Data mining and analysis of oxaliplatin-related adverse events of nervous system / 中国药房

OBJECTIVE To provide reference for clinically safe drug use by mining oxaliplatin-related adverse drug events （ADE） of the nervous system. METHODS Oxaliplatin-related neurologic ADE data reported by the FDA adverse event reporting system （FAERS） between January 1st， 2004 and December 31st， 2022 were collected. The reporting odds ratio and proportional reporting ratio were used for data mining. The data were classified statistically by using systematic organ classification， high-level group term （HLGT） and preferred term （PT） in the MedDRA （version 26.0）. RESULTS A total of 7 266 cases of oxaliplatin- related ADE， which were classified as various neurological， were retrieved， and 100 PT were identified. Of these， fifty-seven PT were unspecified adverse reaction signals in the manual. Among these reports， males （46.85%） were more than females （42.98%）， the age of patients was 45-＜75 years （65.22%）， the number of reports was highest in Italy （16.32%）， and the severe type was hospitalization or prolonged hospitalization （38.16%）. The top 5 PT reports in the list of case number were peripheral neuropathy， paresthesia， neurotoxicity， loss of consciousness and dysarthria. The top 5 PT reports in the list of signal intensities were cold- induced paresthesia， neuromuscular rigidity， acute polyneuropathy， neuronal neuropathy， axonal and demyelinating polyneuropathy. A total of 13 HLGT were involved， with neurological diseases （not classified separately） having the highest number of signals （29）. CONCLUSIONS When using oxaliplatin in clinical practice， it is not only necessary to monitor the high incidence of acute and chronic peripheral neuropathy， but also to pay attention to the patient’s consciousness state and neurological symptoms. We should pay attention to the rare types of adverse reactions， such as guillain-barre syndrome， Lhermitte sign， posterior reversible encephalopathy syndrome， and hyperammoniacal encephalopathy， so as to ensure the safety of medication.

Analysis of etiology and complications in children with stage 5 chronic kidney disease / 中华儿科杂志

Objective: To investigate the etiology, complications, and prognostic factors of stage 5 chronic kidney disease (CKD5) in children. Methods: A case series study was conducted to retrospectively analyze the general situation, clinical manifestations, laboratory tests, genetic testing, and follow-up data (until October 2022) of 174 children with CKD5 who were diagnosed and hospitalized at the Children's Hospital of Chongqing Medical University from April 2012 to April 2021. The characteristics of complications in the children were compared based on age, gender, and etiology. Based on the presence or absence of left ventricular hypertrophy (LVH), patients were divided into LVH group and non LVH group for analyzing the influencing factors of cardiovascular disease. Patients were also divided into death group and survival group, peritoneal dialysis group and hemodialysis group based on the follow-up data for analyzing the prognostic factors. The chi-square test, independent sample t-test, Fisher exact probability test, Mann-Whitney U test and Kruskal Wallis test were used to analyze data among different groups. Multivariate Logistic regression analysis was used to identify the prognostic factors. Results: A total of 174 children with CKD5 were enrolled in the study (96 boys and 78 girls), aged 11.2 (8.2, 13.0) years. Congenital kidney and urinary tract malformations (CAKUT) were the most common causes of the CKD5 (84 cases, 48.3%), followed by glomerular diseases (83 cases, 47.7%), and among which 28 cases (16.1%) were hereditary glomerular diseases. The common complications of CKD5 included anemia (98.2%, 165/168), mineral and bone disorder in chronic kidney disease (CKD-MBD) (97.7%, 170/174), lipid metabolism disorders (87.5%, 63/72), hypertension (81.4%, 127/156) and LVH (57.6%,57/99). The incidences of hypertension in primary glomerular disease were higher than that in CAKUT(93.8%(30/32) vs.73.7%(56/76),χ2=5.59,P<0.05). The incidences of hypertension in secondary glomerular disease were higher than that in CAKUT and that in hereditary kidney disease (100.0%(20/20) vs. 73.7%(56/76), 68.2%(15/22), both P<0.05). The incidence of hypocalcemia in CAKUT, primary glomerular disease, and hereditary kidney disease was higher than that in secondary glomerular disease (82.1%(69/84), 88.2%(30/34), 89.3%(25/28) vs. 47.6%(10/21), χ2=10.21, 10.75, 10.80, all P=0.001); the incidence of secondary hyperparathyroidism in women was higher than that in men (80.0%(64/80) vs. 95.0%(57/60), χ2=6.58, P=0.010). The incidence of LVH in children aged 6-<12 was higher than that in children aged 12-18 (73.5%(25/34) vs. 43.1%(22/51), χ2=7.62, P=0.006). Among 113 follow-up children, the mortality rate was 39.8% (45/113). Compared to the survival group, the children in the death group had lower hemoglobin, higher blood pressure, lower albumin, lower alkaline phosphatase and higher left ventricular mass index ((67±19) vs. (75±20) g/L, 142 (126, 154) vs. 128(113, 145) mmHg(1 mmHg=0.133 kPa), (91±21) vs. (82±22) mmHg, 32 (26, 41) vs. 40 (31, 43) g/L, 151 (82, 214) vs. 215 (129, 37) U/L, 48 (38, 66) vs. 38(32, 50) g/m2.7,t=2.03, Z=2.89, t=2.70, Z=2.49, 2.79, 2.29,all P<0.05), but no independent risk factors were identified (all P>0.05). The peritoneal dialysis group had better alleviation for anemia, low calcium, and high phosphorus than the hemodialysis group ((87±22) vs. (72±16) g/L, (1.9±0.5) vs. (1.7±0.4) mmol/L, (2.2±0.7) vs. (2.8±0.9) mmol/L, t=2.92, 2.29, 2.82, all P<0.05), and the survival rate of the peritoneal dialysis group was significantly higher than that of the hemodialysis group (77.8% (28/36) vs. 48.4% (30/62), χ2=8.14, P=0.004). Conclusions: CAKUT is the most common etiology in children with CKD 5, and anemia is the most common complication. The incidence of complications in children with CKD 5 varies with age, gender and etiology. Anemia, hypertension, hypoalbuminemia, reduced alkaline phosphatase and elevated LVMI may be the prognostic factors in children with CKD5. Peritoneal dialysis may be more beneficial for improving the long-term survival rate.

