Aim To investigate the effect of vanillin on the regulation of cyclic guanylate adenylate synthetase(cGAS)/stimulator of interferon gene(STING)signa-ling pathway on hepatic tissue injury in rats with intra-hepatic cholestasis(IC).Methods SD rats were randomly divided into normal group,IC group,vanillin group,cGAS overexpression group,and vanillin+cGAS overexpression group,with continuous adminis-tration for seven days.The body weight,liver weight and liver to body weight ratio of rats were measured.Liver function(ALT,AST,ALP,LDH),IC(TBIL,TBA)and liver fibrosis(HA,LN,PC Ⅲ)index were determined by ELISA.Liver pathology and fibrosis were observed using HE and Masson staining,and col-lagen volume fraction was calculated.The expression of cGAS/STING pathway related proteins in liver tissue was detected by Western blot.Results Vanillin could improve liver pathology and fibrosis,increase body weight,and decrease liver weight,ALT,AST,ALP,LDH,TBIL,TBA,HA,LN,PC Ⅲ,collagen volume fraction,cGAS,STING protein in IC rats(P＜0.05).Overexpression of cGAS could reverse the effects of vanillin on the above indicators in IC rats(P＜0.05).Conclusions Vanillin may improve liver function,IC,liver fibrosis,and liver tissue damage in IC rats by downregulating the cGAS/STING signaling pathway.

Objective:To investigate the clinical significance of genetic and molecular changes in primary myeloid sarcoma(MS).Methods:Fourteen patients with primary MS were selected in Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences,The First People's Hospital of Lianyungang from September 2010 to December 2021.AML1-ETO fusion,PML-RARα fusion and CBFβ breakage were detected by fluorescence in situ hybridization(FISH),and the mutations of NPM1,CEBPA,FLT3,RUNX1,ASXL1,KIT and TP53 genes were detected by new generation sequencing(NGS).Results:Among 14 patients,the MS occurred in bone,breast,epididymis,lung,chest wall,cervix,small intestine,ovary,lymph nodes and central nervous system.The tumor cells expressed MPO(13 cases),CD34(7 cases),CD43(8 cases),CD68(7 cases),CD99(8 cases)and CD117(6 cases).Cytogenetic abnormalities were observed in 4 cases,including 3 cases of AML1-ETO fusion and 1 case of CBF β breakage,while no PML-RAR α fusion was detected.There were no significant differences in overall survival(OS)and leukemia-free survival(LFS)between patients with and without AML1-ETO fusion/CBFβ breakage(both P＞0.05).Among the 14 patients,the number of NPM1,CEBPA,FLT3-ITD,RUNX1,ASXL1,KIT and TP53 gene mutations was 5,3,5,3,2,2,1.respectively,of which 7 cases had at least one mutation in FLT3-ITD,RUNX1,ASXL1 and TP53 gene.The OS and LFS of patients with FLT3-ITD,RUNX1,ASXL1 or TP53 mutation were shorter than those without mutations(both P＜0.01).Conclusion:The genetic and molecular abnormalities of primary MS can be detected by FISH and NGS techniques.FLT3-ITD,RUNX1,ASXL1 or TP53 mutation indicates a worse prognosis,but further clinical studies are needed to confirm it.

Objective:To evaluate the gene mutation profile and prognostic significance of adult cytogenetically normal acute myeloid leukemia (CN-AML) with CEBPA-bZIP mutation. Methods:Targeted sequencing was implemented on the diagnostic bone marrow DNA samples of 141 adult CN-AML subjects with CEBPA-bZIP mutation. The nomogram model for leukemia-free survival (LFS) rate was generated by combining genetic abnormalities and clinical data. Risk stratification was conducted based on prognostic variables and the effect of risk-adjusted consolidation therapy was investigated by Kaplan-Meier method. Results:Four variables were finally included in our nomogram model after multivariate Cox analysis,and an equation for risk score calculation was obtained,risk score=1.3002×white blood cell (WBC) (≥18.77×109/L)+1.4065×CSF3R mutation positive+2.6489×KMT2A mutation positive+1.0128×DNA methylation-related genes mutation positive. According to the nomogram model,patients were further divided into low-risk group (score=0,n=46) and high-risk group (score>0,n=95). Prognostic analysis showed that the 5-year LFS rate,5-year overall survival (OS) rate,and 5-year cumulative incidence of relapse (CIR) of patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the high-risk group were 93.5％,97.1％,and 3.5％,while those in patients who received maintenance chemotherapy were 32.9％,70.5％,and 63.4％,respectively. The differences were statistically significant (all P<0.05). Allo-HSCT could significantly improve the prognosis of patients in high-risk group. However,no corresponding benefit was observed in the low-risk group. Conclusion:Adult CN-AML with CEBPA-bZIP mutation has a complex co-mutation pattern. The nomogram model based on mutations of CFS3R,KMT2A and DNA methylation-related genes together with WBC count can further divide this subset of patients into a relatively low-risk group and a relatively high-risk group. For individuals in the high-risk group,allo-HSCT is proposed as post-remission therapy. The above data will benefit the prognosis estimation and treatment decision for adult CN-AML with CEBPA-bZIP mutation.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To explore the efficacy of low-dose and short-course glucocorticoid treatment on moderate coronavirus disease 2019(COVID-19)in elderly patients.Methods Clinical data of patients aged ≥80 years,diag-nosed with COVID-19,and admitted to a hospital from December 9,2022,to February 9,2023 were investigated retrospectively.According to whether low-dose glucocorticoids was administered intravenously after admission,pa-tients were divided into non-hormone usage group and hormone usage group.General information and laboratory test results of two groups of patients were described,changes of patients'conditions within 30 days were observed,and difference in efficacy between the two groups was compared.Results A total of 62 patients were recruited,in-cluding 21 in the non-hormone usage group and 41 in the hormone usage group.The general information and labora-tory test indicators before treatment between two groups of patients showed no statistically significant differences(both P＞0.05).Except hormone usage,there was no statistically significant difference in other treatment methods(all P＞0.05).After treatment with glucocorticoids for 10 days,the clinical manifestations of cough(34.1％vs 66.7％),expectoration(19.5％vs 61.9％),palpitation(4.9％vs 23.8％)and shortness of breath(7.3％vs 28.6％)in the hormone usage group decreased compared with those in the non-hormone usage group,differences were statis-tically significant(all P＜0.05).After 10 days of treatment,compared with patients in the non-hormone usage group,the oxygenation indicator and lymphocyte count of patients in the hormone usage group increased,while the values of C-reactive protein and D-dimer decreased,with statistically significant differences(all P＜0.05).The inci-dence of disease exacerbation in the hormone usage group was lower than that in the non-hormone usage group(14.6％vs 47.6％),difference was statistically significant(x2=7.895,P=0.005).Conclusion Low-dose and short-course systemic glucocorticoid usage in elderly patients with moderate COVID-19 can effectively control the progress of the disease and improve prognosis.

