To investigate whether Tasquinimod can influence cisplatin resistance in drug-resistant ovarian cancer (OC) cell lines by regulating histone deacetylase 4 (HDAC4) or p21, we explored its effects on the cell cycle, and associated mechanisms.RT-PCR and Western blot analyses, flow cytometry, CCK8 assay, and immunofluorescence were utilized to investigate the effects of Tasquinimod on gene expression, cell cycle, apoptosis, viability, and protein levels in OC cells. The results showed that Tasquinimod inhibited cell viability and promoted apoptosis in SKOV3/DDP (cisplatin) and A2780/DDP cells more effectively than DDP alone. In combination with cisplatin, Tasquinimod further enhanced cell apoptosis and reduced cell viability in these cell lines, an effect that could be reversed following HDAC4 overexpression. Tasquinimod treatment down-regulated HDAC4, Bcl-2, and cyclin D1, and CDK4 expression and up-regulated the cleaved-Caspase-3, and p21 expression in SKOV3/DDP and A2780/ DDP cells. Additionally, Tasquinimod inhibited DDP resistance in OC/DDP cells. These effects were similarly observed in OC mouse models treated with Tasquinimod. In conclusion, Tasquinimod can improve OC cells' sensitivity to DDP by down-regulating the HDAC4/p21 axis, offering insights into potential strategies for overcoming cisplatin resistance in OC.

Objective:To evaluate the impact of prophylactic cranial irradiation (PCI) on the prognosis of patients with limited-stage small cell lung cancer (SCLC) in the era of widespread application of MRI.Methods:Clinical data were collected from an open-lable prospective clinical trial on thoracic radiotherapy target volumes for limited-stage SCLC conducted in Sun Yat-sen University Cancer Center and Zhejiang Cancer Hospital between June 2002 and January 2017. In this study, patients who achieved complete remission (CR) or partial remission (PR) after definitive chemoradiotherapy (CRT) were retrospectively analyzed. Stratified analysis was performed according to different clinical efficacies. Patients were divided into different groups according to whether PCI was conducted or not. Survival analysis of patients was carried out. Survival data were calculated by Kaplan-Meier method, and Cox proportional hazards model was applied for multivariate prognostic analysis.Results:Among 309 patients with limited-stage SCLC who received CRT, 133 patients achieved CR and 140 cases obtained PR. These 273 patients were enrolled in this study. Among 133 patients with CR, 29 of them did not receive PCI, and 89 (85.6%) of the remaining 104 patients receiving PCI underwent brain MRI to exclude brain metastasis (BM) before PCI. With a median follow-up time of 22.1 months, the cumulative BM rates were 18.3% and 37.9% in patients who received or did not receive PCI ( P=0.020). The median overall survival (OS) was 30.2 and 30.5 months, and the 1-, 3- and 5-year OS rates were 93.3%, 41.9%, 27.7% and 82.8%, 44.8%, 40.8%, respectively ( P=0.910). Multivariate analysis indicated that baseline Karnofsky performance status (KPS) = 90 was a favorable independent prognostic factor for OS in CR patients ( HR=0.93, 95% CI: 0.89-0.98, P=0.006). Among 140 patients achieving PR, 52 cases did not receive PCI and 80 (90.9%) of the remaining 88 patients received brain MRI before PCI. With a median follow-up time of 18.9 months, the cumulative BM rates were 10.2% and 44.2% ( P<0.001). The median OS was 26.0 and 18.0 months, and the 1-, 3-, and 5-year OS rates were 86.4%, 37.9%, 32.2% and 75.0%, 17.3%, 10.8%, respectively ( P=0.001). Baseline KPS = 90 ( HR=0.93, 95% CI: 0.89-0.97, P=0.001) and PCI ( HR=0.54, 95% CI: 0.36-0.80, P=0.002) were favorable prognostic factors for OS in PR patients. Conclusions:PCI significantly reduces the incidence of BM and prolongs the OS in patients with limited-stage SCLC who achieve PR after CRT, but it fails to significantly prolong the OS of CR patients.

