Objective: This study aimed to construct an animal model of heart failure with preserved ejection fraction (HFpEF) that integrates disease and syndrome based on the "deficiency-blood stasis-toxin" pathogenesis and to evaluate it comprehensively. Methods: The HFpEF mouse model was constructed using a combination of Nω-nitro-L-arginine methyl ester (L-NAME) and a high-fat diet. According to the random number table method, SPF-grade male C57BL/6J mice were randomly assigned to the control, L-NAME, high-fat diet, and model groups, 10 in each group. Comprehensive observations and data collection on macroscopic signs (e.g., fur condition, mental state, stool and urine, oral and nasal condition, paw and body condition, etc.) and cardiac function were performed after 10 and 16 weeks of model induction. Additionally, the syndrome evolution was elucidated based on diagnostic criteria for clinical syndromes of heart failure. Furthermore, pathological and molecular biological examinations of myocardial tissue were performed to assess the stability and reliability of the model. Results: Mice in the model group showed typical characteristics of syndrome of qi deficiency and blood stasis, as well as syndrome of internal heat accumulation, including lethargy, slow response, dull paw color and oral/nasal color, exercise intolerance, abnormal platelet activation, dry feces, and dark yellow urine. The time window for these syndromes was between 10 and 16 weeks post-modeling. Cardiac function assessments revealed severe diastolic dysfunction, concentric myocardial hypertrophy, and myocardial fibrosis in the model group. Pathological examinations showed a significantly increased collagen deposition in the myocardial interstitium, enlarged cross-sectional area of cardiomyocytes, and sparse coronary microvasculature in the model group. Molecular biological analyses indicated marked activation of the inducible nitric oxide synthase/nuclear factor kappa-light-chain-enhancer of activated B cells/NOD-like receptor family pyrin domain containing 3 inflammatory pathway and significantly elevated inflammation levels in the myocardial tissue of the model group. Although mice in the L-NAME and high-fat diet groups also showed certain manifestations of qi deficiency syndrome, the substantial cardiac damage was relatively limited compared to the control group. Conclusion This study has constructed an animal model of HFpEF that integrates disease and syndrome based on the "deficiency-blood stasis-toxin" pathogenesis. The macroscopic and microscopic characteristics of this model are consistent with the manifestations of syndrome of qi deficiency and blood stasis, toxin syndrome, and syndrome of internal heat accumulation. Moreover, it can stably simulate the HFpEF state and reflect phenotypic changes in human disease. This model provides a suitable experimental platform to explore the pathogenesis of HFpEF, evaluate the effectiveness of traditional Chinese medicine (TCM) treatment regimens, and promote in-depth research on TCM syndromes of heart failure.

Objective: To investigate the role and mechanism of the heat-clearing and detoxifying drug Laggerae Herba in regulating the nuclear factor-erythroid 2-related factor-2(Nrf2)/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling pathway to inhibit ferroptosis and improve chronic heart failure induced by transverse aortic arch constriction in mice. Methods: Twenty-four male ICR mice were divided into the sham (n=6) and transverse aortic arch constriction groups (n=18) according to the random number table method. The transverse aortic arch constriction group underwent transverse aortic constriction surgery to establish models. After modeling, the transverse aortic arch constriction group was further divided into the model, captopril, and Laggerae Herba groups according to the random number table method, with six mice per group. The captopril (15 mg/kg) and Laggerae Herba groups (1.95 g/kg) received the corresponding drugs by gavage, whereas the sham operation and model groups were administered the same volume of ultrapure water by gavage once a day for four consecutive weeks. After treatment, the cardiac function indexes of mice in each group were detected using ultrasound. The heart mass and tibia length were measured to calculate the ratio of heart weight to tibia length. Hematoxylin and eosin staining were used to observe the pathological changes in myocardial tissue. Masson staining was used to observe the