Objective To investigate the different impacts of the components of metabolic syndrome (MS) on cardiovascular disease (CVD) risk factors and Framingham risk value (FRV) in newly-diagnosed type 2 diabetes mellitus (T2DM) patients without coronary heart disease (CHD).Methods A total of 212 newly-diagnosed T2DM patients was divided into three groups based on the components of MS,including body mass index (BMI),triglyceride (TG),high density lipoproteins cholesterol (HDL-C),and mean arterial pressure (MAP) tertile,respectively.The general CVD risk factors [smoking,BMI,TG,HDL-C,total cholesterol (TC),low density lipoproteins cholesterol (LDL-C),HbA1 C,homeostasis model assessment of insulin resistance (HOMA-IR),and FRV] were compared among the groups.Logistic regression analysis was used to observe the different impact of MS components on CVD risk.Results With the increasing of BMI,TG and MAP tertiles,all the CVD risk factors and the ratio of FRV middle-risk group or high-risk group had the tendency of augmentation.With the increasing of HDL-C tertiles,all the CVD risk factors and the ratio of FRV middle-risk group or high-risk group was in downtrend.Binary logistic regression analysis indicted that BMI,systolic pressure,diastolic pressure,HbA1 c and TG were risk factors of FRV non-low-risk group (middle-risk and high-risk groups),HDL-C was the protective factor.The odds ratios (ORs) of BMI,systolic pressure,diastolic pressure,HbA1 c,TG and HDL-C were 2.794 (95％ CI:2.390-2.408),2.601 (95 ％ CI:1.974-3.701),1.476 (95 ％ CI:1.231-2.048),2.964 (95 ％ CI:1.925-3.282),1.464(95％ CI:0.934-2.294),and 0.732(95％ CI:0.023-0.962),respectively.Logistic stepwise regression analysis indicated that systolic pressure,BMI,HbA1 C,and HDL-C were entered into the regression equation,and the partial regression coefficient was 0.784,1.213,1.679,and-0.854,respectively (P ＜ 0.05 or P ＜ 0.01).Conclusions All the components of MS in newly-diagnosed T2DM were correlated with CVD risk factors.However,they should be weighed differently.

Objective To investigate does intracellular protein degradation pathway play an important role in decrease of endothelial nitric oxide synthase (eNOS) in human umbilical vein endothelial cells (HUVECs).MethodsTo establish a primary HUVECs culture methods,the HUVECs were incubated with concentration gradient group of TNF-α(0.01,0.1,1 and 10 ng/mL) in different time periods (24,48 and 72 h).The HUVECs were pretreated with NH4Cl or treated with caspase inhibitor or MG-132 1.5 h prior to incubation for an additional 24 h with TNF-α.The expression of eNOS was detected via Western blot assay.Results Treatment of the HUVECs with TNF-α(0.01-10 ng/mL) led to a dose-dependent reduction of eNOS expression.And treatment with TNF-α(1 ng/mL) reduced the eNOS expression in a time-depended manner.Compared with the TNF-α group,the protein expression level of eNOS was obviously increased in the co-working group of MG-123 and TNF-α.Conclusions TNF-α induces degradation of eNOS through a ubiquitin-proteasome pathway.

AIM:To investigate the effects of C1q/TNF related protein 3 (CTRP3) on the insulin sensitivity of insulin resistant 3T3-L1 adipocytes.METHODS: The insulin resistance model of 3T3-L1 adipocytes was induced by palmic acid cultivation.The adipocytes were treated with different concentrations of recombinant CTRP3 protein (10, 50, 250,1 250 μg/L) for 12 h, and for different times (2, 6, 12, 24 h) at the concentration of 250μg/L.The glucose con-sumption was detected by the glucose oxidase method.The glucose transport ratio was measured by 2-deoxidation-[3H]-glucose intake method.The contents of TNF-αand IL-6 in the supernatant were detected by ELISA.The mRNA expression of TNF-α, IL-6 and glucose transporter-4 (GLUT-4) was measured by real-time PCR.The protein expression of GLUT-4 was detected by Western blotting.RESULTS:Compared with normal control ( NC) group, the glucose consumption and glucose intake ratio of insulin resistance ( IR) group was decreased by 50.6%and 57.9%, respectively.Compared with IR group, with the increase in CTRP3 (10, 50, 250,1 250 μg/L) in intervention groups, the glucose consumptions were in-creased by 22.1%, 42.9%, 76.6% and 80.5%, respectively, and the glucose intake ratios were increased by 39.0%, 68.0%, 108.0%and 111.0%, respectively.With the increased duration (2, 6, 12 and 24 h) of CTRP3 treatment at the concentration of 250 μg/L, the glucose intake ratio was increased by 23.0%, 79.0%, 109.0%and 114.0%, respectively. The contents of TNF-αand IL-6 in the supernatant were decreased by 17.4%and 17.1%respectively as treated with CTRP3 at the concentration of 250 μg/L for 12 h, and the mRNA expression of TNF-αand IL-6 was decreased by 26.0% and 18.9%respectively, while the mRNA and protein expression of GLUT-4 was increased by 61.5%and 55.6%respectively. CONCLUSION:CTRP3 may increase the insulin sensitivity of insulin resistant 3T3-L1 adipocytes by down-regulating the expression of inflammatory factors, improving the insulin signal transduction and increasing the expression of GLUT-4.

