Background Arsenic is an environmentally harmful substance that causes hepatic insulin resistance and liver damage, increasing the risk of type 2 diabetes mellitus. Objective To explore whether the insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) is involved in insulin resistance in HepG2 cells after arsenic exposure through the peroxisome-proliferator-activated receptor γ (PPAR-γ) / glucose transporter 4 (GLUT4) pathway. Methods Cell viability was determined using cell counting kit 8 (CCK8) and an appropriate NaAsO₂ infection dose was determined. A cellular arsenic exposure model of HepG2 cells was established by four concentrations of NaAsO₂ solution for 24 h (the experiment was divided into four groups: 0, 2, 4, and 8 μmol·L⁻¹); HepG2 cells were firstly treated with pcDNA3.1-IGF2BP2 and pcDNA3.1-NC respectively for 6 h, then with 8 μmol·L⁻¹ NaAsO₂ for 24 h to establish a IGF2BP2 overexpression cell model (the experiment was divided into 4 groups: control, NaAsO₂, NaAsO₂+pcDNA3.1-IGF2BP2, and NaAsO₂+pcDNA3.1-NC); finally the cells were subject to 100 nmol·L⁻¹ insulin stimulation for 30 min. Glycogen and glucose in HepG2 cells were determined by glycogen and glucose assay kits; mRNA expression levels of IGF2BP2 were measured by quantitative real-time PCR; protein expression levels of IGF2BP2, PPAR-γ, and GLUT4 in HepG2 were detected by Western blot (WB); and the binding of IGF2BP2 to PPAR-γ and PPAR-γ to GLUT4 was verified by co-immunoprecipitation (CO-IP) experiment. Results The results of CCK8 experiment showed a dose-effect relationship between NaAsO₂ concentration and cell viability. When the concentration of NaAsO₂ was ≥4 μmol·L⁻¹ , the cell viabilities were lower than that of the control group (P <0.05). With the increasing dose of NaAsO₂ infection, reduced glucose consumption and glycogen levels in HepG2 cells were found in the 2, 4, and 8 μmol·L⁻¹ NaAsO₂ treatment groups compared to the control group (P <0.05). The difference between the mRNA expression level of IGF2BP2 in the HepG2 cells treated with 4 or 8 μmol L⁻¹ NaAsO₂ and the control group was significant (P <0.05). In the IGF2BP2 overexpression cell model, compared with the control group, glucose consumption and glycogen levels were lowered in the NaAsO₂ group (P <0.05), the mRNA expression level of IGF2BP2 and the protein expression levels of IGF2BP2, PPAR-γ, and GLUT4 in the cell membrane were all decreased (P <0.05). Compared with the NaAsO₂ group, the glucose consumption and glycogen levels were increased in the NaAsO₂+pcDNA3.1-IGF2BP2 group (P <0.05), and the mRNA expression level of IGF2BP2 and the protein expression levels of IGF2BP2, PPAR-γ, and GLUT4 in the cell membrane were all increased (P <0.05). The results of CO-IP experiments showed that IGF2BP2 interacted with PPAR-γ as well as PPAR-γ with GLUT4 protein. Conclusion IGF2BP2 is involved in arsenic exposure-induced insulin resistance in HepG2 cells by acting on the PPAR-γ/GLUT4 pathway.

Chemotherapy is an important treatment for tumors， but most patients experience varying degrees of chemotherapy- induced myelosuppression. Four properties theory of traditional Chinese medicine （TCM） has unique advantages in improving chemotherapy-induced myelosuppression. The monomers from TCM with different properties and flavors， such as cold-natured （e.g. Scutellaria baicalensis， Rhus chinensis）， cool-natured （e.g. Ligustrum lucidum， Ophiopogon japonicus）， warm-natured （e.g. Panax ginseng， Epimedium brevicornu， Curcuma longa， Angelica sinensis）， hot-natured （e.g. Cinnamomum cassia， Aconitum carmichaeli）， and neutral-natured （e. g. donkey-hide gelatin， Lycium barbarum， Rhodiola rosea， fungi）， can exert anti- myelosuppressive effects by reducing damage to hematopoietic stem/progenitor cells， improving the bone marrow hematopoietic microenvironment， inhibiting the oxidative stress response， regulating signaling pathways， so as to ultimately repaire inflammatory damage and improve hematopoietic function， thereby playing an anti-myelosuppressive role.

