The clinical antiprotozoal drug nitazoxanide has been demonstrated to improve the experimental diabetes mellitus, lipid metabolism disorders, atherosclerosis and inhibit inflammation. Since the pathogenesis of heart failure with preserved ejection (HFpEF) is multifactorial and closely associated with the aforementioned diseases, we aim to study the effect of nitazoxanide on high-fat diet (HFD) plus L-NAME (N ω-nitro-l-arginine methyl ester)-induced HFpEF and metabolic syndrome in mice. We found that oral nitazoxanide improved cardiac hypertrophy, cardiac fibrosis, cardiac diastolic dysfunction, increased blood pressure, impaired exercise tolerance, impaired glucose handling, serum lipid disorders, hepatic steatosis, increased weight of white adipose tissues and kidney fibrosis in HFD + L-NAME-treated mice. In the established HFD + L-NAME-induced HFpEF and metabolic syndrome mouse model, therapeutic treatment with nitazoxanide rescued HFD + L-NAME-induced pathological phenotypes as mentioned above. The in vitro experiments revealed that tizoxanide, the active metabolite of nitazoxanide, increased the basal mitochondria metabolism of cardiomyocytes, inhibited cardiomyocyte hypertrophy and collagen secretion from cardiac fibroblasts, and relaxed phenylephrine- and U46619-induced constriction of rat mesenteric arteries, indicating that the direct effect of tizoxanide might partly contribute to the protective effect of nitazoxanide against HFpEF in vivo. The present study suggests that nitazoxanide might be a potential drug for HFpEF and metabolic syndrome therapy.

Objective:To explore the clinicopathologic features differences between tall cell variant of papillary thyroid cancer (TCV-PTC) and PTC with tall cell features (PTC-TCF) and the factors influencing efficacy of 131I therapy in patients with TCV-PTC and PTC-TCF. Methods:A retrospective analysis was conducted on 84 patients (28 males, 56 females, age 43.5(35.0, 55.0) years) with pathologically confirmed TCV-PTC or PTC-TCF and who were treated with 131I therapy from January 2018 to June 2023 in the Department of Nuclear Medicine, the Affiliated Hospital of Qingdao University. The patients were divided into structural incomplete response (SIR) group and non-SIR group according to 131I treatment response. Data differences were analyzed by Wilcoxon rank sum test, Fisher exact test, or Mann-Whitney U test. Variables with P<0.1 were enrolled in logistic multivariate regression analysis. The ROC curve was used to obtain the cut-off value of stimulated thyroglobulin (sTg). Results:A total of 37 patients with non-SIR and 6 patients with SIR were found in TCV-PTC group ( n=43), and 33 non-SIR and 8 SIR cases were found in PTC-TCF group ( n=41). Univariate analysis revealed that sTg differed significantly between non-SIR patients and SIR patients in TCV-PTC group ( Z=-2.81, P=0.003), while no significant differences observed for sex, age, multifocality, capsular invasion, T stage, N stage, B-Raf proto-oncogene, serine/threonine-protein kinase (BRAF) V600E mutation, initial recurrence risk, number of metastatic lymph nodes, maximum tumor diameter ( Z values: from -0.74 to -0.11, all P>0.05). In TCV-PTC group, sTg also differed significantly between non-SIR patients and SIR patients ( Z=-4.40, P<0.001), while the other clinical factors above and the proportion of tall cells showed no significant difference ( Z values: from -1.90 to -0.22, all P>0.05). The logistic regression analysis confirmed sTg as an independent risk factor of SIR in both TCV-PTC group (odds ratio ( OR) = 25.156, 95% CI: 2.245-281.812, P=0.009) and PTC-TCF group ( OR=19.214, 95% CI: 2.537-145.502, P=0.004). The ROC curve indicated that the cut-off value of sTg for predicting SIR was 20.75μg/L in TCV-PTC group and 18.55μg/L in PTC-TCF group. Conclusions:sTg is the independent risk factor for predicting the poor prognosis of patients with TCV-PTC (sTg≥20.75μg/L) and PTC-TCF (sTg≥18.55μg/L). However, other clinical characteristics show no statistical difference between TCV-PTC group and PTC-TCF group, suggesting that the invasiveness of PTC-TCF may not be lower than that of TCV-PTC, which close attention should be paid to in clinical practice.