Objective To investigate the impacts of low-grade inflammation on the correlation of serum testosterone (T) and carotid intima-media thickness (CIMT) in type 2 diabetes mellitus (T2DM) men.Methods Based on the concentration of C-reactive protein (CRP) and T,a total of 247 patients was divided into low-grade inflammation with low T group (LI-LT,CRP ≥ 2.0 mg/L,T ＜ 12.0 nmol/L,n =65),low-grade inflammation with normal T group (LI-NT,n =67),non-low-grade inflammation with low T group (NLI-LT,n =56),and non-low-grade inflammation with normal T group (NLI-NT,n =59).General information,medical history,and anthropometry data were collected.Glycosylated hemoglobin AI c (HbA1c),blood fat,and CIMT were detected.Results Compared to NLI-NT group,CIMT in NLI-LT group was increased without statistical significance [(0.87 ±0.09) vs (0.90 ±0.10)mm,t =1.693,P =0.090].CIMT in LI-LT group was increased significantly compared to that of LI-NT group [(0.99 ± 0.10) vs (1.07 ±0.12)mm,t =5.208,P =0.000].Correlation analysis indicated that serum T correlated negatively with CIMT (n =247,r =-0.368,P ＜0.01) in whole.The correlation coefficient of T and CIMT was-0.582 (P =0.000),and-0.098 (P =0.087) in patients with (n =132) and without (n =115) low-grade inflammation,respectively.To make CIMT dependent coefficient and serum T independent coefficient in multiple regression analysis,the partial regression coefficient was-0.062 (95％ CI:-0.094 ～-0.029,P =0.008),and-0.045 (95％ CI:-0.087 ～-0.002,P =0.036),respectively,before and after the adjustment of age,smoking,family history,T2DM course,body mass,blood pressure,HbAlc,and blood fat.After the additional adjustment of CRP,the partial regression coefficient was-0.019 (95％ CI:-0.120 ～ 0.042,P =0.287).Conclusions The negative relationship between serum T and CIMT in T2DM men might be modulated by low-grade inflammation.

Cerebral white matter hyperintensity(WMH)is a type of ischemic alteration that appears as speckled or patchy areas around the ventricles and in the centrocentral area of the semiovals.This alteration can be caused by various factors and indicates a change in the composition of the white matter in the brain.It suggests an alteration in the water content of the hydrophobic white matter fiber bundles.WMH is commonly used as an imaging marker for cerebral small vessel disease.Previous studies have shown that WMH is highly correlated with cognitive impairment.Large-scale longitudinal studies,both population-based and hospital-based,have confirmed the correlation between WMH and clinical symptoms and demonstrated a causal relationship between large-scale WMH and dementia.Adequate differential diagnosis,evaluation,and management are crucial for patients,especially those with early cognitive impairment.Novel imaging techniques may detect subtle impairments before they become visible on an MRI.The purpose of this review is to offer a comprehensive overview of the relationship between WMH and cognitive function.

Objective: To explore the expression of Dickkopf-3(DKK-3) mRNA in oral squamous cell carcinoma(OSCC) and the relationship between the promoter methylation status and the carcinogenesis of OSCC. Methods: The expression of DKK-3 gene in 51 cases of OSCC and corresponding normal mucosa tissue was detected by PT-PCR and methylation-specific PCR, respectively. The relationship between DKK-3 and the clinical pathological features of the patients was analyzed with SPSS 13. 0. Results: The expression level of DKK-3 in OSCC group was lower than that in the control(t =-12. 580, P＜ 0. 05). The methylation rate of DKK-3 gene promoter region in OSCC group was significantly higher than that in the control(χ2 = 19. 273, P＜ 0. 05). The mRNA expression level of DKK-3 gene in OSCC with methylation group was lower than that in the control(t =-2. 817, P＜ 0. 05). Conclusion: Down-regulation of DKK-3 gene expression and hypermethylation of promoter region are important mechanisms in the pathogenesis of OSCC. The hypermethylation of DKK-3 promoter may be the main cause of transcriptional silencing.

Abstract: Cancer immunotherapy, which is an attractive strategy harnessing the host's own immune system to remove tumor cells, has been widely used in clinical practice, yet with low response rate and immune-related adverse events. Unlike traditional chemotherapy, the targets of immunotherapy exhibit high spatial heterogeneity and are distributed in different cell types or secondary organelles, resulting in off-target and on-target toxicity, which greatly reduces the efficacy and safety of treatment. Due to the altered metabolic level, tumor tissues often display a lower pH than normal tissues. In addition, the endocytosis pathway is accompanied by continuous pumping of protons. Therefore, the variation of environmental pH values could serve as an ideal stimulus for precise drug delivery and release. In recent years, pH-responsive materials (e.g., polymers, biomacromolecules, lipid nanoparticles, biofilm, inorganic nanoparticles, and metal-organic frameworks) have been widely investigated in the field of cancer immunotherapy. This paper summarizes recent strategies of pH-responsive drug delivery systems based on different types of carriers, aiming to provide some reference for the design of next generation of tumor-targeting formulations in cancer immunotherapy.

