=8.017, P=0.005) and PFS (χ(2)=6.584, P=0.010). Common risk factors, such as age, high proportion of bone marrow blasts, and BCR-ABL fusion gene expression, had no significant effect on patients' long-term follow-up outcomes. Three patients reached complete remission after reinfusion of humanized CAR-T-cells. However, one patient relapsed one month after his second infusion of murine CAR-T-cells. Conclusions: The results indicate that humanized CAR-T therapy showed durable efficacy in patients with a higher tumor burden in the bone marrow without any influence on safety. Moreover, it could overcome immunogenicity-induced CAR-T resistance, providing treatment options for patients who were not treated successfully with CAR-T therapies.

Immunometabolism: a new dimension in immunotherapy resistance / 医学前沿

Immune checkpoint inhibitors (ICIs) have demonstrated unparalleled clinical responses and revolutionized the paradigm of tumor treatment, while substantial patients remain unresponsive or develop resistance to ICIs as a single agent, which is traceable to cellular metabolic dysfunction. Although dysregulated metabolism has long been adjudged as a hallmark of tumor, it is now increasingly accepted that metabolic reprogramming is not exclusive to tumor cells but is also characteristic of immunocytes. Correspondingly, people used to pay more attention to the effect of tumor cell metabolism on immunocytes, but in practice immunocytes interact intimately with their own metabolic function in a way that has never been realized before during their activation and differentiation, which opens up a whole new frontier called immunometabolism. The metabolic intervention for tumor-infiltrating immunocytes could offer fresh opportunities to break the resistance and ameliorate existing ICI immunotherapy, whose crux might be to ascertain synergistic combinations of metabolic intervention with ICIs to reap synergic benefits and facilitate an adjusted anti-tumor immune response. Herein, we elaborate potential mechanisms underlying immunotherapy resistance from a novel dimension of metabolic reprogramming in diverse tumor-infiltrating immunocytes, and related metabolic intervention in the hope of offering a reference for targeting metabolic vulnerabilities to circumvent immunotherapeutic resistance.

Epidemiological characteristics of a 2019-nCoV outbreak caused by Omicron variant BF.7 in Shenzhen / 中华流行病学杂志

Objective: To explore the epidemiological characteristic of a COVID-19 outbreak caused by 2019-nCoV Omicron variant BF.7 and other provinces imported in Shenzhen and analyze transmission chains and characteristics. Methods: Field epidemiological survey was conducted to identify the transmission chain, analyze the generation relationship among the cases. The 2019-nCoV nucleic acid positive samples were used for gene sequencing. Results: From 8 to 23 October, 2022, a total of 196 cases of COVID-19 were reported in Shenzhen, all the cases had epidemiological links. In the cases, 100 were men and 96 were women, with a median of age, M (Q1, Q3) was 33(25, 46) years. The outbreak was caused by traverlers initial cases infected with 2019-nCoV who returned to Shenzhen after traveling outside of Guangdong Province.There were four transmission chains, including the transmission in place of residence and neighbourhood, affecting 8 persons, transmission in social activity in the evening on 7 October, affecting 65 persons, transmission in work place on 8 October, affecting 48 persons, and transmission in a building near the work place, affecting 74 persons. The median of the incubation period of the infection, M (Q1, Q3) was 1.44 (1.11, 2.17) days. The incubation period of indoor exposure less than that of the outdoor exposure, M (Q1, Q3) was 1.38 (1.06, 1.84) and 1.95 (1.22, 2.99) days, respcetively (Wald χ2=10.27, P=0.001). With the increase of case generation, the number and probability of gene mutation increased. In the same transmission chain, the proportion of having 1-3 mutation sites was high in the cases in the first generation. Conclusions: The transmission chains were clear in this epidemic. The incubation period of Omicron variant BF.7 infection was shorter, the transmission speed was faster, and the gene mutation rate was higher. It is necessary to conduct prompt response and strict disease control when epidemic occurs.