Objective:To investigate the effects of Xuebijing injection on gut microbiota and intestinal mechanical barrier in mice with lipopolysaccharide (LPS)-induced sepsis, and analyze the potential mechanism by which Xuebijing injection protects gastrointestinal tract.Methods:Twenty-four healthy and clean grade male C57BL/6N mice were divided into four groups, control group, LPS group, LPS+ 5 μl/g Xuebijing injection group (5 μl/g Xuebijing injection group), and LPS+ 10 μl/g Xuebijing injection group (10 μl/g Xuebijing injection group), with six mice in each group. A mouse model of sepsis was established by intraperitoneal injection of mice with 10 μg/g LPS. At 0 and 12 h after successful modeling, the mice were intraperitoneally injected with 5 or 10 μl/g Xuebijing injection. Blood, ileum, and colon fecal samples were collected 12 h after the second administration. ELISA was used to detect the levels of diamine oxidase (DAO), D-blood lactic acid (D-Lac), TNF-α, and IL-6. HE staining was used to observe the local ileum damage, and Chiu′s score was used to evaluate the degree of intestinal tissue damage. Immunohistochemical staining and Western blot were used to detect the expression of Claudin-1, Occludin, and zona occludins-1(ZO-1) in ileum tissues, followed by semi quantitative analysis. One-way analysis of variance was used for intergroup comparisons, and LSD or Tamhane′s T2 test was used for pairwise comparisons based on the homogeneity of variance. The diversity and species composition of mouse fecal microbiota, and the differences among groups were analyzed using 16S rRNA sequencing.Results:The levels of DAO, D-Lac, TNF-α, and IL-6 in the LPS group were higher than those in the control group (all P<0.000 1). After the intervention with Xuebijing injection, the levels of DAO, D-Lac, TNF-α, and IL-6 decreased (all P<0.05) and showed no significant differences with those in the control group (all P>0.05). Besides, 10 μl/g Xuebijing injection was more effective than 5 μl/g Xuebijing injection in reducing the concentrations (all P<0.05). Chiu′s score was higher in the LPS group than in the control group and the 10 μl/g Xuebijing injection group (both P<0.05). Western blot showed that the expression levels of Occludin, Claudin-1, and ZO-1 in the LPS group were lower than those in the control group (all P<0.01), and Xuebijing injection intervention significantly increased the expression levels of these proteins in a dose-dependent manner as compared with the LPS group (all P<0.000 1). Apart from the expression level of ZO-1, which showed no significant difference between the two Xuebijing injection groups ( P>0.05), the results of immunohistochemical staining were consistent with those of Western blot. The 16S rRNA sequencing results showed that there were differences in the Alpha and Beta diversity indices, and the composition and structure of gut microbiota among the four groups. The structure of gut microbiota in the mice treated with Xuebijing injection was similar to that in the mice of the control group and it was in a dose-dependent manner. Wilcoxon rank sum test showed that there were statistically significant differences in six gut microbiota groups at the phylum level, and 32 gut microbiota groups at the genus level among the mice of four groups (all P<0.05). Conclusions:Xuebijing injection can provide protective effects on the gastrointestinal tract by protecting the structure of gut microbiota and intestinal barrier function, and the protective effect is somewhat correlated with the drug dosage.

