Tuberculosis, a global infectious disease caused by Mycobacterium tuberculosis infection, ranks among the top ten causes of human death. The BCG vaccine is currently the only tuberculosis vaccine in clinical use, but its effectiveness in protecting adults from tuberculosis remains uncertain. In recent years, protein subunit vaccines have garnered significant attention due to their well-defined composition, high safety profile, and ability to enhance the BCG vaccine′s effects. However, the protein antigens in subunit tuberculosis vaccines typically elicit weak immune responses, necessitating the use of adjuvants to boost their immunogenicity. This review focuses on exploring various types of adjuvants utilized in novel tuberculosis vaccine formulations, ranging from those undergoing clinical trials to those still in preclinical development. The review provides an objective assessment of the advantages, disadvantages, and suitability of different adjuvants, while also highlighting current challenges in adjuvant research and proposing future research directions.

Objective To investigate the effect of Yinchenhao decoction on renal oxidative stress injury in rats with obstructive jaundice and its association with the regulation of the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear translocation. Methods A total of 32 male Sprague-Dawley rats were randomly divided into sham-operation group (S group), model group (O group), low-dose Yinchenhao decoction group (LY group), and high-dose Yinchenhao decoction group (HY group), with 8 rats in each group. For the rats in the S group, the upper common bile duct was isolated without ligation, and for those in the other groups, double ligation of the middle and upper 1/3 of the common bile duct was performed to establish a model of obstructive jaundice. After 7 days, the rats in the LY group and the HY group were given Yinchenhao decoction by gavage at a dose of 6.3 and 18.9 mL/kg, respectively, while those in the S and O groups were given an equal volume of distilled water by gavage every day for 7 consecutive days, and the rats were treated on day 14. ELISA was used to measure the serum levels of total bilirubin (TBil), direct bilirubin (DBil), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), blood urea nitrogen (BUN), and creatinine (Cr); spectrophotometry was used to measure the activity of the oxidative stress factors superoxide dismutase (SOD) and malondialdehyde (MDA) in renal tissue; quantitative real- time PCR and Western blotting were used to measure the mRNA and protein expression levels of Nrf2, Kelch-like ECH-associated protein 1 (Keap1), and NAD(P)H quinone dehydrogenase 1 (NQO1) in renal tissue; immunohistochemistry was used to measure observe the nuclear translocation of Nrf2 protein in renal tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t -test was used for further pairwise comparison within groups. Results Compared with the S group, the O group had significant increases in the levels of TBil, DBil, ALT、GGT, BUN, and Cr, a significant reduction in the activity of SOD, and a significant increase in the level of MDA (all P < 0.05). Compared with the O group, the LY group and the HY group had significant reductions in liver and renal function parameters, a significant increase in the activity of SOD, and a significant reduction in the level of MDA (all P < 0.05). Compared with the S group, the O group had significant reductions in the mRNA and protein expression levels of Nrf2 and NQO1 in renal tissue (all P < 0.05), and compared with the O group, the LY group and the HY group had significant increases in the mRNA and protein expression levels of Nrf2 and NQO1 (all P < 0.05), while there was no significant difference in the protein expression level of Keap1 between groups ( P > 0.05). Compared with the S group, the O group had a significant reduction in the positive rate of Nrf2 in cell nucleus in renal tissue ( P < 0.05), and compared with the O group, the LY group and the HY group had a significant increase in the positive rate of Nrf2 in cell nucleus ( P < 0.05). Conclusion Yinchenhao decoction can effectively alleviate renal injury caused by obstructive jaundice, possibly by upregulating the protein expression of Nrf2 in renal tissue and regulating the nuclear translocation of Nrf2 protein, so as to mediate the protein expression of downstream NQO1, regulate oxidative stress response caused by obstructive jaundice, and thereby alleviate renal injury in rats.

Tuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis. At present, the situation of tuberculosis control in China and even the world is severe. Bacillus Calmette-Guerin (BCG) vaccine is the only approved vaccine for tuberculosis, but its protective effect is limited. Hence, it is imperative to develop more effective tuberculosis vaccines. Currently, many new tuberculosis vaccine candidates are in clinical or preclinical trials. In this paper, to provide reference for the development of tuberculosis vaccines in China, the status of the research on vaccine candidates were reviewed and the progress in new tuberculosis vaccine strategies were summarized.