Research of the mechanism of Huganning tablet in the treatment of nonalcoholic fatty liver disease based on network pharmacology and computer-aided drug design / 药学学报

In this study, we explored the mechanism of Huganning tablet (HGNP) in the treatment of nonalcoholic fatty liver disease (NAFLD) based on network pharmacology and computer-aided drug design. Firstly, the potential ingredients and targets of HGNP were identified from TCMSP database, Swiss Target Prediction database, Chinese pharmacopoeia (2015) and literatures, and then the targets of HGNP intersected with NAFLD disease targets that obtained in GeneCards database to acquired potential targets. The bioconductor bioinformatics package of R software was used for gene ontology (GO) enrichment and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis. The network of “potential ingredient-key target-pathway” was formed in Cytoscape software to study the interactions between potential ingredients of HGNP, key targets, pathways and NAFLD. Based on the results of network pharmacology, the molecular docking analysis of the key targets and potential active ingredients in HGNP tablets with top degree in the network was conducted using Discovery Studio 2020 software, followed by molecular dynamics simulations, binding free energy calculation, drug-likeness properties analysis and ADMET (absorption, distribution, metabolism, excretion and toxicity) properties prediction. In vitro, HepG2 cells were used to establish steatosis model, and the effects of five key compounds on hepatocyte steatosis were analyzed by oil red O staining and triglyceride (TG) content determination. The results showed that 141 ingredients and 151 potential targets were obtained. A total of 2 526 items and 151 pathways were identified by GO and KEGG enrichment analysis. The molecular docking suggested that five components, isorhamnetin, salvianolic acid B, emodin, resveratrol and rhein, exhibited strong binding ability with key targets [retinoic acid receptor RXR-alpha (RXRA), tumor necrosis factor (TNF), glycogen synthase kinase-3 beta (GSK3B), serine/threonine-protein kinase 1 (AKT1)]. It was further verified that isorhamnetin and salvianolic acid B bind to key targets with good structural stability and binding affinity based on molecular dynamics simulations and binding free energy calculations. The drug-likeness properties, pharmacokinetic properties and toxicity of five key compounds were more comprehensively analyzed through drug-likeness properties analysis and ADMET properties prediction. In vitro, all five compounds, isorhamnetin, salvianolic acid B, emodin, resveratrol, and rhein, improved hepatocyte steatosis of HepG2 cells, confirming the reliability of the present study. In conclusion, based on network pharmacology, computer-aided drug design and in vitro validation, this study investigated the mechanism of HGNP for the treatment of NAFLD at multiple levels and provided a basis for its clinical application.

Correlation between cognitive function and resting-state interhemispheric voxel-mirrored homotopic connectivity in patients with chronic schizophrenia / 四川精神卫生

