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.

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.

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: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.

Objective To analyze the characteristics of genotyping and gene polymorphism of Neisseria gonorrhoeae(N.go) with azithromycin(AZM)-resistance(AZM-R) and decreased susceptibility to ceftriaxone(CROD).Methods The minimum inhibitory concentration(MIC) of AZM and CRO were determined.AZM-R isolates were detected for mutations in 23S rRNA,mtrR and penA genes.Genotypes were analyzed by using N.go multi-antigen sequence typing(NG-MAST).Results All total of 485 isolates of N.go were detected.77(15.9%) strains were AZM-R(MIC≥1 mg/L),including 33(6.8%) isolates of AZM low-level resistant(AZM-LLR,MIC=1 mg/L) strains and 44(9.1%) isolates of AZM middle-level resistant(AZM-MLR,MIC≥2 mg/L) strains.There were more CROD(MIC≥0.125 mg/L) strains in AZM-MLR isolates(43.2%),compared with those in AZM-LLR isolates(18.2%,P<0.05).The detected rates of 23S rRNA,mtrR,penA single or combined mutations were without significant differences between AZM-LLR isolates and AZM-MLR isolates(P>0.05).Similar results were found between combined AZM-LLR/CROD isolates and combined AZM-MLR/CROD isolates(P>0.05).No mutation of A2059G and AZM high-level resistant(AZM-HLR,MIC≥256 mg/L) isolate were found.Among 77 AZM-R isolates,67 sequence types(ST) were identified by NG-MAST,of which 30 types were novel.Most ST were represented by a single isolate.Conclusion AZM-R and CROD isolates,presented in this area,might be deserved continuous surveillance to identify the mechanism of concurrent resistance.

Objective To investigate the expression of syntaxin 8(STX8)in glioma and its clinical signif-icance. Methods Specimens of glioma were collected from 57 patients at Beijing Renhe Hospital from May 2013 to December 2015. 57 pieces of glioma tissue were used as a study group ,12 of which were Ⅰ+ Ⅱ(low grade) and the rest 45 were Ⅲ+Ⅳ;normal brain tissues from 15 individuals were used as a control group. Real-time PCR,immunohistochemistry,and Western blot were used to detect expression of STX8. Results As compared with the normal brain tissue ,the mRNA expression of STX8 was significantly increased in glioma tissue ,with a relative expression volume of 1.6855 ± 0.07124 in low grade and 2.8207 ± 0.0692 in high grade tissues,there was significant differences between the two groups;and the difference was also significant as compared with the control group(P < 0.05). The results of immunohistochemistry showed that the expression of STX8 was higher in glioma tissue than in normal tissue. Western Blot showed that the expression of STX8 protein was significantly higher in glioma than in normal tissue(P<0.05);the relative expression volume of STX8 was 2.271 ± 0.1621 in low grade tissue and 4.937 ± 0.1851 in high grade tissue,with a significant difference between the two groups;the difference was also significant as compared with the control group(P<0.05). The correlation analysis showed that higher STX8 expression in glioma was not significantly related to gender,age and pathological types,but there was a significant difference between pathological stages. Conclusion STX8 has abnormal high expression in glioma,which may be closely related with the occurrence and development of glioma.

Objective To compare the safety,efficacy and complications of laparoscopic pyelolithotomy (LPL) and percutaneous nephrolithotomy (PCNL) for treatment of renal pelvic stones larger than 2.5 cm.Methods From 2011 to 2016,32 patients underwent LPL and another 32 patients received PCNL for renal pelvic stones larger than 2.5 cm.The baseline characteristics of the patients,stone size,mean operative time,estimated blood loss,postoperative hospital stay,stone-free rate,postoperative analgesia,blood transfusion,and the intraoperative,early postoperative and long-term complications were compared between the two groups.Results The baseline characteristics and stone size were comparable between the two groups.The mean operative time of LPL and PCNL was 117±23.12 and 118.16±25.45 min,respectively (P＞0.05).The two groups showed significant differences in the mean estimated blood loss (63±11.25 vs 122±27.78 mL,P＜0.01) and blood transfusion rate (0 vs 6.2％,P＜0.01) but not in postoperative hospital stay (4.5±1.34 vs 4.8±2.2 days,P＞0.05),stone-free rate (93.1％ vs 87.5％,P＞0.05) or the postoperative analgesia time (1.7± 0.5 and 1.9 ± 0.6 days,P＞0.05).The incidence of intraoperative complications were significant lower in LPL group than in PCNL group (6.2％ vs 25.0％,P＜0.01),but the incidences of early postoperative complications (25.0％ vs 34.4％,P＞0.05) and long-term postoperative complications (9.4％ vs 12.5％,P＞0.05) were sinilar between them.Conclusion PCNL is the standard treatment for pelvic stones larger than 2.5 cm,but for urologists experienced with laparoscopic technique,LPL provides a feasible and safe option for management of such cases.