Objectives:To analyze the risk factors of atrial fibrillation in patients with non-obstructive hypertrophic cardiomyopathy(NOHCM)and explore the relationship between left ventricular/atrial volume and atrial fibrillation.Methods:Consecutive NOHCM patients admitted at Fuwai Hospital from January 2023 to January 2024 with complete clinical data,satisfactory echocardiography imaging data were included in this analysis,patients were divided into atrial fibrillation group(n=28)and non-atrial fibrillation group(n=57).Left-sided volumetric and functional parameters were measured by one-beat real-time full-volume three-dimensional echocardiography,including left ventricular end-diastolic volume(LVEDV),left ventricular end-systolic volume(LVESV),left ventricular ejection fraction(LVEF),left atrial volume(LAV).The left ventricular end-diastolic volume(LVEDVi)index,left ventricular end-systolic volume index(LVESVi)and left atrial volume index(LAVi)were calculated.Other echocardiographic parameters including interventricular septum(IVSmax)thickness,left ventricular posterior wall thickness(LVPW),and left atrial diameter(LAD)were routinely measured.Mitral valve forward flow spectrum,tissue Doppler,tricuspid regurgitation velocity,and left atrial size were used to evaluate the left ventricular diastolic function of patients,and diastolic dysfunction was classified into grade I,II,and III.Multivariate logistic regression was used to analyze the influencing factors of atrial fibrillation in patients with non-obstructive hypertrophic cardiomyopathy Results:Compared with the non-atrial fibrillation group,LVEDV([143.8±26.7]ml vs.[117.1±21.9]ml)and LVEDVi([79.4±11.9]ml/m2 vs.[64.2±10.6]ml/m2)were smaller in atrial fibrillation group(both P<0.001).Compared with the non-atrial fibrillation group,LAD([40.2±4.7]mm vs.[48.6±4.8]mm)and LAVi([37.3±8.9]ml/m2 vs.[64.4±17.1]ml/m2)were lager in atrial fibrillation group(both P<0.001).Compared with the non-atrial fibrillation group,the proportion of NYHA functional classification≥Ⅲ was higher(15.8%vs.50.0%,P<0.001),LVEF was lower([61.5±5.5]%vs.[57.6±5.0]%,P=0.002),and proportion of severe diastolic dysfunction was higher in atrial fibrillation group(P<0.001).Logistic regression analysis showed that the factors associated with atrial fibrillation in NOHCM patients were LVEDVi(OR=0.744,95%CI:0.575-0.962,P=0.024)and LAVi(OR=1.602,95%CI:1.032-2.486,P=0.036).Conclusions:LVEDVi and LAVi are related factors for atrial fibrillation in patients with non-obstructive hypertrophic cardiomyopathy.LVEDVi is negatively,while LAVi is positively associated with the occurrence of atrial fibrillation in NOHCM patients.

Objective To investigate the characteristics of a novel FANCL mutation identified in a patient with premature ovarian insufficiency(POI)and to explore its potential functional impacts in vitro.Methods A novel FANCL heterozygous mutation c.1033G>A(p.Glu345Lys)was screened in a patient with POI using whole exome sequencing(WES),which was found to be inherited from a mother who had undergone early menopause.The authenticity of the mutation was identified by Sanger sequencing and the conserved nature of the mutation site was predicted by software.Overexpressing FANCL mutant and wildtype plasmids were constructed and transiently transfected into HEK293T cell lines,and the effect of the mutation was detected by qPCR,immunofluorescence and Western blot.Results The mutation site of FANCL was located within the Ring domain of FANCL,which was highly conserved across multiple species.The mutant showed no significant change in mRNA expression level,while the protein expression level was significantly down-regulated.In vitro cellular experiments further revealed that the mutation leads to decreased expression levels by reducing protein stability.Conclusion A FANCL c.1033G>A mutation was found and it may cause disease in the POI patient due to decreased protein stability.