degree of myocardial fibrosis. Wheat germ agglutinin staining was used to observe the degree of myocardial cell hypertrophy. Prussian blue staining was used to observe the iron deposition in myocardial tissue. An enzyme-linked immunosorbent assay was used to detect the amino-terminal pro-brain natriuretic peptide (NT-proBNP) and glutathione (GSH) contents in mice serum. Colorimetry was used to detect the malondialdehyde (MDA) content in mice serum. Western blotting was used to detect the Nrf2, GPX4, SLC7A11, and ferritin heavy chain 1 (FTH1) protein expressions in mice cardiac tissue. Results: Compared with the sham group, in the model group, the ejection fraction (EF) and fractional shortening (FS) of mice decreased, the left ventricular end-systolic volume (LVESV) and left ventricular end-systolic diameter (LVESD) increased, the left ventricular anterior wall end-systolic thickness (LVAWs) and left ventricular posterior wall end-systolic thickness (LVPWs) decreased, the ratio of heart weight to tibia length increased, the myocardial tissue morphology changed, myocardial fibrosis increased, the cross-sectional area of myocardial cells increased, iron deposition appeared in myocardial tissue, the serum NT-proBNP and MDA levels increased, the GSH level decreased, and Nrf2, GPX4, SLC7A11, and FTH1 protein expressions in cardiac tissue decreased (P<0.05). Compared with the model group, in the captopril and Laggerae Herba groups, the EF, FS, and LVAWs increased, the LVESV and LVESD decreased, the ratio of heart weight to tibia length decreased, the myocardial cells were arranged neatly, the degree of myocardial fibrosis decreased, the cross-sectional area of myocardial cells decreased, the serum NT-proBNP level decreased, and the GSH level increased. Compared with the model group, the LVPWs increased, the iron deposition in myocardial tissue decreased, the serum MDA level decreased, and Nrf2, GPX4, SLC7A11, and FTH1 protein expressions in cardiac tissue increased (P<0.05) in the Laggerae Herba group. Conclusion Laggerae Herba improves the cardiac function of mice with chronic heart failure caused by transverse aortic arch constriction, reduces the pathological remodeling of the heart, and reduces fibrosis. Its mechanism may be related to Nrf2/SLC7A11/GPX4 pathway-mediated ferroptosis.

Occupational pneumoconiosis remains the most common occupational disease in China, with occupational mineral dust exposure being its primary causative factor. Although national standards for online monitoring and early warning systems of coal mine dust concentrations have been established, national occupational health standards for rapid and online monitoring of dust concentration and particle size distribution in other industries are still limited. Among dust concentration sensor technologies, the light scattering method is the preferred choice for online dust monitoring owing to its wide measurement range and low cost. The beta-ray absorption method is mature but highly sensitive to humidity. The electrostatic induction method offers high sensitivity, simple structure, and low maintenance costs but exhibits high errors in low-concentration dust monitoring. The tapered element oscillating microbalance method is highly sensitive but costly. Multi-sensor data fusion technology can improve monitoring reliability, however, mature domestic products are not yet available. For monitoring dust particle size distribution, sieving and sedimentation methods are cumbersome. The aerodynamic method shows broad prospects in the online monitoring of respirable dust but has obvious measurement errors for larger dust particles. The use of optical measurement method is limited by dust morphology and is not suitable for monitoring coal dust particle size distribution. The electrical mobility method is primarily applicable to submicron dust. Future research should focus on promoting the application of monitoring technology for respirable dust particle size distribution in online monitoring of industrial dust. By integrating Internet of Things, data mining, and artificial intelligence technologies, along with multi-sensor data fusion and numerical simulation, dust concentration prediction models can be established to achieve accurate dust concentration monitoring and early warning of exceedances. The advancements of technologies will provide scientific support for the assessment of industrial dust hazards and the prevention and control of occupational pneumoconiosis.

