Objective To investigate the protective effect of recombinant Schistosoma japonicum cystatin(rSj-Cys)against acute liver injury induced by lipopolysaccharide(LPS)and D-GalN in mice.Methods Adult male C57BL/6J mice with or without LPS/D-GaIN-induced acute liver injury were given intraperitoneal injections of rSj-Cys or PBS 30 min after modeling(n=18),and serum and liver tissues samples were collected from 8 mice in each group 6 h after modeling.The survival of the remaining 10 mice in each group within 24 h was observed.Serum levels of ALT,AST,TNF-α and IL-6 of the mice were measured,and liver pathologies was observed with HE staining.The hepatic expressions of macrophage marker CD68,Bax,Bcl-2 and endoplasmic reticulum stress(ERS)-related proteins were detected using immunohistochemistry or immunoblotting,and TUNEL staining was used to detect hepatocyte apoptosis.Results The survival rates of PBS-and rSj-Cys-treated mouse models of acute liver injury were 30%and 80%at 12 h and were 10%and 60%at 24 h after modeling,respectively;no death occurred in the two control groups within 24 h.The mouse models showed significantly increased serum levels of AST,ALT,IL-6 and TNF-α and serious liver pathologies with increased hepatic expressions of CD68 and Bax,lowered expression of Bcl-2,increased hepatocyte apoptosis,and up-regulated expressions of ERS-related signaling pathway proteins GRP78,CHOP and NF-κB p-p65.Treatment of the mouse models significantly lowered the levels of AST,ALT,IL-6 and TNF-α,alleviated liver pathologies,reduced hepatic expressions of CD68,Bax,GRP78,CHOP and NF-κB p-p65,and enhanced the expression of Bcl-2.In the normal control mice,rSj-Cys injection did not produce any significant changes in these parameters compared with PBS.Conclusion rSj-Cys alleviates LPS/D-GalN-induced acute liver injury in mice by suppressing ERS,attenuating inflammation and inhibiting hepatocyte apoptosis.

Objective:To establish a rapid pipeline for whole genome sequencing of Chikungunya virus (CHIKV) by combining imbricated multiplex-PCR amplification and Illumina high-throughput sequencing platform.Methods:The primary reference sequences of CHIKV were downloaded from the National Center for Biotechnology Information (NCBI) database, covering all genotypes of CHIKV. After multiple alignments using the Mafft software and phylogenetic analysis, the 20 CHIKV references were selected for primer design. The Primal Scheme tool and Geneious Prime software were used to design, evaluate and optimize the primer panel. Finally, seven CHIKV-positive samples were involved in the validation of the primer panel.Results:All the amplicons of the designed panel were generated successfully. The consensuses generated from the mapping results could cover 100.00% of the coding region of the CHIKV genome when the Ct-value of the sample was less than 33, as the percentage would decrease to 99.38% when the Ct-value reached 35. The mapping percentage could be increased by 5.70%-25.43% when using the stepwise correction mapping strategy.Conclusion:The multiplex-PCR amplification method for CHIKV whole genome sequencing is relatively simple and convenient, which only requires two tubes of PCR amplification and performs well on CHIKV-positive clinical samples with different concentration levels of virus.

Objective To investigate the protective effect of recombinant Schistosoma japonicum cystatin(rSj-Cys)against acute liver injury induced by lipopolysaccharide(LPS)and D-GalN in mice.Methods Adult male C57BL/6J mice with or without LPS/D-GaIN-induced acute liver injury were given intraperitoneal injections of rSj-Cys or PBS 30 min after modeling(n=18),and serum and liver tissues samples were collected from 8 mice in each group 6 h after modeling.The survival of the remaining 10 mice in each group within 24 h was observed.Serum levels of ALT,AST,TNF-α and IL-6 of the mice were measured,and liver pathologies was observed with HE staining.The hepatic expressions of macrophage marker CD68,Bax,Bcl-2 and endoplasmic reticulum stress(ERS)-related proteins were detected using immunohistochemistry or immunoblotting,and TUNEL staining was used to detect hepatocyte apoptosis.Results The survival rates of PBS-and rSj-Cys-treated mouse models of acute liver injury were 30%and 80%at 12 h and were 10%and 60%at 24 h after modeling,respectively;no death occurred in the two control groups within 24 h.The mouse models showed significantly increased serum levels of AST,ALT,IL-6 and TNF-α and serious liver pathologies with increased hepatic expressions of CD68 and Bax,lowered expression of Bcl-2,increased hepatocyte apoptosis,and up-regulated expressions of ERS-related signaling pathway proteins GRP78,CHOP and NF-κB p-p65.Treatment of the mouse models significantly lowered the levels of AST,ALT,IL-6 and TNF-α,alleviated liver pathologies,reduced hepatic expressions of CD68,Bax,GRP78,CHOP and NF-κB p-p65,and enhanced the expression of Bcl-2.In the normal control mice,rSj-Cys injection did not produce any significant changes in these parameters compared with PBS.Conclusion rSj-Cys alleviates LPS/D-GalN-induced acute liver injury in mice by suppressing ERS,attenuating inflammation and inhibiting hepatocyte apoptosis.

