Background: The function of CD69 expressed on T cells in chronic hepatitis B (CHB) remains unclear. We aimed to elucidate the roles of CD69 on T cells in the disease process and in antiviral therapy for CHB. Methods: We enrolled 335 treatment-naive patients with CHB and 93 patients with CHB on antiviral therapy. CD69, antiviral cytokine production by T cells, T-helper (Th) cells, and inhibitory molecules of T cells were measured using flow cytometry, and clinical-virological characteristics were examined dynamically during antiviral therapy. Results: CD69 expression on CD3+, CD4+, and CD8+ T cells was the lowest in the immune-active phase and was negatively correlated with liver transaminase activity, fibrosis features, inflammatory cytokine production by T cells, and Th-cell frequencies but positively with inhibitory molecules on T cells. CD69 expression on CD3+, CD4+, and CD8+ T cells decreased after 48 weeks of antiviral therapy, and patients with hepatitis B e antigen (HBeAg) seroconversion in week 48 showed lower CD69 expression on T cells at baseline and week 48. The area under the ROC curve of CD69 expression on T cells at baseline for predicting HBeAg seroconversion in week 48 was 0.870, the sensitivity was 0.909, and the specificity was 0.714 (P = 0.002). Conclusions CD69 negatively regulates T-cell immunity during CHB, and its expression decreases with antiviral therapy. CD69 expression predicts HBeAg seroconversion in week 48. CD69 may play an important negative role in regulating T cells and affect the efficacy of antiviral therapy.

OBJECTIVE To prepare meloxicam solid dispersions tablets, and to investigate their dissolution in vitro. METHODS Crystal inhibition experiments were carried out to screen the carrier materials, and the solid dispersion was characterized by X-ray diffraction(XRD) amd differential scanning calorimeter(DCS). The improved bioavailability of solid dispersions was evaluated through in vivo pharmacokinetic studies. The optimum preparation process of meloxicam solid dispersion tablets was investigated, and the in vitro dissolution curve similarity factor f2 was used as the main evaluation index to screen and optimize the dosage of pH regulator, filler, disintegrator, lubricant, flow aid and the mixing time in the prescription. RESULTS The solid dispersion prepared with Kollidon@VA64 as carrier effectively maintained the supersaturated state of the drug in solution. The results of XRD and DSC showed that the crystal state of meloxicam in the solid dispersion was completely transformed into amorphous state. Compared with meloxicam, solid dispersions significantly increased the solubility, and its peak blood concentration(Cmax) and relative bioavailability were increased by 208.09% and 241.78%, respectively. The optimal formulation and process of meloxicam solid dispersion tablets prepared by direct powder pressing method were meloxicam solid dispersion 35.2%, lactose∶microcrystalline cellulose =1∶1.5, sodium citrate 9.8%, crosslinked povidone 8%, magnesium stearate 0.75%, silica 0.8%, and mixing time 5 min. The dissolution similarity factor f2 of the prepared meloxicam solid dispersion tablets and the original reference preparation in different pH medium was above 50. CONCLUSION Meloxicam solid dispersible tablets are prepared by hot melt extrusion and powder pressing method. The dissolution and bioavailability of meloxicam are improved, and the dissolution behavior of meloxicam is similar to that of the original reference preparation.

Background and aims:Hepatocellular carcinoma(HCC),which is prevalent worldwide and has a high mortality rate,needs to be effectively diagnosed.We aimed to evaluate the significance of plasma microRNA-15a/16-1(miR-15a/16)as a biomarker of hepatitis B virus-related HCC(HBV-HCC)using the machine learning model.This study was the first large-scale investigation of these two miRNAs in HCC plasma samples. Methods:Using quantitative polymerase chain reaction,we measured the plasma miR-15a/16 levels in a total of 766 participants,including 74 healthy controls,335 with chronic hepatitis B(CHB),47 with compensated liver cirrhosis,and 310 with HBV-HCC.The diagnostic performance of miR-15a/16 was examined using a machine learning model and compared with that of alpha-fetoprotein(AFP).Lastly,to validate the diagnostic efficiency of miR-15a/16,we performed pseudotemporal sorting of the samples to simulate progression from CHB to HCC. Results:Plasma miR-15a/16 was significantly decreased in HCC than in all control groups(P＜0.05 for all).In the training cohort,the area under the receiver operating characteristic curve(AUC),sensitivity,and average precision(AP)for the detection of HCC were higher for miR-15a(AUC=0.80,67.3％,AP=0.80)and miR-16(AUC=0.83,79.0％,AP=0.83)than for AFP(AUC=0.74,61.7％,AP=0.72).Combining miR-15a/16 with AFP increased the AUC to 0.86(sensitivity 85.9％)and the AP to 0.85 and was significantly superior to the other markers in this study(P＜0.05 for all),as further demonstrated by the detection error tradeoff curves.Moreover,miR-15a/16 impressively showed potent diagnostic power in early-stage,small-tumor,and AFP-negative HCC.A validation cohort confirmed these results.Lastly,the simulated follow-up of patients further validated the diagnostic efficiency of miR-15a/16. Conclusions:We developed and validated a plasma miR-15a/16-based machine learning model,which exhibited better diagnostic performance for the early diagnosis of HCC compared to that of AFP.

