Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Objective Pancreatic cancer(PC)is a malignant tumor of the digestive tract that is difficult to diagnose early,easily metastasizes and relapses,and resistant to conventional chemotherapy.PC is a very difficult disease to treat.The key regulatory factors of PC resistance,such as epithelial-mesenchymal transition phenotypic cells,tumor stem cells,and miRNAs,have been reviewed in the past few years,and some new regulatory factors have been discovered as supplements.This review mainly focuses on the characteristics and properties of the key regulatory factors of PC chemotherapy resistance including long noncoding RNAs,nuclear factor KB and exosomes,drug resistance mechanisms,and treatment related strategies,and future treatment directions were predicted.

AIM To study the neoflavonoids from Dalbergia cochinchinensis Pierre ex Laness and their anti-hypoxia/reoxygenation injury activities on H9c2 myocardial cells.METHODS The 70%ethanol extract from D.cochinchinensis was isolated and purified by silica gel,Sephadex LH-20 and reverse-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The CCK-8 method was used to detect their activities on H9c2 cells and protective effects on hypoxia-reoxygenation injury of H9c2 cells,and their structure-activity relationship was analyzed.RESULTS Twelve compounds were isolated and identified as latifolin(1),5-O-methyllatifolin(2),mimosifoliol(3),5-O-methydalbergiphenol(4),dalbergiphenol(5),cearoin(6),2,4-dihydroxy-5-methoxy-benzophenone(7),2-hydroxy-4,5-dimethoxybenzophenone(8),melannoin(9),2,2′,5-trihydroxy-4-methoxybenzophenone(10),dalbergin(11),4-methoxydalbergione(12).The dalbergiphenols and dalbergins had little toxicity to H9c2 cells,and dalbergiphenols had strong activity against hypoxia-reoxygenation injury of H9c2 cells.CONCLUSION Compound 8 is a new natural product.Compounds 4,9 are isolated from this plant for the first time.Dalbergiphenols may be the main neoflavonoids against hypoxia-reoxygenation injury of H9c2 cells.

Objective: To explore the mechanism by which icariin alleviates viral myocarditis. Methods: CVB3-induced cardiomyocytes were used as an in vitro model of viral myocarditis to assess the effects of icariin treatment on cell viability, inflammation, and apoptosis. Moreover, the effects of icariin on ferroptosis and TLR4 signaling were assessed. After AC16 cells were transfected with TLR4 overexpression plasmids, the role of TLR4 in mediating the regulatory effect of icariin in viral myocarditis was investigated. Results: Icariin significantly elevated cell viability and reduced inflammatory factors TNF-α, IL-1β, IL-6, and IL-18. Flow cytometry revealed that icariin decreased apoptosis rate, and the protein expression of Bax and cleaved caspase 3 and 9 in CVB3-induced cardiomyocytes. Additionally, it suppressed ferroptosis including lipid peroxidation and ferrous ion, as well as the TLR4 signaling. However, TLR4 overexpression abrogated the modulatory effects of icariin. Conclusions: Icariin mitigates CVB3-induced myocardial injury by inhibiting TLR4-mediated ferroptosis. Further animal study is needed to verify its efficacy.

Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.

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.

A ratiometric fluorescent probe([Eu(Hpfdap)3(CTMR-Phen-N)])was designed and synthesized for detection of singlet oxygen(1O2)with dimethyl anthracyl-containing β-diketone compound 1,1,1,2-pentafluoro-5-(9',10'-dimethyl-2'-anthracene)-3,5-pentanedione(Hpfdap)as recognition ligand and 5-amino-1,10-phenanthroline conjugated with Rhodamine as auxiliary ligand(CTMR-Phen-N).The results of spectral analysis showed that the europium(Ⅲ)complex had almost no fluorescence due to the presence of anthracene ring in the probe.After reaction with 1O2,the anthracene ring was oxidized to endoperoxide,and the fluorescence of the europium(Ⅲ)complex at 614 nm was restored,followed by the increase of quantum yield from 1.60%to 25.16%.The fluorescence intensity of Rhodamine at 575 nm remained unchanged before and after the reaction with 1O2.Therefore,the ratio of fluorescence intensity at 614 nm and 575 nm could be used to measure 1O2 by the developed rationmetric fluorescence method.The probe showed good selectivity for 1O2,and the detection limit(S/N=3)was as low as 3 μmol/L.The fluorescence imaging results demonstrated that the probe had low cytotoxicity and good membrane permeability,and could be applied to fluorescence imaging of 1O2 in Hela cells.