Objective To evaluate whether Vibrio vulnificus secreted exotoxin-hemolysin (VVH) can activate platelet, an important blood immune cell, and to explore the possible molecular mechanism of platelet activation by VVH. Methods Transcriptomics and immunohistochemistry were used to analyze whether Vibrio vulnificus infection caused platelet activation in mice. Then, flow cytometry was used to identify whether VVH was the main stimulator of platelet activation. Naturally expressed VVH toxin was purified and prepared. The effects of extracellular and intracellular Ca²⁺ signal inhibitors on VVH activated platelets were evaluated by flow cytometry and Western blotting. The immune activation effect of VVH in the early stage of Vibrio vulnificus infection was analyzed in vivo. Results VVH was the main stimulator of platelet activation in Vibrio vulnificus culture supernatant. Natural VVH can induce the increase of P-selectin (CD62P) on platelet surface, the formation of platelet-neutrophil complex (PNC), and the release of platelet microvesicles. The activation mechanism may be related to the VVH pore-dependent Ca²⁺-calmodulin (CaM) -myosin light chain kinase (MLCK) signaling pathway, which led to the release of platelet alpha particles and cascade activation of platelets. In a mouse model of ALD infected by Vibrio vulnificus gavage, VVH was strongly associated with platelet activation. Conclusion This study shows that VVH is an important platelet activating molecule in the early stage of Vibrio vulnificus infection, and its induction of platelet activation may be related to the pathogenic process.
Animals ; Platelet Activation/drug effects* ; Hemolysin Proteins/pharmacology* ; Vibrio vulnificus/metabolism* ; Mice ; Blood Platelets/drug effects* ; Vibrio Infections/immunology* ; P-Selectin/metabolism* ; Bacterial Proteins ; Female

OBJECTIVES: To investigate the effect of Ching Shum Pills (CSP) for alleviating non-alcoholic fatty liver disease (NAFLD) and the underlying mechanism. METHODS: In a mouse model of NAFLD, the therapeutic effect of CSP was evaluated by measuring serum glucose, lipid profiles (TC, TG, LDL-C, HDL-C), and hepatic function markers. Network pharmacology was employed to identify active compounds in CSP and their targets using TCMSP, HERB, SwissTargetPrediction, GeneCards, OMIM, and DisGeNET. Protein-protein interaction (PPI) networks, Gene Ontology (GO), and KEGG pathway analyses were conducted. Molecular docking (AutoDock Vina) was used to assess the compound-target binding affinities. Quantitative real-time PCR (qRT-PCR) was used to validate the mRNA expressions of the core genes in the liver tissue of the mouse models. RESULTS: In the mouse model of NAFLD, treatment with CSP significantly reduced body weight gain and serum TG levels of the mice, and high-dose CSP treatment resulted in obvious reduction of ALT levels and hepatic fat accumulation. Network pharmacology analysis identified quercetin and 2-monolinolenin as the key bioactives in CSP, which target TNF, AKT1, IL6, TP53, and ALB. Docking simulations suggested strong binding between the two core compounds and their target proteins. The results of qRT-PCR showed that high-fat diet induced significant downregulation of Tp53, Cpt1, and Ppara expressions in mice, which was effectively reversed by CSP treatment. CONCLUSIONS CSP can improve lipid metabolism disorders in NAFLD mice through a regulatory mechanism involving multiple targets and pathways to reduce liver fat accumulation and protect liver function. The key components in CSP such as quercetin and linolenic acid monoacylglycerol may participate in the regulation of such metabolic processes as fatty acid oxidation by targeting TP53.
Animals ; Non-alcoholic Fatty Liver Disease/drug therapy* ; Mice ; Drugs, Chinese Herbal/pharmacology* ; Lipid Metabolism/drug effects* ; Molecular Docking Simulation ; Disease Models, Animal ; Liver/metabolism* ; Male ; Lipid Metabolism Disorders/drug therapy* ; PPAR alpha/metabolism* ; Mice, Inbred C57BL ; Network Pharmacology

