Radiation-induced thrombocytopenia(RIT)faces a perplexing challenge in the clinical treatment of cancer patients,and current therapeutic approaches are inadequate in the clinical settings.In this research,oxy-matrine,a new molecule capable of healing RIT was screened out,and the underlying regulatory mecha-nism associated with magakaryocyte(MK)differentiation and thrombopoiesis was demonstrated.The capacity of oxymatrine to induce MK differentiation was verified in K-562 and Meg-01 cells in vitro.The ability to induce thrombopoiesis was subsequently demonstrated in Tg(cd41:enhanced green fluorescent protein(eGFP))zebrafish and RIT model mice.In addition,we carried out network pharmacological pre-diction,drug affinity responsive target stability assay(DARTS)and cellular thermal shift assay(CETSA)analyses to explore the potential targets of oxymatrine.Moreover,the pathway underlying the effects of oxymatrine was determined by Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,Western blot(WB),and immunofluorescence.Oxymatrine markedly promoted MK differentiation and maturation in vitro.Moreover,oxymatrine induced thrombopoiesis in Tg(cd41:eGFP)zebrafish and accelerated thrombopoiesis and platelet function recovery in RIT model mice.Mechanistically,oxymatrine directly binds to toll-like receptor 2(TLR2)and further regulates the downstream pathway stimulator of interferon genes(STING)/nuclear factor-kappaB(NF-κB),which can be blocked by C29 and C-176,which are specific inhibitors of TLR2 and STING,respectively.Taken together,we demonstrated that oxymatrine,a novel TLR2 agonist,plays a critical role in accelerating MK differentiation and thrombopoiesis via the STING/NF-κB axis,suggesting that oxymatrine is a promising candidate for RIT therapy.

AIM To study the chemical constituents from Citri reticulatae Pericarpium Viride and their anti-triple negative breast cancer activities in vitro.METHODS The ethanolic extract of Citri reticulatae Pericarpium Viride was isolated and purified by silica gel,polyamide,MCI,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The anti-triple negative breast cancer activities were screened by SRB assay,and their effects on the proliferation of triple negative breast cancer cell lines HCC1806,HCC1937 and MDA-MB-231 in vitro were evaluated.RESULTS Twenty compounds were isolated and identified as nobiletin(1),tangeritin(2),5,4'-dihydroxy-7,8-dimethoxy flavonoid(3),naringenin(4),artemetin(5),5-demethynobiletin(6),3,5,6,7,8,3',4'-pentamethoxy flavonoid(7),5,4'-dihydroxy-3,6,7,8,3'-pentamethoxyflavone(8),xanthomicrol(9),p-hydroxycinnamic acid(10),5,4'-dihydroxy-6,7,8,3'-tetramethoxyflavone(11),pectolinarigenin(12),4'-dihydroxy-5,6,7-tetramethoxyflavone(13),hispidulin(14),4',5,6,7-tetramethoxy-flavone(15),1-methyl-4-(prop-1-en-2-yl)cyclohexane-1,2-diol(16),umbelliferone(17),5-hydroxymethyl furfural(18),hydroquinone(19),1H-indole-3-carbaldehyde(20).Compound 8 showed a significant inhibitory effect with the IC50 value of(5.36±0.24)μmol/L on HCC1806 cells.CONCLUSION Compound 20 is isolated from genus Citrus for the first time,8,12-13,16-17 are isolated from this plant for the first time.Compound 8 show inhibitory effects on the proliferation of HCC1806,HCC1937 and MDA-MB-231 cells in vitro and have the strongest activities.Compounds 3-4,11-12,15,17 and 19 show strong inhibitory effect on HCC1806 cells.Compounds 15,19 also inhibit the proliferation of HCC1937 cells in vitro.

