Objective To compare TyG index between the patients with CHF and ADHF to eluci-date the metabolic difference between these two stages.Methods A total of 1156 HF patients ad-mitted in Taizhou People's Hospital between January 2020 and December 2022 were enrolled,and according to 2021 ESC Guidelines for Diagnosis and Treatment of Acute and Chronic Heart Fail-ure,they were divided into CHF group(365 cases)and ADHF group(791 cases).The clinical da-ta,results of laboratory tests,and cardiovascular history were collected,and TyG index was calcu-lated.All-cause death outcome was observed in ADHF patients during a follow-up of 1 year.Results The TyG index was significantly lower in the ADHF group than the CHF group[8.27(7.99,8.62)vs 8.35(8.04,8.75),P=0.001].In the ADHF group,the TyG index was positively correlated with SBP,DBP,TC,TG,LDL-C,FPG,HbA1c,BMI,and LVEF,and negatively with age(P＜0.01).In the CHF group,the index was positively correlated with DBP,TC,TG,LDL-C,FPG,BMI,and HbA1c,and negatively with age(P＜0.05,P＜0.01).Both univariate and multiva-riate logistic regression analyses indicated that the TyG index was a protective factor for ADHF(OR=0.647,95％CI:0.503～0.832,P=0.001;OR=0.694,95％CI:0.536～0.898,P=0.005).Multivariate logistic regression analysis showed that the index in ADHF patients was a protective factor for one-year all-cause mortality(OR=0.483,95％CI:0.254-0.916;P=0.026).Conclusion TyG index might be regarded as an important marker for assessing the metabolic status in HF patients and predicting the prognosis in ADHF patients.

Objective To compare TyG index between the patients with CHF and ADHF to eluci-date the metabolic difference between these two stages.Methods A total of 1156 HF patients ad-mitted in Taizhou People's Hospital between January 2020 and December 2022 were enrolled,and according to 2021 ESC Guidelines for Diagnosis and Treatment of Acute and Chronic Heart Fail-ure,they were divided into CHF group(365 cases)and ADHF group(791 cases).The clinical da-ta,results of laboratory tests,and cardiovascular history were collected,and TyG index was calcu-lated.All-cause death outcome was observed in ADHF patients during a follow-up of 1 year.Results The TyG index was significantly lower in the ADHF group than the CHF group[8.27(7.99,8.62)vs 8.35(8.04,8.75),P=0.001].In the ADHF group,the TyG index was positively correlated with SBP,DBP,TC,TG,LDL-C,FPG,HbA1c,BMI,and LVEF,and negatively with age(P＜0.01).In the CHF group,the index was positively correlated with DBP,TC,TG,LDL-C,FPG,BMI,and HbA1c,and negatively with age(P＜0.05,P＜0.01).Both univariate and multiva-riate logistic regression analyses indicated that the TyG index was a protective factor for ADHF(OR=0.647,95％CI:0.503～0.832,P=0.001;OR=0.694,95％CI:0.536～0.898,P=0.005).Multivariate logistic regression analysis showed that the index in ADHF patients was a protective factor for one-year all-cause mortality(OR=0.483,95％CI:0.254-0.916;P=0.026).Conclusion TyG index might be regarded as an important marker for assessing the metabolic status in HF patients and predicting the prognosis in ADHF patients.