Background/Aims: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. Methods: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Results: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. Conclusions Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

Aesculus chinensis is an important medicinal and horticultural plant. Its dried mature seeds, known as "Suoluozi", are a well-known traditional Chinese medicine. Aescins are its main active components, possessing multiple pharmacological activities such as anti-inflammatory and anti-exudative effects. They are widely used in the treatment of diseases such as lumbar disc herniation, postoperative edema, and sports injuries, leading to a continuous increase in market demand in recent years. The DNA binding with one finger(Dof) family is a unique transcription factor family found in the plant kingdom. It plays a crucial role in plant growth, development, stress responses, and regulation of secondary metabolism. However, research on the Dof gene family in A. chinensis is relatively scarce. In this study, we identified 36 AcDof genes from the genome of A. chinensis and analyzed their physicochemical properties, chromosomal localization, phylogenetic relationships, gene structures, cis-acting elements, and expression patterns in different tissues. The results showed that AcDof proteins ranged from 81 to 493 amino acids in length, with molecular weights ranging from 9 270.38 to 55 015.68 and isoelectric points ranging from 4.84 to 10.2. The subcellular localization analysis revealed that 34 AcDof proteins were located in the nucleus, while the remaining two AcDof proteins were located in the chloroplasts. Phylogenetic analysis divided AcDofs into nine subgroups, and gene structure analysis indicated that all AcDof genes possessed a C2-C2 type single zinc finger domain. Gene expression analysis using transcriptome data revealed tissue-specific expression patterns among AcDof family members. Specifically, AcDof04, AcDof02, and AcDof03 exhibited specific expression in seeds, suggesting their potential involvement in the regulation of aescin biosynthesis. This study not only enhances our understanding of the Dof gene family in A. chinensis but also provides important genetic resources for further investigation of the functions and regulatory mechanisms of Dof genes in this species.
Plant Proteins/metabolism* ; Phylogeny ; Gene Expression Regulation, Plant ; Transcription Factors/metabolism* ; Gene Expression Profiling ; Multigene Family

This study aims to investigate the effect of Linggui Zhugan Decoction(LGZGD) on autophagy in the mouse model of chronic heart failure(CHF) induced by myocardial infarction(MI), as well as the regulatory effect of LGZGD on the hypoxia-inducible factor-1α(HIF-1α)/heme oxygenase-1(HO-1) signaling pathway, based on bioinformatics and animal experiments. The active ingredients and corresponding targets of LGZGD were retrieved from the Traditional Chinese Medicine Systems Pharmacology and Analysis Database, and GEO, GeneCards, and DisGeNET were searched for the disease targets. Cytoscape was used to establish a "drug-component-target" network. The protein-protein interaction(PPI) network analysis was performed on STRING. R language was used for Gene Ontology(GO) and Kyoto Encycloperfia of Genes and Genomes(KEGG) enrichment analyses. Molecular docking was adopted to validate the core targets. The mouse model of MI-induced CHF was established by surgical ligation of the left anterior descending coronary artery. The modeled mice were assigned into the sham, model, low-, medium-, and high-dose(2.34, 4.68, and 9.36 g·kg~(-1), respectively) LGZGD, and captopril(3.25 mg·kg~(-1)) groups. After continuous administration for 6 weeks, a Doppler ultrasound imaging system was used to examine the heart function indicators: left ventricular ejection fraction(LVEF), left ventricular fractional shortening(LVFS), left ventricular end-systolic dimension(LVIDs), and left ventricular end-diastolic dimension(LVIDd). The myocardial tissue was stained with hematoxylin-eosin for the observation of morphological changes. The mRNA levels of microtubule-associated protein 1 light chain 3 beta(LC3B), Beclin1, p62, HIF-1α, and HO-1 in the myocardial tissue were determined by RT-qPCR. The protein levels of LC3B, beclin1, p62, autophagy-related protein 5(ATG5), HIF-1α, and HO-1 were determined by Western blot. The results showed that 103 active components of LGZGD, corresponding to 224 targets, were obtained. A total of 3 485 and 6 165 targets related to MI and CHF, respectively, were retrieved. The GSE16499 dataset obtained 3 263 differentially expressed genes. There were 31 common targets. The top 3 core active components were quercetin, naringenin, and 1-methoxyphaseollidin. The topology analysis results showed that the core targets were MAPK3, HMOX1(HO-1), MYC, ADRB2, PPARD, and HIF1A(HIF-1α). The molecular docking results showed strong binding between the core targets and the main active components of LGZGD. LGZGD significantly improved the heart function and alleviated the pathological changes in the myocardial tissue of mice. Western blot and RT-qPCR results showed that the HIF-1α/HO-1 signaling pathway and autophagy were activated in the model group. LGZGD up-regulated the levels of LC3B, Beclin1, ATG5, HIF-1α, and HO-1 while down-regulating the mRNA and protein levels of p62. In summary, LGZGD can enhance autophagy and improve the heart function in the mouse model of CHF after MI by upregulating the HIF-1α/HO-1 signaling pathway.
Animals ; Drugs, Chinese Herbal/chemistry* ; Myocardial Infarction/drug therapy* ; Heart Failure/physiopathology* ; Mice ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Signal Transduction/drug effects* ; Male ; Computational Biology ; Heme Oxygenase-1/genetics* ; Molecular Docking Simulation ; Protein Interaction Maps/drug effects* ; Mice, Inbred C57BL ; Humans ; Chronic Disease ; Disease Models, Animal