Objective With the complex evolution of the social system,patients experience varying degrees of delay in obtaining medical and health services under the combined drive of internal and external environment.In order to alleviate the dilemma of seeking medical treatment in crisis situations,it analyzes the causes of the public's use behavior of Internet medical and health services after delayed medical treatment and the ways to improve it.Methods It employs the method of QCA analysis to explore the crisis management strategies adopted by 183 public.Based on Anderson medical treatment model as the theoretical guidance,conditional variables were constructed.Through deductive logic,it analyzes the complex linkage effect of seven variables,including accessibility level,traumatic life events,panic mood and satisfaction with Internet medical use,on the use of Internet medical services.Results it found that panic has a decisive role in promoting the public's use of Internet medical services.Five behavioural models of Internet medical use are proposed to reveal the potential driving mechanism of the public's adoption of Internet medical strategies.Conclusion By analyzing the synergistic effects between variables,it proposes comprehensive strategies,providing a new perspective for public health emergency management,and offering empirical evidence for policymakers to optimize smart medical services.

Adipose progenitor cells(APCs) represent a prominent stromal cellular component of adipose tissue and are now identified as highly heterogenous populations. However, the role of APCs in regulating systemic metabolism remains unknown. Using single cell RNA-sequencing, we investigated the role of the APC subpopulations in regulating development of type 2 diabetes. CD9 + CD55 low APCs are the novel subset identified in this study, which is significantly increased in type 2 diabetic patients. Transplantation of these cells from type 2 diabetic patients into adipose tissue caused glycemic disturbance in mice. Depletion of pathogenic APCs improved obesity-related glycemic disturbance. Collectively, our data provide deeper insights into human APC functionality and highlights APCs as a potential therapeutic target to combat type 2 diabetes. This study has been published in Nature Communications, 2024, 15(1): 4827.

Objective With the complex evolution of the social system,patients experience varying degrees of delay in obtaining medical and health services under the combined drive of internal and external environment.In order to alleviate the dilemma of seeking medical treatment in crisis situations,it analyzes the causes of the public's use behavior of Internet medical and health services after delayed medical treatment and the ways to improve it.Methods It employs the method of QCA analysis to explore the crisis management strategies adopted by 183 public.Based on Anderson medical treatment model as the theoretical guidance,conditional variables were constructed.Through deductive logic,it analyzes the complex linkage effect of seven variables,including accessibility level,traumatic life events,panic mood and satisfaction with Internet medical use,on the use of Internet medical services.Results it found that panic has a decisive role in promoting the public's use of Internet medical services.Five behavioural models of Internet medical use are proposed to reveal the potential driving mechanism of the public's adoption of Internet medical strategies.Conclusion By analyzing the synergistic effects between variables,it proposes comprehensive strategies,providing a new perspective for public health emergency management,and offering empirical evidence for policymakers to optimize smart medical services.