Objective:To explore the prevalence and risk factors of thyroid nodules in physical examination population.Method:A total of 5934 Han people who underwent physical examination in the physical examination center of the Affiliated Hospital of Hubei University of Arts and Sciences from August 2016 to August 2019 were selected as the research objects. Retrospective research methods were used to divide them into thyroid nodule group and thyroid non nodule group according to the results of thyroid ultrasound examination, and statistical analysis was carried out in combination with relevant data. T-test was used for the comparison between measurement data groups that conform to the normal distribution and χ 2 test was used for the comparison between counting data groups. Binary Logistic regression was used to analyze the relationship between different factors and thyroid nodules, and the odds ratio ( OR) and 95% confidence interval (95% CI) were calculated. Results:(1) The prevalence of thyroid nodules in all population is 28.1% (1 668/5 934), the prevalence of thyroid nodule is 23.1% (977/4 230) in men and 40.6% (691/1 704) in women separately, and the distribution is obviously higher in women than that in male (χ 2=183.13, P=0.008). The prevalence increased with aging in both sexes ( P=0.001). (2) The correlation between the clinical data of physical examination population and thyroid nodules was analyzed according to gender. Among male patients, the rates of BMI≥23.0 kg/m 2 (82.2% (803/977)), diabetes (14.7% (144/977)), hypertension (44.4% (434/977)) and smoking history (63.1% (616/977)) in thyriod nodule group were higher than those in the non thyroid nodule group (78.9% (2 565/3 253), 8% (260/3 253), 29.3% (952/3 253), 56.9% (1 851/3 253)) (χ 2 were 5.17, 39.59, 78.35 and 11.80, respectively; P values were 0.023, 0.009, 0.005 and 0.007, respectively). Among female patients, the rates of BMI ≥23.0 kg/m 2 (55% (380/691)), obesity (31.1% (215/691)), diabetes (6.2% (43/691)), hypertension (28.9% (200/691)), high total cholesterol (43.6% (301/691)), low high-density lipoprotein cholesterol (7.1% (49/691)), high triglycerides (28.4% (196/691)), and high low-density lipoprotein cholesterol (29.1% (201/691)) in thyroid nodule group were higher than those in the non thyroid nodule group (43.6% (442/1 013), 22.5% (228/1 013), 1.9% (19/1 013), 19.2% (195/1 013), 34.7% (352/1 013), 17.9% (181/1 013), 21.5% (218/1 013), 4.5% (46/1 013)), and the differences were statistically significant (χ 2 were 21.23, 15.82, 22.14, 21.68, 13.51, 26.27, 12.69 and 5.08, respectively; P values were 0.007, 0.006, 0.009, 0.007, 0.008, 0.005, 0.005 and 0.024, respectively). (3) Multiple logistic regression analysis reveal that age ( OR=1.530, 95% CI:1.463-1.621, P=0.009), sex ( OR=3.580, 95% CI:2.931-4.381, P=0.005), smoking ( OR=1.360, 95% CI:1.161-1.592, P=0.007) and high blood pressure ( OR=1.290, 95% CI:1.121-1.482, P=0.006) were the risk factors of thyroid nodule. Conclusion:The prevalence of thyroid nodules is 28.1% in XiangYang and surrounding areas, and the elders, women, smoking and high blood pressure were the risk factors of thyroid nodule.

Objective:To explore the application value of artificial intelligence-assisted diagnosis model based on convolutional neural network (CNN) in the differential diagnosis of benign and malignant breast masses.Methods:A total of 10 490 images of 2 098 patients with breast lumps (including 1 132 cases of benign tumor, 779 cases of malignant tumor, 32 cases of inflammation, 155 cases of adenosis) were collected from January 2016 to January 2018 in Beijing Tiantan Hospital Affiliated to the Capital University of Medical Sciences. They were divided into training set and test set and the auxiliary artificial intelligence diagnosis model was used for training and testing. Two sets of data training models were compared by two-dimensional imaging (2D) and two-dimensional and color Doppler flow imaging (2D-CDFI). The ROC curves of benign breast tumors, malignant tumors, inflammation and adenopathy were analyzed, and the area under the ROC curve (AUC) were calculated.Results:The accuracies of 2D-CDFI ultrasonic model for training group and testing group were significantly improved. ①For benign tumors, the result from training set with 2D image was: sensitivity 92%, specificity 95%, AUC 0.93; the result from training set with 2D-CDFI images was: sensitivity 93%, specificity 95%, AUC 0.93; the result for test set with 2D images was: sensitivity 91%, specificity 96%, AUC 0.94; the result for test set with 2D-CDFI images was: sensitivity 93%, specificity: 94%, AUC 0.94. ② For malignancies, the result for training set with 2D images was: sensitivity 93%, specificity 97%, AUC 0.94; the result for training set with 2D-CDFI images was: sensitivity 93%, specificity 96%, AUC 0.94; the result for test set with 2D images was: sensitivity 93%, specificity 96%, AUC 0.94; the result for test set with 2D-CDFI images was: sensitivity 93%, specificity 96%, AUC 0.94. ③For inflammation, the result for training set with 2D images was: sensitivity 81%, specificity 99%, AUC 0.91; the result for training set with 2D-CDFI images was: sensitivity 86%, specificity 99%, AUC 0.89; the result for test set with 2D images was: sensitivity 100%, specificity 98%, AUC 0.98; the result for test set with 2D-CDFI images was: sensitivity 100%, specificity 99%, AUC 0.96. ④For adenopathy, the result for training set with 2D images was: sensitivity 88%, specificity 97%, AUC 0.94; the result for training set with 2D-CDFI images was: sensitivity 93%, specificity 98%, AUC 0.94; the result for test set with 2D images was: sensitivity 94%, specificity 98%, AUC 0.93; the result for test set with 2D-CDFI images was: sensitivity 88%, specificity 99%, AUC 0.90. Its diastolic accuracy was not affected even if the maximum diameter of the tumor was less than 1 cm.Conclusions:Through the deep learning of artificial intelligence based on CNN for breast masses, it can be more finely classified and the diagnosis rate can be improved. It has potential guiding value for the treatment of breast cancer patients.