BackgroundCognitive impairment， a core clinical feature of schizophrenia， is considered to be associated with the aberrant functional connectivity in patients with schizophrenia， whereas previous studies on the characteristics of cognitive impairment in patients with chronic schizophrenia and its correlation with interhemispheric voxel-mirrored homotopic connectivity （VMHC） are somewhat inadequate. ObjectiveTo investigate the characteristics of cognitive impairment in patients with chronic schizophrenia who are clinically stable on their antipsychotic medication， and to explore its correlation with resting-state interhemispheric VMHC， so as to provide theoretical basis for the identification of neurobiological mechanism possibly responsible for cognitive impairment in chronic schizophrenia. MethodsA total of 15 patients with chronic schizophrenia who met the criteria of the International Classification of Diseases， tenth edition （ICD-10） and hospitalized in Suzhou Guangji Hospital from January 2021 to December 2022 were included. Another 15 healthy community-dwelling individuals were concurrently recruited. All participants were requested to complete the Positive and Negative Symptom Scale （PANSS）， Repeatable Battery for the Assessment of Neuropsychological Status （RBANS） and resting-state functional Magnetic Resonance Imaging （rs-fMRI） scanning to evaluate their mental symptoms， cognitive function and interhemispheric functional connectivity. The rs-fMRI data were analyzed with VMHC method. Then Pearson correlation analysis was performed to examine the correlation between VMHC values of regions of interest and scores of RBANS and PANSS within patient group. ResultsPatient group obtained lower scores than control group based on RBANS immediate memory， visuospatial/constructional， language， attention and total score， with statistically significant differences （t=-2.853， -2.107， -5.576， -7.108， -5.354， P<0.05 or 0.01）. The VMHC values of left superior occipital gyrus （t=-5.188， P<0.05） and right cuneus （t=-5.188， P<0.05） in patient group were lower than those in control group， with statistical difference. Correlation analysis denoted that the VMHC values of left superior occipital gyrus （r=0.612， P=0.015） and right cuneus （r=0.612， P=0.015） were positively correlated with visuospatial/constructional index score in RBANS. ConclusionThe resting-state VMHC is abnormal in left superior occipital gyrus and right cuneus of patients with chronic schizophrenia， and yields a correlation with the visuospatial/constructional performance of patients. ［Funded by Suzhou Science and Technology Development Plan Project （number， SKJYD2021131； SKJY2021143）］

Analysis of urine Alzheimer-associated neuronal thread protein level and related factors of middle-aged and elderly people in Mianyang / 四川精神卫生

ObjectiveTo investigate the Alzheimer-associated neurofilament protein （AD7c-NTP） in urine of middle-aged and elderly people and its correlation between common metabolites. MethodsA total of 1 150 middle-aged and elderly people who did their physical exmanination in the health examination center of the Sichuan Science City Hospital and the Third Hopital of Mianyang were recruited from March 2017 to March 2020. The level of urine AD7c-NTP were measured by enzyme-linked immunosorbent assay （ELISA）， and common metabolites in blood were measured by biochemical analyzer. Based on urine AD7c-NTP level ≤1.5 ng/mL， the objects was divided into normal group （n=956） and elevated group （n=194）. Thier demographic data and blood biochemical indicators were collected. ResultsThe urine AD7c-NTP level in middle-aged and elderly people was 0.60（0.30~1.20） ng/mL. The urine AD7c-NTP level was higher in women than that in men ［1.04（0.40~1.30） ng/mL vs. 0.84（0.30~1.00） ng/mL， Z=4.202， P˂0.01］. And the urine AD7c-NTP level was lower in the normal group than that in the elevated group ［0.50（0.30~0.90） ng/mL vs. 2.10（1.70~2.10） ng/mL， Z=22.035， P˂0.01］. The results of the univariate comparison showed that， the differences between the two groups in age （Z=6.545）， fasting glucose （Z=3.506）， blood uric acid （Z=2.574）， urea nitrogen （Z=2.891）， creatinine （Z=2.243）， total bilirubin （Z=3.936）， glutathione （Z=0.969）， total cholesterol （t=3.956） and low density lipoprotein （Z=-5.678） were were statistically significant （P˂0.05 or 0.01）. Spearman correlation analysis showed that， the urine AD7c-NTP level was positively correlated with age and the levels of urea nitrogen， glucose， total cholesterol and low density lipoprotein （r=0.177， 0.178， 0.171， 0.109， 0.149， P˂0.01）， and negatively correlated with the level of total bilirubin （r=-0.172， P˂0.01）. Conclusionthe urine AD7c-NTP level in middle-aged and elderly females was signifitcantly higher than in middle-aged and elderly males.The urine AD7c-NTP level of middle-aged and elderly people was positively correlated with age， urea nitrogen， glucose， total cholesterol and low density lipoprotein， and negatively correlated with total bilirubin.

HbA1c comparison and diagnostic efficacy analysis of multi center different glycosylated hemoglobin detection systems / 中华预防医学杂志

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R2 of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.

Air pollution on daily outpatient visits for diabetes based on time series model / 公共卫生与预防医学

Objective To analyze the effect of air pollution on daily outpatient visits for diabetes, and to provide reference for the management of outpatients with diabetes. Methods Data on outpatient visits for diabetes in a hospital between July 1, 2018 to July 31, 2022 were collected. The correlation between air quality and daily outpatient visits due to diabetes was analyzed using distributed lag non-linear model (DLNM). Results The results showed that the increase in the concentrations of PM2.5 and PM10 in the air was related to the increase in the daily outpatient visits for diabetes, with a lagging effect. The accumulative effect in high PM2.5 concentration was statistically significant for both males and females, and the number of outpatients reached the maximum value at lag5 for males and at lag6 for females. The accumulative effect was not statistically significant either at low or high concentrations of PM2.5 in the young and middle-aged population. However，it was statistically significant in the elderly population, especially when exposed to high concentration of PM2.5, the daily outpatient visits increased significantly. Conclusion PM2.5, PM10 and other harmful pollutants in the air have an impact on the daily diabetic outpatients and increase their visits.

