Three 2,3-diketoquinoxaline alkaloids were isolated from Heterosmilax yunnanensis Gagnep. Their structures were determined through 1D and 2D NMR, HR-ESI-MS, UV, and IR as 1-[5′-(3″-hydroxy-3″-methyl) glutaryl] ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (1), 1-[2′-(3″-hydroxy-3″-methyl) glutaryl]ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (2), and 1-ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (3). Compounds 1 and 2 are novel compounds, and 3 was isolated from H. yunnanensis for the first time. The hepatoprotective activity of these three compounds was evaluated, with compound 3 showing promising hepatoprotective activity.

Objective To investigate changes in the urinary metabolite profiles of children exposed to polycyclic aromatic hydrocarbons(PAHs)during critical brain development and explore their potential link with the intestinal microbiota. Methods Liquid chromatography-tandem mass spectrometry was used to determine ten hydroxyl metabolites of PAHs(OH-PAHs)in 36-month-old children.Subsequently,37 children were categorized into low-and high-exposure groups based on the sum of the ten OH-PAHs.Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to identify non-targeted metabolites in the urine samples.Furthermore,fecal flora abundance was assessed by 16S rRNA gene sequencing using Illumina MiSeq. Results The concentrations of 21 metabolites were significantly higher in the high exposure group than in the low exposure group(variable importance for projection>1,P<0.05).Most of these metabolites were positively correlated with the hydroxyl metabolites of naphthalene,fluorine,and phenanthrene(r=0.336-0.531).The identified differential metabolites primarily belonged to pathways associated with inflammation or proinflammatory states,including amino acid,lipid,and nucleotide metabolism.Additionally,these distinct metabolites were significantly associated with specific intestinal flora abundances(r=0.34-0.55),which were mainly involved in neurodevelopment. Conclusion Higher PAH exposure in young children affected metabolic homeostasis,particularly that of certain gut microbiota-derived metabolites.Further investigation is needed to explore the potential influence of PAHs on the gut microbiota and their possible association with neurodevelopmental outcomes.

AIM To investigate the protective effect of Mongolian medicine Naru-3 on rat rheumatoid arthritis(RA)using imaging method.METHODS With the rats divided into the normal group,the model group,the positive medicine group,and the low,medium and high dose Naru-3 groups(0.1,0.2 and 0.4 g/kg),the rat model of collagen-induced arthritis(CIA)was established by immune induction method.After 4 weeks of corresponding drug administration,the rats had their changes of arthritis index(AI)level and body weight observed;their serum levels of VEGF,TNF-α and IL-1 detected by ELISA;their synovial hyperplasia and neovascularization evaluated by high-frequency ultrasound and contrast-enhanced ultrasound(CEUS);their bone destruction of ankle joint evaluated by X-ray and high-resolution micro-CT;and their synovial membrane and expressions of CD31,VEGF,TNF-α and IL-1 β observed by HE and immunohistochemistry.RESULTS Compared with the model group,the Naru-3 groups displayed increased rat weight(P＜0.05);no significantly changed AI score(P＞0.05);and overally decreased levels of serum VEGF,TNF-α,synovial membrane thickness,blood flow signal by power Doppler imaging(PDI)and contrast intensity revealed,X-ray score,and CD31 expression(P＜0.05),in addition to the decreased level of IL-1 and HE score in high-dose group(P＜0.05).CONCLUSION Naru-3 is protective to the joint tissue in rat model of RA through alleviating synovitis,bone erosion and delaying the progress of the disease by inhibiting synovial neovascularization and inflammatory cytokines.