AIM: To evaluate the efficacy and safety of different Conbercept treatment on diabetic macular edema(DME)with 3+PRN and 5+PRN.METHODS: Retrospective case-control study. A total of 51 patients(92 eyes)with DME who were treated in our hospital during December 2019 and June 2020 were included, and they were divided into 3+PRN group with 26 cases(48 eyes)and 5+PRN group with 25 cases(44 eyes). All patients received monthly follow-up for 12mo and the changes of best-corrected visual acuity(BCVA)and central macular thickness(CMT), the number of intravitreal injections and the occurrence of complications were compared and observed in the two groups.RESULTS:After follow-up for 12mo, there was no difference in the average injection times between the 3+PRN group and the 5+PRN group(7.24±0.91 times vs. 7.56±1.04 times, P=0.117). The BCVA and CMT of the two groups improved at 3, 6, 9, and 12mo after treatment compared with those before treatment(all P<0.05), and the BCVA and CMT of the 5+PRN group were better than those of the 3+PRN group at 6, 9, and 12mo after treatment(all P<0.05). During the follow-up period, no serious adverse events occurred in the two groups of patients, and the total incidence of ocular adverse events in the two groups was 27%. All adverse events were improved after symptomatic treatment.CONCLUSION: Both the 3+PRN and 5+PRN treatment strategy of Conbercept can treat DME safely and effectively, the total times of injection were comparable. However, the BCVA and CMT improved more in the 5+PRN group than that in 3+PRN group.

It has attracted much attention worldwide that the application of artificial intelligence (AI) in primary screening and clinical diagnosis and treatment of eye diseases. In recent years, this technology has also been widely used in various grass-roots eye disease management, effectively improving the current situation of weak eye disease diagnosis ability and shortage of human resources in primary medical institutions. At present, there is no reference standard or guideline for the management mode, implementation content and management method of vision health management based on this technology, which are in urgent need of standardization. The article described the work mode exploration of AI-assisted grass-roots visual health management in Shanghai and shared practical experience. The aim is to provide reference for other provinces in China to carry out relevant work.
Humans ; Artificial Intelligence ; China ; Reference Standards ; Workforce

To explore the relationship between the early or delayed age at natural menopause and metabolic syndrome (MS) in women. A total of 4 734 natural menopausal women who completed the baseline survey from November 2017 to January 2020 in the Guangzhou Middle-aged and Elderly Chronic Disease Prospective Cohort Study were selected in this cross-sectional study. Data on general demographic characteristics, disease history and female physiological health indicators were collected. Logistic regression model and restricted cubic spline curve were used to analyze the relationship between the age at natural menopause and MS. The results showed that the mean age of the subjects was (60±6) years old. The median (Q₁,Q₃) age at natural menopause was 50 (49, 52) years old, and the prevalence of MS was 14.8%(699/4 734). After adjusting for confounders, the age at natural menopause was closely related to MS in an approximate"U"shape. Compared with the group of normal age at natural menopause, the early age at menopause (OR=1.52, 95%CI: 1.12-2.06) and delayed age at menopause (OR=1.77, 95%CI: 1.36-2.30) had a higher risk of MS. In the group with time since menopause ≤6 years and 7-9 years, the risk of MS in the group with delayed age at menopause was 2.40 times (95%CI: 1.54-3.75) and 2.19 times (95%CI: 1.11-4.31) higher than that in the group with normal menopausal age, respectively. In conclusion, the early and delayed age at natural menopause increased the risk of MS. The increased risk of MS in delayed age at natural menopause mainly occurred within 10 years since menopause.
Middle Aged ; Aged ; Female ; Humans ; Child ; Postmenopause ; Metabolic Syndrome/epidemiology* ; Prospective Studies ; Cross-Sectional Studies ; Menopause/physiology* ; Risk Factors

