In managing metabolic dysfunction-associated steatotic liver disease, which affects over 30% of the general population, effective noninvasive biomarkers for assessing disease severity, monitoring disease progression, predicting the development of liver-related complications, and assessing treatment response are crucial. The advantage of simple fibrosis scores lies in their widespread accessibility through routinely performed blood tests and extensive validation in different clinical settings. They have shown reasonable accuracy in diagnosing advanced fibrosis and good performance in excluding the majority of patients with a low risk of liver-related complications. Among patients with elevated serum fibrosis scores, a more specific fibrosis and imaging biomarker has proved useful to accurately identify patients at risk of liver-related complications. Among specific fibrosis blood biomarkers, enhanced liver fibrosis is the most widely utilized and has been approved in the United States as a prognostic biomarker. For imaging biomarkers, the availability of vibration-controlled transient elastography has been largely improved over the past years, enabling the use of liver stiffness measurement (LSM) for accurate assessment of significant and advanced fibrosis, and cirrhosis. Combining LSM with other routinely available blood tests enhances the ability to diagnose at-risk metabolic dysfunction-associated steatohepatitis and predict liver-related complications, some reaching an accuracy comparable to that of liver biopsy. Magnetic resonance imaging-based modalities provide the most accurate quantification of liver fibrosis, though the current utilization is limited to research settings. Expanding their future use in clinical practice depends on factors such as cost and facility availability.

In managing metabolic dysfunction-associated steatotic liver disease, which affects over 30% of the general population, effective noninvasive biomarkers for assessing disease severity, monitoring disease progression, predicting the development of liver-related complications, and assessing treatment response are crucial. The advantage of simple fibrosis scores lies in their widespread accessibility through routinely performed blood tests and extensive validation in different clinical settings. They have shown reasonable accuracy in diagnosing advanced fibrosis and good performance in excluding the majority of patients with a low risk of liver-related complications. Among patients with elevated serum fibrosis scores, a more specific fibrosis and imaging biomarker has proved useful to accurately identify patients at risk of liver-related complications. Among specific fibrosis blood biomarkers, enhanced liver fibrosis is the most widely utilized and has been approved in the United States as a prognostic biomarker. For imaging biomarkers, the availability of vibration-controlled transient elastography has been largely improved over the past years, enabling the use of liver stiffness measurement (LSM) for accurate assessment of significant and advanced fibrosis, and cirrhosis. Combining LSM with other routinely available blood tests enhances the ability to diagnose at-risk metabolic dysfunction-associated steatohepatitis and predict liver-related complications, some reaching an accuracy comparable to that of liver biopsy. Magnetic resonance imaging-based modalities provide the most accurate quantification of liver fibrosis, though the current utilization is limited to research settings. Expanding their future use in clinical practice depends on factors such as cost and facility availability.

In managing metabolic dysfunction-associated steatotic liver disease, which affects over 30% of the general population, effective noninvasive biomarkers for assessing disease severity, monitoring disease progression, predicting the development of liver-related complications, and assessing treatment response are crucial. The advantage of simple fibrosis scores lies in their widespread accessibility through routinely performed blood tests and extensive validation in different clinical settings. They have shown reasonable accuracy in diagnosing advanced fibrosis and good performance in excluding the majority of patients with a low risk of liver-related complications. Among patients with elevated serum fibrosis scores, a more specific fibrosis and imaging biomarker has proved useful to accurately identify patients at risk of liver-related complications. Among specific fibrosis blood biomarkers, enhanced liver fibrosis is the most widely utilized and has been approved in the United States as a prognostic biomarker. For imaging biomarkers, the availability of vibration-controlled transient elastography has been largely improved over the past years, enabling the use of liver stiffness measurement (LSM) for accurate assessment of significant and advanced fibrosis, and cirrhosis. Combining LSM with other routinely available blood tests enhances the ability to diagnose at-risk metabolic dysfunction-associated steatohepatitis and predict liver-related complications, some reaching an accuracy comparable to that of liver biopsy. Magnetic resonance imaging-based modalities provide the most accurate quantification of liver fibrosis, though the current utilization is limited to research settings. Expanding their future use in clinical practice depends on factors such as cost and facility availability.