ObjectiveTo analyze the distribution, drug resistance characteristics, and changing trends of Acinetobacter baumannii (AB) isolated from environmental surfaces and healthcare workers’ hands in a grade Ⅱ level A general hospital in Xuhui District of Shanghai from 2018 to 2023, and to provide reference for infection control in the hospital. MethodsEnvironmental samples were collected quarterly from critical surfaces and healthcare workers’ hands in the intensive care unit (ICU), geriatrics, and respiratory departments from 2018 to 2023. Clinical isolates were obtained from all patients with AB infections in ICU, geriatrics, respiratory department, rehabilitation department, infectious diseases department, emergency department, cardiology department, and orthopedics of the hospital from 2018 to 2023. Retrospective analyses were performed on AB detection rates, strain origins, resistance rates to commonly used antimicrobial agents, and resistance gene features, comparing the antimicrobial resistance between clinically isolated strains and environmentally isolated strains. ResultsFrom 2018 to 2023, a total of 1 416 samples were collected from the hospital and a total of 272 strains of AB were detected, with a positive detection rate of 19.21%. The detection rate gradually decreased year-on-year (χ²_trend=45.290, P<0.001). The majority of samples originated from patient-contacted items (34.56%, 94/272), followed by shared items (26.84%, 73/272) and healthcare worker-contacted items (15.07%, 41/272). From 2018 to 2023, the resistance rate of AB on environmental surfaces and healthcare workers’ hands to commonly tested antibiotics in the hospital ranged from 10% to 40%. The resistance rates to cefotaxime (42.52%) and piperacillin (38.58%) were relative high, while the resistance to polymyxin E (1.57%), polymyxin B (2.36%), and doxycycline (3.94%) maintained low. The annual fluctuations in resistance to cefotaxime, piperacillin, ceftriaxone, tobramycin, doxycycline, minocycline and cotrimoxazole were statistically significant (all P<0.05). There were statistically significant differences in the resistance of clinical and environmental isolates to ampicillin/sulbactam, cefepime, ceftazidime, subamphetamine, meropenem, piperacillin, aztreonam, gentamicin, tobramycin, minocycline, ciprofloxacin, levofloxacin, and cotrimoxazole in the hospital from 2018 to 2023 (all P<0.05). The resistance rate of clinical isolates was generally high, especially to β-lactam and quinolone drugs, which were mostly above 80% [such as cefepime (93.86%), cefotaxime (97.37%), imipenem (98.25%), and ciprofloxacin (99.12%)]. The resistance rate of environmental isolated strains to similar antibiotics was relatively lower, mostly concentrated at 10%‒30%. The whole-genome sequencing of 34 carbapenem-resistant Acinetobacter baumannii (CRAB) strains isolated from the hospital environment in 2023 revealed that the main resistance mechanism was overexpression of efflux pumps (51.97%), followed by changes in target sites (32.46%). Among the 34 CRAB strains, carbapenem resistance genes OXA-23 and OXA-51 were detected in 6 strains (17.65%), while genes such as KPC, IMP, VIM, and SIM were not detected. ConclusionFrom 2018 to 2023, AB in the hospital environment exhibited high resistance rates to certain antimicrobial agents and carried multiple resistance genes, indicating a potential transmission risk. It is necessary to further strengthen bacterial resistance monitoring and hospital infection control, and use antibiotics reasonably.

Vacuum compression molding (VCM) is a novel technology supporting the research and development of pharmaceutical solid dispersions. It is widely applied due to its precision and convenience in sample preparation. This technology integrates the principles of heating, melting, cooling, and vacuum compression to transform solid powders into shaped solids directly. By selecting different molds, temperatures, and pressures, researchers can prepare samples with diverse characteristics. This paper presents an overview of the equipment composition and working principles of VCM technology, demonstrating its distinct advantages in the formulation screening process of amorphous solid dispersions through comparative analysis with hot melt extrusion using case studies, and introduces its applications in the development of drug delivery systems and rheological characterization analysis, with a perspective on the future development of its functions.