Effects and mechanism of Curcumin solid lipid nanoparticles loaded with flower-shaped lactose for inhalation on pulmonary inflammation in COPD model mice / 中国药房

OBJECTIVE To investigate the effects and mechanism of curcumin （Cur） solid lipid nanoparticles （SLN） loaded with flower-shaped lactose （Cur-SLN-FL） for lung inhalation on lung inflammation in chronic obstructive pulmonary disease （COPD） model mice. METHODS Firstly， the irritation of Cur-SLN-FL to lung tissue was investigated， and the local safety of inhalation materials was determined. Then， 10 mice were randomly selected and injected with normal saline through the trachea， and the other 50 mice were all injected with porcine trypsin solution （concentration of 33.3 mg/mL， dosage of 1.0 mL/kg） to induce the COPD model. After normal feeding for 28 days， the mice were divided into sham operation group， model group， budesonide group （20 mg/kg）， Cur-SLN-FL high-dose and low-dose groups （100， 50 mg/kg）， with 10 mice in each group. The corresponding drugs were given to each group， once a day， for 14 consecutive days. Twenty-four hours after the last administration， the bronchoalveolar lavage fluid （BALF） of mice in each group was collected and the differential count of white blood cells was determined. Hematoxylin-eosin （HE） staining was used to observe the histopathology of the trachea and lung tissue in each group. Masson staining was used to detect collagen deposition in the lung tissue of mice in each group. Immunohistochemical method was used to detect the positive expressions of nucleotide-binding oligomerization domains-like receptor protein-3 （NLRP3）， caspase-1 and interleukin-1β （IL-1β） in lung tissue of mice. Western blot assay was used to detect the protein expressions of NLRP3， caspase-1 and nuclear factor of kappa B（NF-κB） in lung tissue. RESULTS Cur-SLN-FL had no obvious pulmonary irritation. Compared with the sham operation group， the total number of white blood cells， neutrophils and eosinophils in BALF of the model group increased significantly， while the number of lymphocytes decreased significantly （P＜0.05）； ciliated columnar epithelium proliferated， thickened and exfoliated in the trachea， mucus accumulated in the cavity and interstitial inflammatory cells infiltrated in the lung tissue；the deposition of collagen fibers in lung tissue increased significantly， the positive expressions of NLRP3， caspase-1 and IL-1β in lung tissue increased significantly， and the expressions of NLRP3， caspase-1 and NF-κB protein in lung tissue all increased significantly （P＜0.05）. After giving Cur-SLN-FL， the above indexes were all improved to certain extent. CONCLUSIONS Cur-SLN-FL can improve the pulmonary inflammatory reaction in COPD model mice，and its mechanism may be through regulating the NLRP3 signaling pathway， inhibiting the expressions of caspase-1， NF-κB and IL-1β， thus alleviating the process of pulmonary fibrosis in COPD model mice.

Isolation and identification of two new compounds from Semen Persicae / 药学学报

Five compounds were isolated from the ethyl acetate fraction of Semen Persicae by using various chromatographic methods, including ODS, Sephadex LH-20, HPLC and semipreparative HPLC. Their structures were identified by 1D-NMR, 2D-NMR, HR-ESI-MS, UV, IR, circular dichroism (CD) and ECD calculation techniques: (2R,3R)-5,7,4′-trihydroxy-3′-methoxy-3-formylflavan-3-ol-5-O-β-D-glucopyranoside (1), (7R,8S)-dihydrodehydrodiconiferyl 6″-benzoyl alcohol-9-O-β-D-glucopyranoside (2), (7R,8S)-dihydrodehydrodiconiferyl alcohol-9-β-O-D-glucopyranosid (3), 2-methoxy-4-(2-propenyl)-phenyl-O-β-D-glucopyranoside (4), 2-[4-(3-hydroxypropyl)-2-methoxyphenoxy]-propane-1,3-diol (5). Compound 1 and 2 are new compounds, and compounds 3-5 were obtained from Prunus davidiana (Carr.) Franch. for the first time.

The Cancer/Testis Antigen CT45A1 Promotes Transcription of Oncogenic Sulfatase-2 Gene in Breast Cancer Cells and Is Sensible Targets for Cancer Therapy / 한국유방암학회지

Conclusion: Overexpression of CT45A1 is associated with poor prognosis in patients with BRCA. CT45A1 promotes SULF2 overexpression by activating the promoter and interacting with SP1. Additionally, SP1 and SULF2 inhibitors suppress breast cancer cell migration, invasion, and tumorigenesis. Our findings provide new insight into the mechanisms of breast cancer metastasis and highlight CT45A1 and SULF2 as sensible targets for developing novel therapeutics against metastatic breast cancer.