Objective To investigate the effects of saikosaponin D(SSD)on the growth of esophageal squamous cell carcinoma(ESCC)Eca109 cells and the hypoxia-inducible transcription factor-2α(HIF-2α)/nuclear factor-κB p65(NF-κB p65)pathway.Methods Different concentrations of SSD(0,3,6,9,12,15,18,21,24 μmol·L-1)were used to treat Het-1a normal esophageal squamous epithelial cells and Eca109 ESCC cells to screen the experimental concentration of SSD.Eca109 cells were separated into control(NC)group,HIF-2α inhibitor(PT2385)group,SSD low and high concentration(SSD-L,SSD-H)groups,SSD-H+empty lentivirus(LV-NC)group,and SSD-H+HIF-2α recombinant lentivirus(LV-HIF-2α)group.MTT assay was applied to detect cell viability.Flow cytometry was applied to detect cell apoptosis.ELISA was applied to detect the levels of TNF-α,IL-1β,and IL-8 in cell culture media.Western blot was applied to detect cell proliferation,apoptosis,and protein expression related to the HIF-2α/NF-κB p65 pathway.The Eca109 cell tumor bearing nude mouse model was established to verify the effect of SSD on the in vivo growth of Eca109 cells.Results 6 and 12 μmol·L-1 SSD were selected as experimental concentrations.Compared with the NC group,the cell viability,TNF-α,IL-1β,IL-8 levels in cell culture medium,PCNA,Bcl-2,HIF-2α,p-NF-κB p65/NF-κB p65 protein levels,subcutaneous transplant tumor volume and weight in nude mice,serum TNF-α,IL-1β,IL-8 levels,and positive expression of HIF-2α and NF-κB p65 proteins in the PT2385 group,SSD-L group,and SSD-H group were lower,the apoptosis rate,Bax,and Cleaved-caspase3 protein levels were higher(P<0.05 or P<0.01).Overexpression of HIF-2α prominently weakened the inhibitory effects of SSD on the proliferation of Eca109 cells and the growth of subcutaneous transplanted tumors in nude mice(P<0.05 or P<0.01).Conclusion SSD can inhibit the proliferation of Eca109 cells,induce cell apoptosis,and suppress the growth of subcutaneous transplanted tumors of Eca109 cells in nude mice.Its effect may be related to the inhibition of the activation of the HIF-2α/NF-κB p65 pathway.

Objective:To explore the effectiveness of teach-back method-based health education in patients with oral fungal infections.Methods:Convenience sampling was used to select patients with oral fungal infections who attended the Dental Clinic of the First Affiliated Hospital of Zhengzhou University from June to December 2023 for the study. The patients were divided into control group and observation group according to the randomized numerical table method. Control group received conventional oral care health education, and observation group was treated with the teach-back method-based health education. Treatment adherence, oral health self-management ability, and oral health were compared between the two groups before and after the intervention. Finally, 62 patients were included in control group and 59 patients in observation group.Results:After the intervention, the treatment adherence score and the oral health care knowledge, oral health care attitude, oral health care behavior scores and total scores of oral health self-management ability in observation group were higher than those of control group, and the differences were statistically significant ( P<0.05). After the intervention, the Chinese version of the Oral Health Impact Profile-49 (OHIP-49) of observation group was lower than that of control group, and the difference was statistically significant ( P<0.05) . Conclusions:The teach-back method-based health education improves adherence, enhances self-management, and promotes oral health in patients with oral fungal infections.

To formulate an expert consensus on the principles of preoperative hair removal and provide scientific guidance for standardized removal of hair before surgical procedures so as to reduce the incidence of surgical site infections.METHODS Led by the Hospital Management Institute of National Health Commission of the People's Republic of China,this consensus was reached with the joint efforts from the expects of relevant fields such as surgeries,interventional therapies,nursing,and infection prevention and control.The consensus facilitates the classification and evaluation of literatures by following the evidence grade formulated by Oxford Evidence-based Medicine Center and focuses on the association of preoperative hair removal with surgical site infection,it reaches the evidence grade of expert consensus and recommendation intensity by integrating with discussions on meetings and clinical experience of the expects from relevant fields.RESULTS A total of 6 items of consensus were reached by summarizing the latest evidence on the aspects including the indications for preoperative hair removal,tools,range,timing and places.CONCLUSION The consensus,to some extent,make supplements to and complete the exiting regulations and standards.It provides guidance for the medical institutions to carry out the preoperative hair removal.