Objective: To investigate the prevalence of metabolic syndrome in adults in Shanghai Chongming area and to analyze the relationship between metabolic syndrome and chronic kidney disease. Methods: A total of 7 679 residents aged 30 years and over in Chongming District of Shanghai were randomly sampled and investigated by questionnaires, physical examinations, and laboratory examinations. The metabolic syndrome was diagnosed by the diagnostic criteria of metabolic syndrome according to the Chinese Guidelines for the Prevention and Treatment of Type 2 Diabetes in 2017. According to the criteria of the International Society of Nephrology Working Group on Improving the Overall Prognosis of Kidney Diseases, estimated glomerular filration rate (eGFR)<60 ml·min^-1·(1.73 m²)^-1 was diagnosed as chronic kidney disease. Results: The prevalence of metabolic syndrome was 38.61% in the total population. The prevalence of metabolic syndrome was 47.06% in males and 34.71% in females. Urinary albumin-creatinine ratio (ACR), eGFR, age, smoking, waist circumference, blood glucose, blood pressure, high density lipoprotein-cholesterol and triglyceride in metabolic syndrome group were significantly higher than those in non- metabolic syndrome group. With the increase of metabolic components, eGFR decreased, and ACR increased. According to logistic regression analysis, age, male, hyperglycemia, hypertension, hypertriglyceride were risk factors for eGFR. Male, hypertension, hyperglycemia, hypertriglyceride, central obesity, smoking history, lower education level were risk factors for ACR. Conclusion The number of metabolic components is related to renal damage. Male, hypertension, hyperglycemia, hypertriglyceride are risk factors for early renal damage.

Objective To investigate the optimal HbA1Cthreshold to be used for the diagnosis of diabetes mellitus in Chongming rural area,and further to evaluate the optimal HbA1Ccutoff values in different age stratifications and body mass index classifications.Methods Data from 9,981 individuals aged greater than 40 years who participated in a population-based cross-sectional survey in Shanghai,China,were analyzed.A 2 h 75 g oral glucose tolerance test(OGTT)value was used to diagnose diabetes.The performance of HbA1Cwas evaluated against the results of the OGTTs by using receiver operating characteristic(ROC)curve analysis.Results At the optimal HbA1C cutoff point of 6.15%for newly diagnosed diabetes, sensitivity was 69.73%, and specificity was 89.71%.The optimal HbA1Ccutoff points for diabetes were 6.05%in subject with age less than 60 years(sensitivity was 72.88%, and specificity was 90.25%),and 6.25%in subjects with age≥60 years(sensitivity was 70.89%,and specificity was 92.34%).The optimal HbA1Ccutoff points for diabetes were 6.05% in normal-weight(with sensitivity 70.94%,and specificity 89.93%),6.25%in overweight(with sensitivity 70.21%,and specificity 90.32%), and 6.35% in obese population(with sensitivity 72.33%, and specificity 92.75%).Conclusion An HbA1C threshold of 6.15%was highly specific for detecting undiagnosed diabetes.The HbA1Cdiagnosis cutoff point can be affected by age and overweight/obesity status.

Objective To explore the effects of immunoglobulin G on tumor necrosis factor (TNF-α) secretion of human peripheral blood mononuclear cells(PBMCs) in type 2 diabetes mellitus complicated with Alzheimer's disease(AD). Methods A total of 20 cases were chosen in each group from patients with type 2 diabetes mellitus complicated with Alzheimer' s disease and patients with type 2 diabetes mellitusm.PBMCs were isolated using density gradient centrifugation method and incu-bated with phytohemagglutinin (PHA) as well as immunoglobulin G extracted from blood serum of the patients with type 2 diabe-tes mellitus.TNF-α concentration in supernatant was measured by enzyme linked immunosorbent assay (ELISA). Results TNF-α concentration in supernatant of PBMCs was significantly increased in type 2 diabetes mellitus complicated with AD com-pared with that in type 2 diabetes mellitus (P<0.01).IgG further increased TNF-α concentration in type 2 diabetes mellitus and type 2 diabetes mellitus complicated with AD(P<0.01). Conclusion IgG extracted from the serum of type 2 diabetes mellitus patients can promote TNF-α secretion in PBMCs of type 2 diabetes mellitus complicated with AD.Immunity injury could play a role in the development of type 2 diabetes mellitus complicated with AD by promoting inflammatory reaction.