MicroRNA-1246 Inhibits NFATc1 Phosphorylation and Regulates T Helper 17 Cell Activation in the Pathogenesis of Severe Alopecia Areata

Background@#We found microRNA (miR)-1246 to be significantly differentially expressed between severe active alopecia areata (AA) patients and healthy individuals. @*Objective@#To explore the role and mechanism of miR-1246 in severe AA. @*Methods@#Expression of miR-1246, dual-specific tyrosine phosphorylation-regulated kinase 1A (DYRK1A), and nuclear factor of activated T cells 1c (NFATc1) in peripheral CD4+ T cells and in scalp tissues of patients were detected using RT-qPCR, Western blot, and immunohistochemistry assays. Peripheral CD4+ T cells from the AA patients were transfected with lentiviral vectors overexpressing miR-1246. RT-qPCR and Western blot analysis were used to measure mRNA or protein expression of retinoic-acid-receptor-related orphan nuclear receptor gamma (ROR-γt), interleukin (IL)-17, DYRK1A, NFATc1, and phosphorylated NFATc1. Flow cytometry was used to assay the CD4+ IL-17+ cells proportion. ELISA was used to measure cytokine levels. @*Results@#miR-1246 levels decreased and DYRK1A and NFATc1 mRNA levels significantly increased in the peripheral CD4+ T cells and scalp tissues of severe active AA samples.NFATc1 protein expression was also significantly increased in the peripheral CD4+ T cells but not in the scalp tissues. NFATc1 positive cells were mainly distributed among infiltrating inflammatory cells around hair follicles. In peripheral CD4+ T cells of severe active AA, overexpression of miR-1246 resulted in significant downregulation of DYRK1A, NFATc1, ROR-γt, and IL-17 mRNA and phosphorylated NFATc1 protein, as well as a decrease in the CD4+ IL-17+ cells proportion and the IL-17F level. @*Conclusion@#miR-1246 can inhibit NFAT signaling and Th17 cell activation, which may be beneficial in the severe AA treatment.

Effects of low-dose radiation on oxidative stress and damage repair in HBE cells / 中国辐射卫生

@#<b>Objective</b> To investigate the effects of lowdose ionizing radiation (LDIR) on oxidative stress and damage repair in human bronchial epithelial (HBE) cells. <b>Methods</b> HBE cells were divided into 0, 50, 100, and 200 mGy groups, and cultured for 24 and 48 h after X-ray irradiation, respectively. The cell viability, levels of glutathione (GSH), malondialdehyde (MDA), and 8-hydroxy-2’-deoxyguanosine (8-OHdG), and transcriptional levels of DNA damage repair genes <i>PPP2R2D</i> and <i>TP53</i> were measured. <b>Results</b> At 24 h after irradiation, there was no significant difference in the cell viability between the dose groups and the control group (<i>P</i> > 0.05); all dose groups had significantly increased MDA level, dose-dependently decreased GSH level, dose-dependently increased 8-OHdG level, and significantly increased mRNA level of <i>PPP2R2D</i> gene (all <i>P</i> < 0.05); the mRNA expression level of <i>TP53</i> gene was significantly increased in the 50 mGy group (<i>P</i> < 0.05). At 48 h after irradiation, there were the highest cell viability, significantly decreased MDA and 8-OHdG levels, and significantly increased mRNA expression levels of <i>PPP2R2D</i> and <i>TP53</i> genes in the 50 mGy group compared with the control group (all <i>P</i> < 0.05); the GSH level in the 100 mGy group was significantly increased (<i>P</i> < 0.05). <b>Conclusion</b> LDIR, especially radiation at 50 mGy, can affect the oxidative-antioxidant level in HBE cells and the transcript-level differential expression of DNA damage repair genes.

Promising roles of non-exosomal and exosomal non-coding RNAs in the regulatory mechanism and as diagnostic biomarkers in myocardial infarction / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Non-exosomal non-coding RNAs (non-exo-ncRNAs) and exosomal ncRNAs (exo-ncRNAs) have been associated with the pathological development of myocardial infarction (MI). Accordingly, this analytical review provides an overview of current MI studies on the role of plasma non-exo/exo-ncRNAs. We summarize the features and crucial roles of ncRNAs and reveal their novel biological correlations via bioinformatics analysis. The following contributions are made: (1) we comprehensively describe the expression profile, competing endogenous RNA (ceRNA) network, and "pre-necrotic" biomarkers of non-exo/exo-ncRNAs for MI; (2) functional enrichment analysis indicates that the target genes of ncRNAs are enriched in the regulation of apoptotic signaling pathway and cellular response to chemical stress, etc.; (3) we propose an updated and comprehensive view on the mechanisms, pathophysiology, and biomarker roles of non-exo/exo-ncRNAs in MI, thereby providing a theoretical basis for the clinical management of MI.