Objective To investigate the effect and molecular mechanism of isolongifolene(ISO)on the apoptosis of intestinal epithelial cells and 2,4,6-trinitrobenzenesulfonic acid(TNBS)-induced Crohn's disease(CD)-like colitis in mice.Methods In the animal experiments,mice were randomly assigned to the wild type(WT)group,TNBS group and TNBS+ISO group,with 8 mice in each group.Colitis models of mice were established in the TNBS group and the TNBS+ISO group by rectal injection of TNBS.After modeling,the mice in the TNBS+ISO group were given ISO intervention via intragastric gavage(10 mg/kg),and the other two groups were given the same amount of normal saline via intragastric gavage.The mice were sacrificed on the 7th day.The changes in body mass,disease activity scores(DAI),and the colon length of mice were measured,and transepithelial electrical resistance(TEER)of the colon tissues was determined.The score of colon inflammation was calculated according to HE staining.The levels of intestinal mucosal inflammatory factors,including tumor necrosis factor alpha(TNF-α),interferon(IFN)-γ,interleukin(IL)-1 β,and IL-6,were measured by RT-PCR and ELISA.The apoptosis of colon tissue cells was determined by TUNEL assay.The expressions of apoptotic proteins(cleaved caspase-3/caspase-3 and Bax),an anti-apoptotic protein(Bcl-2),and tight junction proteins(ZO-1 and claudin-1)were detected by Western blot and immunofluorescence.In the cell experiment,TNF-α was used to induce intestinal epithelial cell Caco-2 apoptosis model,which was treated with ISO.Then,intervention with the AMPK inhibitor Compound C was given.TUNEL assay,Western blot assay,and immunofluorescence assay were performed to measure apoptosis and the expression of apoptosis proteins in the Caco-2 cells.Gene Ontology(GO)enrichment analysis was performed to predict the biological function of ISO.Then,the mechanism involved was verified by examination of the mice and Caco-2 cells.Western blot was performed to determine the expression levels of p-AMPK/AMPK and p-PGC1α in the colon tissues from the mice of different groups and Caco-2 cells.The apoptosis of the cells was determined by TUNEL assay.Results According to the results of the animal experiment,ISO could alleviate experimental colitis and intestinal barrier dysfunction,leading to improvements in body mass loss,colon length shortening,DAI score,inflammatory rating,and TEER values(all P＜0.05)in mice.Furthermore,ISO decreased the expression of pro-inflammatory factors TNF-α,IFN-γ,IL-1β,and IL-6 and increased the expression of the tight junction proteins ZO-1 and claudin-1(all P＜0.05).In the cell experiment,in a TNF-α-induced intestinal epithelial cell model,ISO was also found to protect intestinal barrier against damage.ISO reduced the proportion of apoptotic intestinal epithelial cells,reduced the expression of cleaved-caspase-3/caspase-3 and Bax,and upregulated the level of Bcl-2(all P＜0.05).GO enrichment predictive analysis showed that the role of ISO in improving CD-like enteritis might be associated with the negative regulation of apoptosis.Verification of the mechanism showed that the expression of p-AMPK and p-PGC1α in the mice colon tissue was significantly upregulated after ISO intervention(P＜0.05).In contrast,the AMPK inhibitor Compound C increased the apoptosis rate of ISO-treated Caco-2 cells and decreased the relative expression levels of ZO-1 and claudin-1(P＜0.05).Conclusion ISO reduces intestinal epithelial cell apoptosis at least in part by activating AMPK/PGC1α signaling pathway,thereby alleviating TNBS-induced intestinal barrier dysfunction and CD-like colitis in mice.

In recent years, the development of bispecific antibodies (bsAbs) has been rapid, with many new structures and target combinations being created. The boom in bsAbs has led to the successive issuance of industry guidance for their development in the US and China. However, there is a high degree of similarity in target selection, which could affect the development of diversity in bsAbs. This review presents a classification of various bsAbs for cancer therapy based on structure and target selection and examines the advantages of bsAbs over monoclonal antibodies (mAbs). Through database research, we have identified the preferences of available bsAbs combinations, suggesting rational target selection options and warning of potential wastage of medical resources. We have also compared the US and Chinese guidelines for bsAbs in order to provide a reference for their development.