This study explores the effect of total flavonoids of Rhododendra simsii(TFR) on middle cerebral artery occlusion(MCAO)-induced cerebral injury in rats and oxygen-glucose deprivation/reoxygenation(OGD/R) injury in PC12 cells and the underlying mechanism. The MCAO method was used to induce focal ischemic cerebral injury in rats. Male SD rats were randomized into sham group, model group, and TFR group. After MCAO, TFR(60 mg·kg~(-1)) was administered for 3 days. The content of tumor necrosis factor-α(TNF-α), interleukin-1(IL-1), and interleukin-6(IL-6) in serum was detected by enzyme-linked immunosorbent assay(ELISA). The pathological changes of brain tissue and cerebral infarction were observed based on hematoxylin and eosin(HE) staining and 2,3,5-triphenyltetrazolium chloride(TTC) staining. RT-qPCR and Western blot were used to detect the mRNA and protein levels of calcium release-activated calcium channel modulator 1(ORAI1), stromal interaction molecule 1(STIM1), stromal intera-ction molecule 2(STIM2), protein kinase B(PKB), and cysteinyl aspartate specific proteinase 3(caspase-3) in brain tissues. The OGD/R method was employed to induce injury in PC12 cells. Cells were randomized into the normal group, model group, gene silencing group, TFR(30 μg·mL~(-1)) group, and TFR(30 μg·mL~(-1))+gene overexpression plasmid group. Intracellular Ca~(2+) concentration and apoptosis rate of PC12 cells were measured by laser scanning confocal microscopy and flow cytometry. The effect of STIM-ORAI-regulated store-operated calcium entry(SOCE) pathway on TFR was explored based on gene silencing and gene overexpression techniques. The results showed that TFR significantly alleviated the histopathological damage of brains in MCAO rats after 3 days of admini-stration, reduced the contents of TNF-α, IL-1, and IL-6 in the serum, down-regulated the expression of ORAI1, STIM1, STIM2, and caspase-3 genes, and up-regulated the expression of PKB gene in brain tissues of MCAO rats. TFR significantly decreased OGD/R induced Ca~(2+) overload and apoptosis in PC12 cells. However, it induced TFR-like effect by ORAI1, STIM1 and STIM2 genes silencing. However, overexpression of these genes significantly blocked the effect of TFR in reducing Ca~(2+) overload and apoptosis in PC12 cells. In summary, in the early stage of focal cerebral ischemia-reperfusion injury and OGD/R-induced injury in PC12 cells TFR attenuates ischemic brain injury by inhibiting the STIM-ORAI-regulated SOCE pathway and reducing Ca~(2+) overload and inflammatory factor expression, and apoptosis.
Animals ; Male ; Rats ; Apoptosis ; Brain Ischemia/metabolism* ; Caspase 3 ; Interleukin-1 ; Interleukin-6 ; Rats, Sprague-Dawley ; Reperfusion Injury/metabolism* ; Tumor Necrosis Factor-alpha/genetics* ; Flavonoids/pharmacology* ; Rhododendron/chemistry*

This study investigated the choroplast genome sequence of wild Atractylodes lancea from Yuexi in Anhui province by high-throughput sequencing, followed by characterization of the genome structure, which laid a foundation for the species identification, analysis of genetic diversity, and resource conservation of A. lancea. To be specific, the total genomic DNA was extracted from the leaves of A. lancea with the improved CTAB method. The chloroplast genome of A. lancea was sequenced by the high-throughput sequencing technology, followed by assembling by metaSPAdes and annotation by CPGAVAS2. Bioiformatics methods were employed for the analysis of simple sequence repeats(SSRs), inverted repeat(IR) border, codon bias, and phylogeny. The results showed that the whole chloroplast genome of A. lancea was 153 178 bp, with an 84 226 bp large single copy(LSC) and a 18 658 bp small single copy(SSC) separated by a pair of IRs(25 147 bp). The genome had the GC content of 37.7% and 124 genes: 87 protein-coding genes, 8 rRNA genes, and 29 tRNA genes. It had 26 287 codons and encoded 20 amino acids. Phylogenetic analysis showed that Atractylodes species clustered into one clade and that A. lancea had close genetic relationship with A. koreana. This study established a method for sequencing the chloroplast genome of A. lancea and enriched the genetic resources of Compositae. The findings are expected to lay a foundation for species identification, analysis of genetic diversity, and resource conservation of A. lancea.
Phylogeny ; Atractylodes/genetics* ; Genome, Chloroplast ; Whole Genome Sequencing ; Microsatellite Repeats ; Lamiales