Analysis of the Prognostic Value and Risk Factors of Early Relapse for Newly Diagnosed Multiple Myeloma Patients in the Era of Novel Agents / 中国实验血液学杂志

OBJECTIVE@#To investigate the influece of early relapse in the era of novel drugs on the prognosis of the patients with newly diagnosed multiple myeloma（NDMM） and risk factors, and to provide the basis for the early identification of the high-risk patients and guiding the treatment.@*METHODS@#The clinical data of the patients with NDMM admitted to our hospital from November 2011 to May 2022 were retrospectively analyzed. According to whether the progression free survival（PFS） was more than 12 months, they were divided into early relapse group（≤12 months） and late relapse group（＞12 months）. The high-risk factors of the patients in two groups were analyzed, including age, anemia, renal insufficiency, hypercalcemia, increasing of lactate dehydrogenase（LDH） level, Extramedullary disease (EMD), International Staging System（ISS） stage, Revised International Staging System （R-ISS） stage, cytogenetic abnormalities(CA) detected by fluorescence in situ hybridization（FISH）, and treatment efficacy. The meaningful clinical indicators were screened, and multivariate analysis was used to explore the high-risk factors of early relapse.@*RESULTS@#170 patients with NDMM were collected, including 25 cases in early relapse group and 145 cases in late relapse group. The median OS time of the patients in early death group was 20 months, and 140 months in late relapse group by the end of follow-up, there was significant difference in OS of the patients between two groups（P<0.001）. Fifteen patients（56.0％）in early relapse group obtained ≥VGPR, and 113（77.9%） patients in late relapse group, the difference was statistically significant（P=0.011）. Survival outcomes remained poor among early relapse patients irrespective of depth of response to initial therapy. Multivariate analysis showed that the EMD and high-risk CA predicted early relapse.@*CONCLUSION@#The prognosis of patients with early relapse in NDMM is poor. EMD and high-risk CA is an independent prognostic factor of early relapse.

Quality control mechanism of mitochondria by 3,4-dihydroxybenzaldehyde through OGT-PINK1 pathway / 中国中药杂志

Based on the O-GlcNAc transferase(OGT)-PTEN-induced putative kinase 1(PINK1) pathway, the mechanism of 3,4-dihydroxybenzaldehyde(DBD) on mitochondrial quality control was investigated. Middle cerebral artery occlusion/reperfusion(MCAO/R) rats were established. SD rats were randomized into sham operation group(sham), model group(MCAO/R), DBD-L group(5 mg·kg~(-1)), and DBD-H group(10 mg·kg~(-1)). After 7 days of administration(ig), MCAO/R was induced in rats except the sham group with the suture method. Twenty-four h after reperfusion, the neurological function and the percentage of cerebral infarct area were measured. Based on hematoxylin and eosin(HE) staining and Nissl staining, the pathological damage of cerebral neurons was examined. Then the ultrastructure of mitochondria was observed under the electron microscope, and the co-localization of light chain-3(LC3), sequestosome-1(SQSTM1/P62), and Beclin1 was further detected by immunofluorescence staining. It has been reported that the quality of mitochondria can be ensured by inducing mitochondrial autophagy through the OGT-PINK1 pathway. Therefore, Western blot was employed to detect the expression of OGT, mitophagy-related proteins PINK1 and E3 ubiquitin ligase(Parkin), and mitochondrial kinetic proteins dynamin-like protein 1(Drp1) and optic atrophy 1(Opa1). The results showed that MCAO/R group had neurological dysfunction, large cerebral infarct area(P<0.01), damaged morphological structure of neurons, decreased number of Nissl bodies, mitochondrial swelling, disappearance of mitochondrial cristae, decrease of cells with LC3 and Beclin1, rise of cells with P62(P<0.01), inhibited expression of OGT, PINK1, and Parkin, up-regulated expression of Drp1, and down-regulated expression of Opa1 compared with the sham group(P<0.01). However, DBD improved the behavioral deficits and mitochondrial health of MCAO/R rats, as manifested by the improved morphology and structure of neurons and mitochondria and the increased Nissl bodies. Moreover, DBD increased cells with LC3 and Beclin1 and decreased cells with P62(P<0.01). In addition, DBD promoted the expression of OGT, PINK1, Parkin, and Opa1 and inhibited the expression of Drp1, enhancing mitophagy(P<0.05, P<0.01). In conclusion, DBD can trigger PINK1/Parkin-mediated brain mitophagy through the OGT-PINK1 pathway, which plays a positive role in maintaining the health of the mitochondrial network. This may be a mitochondrial therapeutic mechanism to promote nerve cell survival and improve cerebral ischemia/reperfusion injury.