Aim To explore the neuroprotective effects of salidroside on Parkinson's disease(PD)through modulation of inflammatory responses and the underly-ing mechanisms.Methods Mice were divided into five groups:healthy control group,1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)disease group,low-dose Rhodioloside intervention group,medium-dose salidroside intervention group,and high-dose salidro-side intervention group.MPTP-induced PD mouse model was established,and salidroside intervention was administered.Behavioral changes,inflammatory cyto-kine levels,autophagy-related protein expression,and neurons were observed through histological analysis and immunohistochemical staining.Results After MPTP treatment,mice exhibited significant behavioral chan-ges,increased pro-inflammatory cytokines,decreased anti-inflammatory cytokines,reduced autophagy-related proteins,and evident pyroptosis.Salidroside interven-tion alleviated these changes in a dose-dependent man-ner.Conclusions Salidroside exerts neuroprotective effects on PD by alleviating inflammatory responses and promoting autophagy,thereby protecting neurons.

Fe/Mn/Gd polymetallic nanooxide(FMGN)were prepared by one-step solvent thermal reaction by using Fe(acac)3,Mn(acac)2 and Gd(acac)3 as reaction precursors.Next,hyaluronic acid(HA)was used to modify FMGN to fabricate tumor-targeting T 1-T 2 dual-mode magnetic resonance imaging(MRI)contrast agent(HA-FMGN)for accurate diagnosis of prostate cancer.The structure and morphology of FMGN were observed by transmission electron microscope(TEM).It was found that FMGN exhibited a uniform nanocluster spherical structure when the feeding ratio of iron acetylacetonate,manganese acetylacetonate,and gadolinium acetylacetonate was 3:2:1.X-ray diffraction(XRD)analysis showed that FMGN had a typical inverse spinel structure of Mn doped Fe 3O 4,with Gd existing in the form of amorphous gadolinium oxide.The longitudinal relaxivity(r 1)and transverse relaxivity(r 2)of FMGN were 13.395 and 428.535 L/(mmol·s),respectively,measured by 0.5 T MRI analyzer,which proved that FMGN had excellent T 1-T 2 dual-mode MRI contrast capability.The cytotoxicity and hemolysis test found that HA-FMGN didn't damage red cells and induce toxicity for normal cells,indicating that HA-FMGN had excellent cell biocompatibility.The internalization efficacy of HA-FMGN was observed by CLSM,and the results showed that HA-FMGN possessed excellent prostate tumor-targeting ability.In vivo MRI experiment showed that HA-FMGN significantly enhanced T 1 and T 2 weighted MRI signal to noise ratio(SNR)of prostate tumor,which promoted the accurate diagnosis of orthotopic prostate cancer.

Cancer is the main cause of death,and drug therapy has greatly improved the effectiveness of anti-tumor treatment.However,there are problems such as high adverse reactions and the risk of developing drug resistance after long-term use.There is an urgent need to seek new drug targets.Human antigen R(HuR),as an RNA binding protein,promotes the whole process of tumor occurrence,development and metastasis through post transcriptional regulation of mRNA stability,and HuR is general-ly highly expressed in tumor tissue,making it a new target for an-ti-tumor therapy and a standard for prognosis evaluation.Tradi-tional Chinese medicine formulas and their various chemical components can inhibit tumor proliferation,induce tumor cell ap-optosis,inhibit angiogenesis,suppress immune escape,and re-verse tumor drug resistance by regulating HuR activity.This re-view summarizes the importance of HuR in regulation of tumor progression,as well as analyzes the mechanisms of the antitumor effects through active ingredients of Chinese medicine with the regulation of HuR.It is expected to provide new ideas for tumor therapy and guidance for the development of HuR-targeted anti-tumor drugs.