Objective:To explore the correlation of the expression of lymphocyte immunoglobulin-mucin domain 3 (Tim-3) on T lymphocytes and natural killer (NK) cells with hepatic inflammation and hepatic fibrosis in patients with chronic hepatitis B virus (HBV) infection.Methods:A total of 320 patients of chronic HBV infection who visited the Infectious Diseases Department in the Third Affiliated Hospital of Sun Yat-sen University from June 2016 to June 2018 were enrolled. The patients were divided into four groups: immune tolerant group (IT, n=31), immune active group (IA, n=184), inactive carriers group (IC, n=48), and gray zone group (GZ, n=57). And 17 healthy controls (HC group) were included at the same time. Peripheral blood mononuclear cells were separated and the frequency and mean fluorescence intensity (MFI) of Tim-3 on T cells (CD3 + , CD4 + and CD8 + T cells) and NK cells (NK, NK-bright and NK-dim cells) were detected by flow cytometry. The clinical data of patients were collected and aspartate aminotransferase-to-platelet ratio index (APRI) score was calculated. Kruskal-Wallis H test was used for comparing the data of non-normal distribution among groups, and Mann Whitney U test was used for the comparison between two groups. Enumeration data were expressed as cases (percentage) and compared by the Chi-square test. Spearman rank correlation was used for correlation analysis. Receiver operating characteristic curve (ROC) was used to analyze the predictive value of Tim-3 expression on T cells and NK cells in evaluating liver fibrosis in patients with chronic HBV infection. P<0.05 was considered statistically significant. Results:Significant differences were found in the age, aspartate aminotransferase (AST), alanine aminotransferase(ALT), albumin (Alb), total bilirubin (TBil) and liver stiffness measurement (LSM) among IT, IA, IC, GZ and HC groups ( H=12.40, 169.70, 210.70, 25.17, 24.21 and 86.5, all P<0.05). And the differences in APRI score, proportion of HBeAg-positive patients, HBsAg and HBV-DNA among the IT group, IA group, IC group, GZ group were also significant ( H=89.45, 118.00 and 14.81, χ2=148.20, all P<0.05). The frequency and MFI of Tim-3 on CD3 + , CD4 + and CD8 + T cells, NK cells, NK-bright and NK-dim cells among the IT group, IA group, IC group, GZ group and the HC group were significantly different( H=13.57, 51.55, 8.58, 44.25, 20.32, 47.96 and 12.45, 33.69, 4.96, 32.47, 10.63, 30.46, all P<0.05). Both of the frequency and MFI of Tim-3 on CD3 + , CD4 + and CD8 + T cells were positively correlated with ALT and AST levels in patients with chronic HBV infection ( r=0.2134, 0.4733, 0.2090, 0.4333, 0.1771, 0.4417, 0.1780, 0.3956, 0.2618, 0.4671, 0.2614 and 0.4326, all P<0.05). While the frequency and MFI of Tim-3 on CD8 + T cells and MFI on CD3 + and CD4 + T cells were also positively correlated with TBil levels ( r=0.1342, 0.2635, 0.2739 and 0.2526, all P< 0.05). The frequency and MFI of Tim-3 on NK and NK-dim cells were negatively correlated with the levels of ALT, AST and TBil ( r=-0.2671, -0.4093, -0.2451, -0.4099, -0.1807, -0.1823, -0.2733, -0.4224, -0.2576, -0.4206, -0.1798 and -0.1946, all P<0.05). The MFI of Tim-3 on NK-bright cells was also negatively correlated with ALT, AST and TBil ( r=-0.3775, -0.3562 and -0.1633, all P<0.05). Both of the frequency and MFI of Tim-3 on CD3 + , CD4 + and CD8 + T cells were positively correlated with liver fibrosis( r=0.1789, 0.3896, 0.1518, 0.3521, 0.2117 and 0.3579, all P<0.05). Both of the frequency and MFI of Tim-3 on CD4 + and CD8 + T cells and the MFI of Tim-3 on CD3 + T cells were positively correlated with APRI score ( r=0.1487, 0.2604, 0.2296, 0.4858 and 0.2853, all P<0.05). The expression frequency and MFI of Tim-3 on NK and NK-dim cells and MFI of Tim-3 on NK-bright cells were negatively correlated with LSM ( r=-0.2686, -0.3975, -0.2852, -0.3991 and -0.3531, all P<0.05). The expression frequency and MFI of Tim-3 on NK and NK-dim cells and MFI of Tim-3 on NK-bright were negatively correlated with APRI score ( r=-0.3589, -0.4158, -0.3591, -0.4108 and -0.3966, all P<0.05). The ratio of Tim-3 expression on CD3 + T cells to that on NK cells was shown to be able to predict liver fibrosis in chronic HBV infected patients and the area under the ROC curve was 0.783 (95% CI: 0.723~0.843, P< 0.05), and when the cut-off value was 0.612, the sensitivity was 61.9%, and the specificity was 99.3%. Conclusion:The relationship of Tim-3 expression on T cells with liver inflammation and fibrosis is opposite to that on NK cells in patients with chronic HBV infection, indicating that the ratio of Tim-3 expression on T cells to that on NK cells may be valuable in evaluating liver fibrosis in patients.