Vascularization of intravitreal injection of Conbercept in the treatment of retinopathy of prematurity / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate retinal vascularization caused by the intravitreal injection of Conbercept in the treatment of a series of retinopathy of prematurity(ROP)cases in Type Ⅰ(threshold and pre-threshold period)and aggressive ROP(A-ROP).METHODS: The data of 34 ROP cases(67 eyes)treated by intravitreal injection of Conbercept(IVC)in the ophthalmology department of the Xiamen Children's Hospital from July 2017 to March 2020 were retrospectively analyzed. Reactivation, which refers to recurrence of acute phase features, occurred at any stage of the disease in the presence or absence of other diseases. RESULT: The average gestational age of the 34 children was 28.82±2.32wk. The average birth weight was 1155.18±398.22g. The lesion zone of 19 cases(37 eyes)was Zone Ⅰ. In 10 cases(20 eyes), the lesion was in Zone Ⅱ, and in 5 cases(10 eyes), the lesion was in the posterior Zone Ⅱ. The total effective rate of disease control in ROP children treated with once IVC was 73.1%(49/67), and the vascularization of Zone Ⅱ was completed. The patients showed variable changes in the vascularization in Zone Ⅲ. For the patients who received one treatment and did not reactivate, the average rate of Type Ⅰ vascularization of ROP was 9.11±2.49wk, and the A-ROP was 13.40±4.04wk. The rate of A-ROP vascularization in Zone Ⅱ was significantly longer compared to Type Ⅰ.CONCLUSION: IVC effectively completes vascularization in Zone Ⅱ.

Probing the Impact of Whole Intestinal Microbiota Transplantation from Alzheimer's Disease Model Mice on the Ileal Microenvironment Based on the “Interior-Exterior Relationship Exists Between Heart and Small Intestine” / 中山大学学报(医学科学版)

ObjectiveTo investigate whether the whole intestinal microbiota transplantation in Alzheimer's disease （AD） model mice has more significant effects on ileum intestinal microenvironment in normal mice under the guidance of the theory of traditional Chinese medicine that "interior-exterior relationship exists between the heart and small intestine". MethodsThe whole intestinal microbiota of fourteen 6-month-old specific pathogen free male APP/PS1 double-transgenic AD model mice was transplanted into the gut of six normal C57BL/6J mice of the same age and background treated with mixed antibiotics for 14 days. Then， after 14 days of normal rearing， the mice were sacrificed. Next， the pathological changes in the ileum and colon were observed， and the composition and diversity of the ileal and colonic microbiota was analyzed by sequencing. ResultsAfter the whole intestinal microbiota of AD mice was transplanted into normal mice， pathological analysis showed that only the ileum tissue had mucosal damage and crypt gland epithelial cell degeneration， necrosis， and shedding. Moreover， the microbiota analysis found that only the number of genera （P<0.01）， Chao1 index （P<0.01） and Simpson index of ileal microbiota in normal mice decreased （P<0.01）， and the composition of intestinal microbiota was quite similar to that of AD model mice. ConclusionUnder the effect of whole gut microbiota transplantation in AD mice， the diversity and composition of ileal microbiota change more than that of colonic microbiota in normal mice， and at the same time， it results in pathological damage to the ileal mucosa， indicating that the ileal microenvironment may be more closely related to the occurrence and development of AD， which is highly consistent with the traditional Chinese medicine theory of "interior-exterior relationship between heart and small intestine".

CT-Based Weighted Radiomic Score Predicts Tumor Response to Immunotherapy in Non-Small Cell Lung Cancer / 中国医学科学院学报

Objective To develop a CT-based weighted radiomic model that predicts tumor response to programmed death-1(PD-1)/PD-ligand 1(PD-L1)immunotherapy in patients with non-small cell lung cancer.Methods The patients with non-small cell lung cancer treated by PD-1/PD-L1 immune checkpoint inhibitors in the Peking Union Medical College Hospital from June 2015 to February 2022 were retrospectively studied and classified as responders(partial or complete response)and non-responders(stable or progressive disease).Original radiomic features were extracted from multiple intrapulmonary lesions in the contrast-enhanced CT scans of the arterial phase,and then weighted and summed by an attention-based multiple instances learning algorithm.Logistic regression was employed to build a weighted radiomic scoring model and the radiomic score was then calculated.The area under the receiver operating characteristic curve(AUC)was used to compare the weighted radiomic scoring model,PD-L1 model,clinical model,weighted radiomic scoring + PD-L1 model,and comprehensive prediction model.Results A total of 237 patients were included in the study and randomized into a training set(n=165)and a test set(n=72),with the mean ages of(64±9)and(62±8)years,respectively.The AUC of the weighted radiomic scoring model reached 0.85 and 0.80 in the training set and test set,respectively,which was higher than that of the PD-L1-1 model(Z=37.30,P<0.001 and Z=5.69,P=0.017),PD-L1-50 model(Z=38.36,P<0.001 and Z=17.99,P<0.001),and clinical model(Z=11.40,P<0.001 and Z=5.76,P=0.016).The AUC of the weighted scoring model was not different from that of the weighted radiomic scoring + PD-L1 model and the comprehensive prediction model(both P>0.05).Conclusion The weighted radiomic scores based on pre-treatment enhanced CT images can predict tumor responses to immunotherapy in patients with non-small cell lung cancer.