Background::Cardiovascular disease (CVD) has emerged as the leading cause of death from prostate cancer (PCa) in recent decades, bringing a great disease burden worldwide. Men with preexisting CVD have an increased risk for major adverse cardiovascular events when treated with androgen deprivation therapy (ADT). The present study aimed to explore the prevalence and risk evaluation of CVD among people with newly diagnosed PCa in China.Methods::Clinical data of newly diagnosed PCa patients were retrospectively collected from 34 centers in China from 2010 to 2022 through convenience sampling. CVD was defined as myocardial infarction, arrhythmia, heart failure, stroke, ischemic heart disease, and others. CVD risk was estimated by calculating Framingham risk scores (FRS). Patients were accordingly divided into low-, medium-, and high-risk groups. χ2 or Fisher’s exact test was used for comparison of categorical variables. Results::A total of 4253 patients were enrolled in the present study. A total of 27.0% (1147/4253) of patients had comorbid PCa and CVD, and 7.2% (307/4253) had two or more CVDs. The enrolled population was distributed in six regions of China, and approximately 71.0% (3019/4253) of patients lived in urban areas. With imaging and pathological evaluation, most PCa patients were diagnosed at an advanced stage, with 20.5% (871/4253) locally progressing and 20.5% (871/4253) showing metastasis. Most of them initiated prostatectomy (46.6%, 1983/4253) or regimens involving ADT therapy (45.7%, 1944/4253) for prostate cancer. In the present PCa cohort, 43.1% (1832/4253) of patients had hypertension, and half of them had poorly controlled blood pressure. With FRS stratification, as expected, a higher risk of CVD was related to aging and metabolic disturbance. However, we also found that patients with treatment involving ADT presented an originally higher risk of CVD than those without ADT. This was in accordance with clinical practice, i.e., aged patients or patients at advanced oncological stages were inclined to accept systematic integrative therapy instead of surgery. Among patients who underwent medical castration, only 4.0% (45/1118) received gonadotropin releasing hormone antagonists, in stark contrast to the grim situation of CVD prevalence and risk.Conclusions::PCa patients in China are diagnosed at an advanced stage. A heavy CVD burden was present at the initiation of treatment. Patients who accepted ADT-related therapy showed an original higher risk of CVD, but the awareness of cardiovascular protection was far from sufficient.

Aim To design the pyrimidoindole deriva-tive N-butyl-9H-pyrimido[4,5-b]indole-2-carboxamide(BFPI)and synthesize it to investigate whether it in-hibits macrophage pyroptosis and foaming effects through the NLRP3/Caspase-1 pathway.Methods BFPI was synthesized using 2,4,6-triethoxycarbonyl-l,3,5-triazine and 2-aminoindole as starting materials and structurally characterized by 1H NMR,13C NMR,and ESI-MS.The in vitro cultured mouse monocyte macro-phage cell line RAW264.7 was divided into blank,model(PA)and therapeutic(BFPI)groups,and the cells in each group were treated with the corresponding culture medium for 24 h.The proliferative viability was detected by MTT assay,and the formation of intracel-lular lipid droplets was detected by oil red O staining,and NLRP3 was detected by Western-blot and RT-qPCR,caspase-1 and MCP-1 mRNA and protein ex-pression levels by Western blot and RT-qPCR.Results Compared with the blank group,the proliferation vi-ability of cells in the model group significantly de-creased and the formation of lipid droplets significantly increased;compared with the model group,the prolif-eration viability of cells in the treatment group signifi-cantly increased and the formation of lipid droplets sig-nificantly decreased,and the differences were statisti-cally significant(P＜0.01);compared with the blank group,the cellular NLRP3,caspase-1 and MCP-1 mR-NA and protein expression levels of cells in the model group significantly increased;compared with the model group,the expression levels of the above indexes of the cells in the treatment group significantly decreased,and the difference was statistically significant(P＜0.01).Conclusions BFPI contributes to delaying macrophage-derived foam cell formation during athero-genesis by inhibiting macrophage NLRP3,caspase-1,and MCP-1 expression and thereby promoting their pro-liferation and inhibiting lipid phagocytosis.

Aim To study the molecular mechanism of pterostilbene(PTS)inhibiting the growth of esophage-al squamous cell carcinoma(ESCC).Methods Soft agar assay was used to detect the effect of PTS on the anchored independent growth of KYSE150.TMT-la-beled quantitative proteomics analysis was used to ana-lyze the influence of PTS on the proteome of KYSE150.Then the differentially expressed proteins(DEPs)enrichment was analyzed by GO and KEGG,and signaling pathway interactions were analyzed by STRING database.The molecular docking model of PTS and PPARα was established by computer.Trans-mission electron microscopy was used to observe the in-fluence of PTS on the morphology change of KYSE150.Western blot analysis the effects of PTS on PPARα sig-naling pathway and ferroptosis related proteins expres-sion.Results PTS inhibited the anchorage-independ-ent growth capability of KYSE150.A total of 249 DEPs were identified by proteomic analysis,including 175 up-regulated proteins and 74 down-regulated pro-teins.The DEPs enrichment analysis showed that PPAR signaling pathway was related to unsaturated fat-ty acid synthesis,pyruvate metabolism and other meta-bolic signaling pathways.PTS caused the reduction of mitochondrial volume and mitochondrial cristae of KYSE150.PTS inhibited the expression of PPARα sig-naling pathway and ferroptosis related proteins.Con-clusion PTS induced the ferroptosis of ESCC by in-hibiting PPARα signaling pathway.