Objectives:To analyze the cardiac involvement of patients with Fabry disease(FD)in Anhui region.Methods:This retrospective analysis included 48 previously and currently diagnosed FD patients(25 males)in Anhui region,overall patient and gender specific cardiac involvement was analyzed.Results:The median age of FD patients is 28.0(19.0,46.0)years.The cardiac manifestations of patients with FD were most commonly characterized by palpitations/arrhythmias(13/42 cases)and exertional dyspnea(11/42 cases),electrocardiographic changes were most commonly characterized by T-wave inversion(22/42 cases),ST-segment depression(16/42 cases),and left ventricular hypervoltage(18/42 cases),cardiac structural and functional changes were most common in papillary muscle hypertrophy(29/36 cases),bilateral sign(22/37 cases)and left ventricular hypertrophy(21/46 cases),as well as reduced left ventricular global longitudinal strain(26/39 cases).Neuropathic pain(28/43 cases)was the most common extracardiac manifestation of FD patients.FD patients of different gender differed in age at diagnosis(P=0.018),alpha galactosidase A activity(P<0.001),globotriaosylsphingosine(lyso-GL3)levels(P<0.001),enzyme replacement therapy rate(P=0.043),dyshidrosis(P<0.01),and the incidence of angiokeratoma(P=0.004).Correlation analysis showed that genotype was not correlated with enzyme activity or Lyso-GL-3 levels,whereas the Sokolow-Lyon index was positively correlated with Lyso-GL-3 levels(ρ=0.423,P=0.008),and the Sokolow-Lyon indices(septal thickness:ρ=0.562,P<0.001;left ventricle posterior wall thickness:ρ=0.569,P<0.001)and QRS duration(septal thickness:ρ=0.543,P<0.001;left ventricle posterior wall thickness:ρ=0.557,P<0.001)were positively correlated with left ventricular wall thickness.Conclusions:Cardiac involvement in patients with FD in the Anhui region is characterised by palpitations or arrhythmias,accompanied by nonspecific electrocardiographic changes.Echocardiography frequently reveals papillary muscle hypertrophy.The manifestation of cardiac involvement in patients of different genders is similar.

To explore the effects of different blood loss on liver and kidney function,blood lactic acid levels,and oxidative stress indexes after hemorrhagic shock resuscitation in dogs,10 healthy Chinese rural dogs were randomly divided into 1.5 h blood loss resuscitation group(HSRA group)and 3.5 h blood loss resuscitation group(HSRB group).The changes in liver and kidney function,blood lactic acid,and oxidative stress-related indexes were detected at 2,6,24,48 and 72 h after re-suscitation.The results showed that the liver function indexes of TBIL,ALT,and AST in the HSRB group were higher than those in the HSRA group at each time point after resuscitation.There was no significant change in renal function indexes between the two groups.The level of Lac in the HSRB group was significantly higher than that in the HSRA group at 2 and 6 h after resuscitation.CAT activity in the HSRB group was significantly lower than that in the HSRA group at 2 h after resuscitation.GSH-px activity in the HSRB group was significantly lower than that in the HSRA group at 2,6 and 24 h after resuscitation.SOD activity in the HSRB group was significantly lower than that in the HSRA group at 24 h after resuscitation.MDA content in the HSRB group was sig-nificantly higher than that in the HSRA group at 2,6,24 and 48 h after resuscitation.The results showed that HS could cause liver injury and oxidative stress after resuscitation,and the degree of liver injury and oxidative stress injury in dogs increased with the prolongation of blood loss.

Objective:To investigate the radon exposure levels and health effects among non-uranium miners in Chongqing.Methods:From June 2022 to December 2023, a survey was carried out on basic information, radon exposure and occupational health status of 110 male miners with good cooperation attitudes in 6 non-uranium metal mines in normal operation in Chongqing. The logistic regression model was utilized to statistically analyze the impact of miners′ individual radon doses on abnormalities in chromosomal aberration analysis, micronucleus examination, tumor marker tests, and pulmonary CT imaging.Results:Monitoring results from passive integrated radon personal dosimeters indicated that three miners had an annual dose exceeding 2 mSv. Logistic regression analysis revealed that abnormalities in pulmonary CT imaging were associated with miners′ age, tenure, and alcohol consumption ( χ2=12.18, 9.63, 4.87, P<0.05), with no significant correlation with smoking or individual radon dose. There was a significant correlation between individual radon dose and abnormalities in tumor markers; for every additional 1 mSv of effective dose from radon and its progeny, the risk of abnormality increased by 2.25 times ( χ2=4.57, P < 0.05). Conclusions:Some miners in Chongqing are exposed to an annual dose exceeding 2 mSv, and there is a correlation between individual radon doses and abnormalities in lung cancer serum tumor markers. It is necessary to focus on monitoring the radon exposure risks for miners, carry out regular health checks, and enhance the health protection for the miner population.