Research progress and maturity assessment of continuous manufacturing of traditional Chinese medicine / 中国中药杂志

The pharmaceutical manufacturing model is gradually changing from intermittent manufacturing to continuous manufacturing and intelligent manufacturing. This paper briefly reviewed the supervision and research progress in continuous pharmaceutical manufacturing in China and abroad and described the definition and advantages of continuous pharmaceutical manufacturing. The continuous manufacturing of traditional Chinese medicine(TCM) at the current stage was summarized in the following three terms: the enhancement of the continuity of intermittent manufacturing operations, the integration of continuous equipment to improve physical continuity between units, and the application of advanced process control strategies to improve process continuity. To achieve continuous manufacturing of TCM, the corresponding key technologies, such as material property characterization, process modeling and simulation, process analysis technology, and system integration, were analyzed from the process and equipment, respectively. It was proposed that the continuous manufacturing equipment system should have the characteristics of high speed, high response, and high reliability, "three high(H~3)" for short. Considering the characteristics and current situation of TCM manufacturing, based on the two dimensions of product quality control and production efficiency, a maturity assessment model for continuous manufacturing of TCM, consisting of operation continuity, equipment continuity, process continuity, and quality control continuity, was proposed to provide references for the application of continuous manufacturing technology for TCM. The implementation of continuous manufacturing or the application of key continuous manufacturing technologies in TCM can help to systematically integrate advanced pharmaceutical technology elements and promote the uniformity of TCM quality and the improvement of production efficiency.

Effect of 25G+pars plana vitrectomy combined with preoperative intravitreal injection of Conbercept on proliferative diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the clinical effect of 25G+pars plana vitrectomy(PPV)combined with preoperative intravitreal injection of conbercept in the treatment of patients with proliferative diabetic retinopathy(PDR), and analyze the influence on visual acuity, central foveal thickness(CMT)and serum vascular endothelial growth factor(VEGF)level.METHODS: A retrospective study was conducted from October 2019 to January 2022. A total of 80 patients(87 eyes)with PDR were divided into the two groups according to the treatment method, with 40 patients(45 eyes)treated with 25G+PPV in the control group, and 40 patients(42 eyes)treated with 25G+PPV combined with preoperative intravitreal injection of conbercept in the observation group. The two groups were compared in terms of the best corrected visual acuity(BCVA), intraocular pressure, CMT and serum VEGF level before treatment and at 2wk, 1 and 3mo after treatment. The patients were followed up for 3mo, with postoperative complications and recurrence recorded.RESULTS: The incidence of intraoperative bleeding in the observation group was significantly lower than that in the control group(P&#x0026;#x003C;0.05). After treatment, the BCVA of the two groups was improved(P&#x0026;#x003C;0.05), CMT and serum VEGF level were decreased(P&#x0026;#x003C;0.05), but there was no significant change in intraocular pressure(P&#x0026;#x003E;0.05). The BCVA and CMT of observation group were lower than those of control group at 1 and 3mo after treatment(P&#x0026;#x003C;0.05). Serum VEGF level in the observation group was lower than that in the control group at 3mo after treatment(P&#x0026;#x003C;0.05). The incidence of complications in observation group(5%)within 3mo after treatment was significantly lower than that in control group(18%; P&#x0026;#x003C;0.05). There was no statistically significant difference in recurrence rate of PDR between the two groups(P&#x0026;#x003E;0.05).CONCLUSION: With few complications, 25G+PPV combined with preoperative intravitreal injection of conbercept is effective in the treatment of patients with PDR, which can better promote postoperative vision recovery, improve macular edema, and reduce serum VEGF level.

Preparation of curcumin solid lipid nanoparticles inhalation powder loaded with nanoporous flower-shaped lactose and its in vitro inhibition effect on apoptosis / 中国药房

OBJECTIVE To prepare the nanoporous flower-shaped lactose （FL）-loaded curcumin （Cur） solid lipid nanoparticles （SLN） inhalation powder （Cur-SLN-FL）， and to investigate its inhibition effect on LPS-induced apoptosis of BEAS- 2B cells. METHODS Using different kinds （lactose， sucrose， mannitol， trehalose） and different amounts （2%， 3%， 5%） of freeze-dried protectants as objects， the suspension of Cur-SLN was micronized by freeze-drying technology into lyophilized powder， which was then mixed with FL and sieved by a 200-mesh sieve to obtain Cur-SLN-FL. The physicochemical properties of Cur-SLN-FL was characterized by scanning electron microscopy and laser particle size analyzer. Using BEAS-2B cells cultured in vitro as objects， LPS-induced apoptosis and the changes of mitochondrial membrane potential after treatment of Cur-SLN-FL were detected by Annexin Ⅴ/PI double staining method and JC-1 kit. RESULTS With 3% trehalose as Cur-SLN freeze-dried protective agent， the freeze-dried powder obtained was compact and full in shape， did not shrink and collapse， and was uniform in color and light-yellow powder， which could be completely dissolved in 30 s. When FL and Cur-SLN freeze-dried powder were mixed at a ratio of 1∶2， it had a higher deposition rate of secondary distribution （[ 40.92±0.02）%]. SEM results showed that Cur-SLN-FL had a flower-shaped appearance with an average particle size of （4.95±0.57） μm and an aerodynamic particle size of （4.03±0.40） μm. The critical relative humidity of Cur-SLN-FL was about 54%， and the evacuation rate was （90.34 ± 1.21）%； the quantity of fine particles that could be inhaled by Cur-SLN-FL in the 2-7 receiving discs was （47.5±0.7）%， and the measured aerodynamic particle size was （4.33±0.08） μm. The LD50 of Cur-SLN-FL to BEAS-2B cells was 5.809 mg/mL. The apoptosis rate of model cells was significantly reduced after treatment of Cur-SLN-FL， and the mitochondrial membrane potential was significantly increased （P＜0.05）. CONCLUSIONS The preparation process of Cur-SLN-FL is simple and feasible. Cur-SLN-FL can improve LPS-induced apoptosis of BEAS-2B cells， and this effect is related to the regulation of mitochondrial membrane potential.