Objective:To grasp the distribution of fine antigenic epitope profiles of nucleoprotein (NP) and glycoprotein (GP) fragments of Crimean-Congo hemorrhagic fever virus (CCHFV) and to clarify the value of dominant antigenic epitopes in laboratory testing of Crimean-Congo hemorrhagic fever (CCHF).Methods:In a minimal synthetic short peptide consisting of 8 amino acids was segmentally expressed by CCHFV YL04057 strain using a modified bio-peptide synthesis method from 2014 to 2021 in the laboratory of Xinjiang University, College of Life Sciences. Using CCHFV polyclonal antibody or monoclonal antibody 14B7 (IgM) or CCHFV-positive sheep serum as antibodies, the minimal antigenic epitopes (BCEs) with antigenic activity on NP and GP fragments were identified by immunoblotting, and the obtained BCEs with sequence polymorphism were spatially clustered with CCHFV from different regions using the neighbor-joining method to determine the combination mode of BCEs with geographical correlation of regional distribution, to explore its application in establishing serological diagnosis. A prokaryotic expression plasmid (pET-32a), an E. coli expression plasmid (pGEX-KG) and a prokaryotic expression plasmid with an incomplete glutathione (GST188) tag (pXXGST-ST-1) were used to construct and express six dominant antigenic epitopes of different peptide lengths on NP fragments, and an indirect Enzyme-linked immunosorbent assay (ELISA) was established. CCHF sheep serum identified by immunofluorescence assay (IFA) was used as a control, and the specificity, sensitivity and overall compliance of the recombinant proteins with different peptide lengths of antigenic epitopes with IFA assay results were statistically analyzed. Results:CCHFV, NP and GP fragments had a total of 30 antigenically active BCEs, among which the core intermediate fragment NP2 (aa 170 th-305 th), which had a concentration of antigenic epitopes in the NP fragment, has 6 BCEs, and the NP1 (aa 1 st-200 th) and NP3 (aa 286 th-482 nd) at both ends have 9 BCEs; the Gc (aa 1 st-558 th) and Gn (aa 533 th-708 th) fragments of the GP fragment have 14 BCEs and a long antigenic peptide (AP) containing 15 amino acids, and the amino acid sequence homology of the NP fragment BCEs was 97.1% and that of the GP fragment BCEs was 89.1%. There was a significant difference ( P=0.0281, P<0.05). Among the 9 BCEs with sequence polymorphism in the GP fragment, 6 combined BCEs from GnEc1, GnE2, GnE4, GcE3, GcE6 and GcAP-4 (Ap) could cluster 15 CCHFV strains from different regions of the world into 5 geographical taxa, AsiaⅠ, AsiaⅡ, AficaⅠ, AficaⅡ and Europe. The constructs expressing PET-32a-NP (full length), PGEX-KG-NP2 (aa 170 th-305 th), pGEX-KG-NP2-1 (aa 235 th-275 th), PGEX-KG-NP2-1-1 (aa 237 th-256 th), pXXGST-1-NP2-1-2 (aa 250 th-265 th) and PGEX KG-NP2-1-3 (aa 260 th-276 th), six recombinant proteins CCHFV NP rabbit polyclonal antiserum (pAb) Western Blotting reaction positive, 33 sheep sera tested by IFA XHF as a reference, the sensitivity of the assay established by indirect ELISA using the recombinant proteins constructed from two fragments of NP2 and NP2-1 as antigens. The sensitivity, specificity and overall compliance were the best, with 73.4% (11/15) and 66.7% (10/15) for sensitivity, 100% (18/18) and 94.4% (17/18) for specificity, and 87.9% (29/33) and 81.8% (27/33) for overall compliance. Conclusion:CCHFV NP and GP are distributed with a high number of BCEs with antigenic immunoreactivity, among which the dominant antigenic epitopes are of high value in the laboratory serological diagnosis of CCHF.

Objective:To analyze the clinical characteristics of patients with acute glyphosate herbicide poisoning and the differences in the severity of poisoning.Methods:A retrospective analysis was performed on patients with acute glyphosate herbicide poisoning admitted to the First Affiliated Hospital of Zhengzhou University from January 2014 to December 2020. The general information, exposure time, poisoning dose, poisoning cause, poisoning route, clinical manifestations, laboratory examination results during hospitalization, treatment measures, hospital stays and prognosis of the patients were collected. The patients were graded according to the poisoning severity scoring standard of Chinese Expert Consensus on Diagnosis and Treatment of Acute Poisoning in 2016. The highest severity score during hospitalization was used as the final grade. According to the final grade, asymptomatic and mild patients were included in the mild group, and moderate, severe and death patients were included in the severe group. The independent sample T test or Mann-Whitney U test was used for measurement data, and χ2 test or Fisher's exact test was used for counting data. The differences of general data and clinical data between the two groups were compared. Results:According to the inclusion and exclusion criteria, 83 patients with acute glyphosate herbicide poisoning were selected as the study subjects. All patients survived, mainly mild poisoning (56.6%), with a male to female ratio of 33∶50, and an average age of 39 years. The number of poisoning cases increased yearly (the highest in 2019), and most cases occurred in spring and summer. The main cause of poisoning was suicide (71.1%), direct oral administration (83.1%) was the primary route of poisoning, and the dominating clinical manifestations were digestive symptoms (71.1%). Laboratory tests showed increased white blood cell count (WBC), neutrophil percentage (NEUT %) and D-dimer, and decreased hemoglobin and potassium. Compared with the mild group, patients in the severe group were older [(51±17) years vs. (35±19) years], had a higher proportion of suicide and direct oral administration, a longer hospital stay [8.0 (4.8, 12.0) d vs. 3.0 (2.0, 5.5) d], a higher dose of poisoning [200.0 (50.0, 200.0) mL vs. 30.0 (11.3, 57.5) mL], and higher NEUT % within 24 h of admission [(83.4±10.4) vs. (73.2±12.8)]. The increase of WBC, NEUT %, aspartate aminotransferase, prothrombin time, D-dimer and the decrease of serum potassium were more common in the severe group than the mild group, with statistical significance (all P<0.05). Conclusions:The number of patients with acute glyphosate herbicide poisoning is increasing yearly. Generally, the condition is mild and the prognosis is satisfying. The severity is more serious in the middle-aged and elderly patients andthose with direct oral administration, high toxic dose, and high NEUT % within 24 h of admission. Severe poisoning is more likely to cause changes in laboratory indicators.