Objective To study the role of sphingosine-1-phosphate(S1P)signal on the proliferation of breast cancer BT549 cells.Methods Cells were divided into control group and experimental group,experimental group were treated with 0.1,1.0,10.0 μmol·L-1 S1P receptor agonist SEW2871 for 72 h.Control group was cultured with 0.1％fetal bovine serum.Cell proliferation was detected by methyl thiazolyl tetrazolium(MTT)assay.Cell models of overexpressing S1P receptors in BT549 were divided into three groups:blank plasmid group(LUC),wild type S1P receptor overexpression group(WT),S1P receptor phosphorylation site mutation overexpression group(MUT);the proliferation ratio was detected by MTT,the number of cell clones was counted by colony formation experiment.S1P antagonist W146(10 μmol·L-1)and protein kinase(AKT)signaling inhibitor MK2206(90 nmol·L-1)were used to detect the role of S1P signaling in the proliferation of breast cancer cells.The expression of phosphorylate signal transducer and activator of transcription 3(p-STAT3),c-Myc proteins were detected by Western blot.Results The growth ratio of BT549 cells in control group and 0.1,1.0,10.0 μmol·L-1experimental groups were 1.00±0.03,1.13±0.06,1.06±0.10 and 1.07±0.03,0.1 μmol·L-1 SEW2871 promot the cell proliferation(P＜0.05).Compared between WT group,MUT group and LUC group,the growth rate and the number of clonal colonies were increased after overexpression of S1P receptor(all P＜0.05).The growth ratio of BT549 cells after treatment with W146 and MK2206 in the LUC group,WT group and MUT group were 1.25±0.12,1.31±0.03,1.43±0.14 and 0.87±0.15,0.77±0.03,0.88±0.02.Compared between MUT group,WT group and corresponding DMSO group,the differences were statistically significant(all P＜0.01).The number of cell clony formation number after treatment with W146 were 65.65±5.12,141.48±5.63 and 93.64±5.14;compared between MUT,WT group and corresponding DMSO group,the differences were statistically significant(all P＜0.05).The relative protein expression levels of p-STAT3 in LUC group,WT group and MUT group were 0.67±0.04,0.69±0.08 and 0.81±0.06,the relative protein expression levels of proto-oncogene c-Myc were 1.69±0.03,0.70±0.10 and 0.67±0.07,compared between WT group,MUT group and corresponding DMSO group,the difference was statistically significant(P＜0.05).Conclusion S1P signaling can promote proliferation in breast cancer BT549 cells,and the mechanism could be related to AKT and STAT3 signaling pathway.

Objective To observe the effect and safety of clindamycin phosphate gel combined with photodynamic therapy in the treatment of acne rosacea.Methods Patients with acne rosacea were divided into treatment group and control group by random number table method.The control group was treated with external application of clindamycin phosphate gel twice a day for 4 weeks.The treatment group was given 5-aminolevulinic acid photodynamic therapy on this basis,once a week for 4 weeks.The clinical efficacy of the two groups was evaluated.The erythema,papulopustule,demodex folliculorum and quality of life[dermatology life quality index(DLQI)]of the two groups were compared after 2 weeks and 4 weeks of treatment.The recurrence status was followed up and the safety of the treatment regimen was evaluated.Results There were 70 cases in treatment group and 70 cases in control group.The total clinical effective rate after 4 weeks of treatment in treatment group was 87.14％,which was higher than 72.86％in control group(P＜0.05).After 2 weeks of treatment,the erythema scores in treatment group and control group were(2.14±0.57)and(2.63±0.52)points;the papulopustule scores were(2.28±0.46)and(2.56±0.49)points;the total counts of demodex folliculorum of(2 mm ×2 mm)were 10.12±3.55 and 11.74±4.31;DLQI scores were(11.27±2.49)and(12.57±2.28)points.After 4 weeks of treatment,the erythema scores in treatment group and control group were(1.16±0.32)and(1.59±0.38)points;the papulopustule scores were(0.92±0.27)and(1.37±0.41)points;the total counts of demodex folliculorum of(2 mm ×2 mm)were 6.08±2.39 and 8.69±2.47;and the DLQI scores were(5.09±1.22)and(6.88±2.16)points,all with significant difference(all P＜0.05).During treatment,there was no statistical significance in the incidence of adverse drug reactions between treatment group and control group(28.57％vs 18.57％,P＞0.05).Follow-up to 3 months after the end of treatment,the recurrence rates in treatment group and control group were 4.29％and 14.29％,with statistical difference(P＜0.05).Conclusion Clindamycin phosphate gel combined with photodynamic therapy has an exact efficacy in the treatment of acne rosacea,and it has obvious advantages in relieving symptoms,improving demodex folliculorum infection and enhancing quality of life of patients,and it does not increase the incidence of adverse drug reactions.