Objective:To investigate the inhibitory effects of nucleolar and spindle associated protein 1 (NUSAP1) on lung cancer and the related mechanisms.Methods:A549 cells were transfected with NUSAP1 siRNA, the cell proliferation, migration and invasion, and apoptosis were detected by CCK8, Transwell and flow cytometry, respectively. Western blot was used to detect the expressions of apoptosis and AKT/mTOR signal pathway related proteins.Results:Compared with the negative control group, the proliferation [(0.610±0.058) vs (1.724±0.067), P<0.05], migration [(178.267±14.780) vs (272.464±36.232), P<0.05] and invasion [(73.527±6.617) vs (120.585±13.235), P<0.05] of NUSAP1 deleted A549 cells were significantly inhibited, while the apoptosis [(3.572±0.214)% vs (11.358±1.047)%, P<0.05] was significantly increased. The expressions of apoptosis related protein Bax and active-caspase 3 were increased ( P<0.05), while the expressions of anti-apoptosis protein Bcl-2 and proliferation related protein P70, the phosphorylation levels of AKT and mTOR were reduced in NUSAP1 knockdown cells ( P<0.05). Conclusion:NUSAP1 knockdown can inhibit the proliferation, migration and invasion, and promote the apoptosis of tumor cells through suppressing AKT/mTOR signaling pathway in lung cancer cells.

Objective:To investigate the inhibitory effects of nucleolar and spindle associated protein 1 (NUSAP1) on lung cancer and the related mechanisms.Methods:A549 cells were transfected with NUSAP1 siRNA, the cell proliferation, migration and invasion, and apoptosis were detected by CCK8, Transwell and flow cytometry, respectively. Western blot was used to detect the expressions of apoptosis and AKT/mTOR signal pathway related proteins.Results:Compared with the negative control group, the proliferation [(0.610±0.058) vs (1.724±0.067), P<0.05], migration [(178.267±14.780) vs (272.464±36.232), P<0.05] and invasion [(73.527±6.617) vs (120.585±13.235), P<0.05] of NUSAP1 deleted A549 cells were significantly inhibited, while the apoptosis [(3.572±0.214)% vs (11.358±1.047)%, P<0.05] was significantly increased. The expressions of apoptosis related protein Bax and active-caspase 3 were increased ( P<0.05), while the expressions of anti-apoptosis protein Bcl-2 and proliferation related protein P70, the phosphorylation levels of AKT and mTOR were reduced in NUSAP1 knockdown cells ( P<0.05). Conclusion:NUSAP1 knockdown can inhibit the proliferation, migration and invasion, and promote the apoptosis of tumor cells through suppressing AKT/mTOR signaling pathway in lung cancer cells.

Objective To explore the psychological projection on improving the quality of marriage of patients with breast cancer after chemotherapy. Methods From January to December 2015, a total of 32 breast cancer patients with postoperative chemotherapy who admitted to Department of General Surgery Huai'nan North Hospital and Huai'nan Eastern Hospital were selected as the research object. Olson marital quality questionnaire was issued when patients firstly receiving chemotherapy in hospital, at the same time they were evaluated by the Rorschach Inkblot Test. In view of the negative projection in the patient's test, the intervention was carried out by painting projective therapy, sand plate therapy, deep hypnosis and cognitive behavioral therapy. The marital quality of patients were investigated again at 1 month after discharge or the second time receiving chemotherapy. The scores of Olson marital quality questionnaire were compared before and after the intervention. Results Before the intervention of psychological projection, the score of marital satisfaction, husband and wife communication and sexual life dimension in the Olson quality of marriage questionnaire were (33.3±5.6), (30.9±5.5) and (28.2±4.2) respectively. The scores of each dimension after intervention were (36.1±4.6), (34.2±4.3), and (30.7±5.3) respectively. They were all improved in the Olson marital quality questionnaire, and the differences were statistically significant (t=2.19, 2.67,2.09; P<0.05). Conclusions The intervention of psychological projection can relieve the physical and psychological trauma caused by breast cancer in patients with postoperative chemotherapy of breast cancer and improve the quality of marriage.