OBJECTIVETo investigate the role of glycogen synthase kinase 3β (GSK-3β) in the maturation and function of murine bone marrow-derived dendritic cells (BMDCs).

METHODSMature DCs (mDCs) induced by LPS were examined for GSK-3β phosphorylation level with Western blotting before and after LPS exposure. To explore the role of GSK-3β in maturation and function of DCs, we added SB216763, a selective inhibitor of GSK-3β, in the cell culture of immature DCs (iDCs), and examined CD40 and CD86 expressions in the cells by flow cytometry and the expression of IL-6, IL-12 and IL-10 mRNA by real-time PCR; the changes of the immunogenicity of the cells was evaluated by mixed lymphocyte reaction. The expression of GSK-3β and RelB was examined by Western blotting in DC2.4 cells transfected with a lentiviral vector over-expressing murine GSK-3β gene.

RESULTSLPS exposure significantly lowered GSK-3β activity in iDCs as demonstrated by increased Ser9 phosphorylation and reduced Tyr216 phosphorylation. GSK-3β inhibition induced DC maturation by increasing the expression of surface costimulatory molecules CD40 and CD86, lowered the expressions of IL-6 and IL-12 while enhanced the expression of IL-10 in iDCs, and impaired mixed lymphocyte reaction of the cells. In DC2.4 cells, lentivirus-mediated over-expression of GSK-3β obviously down-regulated the expression of RelB.

CONCLUSIONSGSK-3β is a crucial enzyme involved in the differentiation and maintenance of an immature phenotype of DCs. GSK-3β is constitutively active in iDCs to inhibit their spontaneous maturation. DCs become phenotypically mature after inhibition of GSK-3β, which also executes a proinflammatory task in DC activation. The reduction of RelB protein levels as a result of GSK-3β overexpression supports GSK-3β as a new target for inducing tolerogenic DCs.

Animals ; B7-2 Antigen ; metabolism ; CD40 Antigens ; metabolism ; Cell Differentiation ; Cells, Cultured ; Culture Media ; chemistry ; Dendritic Cells ; enzymology ; Glycogen Synthase Kinase 3 ; metabolism ; Glycogen Synthase Kinase 3 beta ; Indoles ; chemistry ; Interleukin-10 ; metabolism ; Interleukin-12 ; metabolism ; Interleukin-6 ; metabolism ; Lentivirus ; Lymphocyte Culture Test, Mixed ; Maleimides ; chemistry ; Mice ; Myeloid Cells ; enzymology ; Phosphorylation ; RNA, Messenger ; Real-Time Polymerase Chain Reaction ; Signal Transduction

Objective To investigate the role of glycogen synthase kinase 3β(GSK-3β) in the maturation and function of murine bone marrow-derived dendritic cells (BMDCs). Methods Mature DCs (mDCs) induced by LPS were examined for GSK-3βphosphorylation level with Western blotting before and after LPS exposure. To explore the role of GSK-3βin maturation and function of DCs, we added SB216763, a selective inhibitor of GSK-3β, in the cell culture of immature DCs (iDCs), and examined CD40 and CD86 expressions in the cells by flow cytometry and the expression of IL-6, IL-12 and IL-10 mRNA by real-time PCR;the changes of the immunogenicity of the cells was evaluated by mixed lymphocyte reaction. The expression of GSK-3βand RelB was examined by Western blotting in DC2.4 cells transfected with a lentiviral vector over-expressing murine GSK-3βgene. Results LPS exposure significantly lowered GSK-3βactivity in iDCs as demonstrated by increased Ser9 phosphorylation and reduced Tyr216 phosphorylation. GSK-3β inhibition induced DC maturation by increasing the expression of surface costimulatory molecules CD40 and CD86, lowered the expressions of IL-6 and IL-12 while enhanced the expression of IL-10 in iDCs, and impaired mixed lymphocyte reaction of the cells. In DC2.4 cells, lentivirus-mediated over-expression of GSK-3βobviously down-regulated the expression of RelB. Conclusion GSK-3βis a crucial enzyme involved in the differentiation and maintenance of an immature phenotype of DCs. GSK-3β is constitutively active in iDCs to inhibit their spontaneous maturation. DCs become phenotypically mature after inhibition of GSK-3β, which also executes a proinflammatory task in DC activation. The reduction of RelB protein levels as a result of GSK-3β overexpression supports GSK-3β as a new target for inducing tolerogenic DCs.