Objective:To determine the total and age-specific cut-off values of total prostate specific antigen (tPSA) and the ratio of free PSA divided total PSA (fPSA/tPSA) for screening prostate cancer in China.Methods:Based on the Chinese Colorectal, Breast, Lung, Liver, and Stomach cancer Screening Trial (C-BLAST) and the Tianjin Common Cancer Case Cohort (TJ4C), males who were not diagnosed with any cancers at baseline since 2017 and received both tPSA and fPSA testes were selected. Based on Cox regression, the overall and age-specific (＜60, 60-＜70, and ≥70 years) accuracy and optimal cut-off values of tPSA and fPSA/tPSA ratio for screening prostate cancer were evaluated with time-dependent receiver operating characteristic curve (tdROC) and area under curve (AUC). Bootstrap resampling was used to internally validate the stability of the optimal cut-off value, and the PLCO study was used to externally validate the accuracy under different cut-off values.Results:A total of 5 180 participants were included in the study, and after a median follow-up of 1.48 years, a total of 332 prostate cancer patients were included. In the total population, the tdAUC of tPSA and fPSA/tPSA screening for prostate cancer were 0.852 and 0.748, respectively, with the optimal cut-off values of 5.08 ng/ml and 0.173, respectively. After age stratification, the age specific cut-off values of tPSA in the <60, 60-<70, and ≥70 age groups were 3.13, 4.82, and 11.54 ng/ml, respectively, while the age-specific cut-off values of fPSA/tPSA were 0.153, 0.135, and 0.130, respectively. Under the age-specific cut-off values, the sensitivities of tPSA screening for prostate cancer in males <60, 60-70, and ≥70 years old were 92.3%, 82.0%, and 77.6%, respectively, while the specificities were 84.7%, 81.3%, and 75.4%, respectively. The age-specific sensitivities of fPSA/tPSA for screening prostate cancer were 74.4%, 53.3%, and 55.9%, respectively, while the specificities were 83.8%, 83.7%, and 83.7%, respectively. Both bootstrap's internal validation and PLCO external validation provided similar results. The combination of tPSA and fPSA/tPSA could further improve the accuracy of screening.Conclusion:To improve the screening effects, it is recommended that age-specific cut-off values of tPSA and fPSA/tPSA should be used to screen for prostate cancer in the general risk population.

Objective To investigate whether Heshouwuyin can delay the aging of Leydig cells in rat testis through DNA methyltransferase 1(DNMT1).Methods Totally 40 male Wistar rats were randomly divided into 4 groups,with 10 rats in each group.Immunohistochemistry was used to detect the expression levels of DNMT1 in testis tissue of rats.Testosterone content in serum of rats in each group was detected by ELISA test.A rat Leydig cell aging model was established by free radical oxidative damage.DNMT1 was knocked down by lentivirus in Leydig cells,and the cell senescence status and the testosterone content and testosterone synthesis key enzyme 3β-hydroxysteroid dehydrogenase(3β-HSD),cytochrome P450 family member 11A1(CYP11A1)content secreted by cells were detected by β-galactosidase(β-GAL)staining,immunofluorescenct staining and ELISA.Results Compared with the young control group(YCG),the expression of P16 protein and the positive rate of β-GAL in the testis tissue of rats in the natural aging group(NAG)increased significantly,and the expression of DNMT1 and serum testosterone levels decreased(P＜0.05).However,after Heshouwuyin intervention,the expression of P16 protein and the positive rate of β-GAL in the testis of aging rats were reduced,and DNMT1 expression and the serum testosterone levels increased(P＜0.05).The same trend was observed in Leydig cells.Knockdown of DNMT1 in Leydig cells,β-GAL positivity and P16 protein expression increased significantly,and testosterone secretion and testosterone synthesis key enzymes 3β-HSD,CYP11A1 content from Leydig cells decreased significantly,compared with the normal control group(NCG)(P＜0.05).When Heshouwuyin was added,the above phenomenon was improved.Conclusion Heshouwuyin can delay the aging of rat Leydig cells through DNMT1.

Objective:To determine the total and age-specific cut-off values of total prostate specific antigen (tPSA) and the ratio of free PSA divided total PSA (fPSA/tPSA) for screening prostate cancer in China.Methods:Based on the Chinese Colorectal, Breast, Lung, Liver, and Stomach cancer Screening Trial (C-BLAST) and the Tianjin Common Cancer Case Cohort (TJ4C), males who were not diagnosed with any cancers at baseline since 2017 and received both tPSA and fPSA testes were selected. Based on Cox regression, the overall and age-specific (＜60, 60-＜70, and ≥70 years) accuracy and optimal cut-off values of tPSA and fPSA/tPSA ratio for screening prostate cancer were evaluated with time-dependent receiver operating characteristic curve (tdROC) and area under curve (AUC). Bootstrap resampling was used to internally validate the stability of the optimal cut-off value, and the PLCO study was used to externally validate the accuracy under different cut-off values.Results:A total of 5 180 participants were included in the study, and after a median follow-up of 1.48 years, a total of 332 prostate cancer patients were included. In the total population, the tdAUC of tPSA and fPSA/tPSA screening for prostate cancer were 0.852 and 0.748, respectively, with the optimal cut-off values of 5.08 ng/ml and 0.173, respectively. After age stratification, the age specific cut-off values of tPSA in the <60, 60-<70, and ≥70 age groups were 3.13, 4.82, and 11.54 ng/ml, respectively, while the age-specific cut-off values of fPSA/tPSA were 0.153, 0.135, and 0.130, respectively. Under the age-specific cut-off values, the sensitivities of tPSA screening for prostate cancer in males <60, 60-70, and ≥70 years old were 92.3%, 82.0%, and 77.6%, respectively, while the specificities were 84.7%, 81.3%, and 75.4%, respectively. The age-specific sensitivities of fPSA/tPSA for screening prostate cancer were 74.4%, 53.3%, and 55.9%, respectively, while the specificities were 83.8%, 83.7%, and 83.7%, respectively. Both bootstrap's internal validation and PLCO external validation provided similar results. The combination of tPSA and fPSA/tPSA could further improve the accuracy of screening.Conclusion:To improve the screening effects, it is recommended that age-specific cut-off values of tPSA and fPSA/tPSA should be used to screen for prostate cancer in the general risk population.

