Objective To assess the prevalence and clinical features of nonalcoholic fatty liver disease(NAFLD)and its risk factors in patients with CHF,so as to provide the reference for early identification of NAFLD.Methods The data from 1120 CHF patients aged 14～89 was collected,including the general demographic information(age,gender,smoking status,height,weight,BMI,etc.),clinical diagnosis and treatment data(blood pressure,NYHA heart function classification,blood biochemical indicators,etc.),and medication use status.SPSS 27.0 was applied to analyze the clinical characteristics of CHF combined with NAFLD,and binary multivariate logistic regression was used to analyze the independent risk factors of CHF combined with NAFLD.Results Among the 1120 patients,634(56.6%)were male and 486(43.4%)were female.The prevalence of CHF patients with NAFLD was 25.0%.The results of univariate analysis showed that the weight of NAFLD patients BMI,systolic blood pressure,diastolic blood pressure,FPG,UA,left room expansion ratio,ALT,CHO,TG,obesity rate,hyperuricemia rate and β-blocker usage rate were all higher than those of non NAFLD patients.The age,BNP,HDL and ACEI/ARB/ARNI usage rate of NAFLD patients were lower than those of non NAFLD patients(all P<0.05).Logistic regression analysis showed that age(OR=0.988),FPG(OR=1.099),overweight(OR=3.497)and obesity(OR=9.193)were independent risk factors for CHF patients with NAFLD.Conclusion NAFLD may be a common complication in CHF patients,especially those who are young,have high FPG,overweight and obese.In the clinical practice,NAFLD screening,evaluation and management should be focused on CHF patients who are young,have high fasting blood sugar,overweight,and obese.

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.

OBJECTIVES: There is less clinical data on multiple myeloma (MM) in China, and the aim of this study was to collect and analyze the clinical data of newly diagnosed multiple myeloma (NDMM) patients in Hunan Province during 1 year, to understand the real clinical features and treatment outcome for Hunan Province patients with MM, and to strengthen the understanding of the standardized diagnosis process and treatment plan of MM. METHODS: The clinical data of 529 patients with NDMM in 12 large-scale general hospitals in Hunan Province from January 1 to December 31, 2019 were collected and analyzed, including baseline data, treatment regimens, duration of treatment, and adverse reactions. The clinical characteristics, treatment, and safety of patients were analyzed by SPSS 21.0. RESULTS: Among the 529 NDMM patients, the age was 33-90 (median 64) years and the male-female ratio was 1.38꞉1. The clinical features ranged from high to low were as follows: Bone pain (77.7%), anemia (66.8%), renal insufficiency (40.6%), hypercalcemia (15.1%). Typing: IgG 46.5%, IgA 24.6%, IgD 2.6%, IgM 0.8%, light chain 15.7%, double clone 3.0%, no secretion 0.6%, absence 6.2%. Staging: Durie-Salmon stage I, II, and III were 4.5%, 10.6%, 77.3%, respectively, and 40 cases (7.6%) missed this data. International Staging System (ISS) stage I, II, and III were 10.4%, 24.4%, and 47.6%, respectively, and 93 cases (17.6%) were missing. Revised International Staging System (R-ISS) stage I, II, and III were 5.5%, 27.0%, 23.1%, respectively, and 235 cases (44.4%) missed this data. Among the 98 NDMM patients in the Third Xiangya Hospital, Central South University, Durie-Salmon (DS) stage missing 2.0%, ISS stage missing 12.3%, and R-ISS stage missing 12.3%.Treatment: Among the 529 patients,475 received treatment, the rate of treatment was 89.8%; 67.4% of the patients were able to complete four courses of chemotherapy at induction phase, 90.3% of the patients received proteasome inhibitor based combination chemotherapy regimen more than once, 67.2% received immunomodulator based regimen more than once, and 59.8% of the patients received proteasome inhibitor and immunomodulator based combination chemotherapy regimen more than once. Curative: Overall response rate (ORR) and high quality response rate (HQR) of the 4-course group were better than those of the 2-course group (ORR: 85% vs 65%, P=0.006; HQR: 68.3% vs 24.0%, P<0.001). The HQR of the standard chemotherapy group was better than that of the non-standard chemotherapy group (65.1% vs 48.2%, P=0.035). Adverse reactions during treatment included hematologic toxicity (17.5%), peripheral neuropathy (24.8%), gastrointestinal adverse events (23.8%), pulmonary infection (25.9%), herpes zoster (4.6%), and venous thrombotic events (1.7%). CONCLUSIONS In 2019, the missed diagnosis rate of MM patients was high, the medium age of diagnosis was older, and the accuracy of patient diagnosis was not high. There is a great difference among medical centers, especially in the stage and risk stratified, nearly half of NDMM patients are not diagnosed with R-ISS stage; the lack of cytogenetic data needs to be supplemented by follow-up studies. A high proportion of patients with NDMM present with bone pain and anemia.Patients received treatment have higher use of chemotherapy regimens containing proteasome inhibitors and/or immunomodulators, but there is a significant gap among different medical centers, and standardized treatment needs to be strengthened. The safety during chemotherapy is controllable.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Female ; Humans ; Immunologic Factors/therapeutic use* ; Male ; Middle Aged ; Multiple Myeloma/therapy* ; Neoplasm Staging ; Pain ; Prognosis ; Proteasome Inhibitors/therapeutic use*