Objective:To investigate the expression of chondroitin sulfate proteoglycan 4 pseudogene 12(CSPG4P12)in the small cell lung cancer(SCLC)tissue,its relationship with immune infiltration,and its effect on cell biological functions,and to clarify its effect in the occurrence and development of SCLC.Methods:The E-GEOD-60052 cohort was obtained by searching the ArrayExpress database for SCLC.The R language Bioconductor package was used to complete data filtering standardization,and 63 samples of SCLC tumor tissues and 7 samples of normal tissues were obtained.The Mann-Whitney U test was used to analyze the difference in CSPG4P12 expression levels between two groups.Pearson correlation analysis was used to evaluate the associations between CSPG4P12 expression levels and 47 immune checkpoint genes.The ESTIMATE algorithm and CIBERSORT algorithm were used to evaluate the correlations between CSPG4P12 expression and tumor immune cell infiltration.A case-control study was used to analyze the clinical data.A total of 230 patients with SCLC were selected as case group,and 230 healthy subjects were selected as control group.The genotyping of CSPG4P12 rs2880765,rs6496932 and rs8040855 was performed using TaqMan-MGB fluorescent probe labeling method.Odds ratio(OR)and 95％confidence interval(CI)were calculated by unconditional Logistic regression model to analyze the association between polymorphic genetic variation of CSPG4P12 gene and the risk of SCLC.The SCLC DMS114 cells were transfected with pUC-57 plasmid(control group)and CSPG4P12 over-expression plasmid(OV-CSPG4P12 group),respectively.The efficiencies of CSPG4P12 over-expression in two groups were verified by real-time fluorescence quantitative PCR(RT-qPCR)method.Cell counting kit-8(CCK-8)method was used to detect the cell proliferation activities of cells in two groups.Transwell chamber assay was used to detect the numbers of migration and invasion cells in two groups,respectively.Hoechst 33342 fluorescence staining was used to observe the cell apoptosis in two groups.Results:The ArrayExpress database E-GEOD-60052 cohort analysis showed that the expression level of CSPG4P12 mRNA in SCLC tissue was decreased compared with normal tissue(P＜0.001).The expression of CSPG4P12 had positive correlations with the immune checkpoint genes including leukocyte associated immunoglobulin like receptor 1(LAIR1)(r=0.47,P＜0.001),tumor necrosis factor(TNF)receptor superfamily member 9(TNFRSF9)(r=0.38,P＜0.01),and TNF superfamily member 9(TNFSF9)(r=0.44,P＜0.001).The ESTIMATE algorithm results showed that the matrix score,immune score and ESTIMATE composite score of the patients in CSPG4P12 low expression group were lower than those in CSPG4P12 high expression group(P＜0.01).The CIBERSORT algorithm results showed that compared with CSPG4P12 high expression group,the infiltration of M0 macrophages in CSPG4P12 low expression group was increased(P＜0.05)and the infiltration of mast cells resting was decreased(P＜0.05).The CSPG4P12 expression level had positive correlations with infiltration of mast cells resting(r=0.35,P=0.03)and mononuclear cell infiltration(r=0.34,P=0.034).In case-control studies,compared with AA genotype,CSPG4P12 rs2880765 AT and TT genotype carriers had a higher risk of SCLC(OR=1.68,95％CI=1.15-2.45,P＜0.01).The stratified analysis showed that genetic variation of rs2880765 A＞T increased the risk of SCLC in the male,younger age group(≤60 years)and smoking subgroups(males:OR=1.86,95％CI=1.18-2.93,P＜0.01;≤60 years:OR=1.73,95％CI=1.11-2.68,P＜0.01;smoking:OR=2.76,95％CI=1.49-5.13,P=0.001).The cell biology experiment showed that compared with control group,the proliferation abilities of the cells in OV-CSPG4P12 group were significantly decreased at 48 and 72 h(P＜0.01),while the number of migration cells at 24 h was significantly decreased(P＜0.01),the number of apoptotic cells at 24 h was increased(P＜0.05)and the number of invasion cells at 48 h was significantly decreased(P＜0.01).Conclusion:CSPG4P12 is lowly expressed in SCLC tumor tissue,which is associated with immune infiltration.The genetic variation of CSPG4P12 rs2880765 A＞T can increase the risk of SCLC,and its over-expression can inhibit cell proliferation,migration and invasion,and promote apoptosis.