This study aims to analyze the screening results and epidemiological characteristics of prostate cancer (PCa) among elderly males in the rural areas of Songjiang, Shanghai City, through the implementation of a preliminary prostate-specific antigen (PSA) screening based on a community-linkage model, and to explore an effective screening approach. A retrospective observational study design was employed to collect data from residents who underwent PSA screening at Songjiang Hospital affiliated to Shanghai Jiao Tong University School of Medicine, in collaboration with multiple community health service centers in Songjiang District, Shanghai City, between June 2022 and June 2024, through free clinics and annual health examinations. Prostate biopsy was recommended for individuals with total PSA (tPSA) levels >10 ng/ml and those with 4 ng/ml≤tPSA≤10 ng/ml and abnormal free-to-total PSA (f/tPSA) ratios. Clinical characteristics of detected PCa patients were analyzed. Follow-up was conducted through phone calls and home visits by family doctors, coupled with enhanced health education. The results indicated that a total of 17 198 residents participated in the screening, among which 2 234 (12.99%) had tPSA levels between 4 ng/ml and 10 ng/ml, and 257 (1.49%) had tPSA levels >10 ng/ml. Ultimately, 417 residents underwent prostate biopsy, with 171 being diagnosed with PCa, yielding a positive biopsy rate of 41.00% and a PCa detection rate of 0.99%. The predominant pathological subtype among PCa patients was adenocarcinoma (168 cases, 98.24%). Of the 146 PCa patients who received treatment, the majority were classified as intermediate or high-risk (124 cases, 84.93%). Furthermore, with the optimization of the screening model, there was a significant increase in the proportion of subsequent outpatient visits. In conclusion, the community-linkage-based PSA screening model demonstrated high effectiveness in screening for PCa among elderly males in the rural areas of Songjiang, Shanghai City. Epidemiological findings revealed that PCa patients in this region are primarily composed of intermediate and high-risk groups, highlighting the need for intensified early screening and health education.

Objective:To investigate the application value of cardiac magnetic resonance imaging(CMR) in evaluating the perioperative risk of surgical treatment in patients of coronary artery disease and heart failure with reduced ejection fraction.Methods:A total of 78 patients diagnosed with CAD and HFrEF who underwent CABG in Beijing Anzhen Hospital from January 2018 to October 2021 were retrospectively enrolled. All patients underwent CMR examination before CABG. The perioperative data of the two groups were compared, and the risk factors that may lead to perioperative MACCE were analyzed by LASSO regression. Then, logistic regression was used to establish a prediction model and internal validation was performed to evaluate the diagnostic efficiency and accuracy of the model by Bootstrap method. Results:There were 24 patients(30.8%) with perioperative MACCE and 54 patients(69.2%) without perioperative MACCE. LASSO regression was used to screen out three factors related to the outcome. Multivariate logistic regression analysis showed that LGE in the third and eighth segment of left ventricle and diastolic radial strain rate were independent risk factors for perioperative MACCE. The area under the curve of the prediction model constructed with CMR was 0.799(95% CI: 0.696-0.901), so the discrimination was good. The calibration curve showed that the prediction curve was basically fit to the standard curve, and the Hosmer- Lemeshow test P=0.797, indicating high prediction accuracy. Conclusion:CMR is a valuable test for evaluating perioperative risk in patients with coronary heart disease complicated with HFrEF. To establish the risk prediction model combined with CMR can provide some reference for the assessment of perioperative risk in these patients undergoing surgical treatment.

AIM To study the chemical constituents from ethyl acetate fraction of Balanophora harlandii Hook.f.and their tyrosinase inhibitory activity.METHODS Separation and purification were performed using silica gel,MCI,ODS,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The monophenolase inhibitory activity was determined by the tyrosinase-catalyzed oxidation of L-tyrosine.RESULTS Twenty-four compounds were isolated and identified as sesamin(1),methyl caffeate(2),quercetin(3),5,7-dihydroxychromanone(4),methyl 3,4-dihydroxybenzoate(5),esculetin(6),kaempferol(7),naringenin(8),pyrogallic acid(9),pinosylvin(10),methyl propionate(11),caffeic acid(12),saccharinol(13),ferulic acid(14),trans-p-hydroxycinnamic acid(15),cinnamic acid(16),vanillic acid(17),vanillin(18),4-hydroxyacetophenone(19),4-hydroxybenzaldehyde(20),apigenin(21),(-)-isolariciresinol(22),(-)-secoisolariciresinol(23)and meso-2,3-di(3′,4′-methylenedioxybenzyl)butane-1,4-diol(24).The IC50 values of compounds 3,5,7,8,19,and 20 ranged from(0.246 5±0.028 3)to(1.278 2±0.021 3)mmol/L.CONCLUSION Compounds 1-9、11、15、17-21、24 are isolated from this plant for the first time,and 1,6,9,17-19,24 are first isolated from genus Balanophora.Compounds 3、5、7、8、19 and 20 have tyrosinase inhibitory activity.