Objective:To establish a rapid pipeline for whole genome sequencing of Chikungunya virus (CHIKV) by combining imbricated multiplex-PCR amplification and Illumina high-throughput sequencing platform.Methods:The primary reference sequences of CHIKV were downloaded from the National Center for Biotechnology Information (NCBI) database, covering all genotypes of CHIKV. After multiple alignments using the Mafft software and phylogenetic analysis, the 20 CHIKV references were selected for primer design. The Primal Scheme tool and Geneious Prime software were used to design, evaluate and optimize the primer panel. Finally, seven CHIKV-positive samples were involved in the validation of the primer panel.Results:All the amplicons of the designed panel were generated successfully. The consensuses generated from the mapping results could cover 100.00% of the coding region of the CHIKV genome when the Ct-value of the sample was less than 33, as the percentage would decrease to 99.38% when the Ct-value reached 35. The mapping percentage could be increased by 5.70%-25.43% when using the stepwise correction mapping strategy.Conclusion:The multiplex-PCR amplification method for CHIKV whole genome sequencing is relatively simple and convenient, which only requires two tubes of PCR amplification and performs well on CHIKV-positive clinical samples with different concentration levels of virus.

Objective To investigate the impact of the Shared Medical Appointment (SMA) model on blood glucose levels and self-management behaviors in patients with gestational diabetes mellitus (GDM). Methods A total of 87 pregnant women diagnosed with GDM at the Obstetrics and Gynecology and Endocrinology Outpatient Departments of the Affiliated Suqian Hospital of Xuzhou Medical University from October 2021 to October 2022 were enrolled and divided into treatment group (n=44) and control group (n=43). The treatment group received SMA-based GDM management, while the control group underwent routine outpatient follow-up. Baseline data, flash glucose monitoring (FGM)-related indicators before and after treatment, and self-management behavior scale scores were compared between the two groups. Results No statistically significant differences were observed between the two groups in age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), blood urea nitrogen (BUN), creatinine (Cr), uric acid (UA), triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and glycated hemoglobin (HbA1c) (P>0.05). After treatment, the time in range (TIR) of glucose was higher in the treatment group than that in the control group, while mean amplitude of glycemic excursions (MAGE), standard deviation of blood glucose (SDBG), coefficient of variation (CV), and mean blood glucose (MBG) were lower in the treatment group (P < 0.05). Within the treatment group, post-treatment TIR was higher, and MAGE, CV, SDBG, and MBG were lower than pre-treatment levels (P < 0.05). In the control group, post-treatment TIR was higher, and SDBG and MBG were lower than pre-treatment levels (P < 0.05). After treatment, the total score and scores for dietary management, exercise management, medication management, and blood glucose monitoring management in the self-management behavior scale were significantly higher in the treatment group than in the control group (P < 0.05). In the treatment group, post-treatment scores for all self-management behaviors were higher than pre-treatment levels, while post-treatment total scores and scores for medication management and blood glucose monitoring management in the control group were higher than pre-treatment levels (P < 0.05). Conclusion SMA management model can comprehensively improve blood glucose levels and enhance self-management behavior capabilities in GDM patients.

Drug metabolism and pharmacokinetics (DMPK) is an important branch of pharmaceutical sciences. The nature of ADME (absorption, distribution, metabolism, excretion) and PK (pharmacokinetics) inquiries during drug discovery and development has evolved in recent years from being largely descriptive to seeking a more quantitative and mechanistic understanding of the fate of drug candidates in biological systems. Tremendous progress has been made in the past decade, not only in the characterization of physiochemical properties of drugs that influence their ADME, target organ exposure, and toxicity, but also in the identification of design principles that can minimize drug-drug interaction (DDI) potentials and reduce the attritions. The importance of membrane transporters in drug disposition, efficacy, and safety, as well as the interplay with metabolic processes, has been increasingly recognized. Dramatic increases in investments on new modalities beyond traditional small and large molecule drugs, such as peptides, oligonucleotides, and antibody-drug conjugates, necessitated further innovations in bioanalytical and experimental tools for the characterization of their ADME properties. In this review, we highlight some of the most notable advances in the last decade, and provide future perspectives on potential major breakthroughs and innovations in the translation of DMPK science in various stages of drug discovery and development.