Background The high work intensity and possible subsequently increased susceptibility to occupational hazards of calcium carbide plants may lead to hypertension in workers, but there are few studies on the relationship between occupational hazard exposure and hypertension in workers involving the production process of calcium carbide. Objective To explore the influence of occupational hazards on the incidence of hypertension in calcium carbide plants. Methods Using historical cohort design, the employees of a calcium carbide factory in the western part of Inner Mongolia Autonomous Region were selected as research subjects. According to the pre-determined inclusion and exclusion criteria, the study population comprised an exposure group of 377 employees (including furnace workers, inspection workers, and maintenance workers) exposed to dust, noise & carbon monoxide, and a control group of 388 employees (including central control workers, electricians, and administrative personnel) without above-mentioned exposure. The total sample size was 765 participants. The follow-up period was from April 2011 to October 2022, and the study endpoint was defined as the conclusion of the follow-up period or diagnosed hypertension in annual occupational health examination. Information on general demographic characteristics, living habits, and work status was collected from all study subjects. Cox proportional hazards regression model was used to analyze the association between occupational hazard exposure and the risk of hypertension among the calcium carbide plant employees. Results The average age, mean systolic and diastolic blood pressure, proportion of males, smoking rate, and alcohol consumption rate in the exposure group were higher than those in the control group (P<0.05). Compared to baseline, both systolic and diastolic blood pressure levels increased in the exposure group and the control group at the end of the follow-up (P<0.05). At the end of the follow-up, the average differences between systolic/ diastolic blood pressure and baseline values in the exposure group were higher than those in the control group (P<0.05). During the follow-up period, a total of 223 cases of hypertension occurred, with a total follow-up of 2785 person-years, resulting in an incidence density of 8007.18 per 100000 person-years, an average age of onset of (35.90±8.22) years, and an average working age of onset of (2.69±1.97) years. The incidence density in the exposure group was 128.71% higher than that in the control group, and the risk of hypertension in the exposure group was 2.115 times that of the control group. The risk of hypertension was 2.199 times higher for men than for women, 1.344 times higher for those aged 30 and above than for those under 30, 1.546 times higher for smokers than for non-smokers, and 1.750 times higher for drinking workers than for non-drinking ones. The results of Cox proportional hazards regression modeling indicated that the hazard ratio (95%CI) of hypertension among the employees exposed to dust, noise, and carbon monoxide was 2.254 (1.703, 2.982), 1.594 (1.107, 2.295), and 1.567 (1.079, 2.274), respectively, when different covariates (gender, age, smoking, and alcohol consumption) were included. The results of Log-rank test showed that there were statistically significant differences in the distribution of disease-free survival between the exposure group and the control group (P<0.05). Conclusion Occupational exposures to dust, noise, and carbon monoxide may increase the risk of hypertension among calcium carbide plant workers.

A long-acting feline ω-interferon fusion protein(FSA-FeIFNω)was designed and its bio-logical function validated.According to the optimization of the sequence of feline serum albumin and feline ω interferon in NCBI,the recombinant plasmid pET-30a(+)-FSA-FeIFNω was con-structed,which was transformed into E.coli BL21(DE3)competent cells,the expression of re-combinant protein FSA-FeIFNω was induced by IPTG,and the expressed inclusion body protein was identified by Western blot,the refolding product was purified by Ni-NTA affinity chromatog-raphy,and the concentration of dialysis and concentrated protein after purification was determined by BCA method.The antiviral activity of recombinant protein was detected by micro-cytopathic in-hibition method in the CRFK/VSV system,the in vitro half-life was detected by 50％mouse plas-ma method,the tumor cell proliferation inhibition activity was detected by MTT method,and anti-tumor activity was detected by mouse melanoma model.The pET-30a(+)-FeIFNω and pET-30a(+)-FSA-FeIFNω expression vectors were successfully constructed,and 87 kDa recombinant FSA-FeIFNω protein was obtained in E.coli,with a purified protein purity of 95％,with a concen-tration of 1 g/L,and the biological activity was 2.56 × 106 IU/mg,the plasma half-life was significantly prolonged(＞24 h),and the half-inhibitory concentration IC50 of B16-F10 in mouse melanoma cells was 56.01 mg/L.The FSA-FeIFNω group significantly inhibited tumor growth,and the treatment effect was better than that of the control group and other experimental groups.The recombinant FSA-FeIFNω protein obtained in this study had long-acting effect and good biological activity.