To understand the distribution of ticks in the Wuwei Region,enrich tick species data,and provide a basis for the prevention of tick-borne diseases,tick were collected using flagging and tick-picking methods during the highest activity period from April to September in 2021 and 2022 in the mountainous areas of Wuwei City.The ticks were identified based on morpho-logical and molecular biological characteristics,and characteristic sequences were obtained.A systematic evolutionary tree was constructed using the neighbor-joining method in MEGA 11.0 software.In total,7 342 ticks collected in Wuwei,which be-longed to 5 species from 4 genera with in the Ixodidae family,which included Dermacentor nuttalli,Hyalomma asiaticum,Ixodes canisuga,Haemaphysalis longicornis and Haema-physalis danieli.Ticks of the same species clustered together into the same branch of an evolutionary tree.In the Wuwei Re-gion,five common tick species are found across various habi-tats,with each habitat featuring different distributions of tick species and populations.The Dermacentor nuttalli is the dom-inant tick species in this area.

Objective:To investigate the clinical characteristics and prognosis of single center adult chronic myeloid leukemia in chronic phase(CML-CP).Methods:Clinical data of 41 adult CML-CP patients in Department of Hematology,Shanghai Fengxian District Central Hospital from January 2015 to May 2021 were retrospectively analyzed.The clinical characteristics and prognosis of patients between＜60 years group and ≥ 60 years group were compared.Results:The 41 patients included 27(65.9％)males and 14(34.1％)females.The median age of the patients was 56(19-84)years,with 22 cases(53.7％)＜60 years and 19 cases(46.3％)≥60 years.Univariate analysis indicated that the proportions of patients with comorbidities,intermediate/high-risk Sokal score,myelofibrosis,and lactate dehydrogenase ≥1 000 U/L were significantly increased in ≥60 years group compared with＜60 years group at initial diagnosis(all P＜0.05).There were no statistical differences in the distribution of sex,ELST score,white blood cell count,platelet count,peripheral blood basophil percentage,peripheral blood eosinophil percentage and bone marrow primitive cell percentage between the two groups(P＞0.05).The proportion of patients taking reduced-dose imatinib in≥60 years group significantly increased(P＜0.001).Patients＜60 years had a higher proportion of molecular biological remission after treatment of tyrosine kinase inhibitors(TKIs)than patients ≥ 60 years(P＜0.001).The incidence of non-hematologic adverse reactions to TKI therapy significantly increased in patients ≥ 60 years(P＜0.001).Multivariate analysis showed that no adverse factors affecting the efficacy and prognosis of TKI.Conclusion:Compared with adult CML-CP patients＜60 years,patients ≥ 60 years gain fewer benefits from TKI treatment and increased adverse reactions.

AIM To explore the clinical effects of Cangfu Daotan Pills combined with abdominal acupuncture on patients with obesity and polycystic ovary syndrome.METHODS Ninety-eight patients were randomly assigned into control group(49 cases)for 3-month intervention of Metformin Hydrochloride Enteric-coated Tablets,and observation group(49 cases)for 3-month intervention of both Cangfu Daotan Pills and abdominal acupuncture.The changes in FPG,FINS,HOMA-IR,IL-6,TNF-α,MCP-1,FSH,LH,AMH,AFC,E2 and incidence of adverse reactions were detected.RESULTS After the treatment,the two groups displayed decreased FPG,FINS,HOMA-IR,IL-6,TNF-α,MCP-1,FSH,LH,AMH,AFC(P＜0.05),and increased E2(P＜0.05),especially for the observation group(P＜0.05).No significant difference in incidence of adverse reactions was found between the two groups(P＞0.05).CONCLUSION For the patients with obesity and polycystic ovary syndrome,Cangfu Daotan Pills combined with abdominal acupuncture can safely and effectively restore ovarian functions,which may contribute to the improvement of insulin resistance and reduction of inflammatory factor levels.