Objective:To investigate the effects of the expanded lateral thoracic artery perforator flap in the reconstruction of breast scar contracture deformity after burns in minor females.Methods:The study was a retrospective observational study. From July 2018 to October 2023, 8 female children aged 4 to 12 years and with breast scar contracture deformity after burns, who met the inclusion criteria, were admitted to the Department of Burns and Plastic Surgery of Guangzhou Red Cross Hospital of Jinan University. The skin and soft tissue expander (hereinafter referred to as expander) was placed in the first stage. The contracture scar was removed and released in the second stage, and the wound formed after the scar was removed measured between 9 cm×8 cm and 15 cm×10 cm. The expanded lateral thoracic artery perforator flap was designed and transferred to repair the wound with resected flap area of 10 cm×9 cm to 16 cm×11 cm, and the wound at the flap donor area was directly sutured. The complications such as incision infection, hematoma, and expander exposure were observed after stage Ⅰ surgery. After stage Ⅱ surgery, the survival of the flap and the wound healing at the flap donor area were observed. During the 1-year follow-up after the stage Ⅱ surgery, the breast development was evaluated according to tanner staging performance of female pubertal breast development, the aesthetic effect of the affected breast was evaluated by using the aesthetic effect evaluation standard after breast surgery, the Vancouver scar scale (VSS) was used to score the scar condition at the flap donor and recipient areas, and the satisfaction of the children's families with the surgical outcomes was investigated by using a self-made scale.Results:After stage Ⅰ surgery, no incision infection, hematoma, expander exposure, or other complications occurred in 8 children. After stage Ⅱ surgery, only one child had tissue necrosis at the distal end of the flap with a size of about 2 cm×1 cm, which healed after dressing change, and the flap in other children had good blood supply, soft texture, moderate thickness, and similar color to the skin at the recipient area. The wounds at all flap donor areas healed well. During the 1-year follow-up after stage Ⅱ surgery, 7 children had normal breast development, with their breast volume, height, and shape being almost the same as or similar to the healthy side, with the aesthetic effect of all being grade Ⅰ; the breast in one child had not yet developed, and these indicators were not evaluated. The locations of nipple areola complex in 8 children were almost the same as or similar to those in the healthy side, and their skin color, integrity, texture, and elasticity of the partial breast repaired by the transferred flap were similar to those in the healthy side, with the aesthetic effect of all being grade Ⅰ. The shapes of nipple and areola in 5 children were inconsistent with those in the healthy side because of the original scar, with the aesthetic effect of all being grade Ⅱ, and the shapes of nipple and areola in the other 3 children were consistent with those in the healthy side, with the aesthetic effect of all being grade Ⅰ. The VSS score of the scar at the flap recipient area was 2-5, and the VSS score of the scar at the flap donor area was 1-3. Seven children's families were satisfied with the surgical effect, and one child's family was basically satisfied with the surgical effect.Conclusions:For the breast scar contracture deformity of minor females after burns, the expanded lateral thoracic artery perforator flap is used for reconstruction before puberty, which results in fewer postoperative complications, good breast shape, and hidden scar at the flap donor area. It is beneficial for the normal development of adolescent breasts, and is one of the safe and effective methods for the treatment of breast scar contracture deformity in minor females after burns.