Objective:To explore the association of hemoglobin(HGB) levels with bone mineral density(BMD) and osteoporosis in patients with type 2 diabetes mellitus(T2DM).Methods:A cross-sectional study was conducted in 364 patients with T2DM who were hospitalized in the Department of Endocrinology and Geriatrics of the Affiliated Huaian No. 1 People′s Hospital of Nanjing Medical University from September 2019 to September 2020. Participants were stratified into tertiles(lower, middle, and upper) according to femoral BMD determined by dual-energy X-ray absorptiometry. Demographic characteristics, medical history, chronic diabetes complications, and comorbid conditions were compared among the 3 groups. The association between hemoglobin levels and BMD/osteoporosis was examined using multivariable logistic regression analyses. Interaction and stratified analyses were conducted according to age, body mass index(BMI), duration of diabetes, estimated glomerular filtration rate(eGFR), glycosylated hemoglobin(HbA 1C), total cholesterol(TC), triglycerides(TG), high-density lipoprotein-cholesterol(HDL-C), low-density lipoprotein-cholesterol(LDL-C) and uric acid(UA). Results:After adjusting for age, BMI, and duration of diabetes, there were no significant differences observed in the association between hemoglobin levels and BMD or osteoporosis among postmenopausal women with T2DM(all P>0.05). After adjusting for age, BMI, duration of diabetes, and eGFR, men aged≥50 years with hemoglobin≥130 g/L showed a positive association between hemoglobin level and femoral neck BMD compared to those with hemoglobin<130 g/L( β=0.057, 95% CI 0.014-0.100, P=0.011). However, no significant associations were observed between hemoglobin level and BMDs at the total hip or lumbar spine(L1-L4), nor the risk of osteoporosis(all P>0.05). Stratified analyses revealed no significant differences in the subgroups classified based on age, BMI, diabetes duration, eGFR, HbA 1C, TC, TG, HDL-C, LDL-C, and UA(all interaction P>0.05). Conclusion:In males aged 50 and above with T2DM, elevated hemoglobin levels may be a protective factor for femoral neck bone density.

Objective To investigate the effects of astragaloside Ⅳ(AS-Ⅳ)on axon growth inhibitory factor A(Nogo-A)and its downstream pathway protein RHO-associated coiled spiral kinase 2(ROCK2)in experimental autoimmune encephalomyelitis(EAE)mice,and to explore the mechanism by which it promotes axon repair and regeneration.Methods EAE model was induced in C57BL/6 female mice by subcutaneous injection of myelin oligodendrocyte glycoprotein 35-55(MOG35-55).Mice were randomly divided into EAE group and AS-Ⅳ group(n=8 per group).EAE group received intraperitoneal injection of PBS on the 3rd day post-immunization,while AS-Ⅳ group was administered AS-Ⅳ at a dosage of 30mg/(kg.d)once daily,0.2 ml per injection,for 25 consecutive days.On the 28th day post-immunization,the expression levels of growth-associated protein 43(GAP-43),neuronal core antigen(NeuN),microtubule associated protein 2(MAP-2),glial fibroacidic protein(GFAP),and Iba1 in the spinal cord were detected using immunofluorescence assay.Real-time fluorescence quantitative PCR(qRT-PCR)was conducted to detect mRNA expression levels of GAP-43,Nogo-A,and Nogo receptor(NgR)genes.Western blotting was utilized to determine the expression levels of GAP-43,Nogo-A,ROCK2,phosphorylated myosin phosphatase(p-MYPT1),B-lymphoblastoma-2(Bcl-2),and Bcl-2 associated X protein(Bax).Results Compared with EAE group,AS-Ⅳ treatment significantly reduced the positive cell expression rates of Iba1 microglia and GFAP astrocyte in spinal cord(P<0.01 and P<0.001,respectively),while it also increased the positive expression rates of NeuN and MAP-2(P<0.001 and P<0.05,respectively).The treatment also upregulated the expression level of anti-apoptotic factor Bcl-2(P<0.001)and downregulated the expression level of pro-apoptotic factor Bax(P<0.05),leading to an increase in Bcl-2/Bax ratio(P<0.05).Furthermore,AS-Ⅳ enhanced the expression of GAP-43 protein(P<0.05)and decreased the mRNA expression levels of neuroregeneration inhibitor Nogo receptor(NgR)and ROCK2 gene(P<0.001,P<0.05,respectively);as well as decreased the expression levels of Nogo-A,ROCK2 and p-MYPT1 proteins(P<0.05,P<0.001).Conclusion AS-Ⅳ may inhibit the activation of microglia and astrocytes and neuronal apoptosis in EAE mice by inhibiting Nogo-A and downstream pathway ROCK 2,thereby promoting the expression of GAP-43,NeuN and MAP-2,alleviating neuronal damage,and facilitating axon repair and regeneration.