This study aims to construct a recombinant vaccine containing the tetanus toxin C frag-ment(HC)with a built-in adjuvant of metallothionein 3(MT-3)and evaluate its immune effect in mice.The gene sequences of MT-3 and HC were fused via a linker to create the pET30a-MT-3-HC recombinant plasmid,which was then transformed into E.coli BL21(DE3)competent cells.The re-combinant plasmid was confirmed through double enzyme digestion.The M3C recombinant protein expression was induced,identified by SDS-PAGE and Western blot,and purified using Ni-NTA af-finity chromatography.Five groups of vaccines,including PBS,HC,TT(tetanus toxoid),M3C,and M3C+CpG(composite adjuvant),were administered to mice via intramuscular injection at 7-day intervals for three immunizations.Blood samples were periodically collected from the tail vein.ELISA was used to measure changes in specific IgG antibody titers in the serum,and on day 28,antibody subtypes(IgG1,IgG2a,IgG2b,IgG3,and IgM)and cytokine levels(IL-4,IFN-γ)were also measured.The results demonstrated that the pET30a-MT-3-HC recombinant plasmid was cor-rectly constructed,and the M3C recombinant protein was highly expressed in the supernatant fol-lowing ultrasonic disruption of the induced bacterial culture,with a single band observed post-puri-fication.ELISA results showed that the titer of specific IgG antibodies in the M3C+CpG group peaked at 3.54×105 14 days after the third immunization,which was 141 times,70 times,and 6.6 times higher than that in HC,TT,and TT groups,respectively.Antibody subtype analysis revealed significantly higher specific antibody subtype titers in the M3C and M3C+CpG groups compared to the PBS,HC,and TT groups(P＜0.05),with the M3 C group showing an IgG1/IgG2a ratio greater than 1,and the M3C+CpG group having an IgG1/IgG2a ratio of approximately 1.Serum concentrations of IFN-γ and IL-4 in the M3C and M3C+CpG groups were also significantly higher than those in the other experimental groups(P＜0.05).These results showed that the recombinant antigen containing MT-3 built-in adjuvant and tetanus toxin C fragment was successfully expressed and showed strong immunogenicity,which laid the experimental foundation for the development of this recombinant vaccine.

Objective To construct an evaluation index system for the Medical Ethics Committee of Henan Province,and provide technical support for evaluating the construction of Medical Ethics Committee.Methods Delphi method was used to construct medical ethics evaluation indicators,and the AHP analytic hierarchy process was used to determine the weights of the indicators.Results After two rounds of expert consultation,it was determined that the evaluation indicators of the Medical Eth-ics Committee include 5 primary indicators and 30 secondary indicators;Basic conditions and management mechanisms are rela-tively important in primary indicators;The weight of the average number of training sessions conducted by the ethics committee per year and the number of training sessions received by the ethics committee per year is relatively high.Conclusion The evalu-ation index system for medical ethics committees constructed in this study has high authority and scientificity,providing a refer-ence for the evaluation of medical ethics committees at all levels.