AIM:To observe the effects of Huazhuo granules on phosphatidylinositol 3-kinase(PI3K)/protein kinase B(PKB/Akt)/glycogen synthase kinase-3β(GSK-3β)and PI3K/Akt/forkhead box protein O1(FOXO1)signaling pathways in the liver tissue of type 2 diabetes mellitus(T2DM)rats,and to explore its mechanism of action in regulating glycogen synthesis and gluconeogenesis.METHODS:Thirty 8-week-old SPF-grade male SD rats were chosen,with 5 ran-domly selected ones as the blank control group.The remaining 25 rats were fed to a high-sugar and high-fat diet for 4 weeks,followed by a single intraperitoneal injection of streptozotocin to establish a T2DM rat model.After successful mod-eling,these rats were randomly divided into 5 additional groups:the model group,a positive control group treated with met-formin,and low,medium,and high-dose Huazhuo granule groups,resulting in a total of 6 groups with 5 rats in each.Rats in the treatment groups were gavaged with the corresponding doses of medication,while those in the blank control and model groups were gavaged with an equal volume of saline once daily for 4 consecutive weeks.After 24-hour fasting with free access to water,the rats were euthanized to measure blood glucose,serum insulin levels,and serum triglyceride(TG),total cholesterol(T-CHO),high-density lipoprotein cholesterol(HDL-C),aspartate aminotransferase(AST)and alanine aminotransferase(ALT)levels.Liver pathological morphology was assessed by hematoxylin-eosin staining,and liver glycogen storage was detected by periodic acid-Schiff staining.Immunohistochemistry and Western blot analysis were employed to detect the protein levels of p-PI3K,p-Akt,p-FOXO1 and p-GSK-3β in the liver of rats in each group.The mRNA levels of phosphoenolpyruvate carboxykinase(PEPCK),glucose-6-phosphatase(G6Pase),GSK-3β,FOXO1,PI3K and Akt in liver tissues were detected by RT-qPCR.RESULTS:Compared with the model group,the rats in the high-dose Huazhuo Granule group and the metformin group exhibited decreased blood glucose and insulin levels(P<0.01),reduced AST,ALT,TG,and T-CHO concentrations(P<0.01),and increased HDL-C concentrations(P<0.01).The phosphorylation levels of PI3K,Akt,FOXO1,and GSK-3β proteins were up-regulated(P<0.01).In con-trast,the gene expressions of G6Pase,PERCK,FOXO1,and GSK-3β were all down-regulated(P<0.01).Conversely,the gene expressions of PI3K and Akt were upregulated(P<0.01).Pathological morphology of the liver tissue improved,accompanied by increased glycogen deposition in hepatocytes.CONCLUSION:Huazhuo granule manifests effects in lowering blood glucose and serum insulin levels,ameliorating blood lipids,and enhancing liver function in rats.These ef-fects are revealed to increase glycogen synthesis by activating the PI3K/Akt/GSK-3β signaling pathway and reduce gluco-neogenesis by activating the PI3K/Akt/FOXO1 signaling pathway.

Ferroptosis, a newly discovered form of iron-dependent regulation of cell death, has been found to be associated with the development of various cancers, including melanoma. This review summarizes recent progress in roles of ferroptosis in the pathogenesis, metastasis and treatment of melanoma, aiming to provide a theoretical basis for the development of new drugs and new treatment strategies for melanoma in clinical practice.

As a critical component of global agriculture,the dairy industry is essential for the food security and economic development.In China,the dairy sector in plateau regions plays an important role in addressing the nutritional needs of residents,boosting farmers' incomes,and fostering re-gional economic growth.However,the harsh high-altitude conditions,such as low oxygen,low at-mospheric pressure,and severe climate,pose significant challenges to the health and survival of dairy cows.This article summarizes the changes in physiological characteristics,metabolic perform-ance,production performance,and health status of dairy under high altitude areas,providing in-sights for the identification of adaptive traits in dairy to plateau.Also,the genetic and epigenetic mechanisms behind these phenotypic adaptations are discussed,and future directions and strategies for enhancing adaptability of dairy of dairy n plateau regions are outlined,thereby guiding re-searchers in adaptation evolution and breeding of dairy cattle.