Objective:The purpose of this study was to analyze the epidemiological characteristics of hand, foot, and mouth disease (HFMD) among individuals aged 6 years and above in Guangzhou from 2010 to 2023, with the intention that a scientific basis be provided for effective prevention and control measures in older age groups.Methods:Data on HFMD incidence among individuals aged 6 years and above in Guangzhou from 2010 to 2023 were collected and analyzed. Descriptive epidemiological methods were used to analyze the distributions and pathogen components of HFMD cases in Guangzhou residents aged 6 years and above. Spatial autocorrelation analysis and Getis-Ord Gi* analysis were conducted to identify the spatial clustering patterns of HFMD at the street town level. Results:From 2010 to 2023, the gender ratio of HFMD cases in persons aged 6 and above was 1.49∶1 in Guangzhou. The average annual incidence rate of HFMD among individuals aged 6 years and above in Guangzhou was 25.75 per 100 000. Furthermore, the reported incidence rate indicated an increased tendency. The annual incidence showed a bimodal distribution, with the main peak occurring from May to July and the secondary peak from September to October. HFMD incidence rates vary by townships, with hotspots clustered in urban and urban-rural regions. The dominant pathogen shifts from year to year. Enterovirus 71 (EV71) was the prevalent strain in 2010, followed by other enteroviruses and Coxsackievirus (CV)-A16 from 2011 to 2016. Since 2017, CV-A6 has steadily become the major pathogen.Conclusions:The incidence of HFMD cases among individuals aged 6 years and above in Guangzhou increased generally from 2010 to 2023, with hotspots localized in urban and urban-rural areas. The pathogen composition altered dramatically, with the proportion of EV71 dropping overall, while CV-A6 eventually became the dominating strain. Therefore, it is imperative to focus on the prevention and control of HFMD in this age group, especially by strengthening measures in areas with high prevalence.

To investigate whether Tasquinimod can influence cisplatin resistance in drug-resistant ovarian cancer (OC) cell lines by regulating histone deacetylase 4 (HDAC4) or p21, we explored its effects on the cell cycle, and associated mechanisms.RT-PCR and Western blot analyses, flow cytometry, CCK8 assay, and immunofluorescence were utilized to investigate the effects of Tasquinimod on gene expression, cell cycle, apoptosis, viability, and protein levels in OC cells. The results showed that Tasquinimod inhibited cell viability and promoted apoptosis in SKOV3/DDP (cisplatin) and A2780/DDP cells more effectively than DDP alone. In combination with cisplatin, Tasquinimod further enhanced cell apoptosis and reduced cell viability in these cell lines, an effect that could be reversed following HDAC4 overexpression. Tasquinimod treatment down-regulated HDAC4, Bcl-2, and cyclin D1, and CDK4 expression and up-regulated the cleaved-Caspase-3, and p21 expression in SKOV3/DDP and A2780/ DDP cells. Additionally, Tasquinimod inhibited DDP resistance in OC/DDP cells. These effects were similarly observed in OC mouse models treated with Tasquinimod. In conclusion, Tasquinimod can improve OC cells' sensitivity to DDP by down-regulating the HDAC4/p21 axis, offering insights into potential strategies for overcoming cisplatin resistance in OC.

To investigate whether Tasquinimod can influence cisplatin resistance in drug-resistant ovarian cancer (OC) cell lines by regulating histone deacetylase 4 (HDAC4) or p21, we explored its effects on the cell cycle, and associated mechanisms.RT-PCR and Western blot analyses, flow cytometry, CCK8 assay, and immunofluorescence were utilized to investigate the effects of Tasquinimod on gene expression, cell cycle, apoptosis, viability, and protein levels in OC cells. The results showed that Tasquinimod inhibited cell viability and promoted apoptosis in SKOV3/DDP (cisplatin) and A2780/DDP cells more effectively than DDP alone. In combination with cisplatin, Tasquinimod further enhanced cell apoptosis and reduced cell viability in these cell lines, an effect that could be reversed following HDAC4 overexpression. Tasquinimod treatment down-regulated HDAC4, Bcl-2, and cyclin D1, and CDK4 expression and up-regulated the cleaved-Caspase-3, and p21 expression in SKOV3/DDP and A2780/ DDP cells. Additionally, Tasquinimod inhibited DDP resistance in OC/DDP cells. These effects were similarly observed in OC mouse models treated with Tasquinimod. In conclusion, Tasquinimod can improve OC cells' sensitivity to DDP by down-regulating the HDAC4/p21 axis, offering insights into potential strategies for overcoming cisplatin resistance in OC.