This study was aimed at analyzing the effectiveness of vector control efforts at the 19th Asian Games in Hang-zhou,to provide a reference for future vector control at similar large-scale events.We collected and analyzed vector organism monitoring data for various venues at Asian Games(branch)villages and designated reception hotels(hotels and guesthouses)associated with the Asian Games in Hangzhou from April to October of 2023.Excel 2019 software and SPSS 20.0 software were used to organize the data.Paired t tests(for normally distributed data)or Wilcoxon signed rank tests(for data not nor-mally distributed)were performed,and count data were analyzed statistically with x2 tests.The larva mosquito path index at Asian Games venues peaked in June and then declined month by month.The first circle area of the adult mosquito human trapping index peaked in June,and the second circle area peaked in July.The mosquito indicators reached the corre-sponding control standards before the Asian Games.Moreo-ver,the differences in mosquito density before and after the Asian Games were statistically significant(all P＜0.05).Both the positivity rate and density of flies in rooms reached level A in the first and second circle areas from April to October.The proportion of indoor fly-proof facilities meeting the standards was lowest in May,then gradually increased.The corresponding control standards were reached in the first round in the fourth week of September,and in the second round in the first week of October.The difference in the density of positivity for room flies before and after the Asian Games was statistically significant(all P＜0.05).Rodent density reached the corre-sponding control standards in the second week of September.The proportion of anti-rodent facilities meeting the standards was lowest in June,and then gradually increased.The first round began to meet the corresponding control standards in the fourth week of September,and the second round began to meet the corresponding control standards in the first week of October.Ex-cept for the outdoor rat density path index,which was statistically significant before and after the Asian Games,the other indi-cators showed no statistical significance(P＞0.05).The cockroach density in the first circle area reached level A in all months,and that in the second circle area reached level B in mid-August.Vector control in the Hangzhou Asian Games achieved the ex-pected results,with no vector infringement or local vector-borne infectious diseases occurring.In future vector control for large-scale events,vector density monitoring should be performed as early as possible,and comprehensive prevention and control measures should be taken to maintain low vector density and prevent vector infringement incidents.

Aim To investigate the changes in the proliferation and apoptosis of Siha cells after knocking down Rho GTPase-activating protein 30(ARHGAP30).Methods After designing specific shARHGAP30 primers and connecting them to the pLKO.1 vector,we transformed them into Escherichia coli competent cells,then co-transfecting them with lentiviral helper plasmids into HEK-293T cells.We collected and filtered cell supernatant to obtain the vi-rus to infect Siha cells.RT-qPCR and Western blot were used to detect knockdown efficiency,as well as changes in the expression of Bax and Bcl-2 after trans-fection.The CCK-8 method was employed to measure the proliferation level of cells after knockdown.Results After successful construction of a lentiviral plasmid with knockdown of the ARHGAP30 gene and establish-ment of stably transfected Siha cells,ARHGAP30 tran-scription and translation(P＜0.01)in Siha cells de-creased,Bax/Bcl-2 significantly decreased(P＜0.01),indicating decreased apoptosis and increased cell proliferation(P＜0.01).Conclusions This study suggests the involvement of ARHGAP30 in the proliferation and apoptosis of Siha cells,and regulating the ARHGAP30 gene may interfere with the occurrence and development of cervical cancer.