Objective To investigate the effects of saikosaponin D(SSD)on the growth of esophageal squamous cell carcinoma(ESCC)Eca109 cells and the hypoxia-inducible transcription factor-2α(HIF-2α)/nuclear factor-κB p65(NF-κB p65)pathway.Methods Different concentrations of SSD(0,3,6,9,12,15,18,21,24 μmol·L-1)were used to treat Het-1a normal esophageal squamous epithelial cells and Eca109 ESCC cells to screen the experimental concentration of SSD.Eca109 cells were separated into control(NC)group,HIF-2α inhibitor(PT2385)group,SSD low and high concentration(SSD-L,SSD-H)groups,SSD-H+empty lentivirus(LV-NC)group,and SSD-H+HIF-2α recombinant lentivirus(LV-HIF-2α)group.MTT assay was applied to detect cell viability.Flow cytometry was applied to detect cell apoptosis.ELISA was applied to detect the levels of TNF-α,IL-1β,and IL-8 in cell culture media.Western blot was applied to detect cell proliferation,apoptosis,and protein expression related to the HIF-2α/NF-κB p65 pathway.The Eca109 cell tumor bearing nude mouse model was established to verify the effect of SSD on the in vivo growth of Eca109 cells.Results 6 and 12 μmol·L-1 SSD were selected as experimental concentrations.Compared with the NC group,the cell viability,TNF-α,IL-1β,IL-8 levels in cell culture medium,PCNA,Bcl-2,HIF-2α,p-NF-κB p65/NF-κB p65 protein levels,subcutaneous transplant tumor volume and weight in nude mice,serum TNF-α,IL-1β,IL-8 levels,and positive expression of HIF-2α and NF-κB p65 proteins in the PT2385 group,SSD-L group,and SSD-H group were lower,the apoptosis rate,Bax,and Cleaved-caspase3 protein levels were higher(P<0.05 or P<0.01).Overexpression of HIF-2α prominently weakened the inhibitory effects of SSD on the proliferation of Eca109 cells and the growth of subcutaneous transplanted tumors in nude mice(P<0.05 or P<0.01).Conclusion SSD can inhibit the proliferation of Eca109 cells,induce cell apoptosis,and suppress the growth of subcutaneous transplanted tumors of Eca109 cells in nude mice.Its effect may be related to the inhibition of the activation of the HIF-2α/NF-κB p65 pathway.

Objective To evaluate the surgical technique and clinical value of laparoscopic bladder diverticulectomy guided by inserting ureteral catheters into the diverticulum under plasmakinetic resectoscope.Methods From December 2018 to May 2024,9 patients underwent laparoscopic bladder diverticulectomy in combination with resectoscope.Each patient had a solitary bladder diverticulum with a median maximum diameter of 6.40(5.70,7.40)cm(range:5.0～8.5 cm).Among the 9 patients,3 patients had concurrent benign prostatic hyperplasia(BPH)and simultaneously underwent transurethral plasmakinetic resection of the prostate;1 patient had concurrent both BPH and bladder calculi,requiring simultaneously underwent plasmakinetic resection of the prostate and bladder calculi removal;2 patients required ureteral reimplantation as the diverticulum was directly involving the ureteral orifice;1 case underwent ureteroscopic double-J stent implantation because the opening of the ipsilateral ureter was adjacent to the entrance of the diverticulum.Results Bladder diverticulectomy was successfully performed in the all patients.Median operative time was 160.00(120.00,317.50)min(range:85～345 min).Median estimated blood loss was 20.00(10.00,150.00)mL(range:10～300 mL).No iatrogenic injuries to adjacent organs were observed.Pelvic drains were removed 1～3 d postoperatively,with no urine leakage.Urinary catheters were maintained for 7～10 d after operation.Follow-up at 3～12 months showed no recurrence or hydronephrosis in any of the patients.Conclusion Laparoscopic resection of bladder diverticula guided by ureteral catheter placed into bladder diverticula by means of resectoscope has the advantages of less trauma,less bleeding and faster recovery,and is an effective measure for the treatment of bladder diverticula.

Self-aid and buddy-aid are primary steps in battlefield first aid,offering the timeliest treatment effectiveness.Medications are indispensable key supplies in battlefield first aid,playing a crucial role in the timely treatment of the injured.This review provides an overview of medication preparation for battlefield first aid both domestically and internationally,aiming to provide reference for the medication preparation for self-aid and buddy-aid of naval combat injuries,so as to enhance the Navy's first-aid capability and medical support capability.