The medical fungus Hirsutella sinensis has been used as a Chinese folk health supplement because of its immunomodulatory properties. Our previous studies established the antifibrotic action of Hirsutella sinensis mycelium (HSM) in the lung. The epithelial-mesenchymal transition (EMT) is involved in the pathogenesis of idiopathic pulmonary fibrosis. The present study investigates the role of HSM in mediating EMT during the development of pulmonary fibrosis. HSM significantly inhibits bleomycin (BLM)-induced pulmonary fibrosis by blocking the EMT. In addition, the expression levels of midkine are increased in the lungs of the BLM-induced group. Further analysis of the results indicates that the mRNA level of midkine correlated positively with EMT. HSM markedly abrogates the transforming growth factor β-induced EMT-like phenotype and behavior in vitro. The activation of midkine related signaling pathway is ameliorated following HSM treatment, whereas this extract also caused an effective attenuation of the induction of EMT (caused by midkine overexpression) in vitro. Results further confirm that oral medication of HSM disrupted the midkine pathway in vivo. Overall, findings suggest that the midkine pathway and the regulation of the EMT may be considered novel candidate therapeutic targets for the antifibrotic effects caused by HSM.
Bleomycin ; Epithelial-Mesenchymal Transition ; Humans ; Midkine ; Mycelium ; Pulmonary Fibrosis/drug therapy*

Objective? To analyze the risk factors of nosocomial infection in the pediatric ward in a hospital and nursing care for relevant prevention and control. Methods? Totally 1 460 pediatric inpatients admitted in Taizhou First People's Hospital from June 2017 to January 2019 were retrospectively analyzed and divided into the infection group and the control group according to the existence of infection. The children＇s medical records were organized; the risk factors of nosocomial infection in pediatric inpatients were analyzed;and relevant nursing measures were summarized. Results? Nosocomial infection was found in 89 out of the 1 460 children; most children were found with respiratory tract infection and digestive canal infection in the infected children, which accounted for 36 cases (40.4%) and 23 cases (25.8%), respectively; the proportion of children aged ＜3 years, hospitalized for ＞10 days, with malnutrition, invasive operation, receiving antibiotics for ＞10 days, or receiving immunosuppressors or unqualified sterile operation in the infection group was higher than that in the control group, and there was statistically significant difference between the two groups (P＜ 0.05). Logistic regression analysis revealed that nosocomial infection in pediatric inpatients was associated with length of hospital ＞ 10 days, invasive operation, use of antibiotics for ＞ 10 days, use of immunosuppressors and unqualified sterile operation. Conclusions? Pediatric inpatients are prone to nosocomial infection, and the type of infection is mainly respiratory tract infection and digestive canal infection. Relevant nursing measures should be taken based on the factors of infection in order to reduce the incidence rate of nosocomial infection in children.

Objective:The effects of IL-13 ( Interleukin-13 ) on SDF-1 ( Stromal cell derived factor 1 ) and EGF ( Epidermal growth factor) expression in fibroblasts co-cultured with breast cancer cells were investigated to explore the mechanism for IL-13 in the development of breast cancer.Methods:The co-culture of human breast cancer cell line MDA-MB-231 with the human skin fibroblast line CCC-ESF-1 ( ESF) was used in vitro and in tumor-burdened nude mice.The effects of IL-13 on SDF-1 and EGF expression in the co-cultured fibroblasts in vitro were analyzed using reverse transcription quantitative polymerase chain reaction ( RT-qPCR ) , flow cytometry and Western blot assay.The proliferation of the co-cultured human breast cancer cells in vitro was detected by Cell counting kit-8(CCK-8).The effects of IL-13 on SDF-1 and EGF expression in the fibroblasts of tumor tissue of tumor-burdened nude mice were analyzed using immunofluorescence and laser confocal microscope, and the tumor volumes were examined.Results: IL-13 could up-regulate SDF-1 and EGF expression in the fibroblasts co-cultured with breast cancer cells in vitro,and promoted the proliferation of the co-cultured breast cancer cells.In tumor-burdened nude mice,IL-13 enhanced SDF-1 and EGF expression of fibroblasts in tumor tissue, and accelerated tumor growth.Conclusion:IL-13 up-regulates SDF-1 and EGF expression of fibroblasts co-cultured with breast cancer cells.The molecular mechanism of promoting effect of IL-13 on breast cancer relates to SDF-1 and EGF of fibroblasts in breast cancer stroma.

Objective To compare the different methods for treating aerobic vaginitis and mixed clinical effects of infection.Methods A randomized controlled method was used,298 cases of aerobic vaginitis and mixed infections were randomly divided into control group(149 cases):the use of combination anti -infective therapy,the treatment group(149 cases):the use of combination anti -infective at the same treatment plus lactobacillus vaginal medication.And the therapeutic effect was evaluated.Results The difference of the clinical efficacy of aerobic vagi-nitis treatment of mixed infections was not statistically significant (total effective rate of 95.3% in the treatment group,92.6% in the control group).With the time of treatment extended,the effective rate increased,the use of com-bination anti -infective therapy at the same time plus lactobacillus vaginal administration group of aerobic bacteria vaginosis and recurrence rate was significantly reduced in patients with mixed infection (recurrence rate was 6.0% in the treatment group and 12.8% was in the control group,χ2 =3.941 3,P <0.05).Conclusion The combination of anti -infective therapy at the same time plus lactobacillus vaginal drug treatment aerobic mixed infections and vagini-tis has slightly higher effective rate than the use of combination anti -infective treatment,the former relapse rate was significantly reduced.