Activation of nuclear factor erythroid 2-related factor 2(Nrf2)by Kelch-like ECH-associated protein 1(Keap1)alkylation plays a central role in anti-inflammatory therapy.However,activators of Nrf2 through alkylation of Keap1-Kelch domain have not been identified.Deoxynyboquinone(DNQ)is a natural small molecule discovered from marine actinomycetes.The current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of Keap1.DNQ exhibited signif-icant anti-inflammatory properties both in vitro and in vivo.The pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be the α,β-unsaturated amides moieties by a chemical reaction between DNQ and N-acetylcysteine.DNQ exerted anti-inflammatory effects through activation of Nrf2/ARE pathway.Keap1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving alkylation.The specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass spectrometry.DNQ triggered the ubiquitination and subsequent degra-dation of Keap1 by alkylation of the cysteine residue 489(Cys489)on Keap1-Kelch domain,ultimately enabling the activation of Nrf2.Our findings revealed that DNQ exhibited potent anti-inflammatory capacity through α,β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain,suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective To evaluate clinical efficacy and safety of Bizheng Granules combined with basic therapy in the treatment of liver and kidney insufficiency and phlegm-dampness cross-blocking syndrome of nerve root type cervical spondylosis radiculopathy.Methods Totally 108 patients with nerve root type cervical spondylosis radiculopathy were selected and divided into Bizheng Granules group,Jingfukang Granules group,and Bizheng Granules placebo group according to random number table method,with 36 cases in each group.The three groups were treated with the basic treatment(oral methylcobalamin tablets of 0.5 mg,three times a day,and cervical spine intermittent traction once a day,each time for 15 min),and Bizheng Granules were given in the Bizheng Granules group,and Jingfukang Granules in the Jingfukang Granules group,and Bizheng Granules placebo in the Bizheng Granules placebo group,twice a day after meals.All three groups were treated continuously for 2 weeks and followed up at 4 and 12 weeks after treatment.Visual analog scale(VAS),cervical dysfunction index(NDI),and 36-items short form survey(SF-36)score were recorded in the 3 groups before and after treatment and 4 and 12 weeks after treatment,respectively.Adverse reactions during treatment and follow-up were recorded in the 3 groups.Results 3 cases lost in the Bizheng Granules group,3 cases in the Jingfukang Granules group,and 1 case in the Bizheng Granules placebo group.Compared with the pre-treatment period,the differences in VAS score,NDI score,and SF-36 score among the three groups of patients at all time points of treatment and follow-up were statistically significant(P<0.05).At 12 weeks after treatment,the VAS score and NDI score of the Bizheng Granules group and the Jingfukang Granules group were lower than those of the Bizheng Granules placebo group,but the differences in VAS score and NDI score between Bizheng Granules group and Jingfukang Granules group were not statistically significant(P>0.05).12 weeks after treatment,the SF-36 score of Bizheng Granules group were higher than those of Bizheng Granules placebo group,but the difference in SF-36 score between Bizheng Granules group and Jingfukang Granules group was not statistically significant(P>0.05).The total effective rate of Bizheng Granules group was better than that of the Jingfukang Granules group and Bizheng Granules placebo group(P<0.05).The incidence of adverse reactions in the three groups was not statistically significant(P>0.05).There were no serious adverse events in the three groups.Conclusion Bizheng Granules combined with basic therapy has a definite therapeutic effect in improving pain,restoring cervical dysfunction,and improving quality of life in the treatment of liver and kidney insufficiency and phlegm-dampness cross-blocking syndrome of nerve root type cervical spondylosis radiculopathy,with good safety.

BACKGROUND:Nano-zirconium dioxide has good application potential in the field of bone tissue repair.Studying the effect of nano-zirconium dioxide on osteogenic differentiation will help to promote the clinical application of nano-zirconium dioxide in the treatment of bone defects. OBJECTIVE:To explore the effect of nano-zirconium dioxide on the osteogenic differentiation of ectomesenchymal stem cells in the nasal mucosa. METHODS:Ectomesenchymal stem cells derived from rat nasal mucosa were isolated and cultured,and the biotoxicity of nano-zirconium dioxide to the cells was detected by CCK-8 assay.The biosafety concentration was selected according to the cytotoxicity,and the cells were randomly divided into a control group,a nano-zirconium dioxide group,and a nano-hydroxyapatite group.Osteogenic differentiation of cells was directionally induced in each group.On day 7 of induced differentiation,alkaline phosphatase staining was performed.qRT-PCR and western blot assay were used to detect the expression of early osteogenic markers(Runx2 and Osx).On day 21 of induced differentiation,alizarin red staining was conducted.qRT-PCR and western blot assay were utilized to determine the expression levels of late osteogenic markers(OPN and OCN). RESULTS AND CONCLUSION:(1)The median lethal concentration of nano-zirconium dioxide on ectomesenchymal stem cells in nasal mucosa was 0.6 mg/mL.In the experiment,the mass concentration of 200 μg/mL was selected for intervention.Zirconium dioxide had no significant effect on the proliferation of the cells.(2)Compared with the control group,the alkaline phosphatase staining of the cells in the nano-zirconium dioxide group was more obvious and the level of cell mineralization was higher,but there was no significant difference compared with the nano-hydroxyapatite.(3)Compared with the control group,the expression of bone-related genes and proteins increased significantly,but there was no significant difference compared with nano-hydroxyapatite.(4)The results show that nano-zirconium dioxide has good biological safety and can promote the osteogenic differentiation of ectomesenchymal stem cells in the nasal mucosa.This promoting effect is equivalent to that of nano-hydroxyapatite.