Objective To investigate the impact of body mass index (BMI) on short-term and long-term prognosis in the patients with ST-segment elevation myocardial infarction (STEMI).Methods The clinical data of inpatients with STEMI in our hospital during 2014 were retrospectively collected.The patients conforming to the inclusion and exclusion criteria were divided into 4 groups according to BMI,low BMI group (n=31),normal BMI group (n=139),overweight group (n=71) and obesity group(n=26).The clinical baseline data were analyzed and compared among 4 groups,and the all-cause mortality on 7 d and within 1 year after myocardial infarction(MI) was followed up.Results The higher the BMI increased,the younger the patient's onset age (P＜0.01),the smaller the female proportion(P=0.001),among them,the albumin and hemoglobin levels in the obesity group were relatively higher(P=0.004;P =0.006);the all-cause mortality at 1 year after MI was significantly decreased with BMI increasing (P =0.003),while which on 7 d after MI had no statistical difference (P=0.287).Conclusion BMI is correlated with the long-term prognosis in the patients with STEMI,and "obesity contradiction" phenomenon exists in the patients with STEMI.However,the influence of BMI on the prognosis in the patients with STEMI should be comprehensively evaluated by combining with the multiple factors such as the patient's age,sex,complications and medication therapy.

Objective:To evaluate the effect of three teaching methods of case-based learning (CBL), problem-based learning (PBL) and blended learning (CBL+PBL) on the teaching of clinical clerkship of cardiovascular internal medicine among medical students.Methods:A total of 175 third-year medical students were divided into three groups (CBL, PBL and CBL+PBL). They entered the clinical clerkship in batches, and then received written examination and questionnaire survey after the teaching. The data were processed by SPSS 19.0 and were compared by one-way ANOVA or chi-square test (R × C) among groups.Results:The total average scores of students in CBL, PBL and CBL+PBL groups were 15.34±2.88, 14.67±2.98 and 17.13±2.82, respectively ( P<0.05), and the proportion of students with "excellent" scores were 27.4%(17/62), 14.5%(9/62) and 58.1%(36/162), respectively. Most students in CBL group did not agree that CBL helped to train literature access skills [70.7%(41/58)] or teamwork ability [82.8%(48/58)], compared with which 70.9%(39/55) in PBL group thought it helped to train literature access skills but only 7.3%(4/55) well accepted PBL. In addition, majority of students in CBL+PBL group believed it was helpful to gain learning interest [64.3%(36/56)] and train team cooperation ability [62.5%(35/56)], and [53.6%(30/56)] favored this teaching method. Conclusion:Compared with traditional CBL, PBL fails to attract students or improve teaching performance; while blended learning is benefited for the students and can improve teaching quality.

Objective To summarize the clinicopathological characteristics and prognostic factors of salivary duct carcinoma(SDC)patients.Methods This study was reviewed and approved by the Ethics Committee,and informed consent was obtained from the patients.The clinical data of 30 SDC patients who were admitted to the Fourth Hospital of Hebei Medical University from 2014 to 2022,including case records,pathological diagnoses,immunohistochemical indicators,treatment methods,follow-up data,and other data,were retrospectively analyzed.SPSS 26.0 software was used to process the data and construct relevant curves.The chi-square test was used to analyze the correlation between different immunohistochemical indices and the recurrence and metastasis of SDC,and a single factor was used to ana-lyze clinical prognostic factors.Results Among the 30 SDC patients,the male-to-female ratio was 5∶1,with a median age of 61.5 years.Approximately 60％of cases occurred in the parotid gland,whereas the remainder occurred in the submaxillary gland,sublingual gland,or minor salivary gland.Among them,19 patients were androgen receptor-positive,23 patients were human epidermal growth factor receptor-2 positive,and 26 patients were Ki-67 positive.Postoperative follow-up was 18-94 months,with a median follow-up of 37 months.There were 13 cases of recurrence and 14 cases of distant metastasis.The 5-year overall survival rate was only 31.2％.The long-term survival of patients who underwent postoperative radiotherapy and chemoradiotherapy was better than that of patients who underwent surgery alone(P=0.027).T stage and lymph node invasion were associated with prognosis and survival(P＜0.05).There was a correlation between a Ki-67-positive cell count ≥ 40％and postoperative recurrence or metastasis(P=0.025).Conclusion Radi-cal surgery combined with postoperative radiotherapy and chemoradiotherapy is helpful for improving long-term overall survival,and tumor T stage and lymph node metastasis may be the main factors affecting the prognosis of patients with SDC.Patients with Ki-67-positive cell counts ≥ 40％are prone to postoperative recurrence or metastasis.