Objective:To explore the effect of decalcified bone matrix (DBM) rich in biological activity on surgical-grade medical calcium sulfate, and to observe the change of different content of DBM on the physical and chemical properties of calcium sulfate, which provide theoretical basis for the preparation of calcium sulfate bone cement with osteogenic and injectable properties.Methods:DBM with weight content of 0, 5%, 10%, 20%, 30%, 40% was fully mixed with CSH. Dissolve 0.3 g of methyl cellulose in 10 ml of deionized water to prepare a 3% methyl cellulose solution. Methylcellulose solution was added according to the liquid-solid ratio of 0.4. The mixture was evenly stirred to form slurry, then the degradation rate, compressive strength, setting time and and pH value of calcium sulfate in vitrowas measured.Results:The initial setting time and final setting time of calcium sulfate were 4.96±0.20 and 5.83±0.12 min respectively. With the increase of DBM content, the initial setting time and final setting time increased significantly ( F=49.275, P<0.05; F=124.859, P<0.05). The compressive strength of pure calcium sulfate is 23.33±6.35 MPa; when the content is 40%, the compressive strength is only 3.33 MPa. With the increase of DBM content, the compressive strength first increased and then decreased; the content of 5%, 10%, 20% DBM had little effect on the compressive strength ( P>0.05), while the compressive strength of 30% and 40% groups decreased significantly ( t=3.259, P<0.05). DBM with different contents can significantly change the degradation rate of calcium sulfate complex. When the content of DBM is 30% and 40%, the complete degradation time in vivo is only 10 d, while the degradation rate of calcium sulfate is 63% in 30 d. At any time point in vitro degradation, DBM had no significant effect on the pH value of calcium sulfate complex culture medium, and the change law was consistent with that of pure calcium sulfate. Conclusion:With the increase of DBM content, the degradation rate is gradually accelerated, the compressive strength is reduced, and the setting time is prolonged, which is not conducive to the preparation of injectable calcium sulfate cement.

Objective To determine the methylation level of P15INK4B gene promoter in different types of myelodysplastic syndromes (MDS) and its correlation with its prognosis.Methods Methylation frequency of the P15INK4B gene promoter in 44 cases of MDS were determined by methylation-specific polymerase chain reaction (PCR) and pyrosequencing,and its correlation with clinical classification and characteristics of MDS were statistically analyzed.Results Frequency of P15INK4B gene promoter methylation in myelodysplastic syndromes-refractory anemia with excess blasts Ⅱ (MDS-RAEB Ⅱ) patients was (46.89 ± 15.41) ％,significandy higher than that in other types of MDS (P ＜ 0.05),but no difference in promoter methylation frequency was detected among the other types of MDS (P ＞ 0.05) ; frequency of P15INK4B gene promoter methylation was found to be correlated with decline in platelet upon diagnosis (t =9.02,P ＜ 0.01),but showed no significant correlation with drop of hemoglobin or leukopenia (P ＞0.05).As for the correlation between P15INK4B gene promoter methylation and MDS risk stratification,no significant difference was detected between the low-risk and very low-risk groups (P ＞ 0.05),but significant differences were detected among the medium-risk,high-risk,and very high-risk groups (P ＜ 0.05).In addition,frequency of P15INK4B gene promoter methylation was (49.21 ± 8.78)％ in MDS patients that developed leukemia in the following two year,significantly higher than that in MDS patients who didn't (19.64 ± 6.24) ％ (P ＜ 0.05).Conclusions P15INK4B gene promoter methylation frequency is a valuable indicator of prognosis of MDS patients.

Objective To explore the mental health and its relationship with mental quality of training logistic soldiers in field.Methods Symptom Checklist 90(SCL-90) and Mental Quality Questionnaire for armymen (MQQA) were employed to evaluate the mental health and mental quality of 230 training logistic soldiers in field,and then an analysis was carried out on the characteristics of the training logistic soldiers on mental health and its relationship with mental quality.Results ①The psychological problem's ratio of training soldiers was 21.3％,and the ratio of the male(22.8％) was significantly higher than that of the female(15.2％) (x2 =8.64,P=0.00).In SCL-90,the scores of somatization (1.46 ± 0.63),hostility (1.49 ± 0.75) and psychotism (1.43 ±0.68) were all higher in training soldiers than the army norm.The factor scores of somatization (1.49 ± 0.66)and psychotism(1.46 ± 0.72) in the male training soldiers were considerably higher than those of the male soldiers norm (P ＜ 0.05),but not in the female(P ＞ 0.05).②There existed a significantly negative correlation between the factor scores of the mental quality and that of SCL-90 (P ＜ 0.05,P ＜ 0.01).③The SCL-90 scores existed clear differences in obsessive-compulsive,interpersonal sensitivity,depression,hostility and paranoid ideation among different mental quality groups (P ＜ 0.05).Conclusion The mental health of training logistic soldiers is poor.The mental health is closely related to the mental quality.Therefore,the mental health education and mental quality training should be strengthened to the training logistic soldiers.

Objective To investigate the diagnostic value of JAK2V617F mutation detection in the diagnosis of polycythemia vera,and screen a more simple method for clinic laboratory to detect the mutation of JAK2V617F.Method DNA was extracted by standard procedures after isolating total leukocytes from peripheral blood mononuclear cells by density gradient centrifugation over Histopaque 1077.DNA samples were amplified,and single-stranded biotinylated PCR products were prepared for sequencing.At the same time,in order to testify the reliability of the allele-specific PCR,two forward primer and one common reverse primers were applied for identifying the mutation.Result In 32 of 38 patients with polycythemia vera,JAK2V617F mutation was determined by conventional DNA sequencing.35 JAK2V617F mutations were detected by the allele-specific PCR.and these mutations were confirmed by DNA sequencing.None mutation was found in secondary polycythemia and normal control.Conclusion JAK2V617F function mutation occuis in nearly all patients with PV,and JAK2V617F mutation should be a molecular marker in the diagnosis of polycythemia vera.Allele-specific PCR is a very sensitive and specific method for detecting JAK2V617F mutation.