Objective:To explore the factors affecting bone mineral density (BMD) in adult males with low-to-moderate fluoride exposure in Henan Province.Methods:Adult male villagers from low-to-moderate fluoride exposure areas in Tongxu County, Kaifeng City, Henan Province were recruited from April to May 2017 based on cluster random sampling. Questionnaire survey, physical measurements and urinary samples collection were conducted respectively. Urinary fluoride (UF) was determined by fluoride ion-selective electrode. Ultrasound bone densitometer was used to measure BMD (T-score). Partial correlation analysis and multiple linear regression were used to analyze the influence factors of BMD.Results:A total of 439 adult males were included in this study. Age, body mass index (BMI), UF content, and T-score of the participants were (47.99 ± 8.49) years, (25.77 ± 3.23) kg/m 2, (1.34 ± 0.74) mg/L, and-1.79 ± 0.79, respectively. Partial correlation analysis showed a significantly positive correlation between BMI and T-score after age adjustment ( r = 0.194, P < 0.05). Multiple linear regression showed that T-score decreased by 0.015 (95% CI:-0.024 -- 0.005, P < 0.05) for each 1-year increase in age and T-score increased by 0.034 (95% CI: 0.009-0.059, P < 0.05) for each 1.0 kg/m 2 increase in BMI. Interaction analysis showed that T-score was closely related to the interaction between overweight (≥24.0 kg/m 2), non-smoking, tea drinking and UF [ β (95% CI): 0.134 (0.001-0.269), 0.163 (- 0.015-0.337), 0.215 (- 0.006-0.436), P < 0.10]. Conclusions:Our findings reveal a negative correlation between age and BMD, and a positive correlation between BMI and BMD in adult males with low-to-moderate fluoride exposure in Henan Province. In addition, low-to-moderate fluoride exposure is more likely to damage the BMD of smokers.

Objective:To investigate the clinical features of patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis misdiagnosed as mental disorder, improve the early diagnosis rate and reduce misdiagnosis.Methods:The clinical data of patients with anti-NMDA receptor encephalitis diagnosed at the First Affiliated Hospital of Zhengzhou University from 2012 to 2018 were collected. Patients misdiagnosed as mental disorders were screened out. Their psychiatric symptom characteristics, disease course characteristics, imaging and laboratory findings, treatment and prognosis were retrospectively analyzed.Results:A total of 121 cases of anti-NMDA receptor encephalitis were collected, and 43 cases of mental disorders were screened out. Sixteen of the 43 patients (37.2%) had prodromal symptoms, and all the patients had psychiatric behavioral abnormalities (100%), including 32 cases (74.4%) of seizures, 13 cases (30.2%) of decreased level of consciousness, 21 cases (48.8%) of involuntary movements, 15 cases (34.9%) of decreased memory, 8 cases (18.6%) of speech dysfunction, and 8 cases (18.6%) of other neurological symptoms (central hyperventilation, autonomic dysfunction). Memory loss was observed in 15 cases (34.9%), speech dysfunction in 8 cases (18.6%), other neurological symptoms (central hypoventilation, autonomic dysfunction) in 8 cases (18.6%), and various symptoms may appear simultaneously or successively in the same patient. Thirty-eight cases had complete resolution of symptoms or only minor physical impairment, and 5 cases had recurrent admissions with mental abnormalities and seizures. The recurrence rate accounted for 11.6% (5/43).Conclusions:The clinical manifestations of anti-NMDA receptor encephalitis are complex and varied. Most of them have mental behavior abnormalities as the first symptom, which is easily misdiagnosed as mental disorder and delayed treatment will lead to prolonged disease course and poor prognosis.

To explore the threshold effect of body mass index (BMI) on bone mineral density (BMD) in Chinese women living in the fluorosis area, we conducted a cross-sectional study and recruited 722 women in rural areas in Henan Province, China. After detection and analyses, we found that compared with the normal BMI group, the risk of osteoporosis in the overweight and obese groups were reduced by 32% and 69%, respectively. Threshold effect analysis showed that BMD was positively correlated with BMI when BMI was 16.8-31.2 kg/m 2; while when BMI was greater than 31.2 kg/m 2, the correlation reached saturation. The correlation observed between low-to-moderate fluoride exposure and BMD in rural women was not significant.

To explore the threshold effect of body mass index (BMI) on bone mineral density (BMD) in Chinese women living in the fluorosis area, we conducted a cross-sectional study and recruited 722 women in rural areas in Henan Province, China. After detection and analyses, we found that compared with the normal BMI group, the risk of osteoporosis in the overweight and obese groups were reduced by 32% and 69%, respectively. Threshold effect analysis showed that BMD was positively correlated with BMI when BMI was 16.8-31.2 kg/m 2; while when BMI was greater than 31.2 kg/m 2, the correlation reached saturation. The correlation observed between low-to-moderate fluoride exposure and BMD in rural women was not significant.