Objective To construct an animal model of dilated cardiomyopathy(DCM)with heart failure toxin syndrome that conforms to the characteristics of traditional Chinese medicine(TCM)syndrome and identify potential biomarkers or intervention targets for DCM with heart failure toxin syndrome.Methods Fifteen male SD rats were divided into a blank control,doxorubicin,or DCM with heart failure toxin syndrome group using a random number table method,with five rats per group.The doxorubicin group received intraperitoneal injection of doxorubicin at a dose of 1.25 mg/kg,administered on the first and fourth days of each week,along with a standard diet.The DCM with heart failure toxin syndrome group,in addition to the doxorubicin treatment,was given 42％white liquor(10 mL/kg)via gavage every other day,along with a 45％high-fat feed and 10％fructose water.The blank control group received intraperitoneal injection of an equivalent volume of phosphate-buffered saline at the same time points as the doxorubicin group,along with a standard diet.The model was established for 10 weeks.At the fourth and tenth weeks of modeling,echocardiography was performed to measure left ventricular ejection fraction(LVEF),fractional shortening(FS),systolic left ventricular posterior wall thickness(LVPWs),diastolic left ventricular posterior wall thickness,systolic left ventricular internal diameter(LVIDs),and diastolic left ventricular internal diameter(LVIDd);macroscopic changes in fur color of the rats were assessed using the red-green-blue colorimetric method.After modeling,the open field test was conducted to evaluate the exercise tolerance of the rats,and the grip strength test was performed to assess changes in forelimb grip strength.Hematoxylin-eosin,Masson,and wheat germ agglutinin staining were used to evaluate pathological changes in cardiac tissue.Bulk RNA sequencing analysis was performed to identify differentially expressed genes(DEGs)in the hearts of rats between the blank control and the DCM with heart failure toxin syndrome groups.Using DCM,the Blue value of rat fur color,and forelimb grip strength as phenotypic traits,weighted gene co-expression network analysis(WGCNA)was performed to screen for characteristic module gene sets(MEs)associated with DCM with heart failure toxin syndrome.Overlapping analysis was performed on DEGs,immune-related gene sets,and MEs,and the intersecting genes were identified as potential biomarkers or intervention targets for DCM with heart failure toxin syndrome.The sensitivity and specificity of these targets were evaluated using receiver operating characteristic(ROC)curve analysis.Results Compared with the blank control group,at the tenth week of modeling,the LVEF,FS,and LVPWs of rats in the doxorubicin group and the DCM with heart failure toxin syndrome group decreased,whereas LVIDs and LVIDd increased,and the movement distance of the open field test and forelimb grip strength were reduced(P＜0.05).At the 10th week of modeling,the Blue value of fur color in the DCM with heart failure toxin syndrome group was significantly lower than that of the blank control and doxorubicin groups(P＜0.05).Compared with the blank control group,rats in the doxorubicin and DCM with heart failure toxin syndrome groups exhibited significant cardiac dilation and increased immune cell infiltration in cardiac tissue,accompanied by collagen deposition and cardiomyocyte hypertrophy.Bulk RNA sequencing identified 2,003 DEGs,including 1,082 downregulated genes and 921 upregulated genes.WGCNA results revealed that the MEturquoise module had the strongest positive correlation with DCM and the strongest negative correlation with the Blue value and forelimb grip strength.The overlapping analysis identified four intersecting genes:bone morphogenetic protein 6(Bmp6),serine-threonine-protein kinase 1(Pak1),proto-oncogene JunD(JunD),and S100 calcium-binding protein A3(S100A3).ROC curve analysis demonstrated that these four genes exhibited high sensitivity and specificity for DCM with heart failure toxin syndrome.Conclusion The rat model constructed by intraperitoneal injection of doxorubicin combined with a high-fat feed,fructose water,and white liquor gavage closely aligns with the characteristics of the DCM with heart failure toxin syndrome.Bmp6,JunD,Pak1,and S100A3 are potential biomarkers or therapeutic targets for DCM heart failure toxin syndrome.