Objective: To investigate the epidemic situation of notifiable infectious diseases in Zhejiang Province in 2024, so as to summarize the epidemic characteristics. Methods: Data of notifiable infectious diseases cases in Zhejiang Province from January 1 to December 31, 2024 were collected from the Infectious Disease Surveillance System of Chinese Disease Prevention and Control Information System. The epidemiological characteristics were analyzed according to the classification and transmission routes using the descriptive epidemiological method. Results: A total of 32 types of notifiable infectious diseases with 1 858 695 cases and 392 deaths were reported in Zhejiang Province in 2024, with a reported incidence of 2 804.73/105 and a reported mortality of 0.591 5/100 000. A total of 238 infectious disease public health emergencies were reported, of which 218 (91.60%) occurred in schools and kindergartens. There were 22 types of class A and B notifiable infectious diseases reported, with incidence of 470.62/100 000 and mortality of 0.591 5/100 000. Totally 10 types of class C notifiable infectious diseases, with a reported incidence of 2 334.11/105, and no deaths were reported. Classified by transmission route, respiratory infectious diseases had the highest reported incidence of 2 423.87/100 000, among which influenza exhibited the highest reported incidence of 2 024.22/100 000. The reported incidence of intestinal infectious diseases was 312.94/105, among which the incidence of other infectious diarrhea and hand-foot-mouth disease (HFMD) were high, with reported incidences of 169.52/100 000 and 136.18/100 000, respectively. Blood-borne and sexually transmitted infectious diseases accounted for the largest number of reported deaths, among which AIDS had the highest mortality of 0.424 0/100 000. Natural and insect-borne infectious diseases exhibited a low reported incidence of 1.37/105. The reported incidence of dengue fever was 0.40/100 000, and 95.08% of the cases were imported. Conclusions The reported incidence of respiratory and intestinal infectious diseases and the reported mortality of AIDS were high in Zhejiang Province in 2024. It is recommended to strengthen the prevention and control of infectious diseases such as influenza, other infectious diarrhea, and HMFD in schools and kindergartens.

Objective To investigate the role of long non coding RNA(lncRNA)Gm14461 in promoting trigeminal neuralgia(TN)and its potential molecular mechanisms.Methods A TN mouse model was induced by surgery for chronic compression injury of the infraorbital nerve.Short hairpin RNA(shRNA)of Gm14461 was injected into TN mice,and the expression level of Gm14461 and mechanical pain threshold(MWT)in the trigeminal ganglia of the mice were measured.A TN cell model was established in vitro using tumor necrosis factor-α(TNF-α)to induce trigeminal ganglia,and the trigeminal ganglia were treated with sh-Gm14461 and cleavage stimulation factor subunit 2(CSTF2)overexpression vector(OE-CSTF2).RNA immunoprecipitation(RIP)analysis of CSTF2 binding to Gm14461,calcitonin gene-related peptide(CGRP),purine receptors P2X3 and P2X7 mRNA.Results Compared with the sham surgery group,the expression of Gm14461 in the trigeminal ganglia of TN group mice was significantly increased(t=35.450),and the MWT value of mice decreased in a time-dependent manner(t=8.427～28.190),with statistical significance(all P<0.05).The expression levels of inflammatory factors TNF-α,IL-1 β and IL-6,as well as pain related proteins CGRP,P2X3,and P2X7,were significantly increased in the trigeminal ganglia of TN mice,and the differences were statistically significant(t=31.750～50.240,all P<0.05).Knocking down Gm14461 significantly improved MWT(t=6.019～26.548),reduced inflammatory factors(t=43.959,26.416,25.431),and pain related protein levels(t=38.709,43.257,45.807)in TN mice,with statistically significant differences(all P<0.05).Compared with the control group,TNF-α induced upregulation of Gm14461 expression in the trigeminal ganglia(t=27.710),significantly increased levels of inflammatory factors and pain related protein expression(t=23.076～29.508),and the differences were statistically significant(all P<0.05).After knocking down Gm14461,the expression of Gm14461 was significantly reduced(t=3.641),and the levels of inflammatory factors and pain related proteins in the trigeminal ganglia induced by TNF-α were significantly reduced(t=20.560～25.136),with statistical significance(all P<0.05).Gm14461 upregulates CSTF2 protein levels by binding to CSTF2,and upregulates CSTF2 protein by binding to mRNA of CGRP,P2X3,and P2X7 and promoting their expression.Overexpression of CSTF2 can reverse the inhibitory effect of Gm14461 knockdown on TNF-α-induced inflammation and pain related protein expression in trigeminal ganglia(TGs)(t=18.870～24.399,all P<0.05).Conclusion Gm14461 upregulates the expression of CGRP,P2X3,and P2X7 by recruiting CSTF2,promotes inflammatory response,thereby reducing the mechanical pain threshold of TN mice and promoting pain.