Effects of umbilical moxibustion on phobic behavior and monoamine neurotransmitters in stress-model rats / 中国针灸

OBJECTIVE@#To investigate the effects of umbilical moxibustion therapy on phobic behavior and the contents of norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) in different brain regions of the stress-model rats and explore the potential mechanism of umbilical moxibustion on phobic behavior.@*METHODS@#Among 50 Wistar male rats, 45 rates were selected and randomly divided into a control group, a model group and an umbilical moxibustion group, 15 rats in each one; and the rest 5 rats were used for preparing the model of electric shock. The bystander electroshock method was adopted to prepare phobic stress model in the model group and the umbilical moxibustion group. After modeling, the intervention with umbilical moxibustion started in the umbilical moxibustion group, in which, the ginger-isolated moxibustion was applied at "Shenque" (CV 8), once daily, 2 cones for 20 min each time, for consecutively 21 days. After modeling and intervention completed, the rats in each group were subjected to the open field test to evaluate the state of fear. After intervention, the Morris water maze test and fear conditioning test were performed to evaluate the changes in learning and memory ability and the state of fear. Using high performance liquid chromatography (HPLC), the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were determined.@*RESULTS@#Compared with the control group, the horizontal and vertical activity scores were lower (P<0.01), the number of stool particles was increased (P<0.01), the escape latency was prolonged (P<0.01), the times of target quadrant were reduced (P<0.01), and the freezing time was prolonged (P<0.05) in the rats of the model group. The horizontal and vertical activity scores were increased (P<0.05), the number of stool particles was reduced (P<0.05), the escape latency was shortened (P<0.05, P<0.01), the times of target quadrant were increased (P<0.05), and the freezing time was shortened (P<0.05) in the rats of the umbilical moxibustion group when compared with the model group. The trend search strategy was adopted in the control group and the umbilical moxibustion group, while the random search strategy was used in rats of the model group. Compared with the control group, the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were reduced (P<0.01) in the model group. In the umbilical moxibustion group, the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were increased (P<0.05, P<0.01) when compared with the model group.@*CONCLUSION@#Umbilical moxibustion can effectively relieve the state of fear and learning and memory impairment of phobic stress model rats, which may be related to the up-regulation of contents of brain neurotransmitters, i.e. NE, DA, and 5-HT.

Clinical Characteristics and Nomogram Model of Nosocomial Infection in Patients with Newly Diagnosed Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To explore the clinical characteristics of nosocomial infection in newly diagnosed multiple myeloma(NDMM) patients, and establish a predictive nomogram model.@*METHODS@#The clinical data of 164 patients with MM who were treated in Shanxi Bethune Hospital from January 2017 to December 2021 were retrospectively analyzed. The clinical characteristics of infection were analyzed. Infections were grouped as microbiologically defined infections and clinically defined infections. Univariate and multivariate regression models were used to analyze the risk factors of infection. A nomogram was established.@*RESULTS@#164 patients with NDMM were included in this study, and 122 patients (74.4%) were infected. The incidence of clinically defined infection was the highest (89 cases, 73.0%), followed by microbial infection (33 cases, 27.0%). Among 122 cases of infection, 89 cases (73.0%) had CTCAE grade 3 or above. The most common site of infection was lower respiratory in 52 cases (39.4%), upper respiratory tract in 45 cases (34.1%), and urinary system in 13 cases (9.8%). Bacteria(73.1%) were the main pathogens of infection. Univariate analysis showed that ECOG ≥2, ISS stage Ⅲ, C-reactive protein ≥10 mg/L, serum Creatinine ≥177 μmol/L had higher correlation with nosocomial infection in patients with NDMM. Multivariate regression analysis showed that C-reactive protein ≥10 mg/L (P＜0.001), ECOG ≥2 (P=0.011) and ISS stage Ⅲ （P=0.024） were independent risk factors for infection in patients with NDMM. The nomogram model established based on this has good accuracy and discrimination. The C-index of the nomogram was 0.779（95%CI: 0.682-0.875）. Median follow-up time was 17.5 months, the median OS of the two groups was not reached (P=0.285).@*CONCLUSION@#Patients with NDMM are prone to bacterial infection during hospitalization. C-reactive protein ≥10 mg/L, ECOG ≥2 and ISS stage Ⅲ are the risk factors of nosocomial infection in NDMM patients. The nomogram prediction model established based on this has great prediction value.