To develop a novel immunocastration vaccine for animals,researchers designed and syn-thesized the recombinant plasmid pET-30a-SF which could express the recombinant protein SF.This protein was then conjugated in vitro with the synthetic peptide STGP to prepare the SF-STGP nanoparticle vaccine,and its immunocastration effect on mice was studied.The Spy Catcher and ferritin amino acid sequences were connected via GGGGS,and after codon optimization for E.coli,the recombinant plasmid pET-30a-SF was constructed and transformed into E.coli for in-duced expression.The recombinant protein SF was purified using Ni-column affinity chromatogra-phy and characterized.The peptide STGP,composed of Spy Tag,GnRH,and PADRE connected by GGGS,was conjugated with the recombinant protein SF in vitro.The self-assembled nanoparticles were observed using transmission electron microscopy(TEM)and dynamic light scattering(DLS).The prepared SF-STGP nanoparticles were mixed with MONTANIDE ISA 206 VG at a 1∶1 ratio to form the vaccine,which was then subcutaneously injected into male BALB/c mice for immunocastration evaluation.The recombinant protein SF showed the highest soluble expression when induced at 18 ℃ with 0.25 mmol/L IPTG for 14 h,and the maximum conjugation efficiency with STGP was achieved at a 1∶8 molar ratio.TEM and DLS analyses revealed that both the re-combinant protein SF and SF-STGP could self-assemble into nanoparticles with average diameters of 16.2 nm and 17.8 nm,respectively.Mouse immunization results demonstrated that the SF-STGP nanoparticle vaccine generated specific GnRH antibodies after the first immunization,with the spe-cific antibody D45o reaching its peak at the 10 th week.The SF-STGP+ISA 206 immunization group showed a peak D450 value of 2.8,and the specific antibody levels in all immunization groups were significantly higher than those in the control group(P＜0.05).Additionally,the SF-STGP nanoparticle vaccine effectively reduced serum testosterone levels in mice,with the testosterone concentration in the immunization groups being significantly lower than that in the control group(P＜0.05).Compared to the control group,the immunization group exhibits testicular atrophy.The constructed SF-STGP nanoparticle vaccine proves to be a highly effective immunogen,capable of inducing testicular atrophy and reducing gonadal hormone concentrations,demonstrating excellent castration effects.This study provides new insights into immunocastration vaccines for mammals.

Objective To analyze the risk factors for delayed hemorrhage in patients with early gastric carcinoma(EGC)after endoscopic submucosal dissection(ESD),as well as to explore the predictive value of predictive models.Methods The clinical data of 386 EGC treated with ESD patients from July 2019 to March 2024 were retrospectively analyzed.They were followed up for a short period of time(24 h～30 d postoperatively)after ESD,and were divided into the group of occurrence(50 cases)and the group of non-occurrence(336 cases)according to the occurrence or non-occurrence of delayed hemorrhage.To understand the clinical data of the patients,multivariate Logistic regression was used to analyze the risk factors for delayed hemorrhage in patients with EGC after ESD,and plot receiver operating characteristic curve(ROC curve)to analyze the predicted value.Results The proportions of cardia gastric fundus,lesion diameter ≥ 3 cm,submucosa with fibrosis,coarse blood vessels,and having ulcer or scar in the occurrence group were significantly higher than those in the non-occurrence group,the differences were statistically significant(P＜0.05).The results of multivariate Logistic regression analysis(with an introduction level of 0.05)showed that the lesion location was cardia-gastric fundus(OR=1.088,95％CI:1.040～1.138),the diameter of the lesion was ≥3 cm(OR=1.095,95％CI:1.057～1.135),and fibrosis under the mucosa(OR=1.130,95％CI:1.061～1.203),thick blood vessels under the mucosa(OR=1.177,95％CI:1.116～1.241),and the presence of ulcer or scar(OR=1.082,95％CI:1.057～1.108)were the risk factors for the occurrence of delayed hemorrhage in patients with EGC after ESD(P＜0.05).A prediction model was established:Logit(P)=-9.238+Location of lesion as cardia-gastric fundus × 0.084+Diameter of lesion ≥ 3 cm× 0.091+Submucosal with fibrosis × 0.122+Submucosal with thick blood vessels × 0.163+Ulcer or scar×0.079(P＜0.05),the likelihood ratio test yielded x2=131.09,DF=8,P＜0.05,which indicated that the constructed prediction model was valid.Hosmer-Lemeshow goodness-of-fit test showed a good model fit(P＞0.05).The ROC curve showed an area under the curve(AUC)value of 0.929 at a cutoff value of 12.00,with a sensitivity of 88.00％(95％CI:0.757～0.955)and a specificity of 83.04％(95％CI:0.780～0.869).Conclusion Postoperative delayed hemorrhage in patients with EGC treated with ESD is associated with cardia-gastric fundus,lesion diameter ≥3 cm,submucosal fibrosis,thick blood vessels,and the presence of ulcer or scar,and the prediction value of the prediction model constructed accordingly is good.