Heart failure with preserved ejection fraction (HFpEF) accounts for about half of the number of patients with heart failure. In addition to the typical features of heart failure such as myocardial stiffness and diastolic function impairment, the key characteristic of HFpEF is the normal left ventricular ejection fraction, which increases the difficulty of clinical diagnosis. QiShenYiQi Dripping Pills (QSYQ) is a standardized traditional Chinese medicine approved by the China Food and Drug Administration (CFDA), and many clinical studies have demonstrated the efficacy and safety of QSYQ in the treatment of heart failure with reduced ejection fraction, but the role of QSYQ in HFpEF has not been clarified. In this paper, high fat diet (HFD) and drinking water containing N-nitro-L-arginine methyl ester (L-NAME, 0.5 g·L^-1, pH=7.4) were used in C57BL/6N male mice to construct the classical HFpEF model (the experiment was approved by the Animal Ethics Committee of Hefei University of Technology, the approval number is HFUT20220921002), and at the 8^th week, the mice were dosed with ① empagliflozin, ② low-dose QSYQ (LQ), ③ high-dose QSYQ (HQ), ④ empagliflozin plus low-dose QSYQ (ELQ) for 4 weeks, the body weight of the mice was recorded during the experiment, echocardiography, blood pressure and glucose tolerance were detected and the exercise capacity of mice was evaluated, and pathological and biochemical experiments were used to detect cardiac fibrosis, liver fibrosis and serum biochemical indexes in mice, RNAseq assay was performed with mice heart tissues. The results showed that QSYQ as well as QSYQ+empagliflozin could significantly reduce the body weight, improve diastolic function and hypertension, improve glucose tolerance and enhance exercise ability of HFpEF mice. At the biochemical and molecular levels, QSYQ and QSYQ+empagliflozin can reduce the cross-sectional area of cardiomyocytes and reduce cardiac collagen contents, thereby alleviating myocardial hypertrophy and fibrotic phenotypes, and improve metabolic disorders. The RNAseq results suggest that the function of QSYQ in improving HFpEF may be related to calsequestrin 1. In conclusion, this study shows that QSYQ and QSYQ+empagliflozin can significantly improve HFpEF-related cardiac dysfunction and metabolic disorders, which provides a theoretical basis for the clinical treatment of HFpEF.

This study aimed to explore the possible effect of Xixin Decoction(XXD) on the learning and memory ability of Alzheimer's disease(AD) model senescence-accelerated mouse-prone 8(SAMP8) and the related mechanism in enhancing neuroprotective effect and reducing neuroinflammation. Forty SAMP8 were randomly divided into a model group(10 mL·kg~(-1)·d~(-1)), a probiotics group(0.39 g·kg~(-1)·d~(-1)), a high-dose group of XXD granules(H-XXD, 5.07 g·kg~(-1)·d~(-1)), a medium-dose group of XXD granules(M-XXD, 2.535 g·kg~(-1)·d~(-1)), and a low-dose group of XXD granules(L-XXD, 1.267 5 g·kg~(-1)·d~(-1)). Eight senescence-accelerated mouse-resistant 1(SAMR1) of the same age and strain were assigned to the control group(10 mL·kg~(-1)·d~(-1)). After ten weeks of intragastric administration, the Morris water maze was used to test the changes in spatial learning and memory ability of mice after treatment. Meanwhile, immunofluorescence staining was used to detect the positive expression of receptor for advanced glycation end products(AGER), Toll-like receptor 1(TLR1), and Toll-like receptor 2(TLR2) in the hippocampal CA1 region of mice. Western blot was employed to test the protein expression levels of silencing information regulator 2 related enzyme 1(SIRT1), AGER, TLR1, and TLR2 in the hippocampus of mice. Enzyme linked immunosorbent assay(ELISA) was applied to assess the levels of Aβ_(1-42) in the hippocampus of mice and the levels of nuclear factor κB p65(NF-κB p65), NOD-like receptor protein 3(NLRP3), tumor necrosis factor-α(TNF-α), and interleukin-1β(IL-1β) in the serum and hippocampus of mice. Compared with the model group, XXD significantly improved the spatial learning and memory ability of SAMP8, increased the expression of neuroprotective factors in the hippocampus, decreased the levels of neuroinflammatory factors, and inhibited the expression of Aβ_(1-42). In particular, H-XXD significantly increased the expression of SIRT1 in the hippocampus of mice, reduced the expression levels of NF-κB p65, NLRP3, TNF-α, and IL-1β in the serum and hippocampus of mice, and decreased the expression of AGER, TLR1, and TLR2 in the hippocampus of mice(P<0.05 or P<0.01). XXD may improve the spatial learning and memory ability of AD model SAMP8 by enhancing the neuroprotective effect and inhibiting neuroinflammation.
Humans ; Neuroprotective Agents/therapeutic use* ; Sirtuin 1/metabolism* ; Toll-Like Receptor 2/metabolism* ; NF-kappa B/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Neuroinflammatory Diseases ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Toll-Like Receptor 1/metabolism* ; Alzheimer Disease/genetics* ; Hippocampus