OBJECTIVE To investigate the effects and mechanism of Yigan huayu formula in alleviating liver fibrosis in mice. METHODS Mice were randomly divided into blank group （normal saline）， model group （normal saline）， Yigan huayu formula low- and high-dose groups （28.98， 57.96 g/kg， calculated by crude drug）， with 8 mice in each group. Except for the blank group， the liver fibrosis model was induced by intraperitoneal injection of 15%CCl 4 -olive oil solution. From the third week， the mice received the medicine/normal saline intragastrically， once a day， for 4 consecutive weeks. After the last medication， liver indexes were calculated， the activities of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） in serum， as well as the hydroxyproline （HYP） content in liver tissue， were measured. Liver histopathology was evaluated. Differentially expressed proteins （DEPs） in liver tissue were analyzed based on proteomics， followed by bioinfo rmatics analysis. The expressions of core DEPs were validated using Western blot （WB） and immunohistochemistry （IHC） methods. RESULTS Compared with the blank group， the model group showed significantly elevated liver indexes， serum activities of ALT and AST， and hepatic HYP content （ P ＜0.05）， along with obvious pathological damage and collagen deposition. Compared with the model group， the above indexes of mice in the Yigan huayu formula high-dose group were decreased significantly （ P ＜0.05）， with marked improvement in liver pathological damage and collagen deposition. Proteomics identified 210 DEPs between the model group and Yigan huayu formula high-dose group. DEPs were significantly enriched in extracellular matrix （ECM）-receptor interaction and lipid metabolism pathways. WB and IHC confirmed that Yigan huayu formula could significantly inhibit the abnormally elevated expressions of collagen type Ⅳ alpha1 chain （COL4A1）， secreted protein acidic and rich in cysteine （SPARC）， vitronectin （VTN） and laminin subunit alpha5 （LAMA5） in liver tissue of mice （ P ＜0.05）. CONCLUSIONS Yigan huayu formula may exert anti-hepatic fibrosis effects by inhibiting the expressions of proteins such as COL4A1， LAMA5， SPARC， and VTN， thereby blocking the ECM-receptor interaction signaling pathway， and subsequently suppressing excessive ECM deposition and basement membrane remodeling.

Objective The study aimed to investigate whether montelukast sodium could alleviate airway inflammatory responses in asthmatic mice by affecting the PHD2/HIF-1α pathway.Methods An allergic asthma model was established by ovalbumin(OVA)induction,and 18 female BALB/c mice were randomly divided into a control group(Con group),an asthma group(OVA group),and an asthma group with montelukast sodium intervention(30 mg/kg montelukast sodium by oral administration 1 h before OVA challenge,Mon group).HE staining was used to analyze the pathological changes in the lungs of mice.Blood cell analyzer and kits were used to determine the number of inflammatory cells and the levels of cytokines,the content of lactic acid and pyruvic acid in the lungs,respectively.RT-PCR and Western blot were used to detect the mRNA and protein expression of HIF-1α,PHD2,E-cad and p120 in the lungs of mice.Results Compared with the Con group,there was a significant increase in the number of eosinophils,lymphocytes,neutrophils and monocytes,the levels of IL-5,IL-13,complement factor D(CFD)and contents of lactate and pyruvate in the lungs of mice in the OVA group.Lung HIF-1α,PHD2,p120 and E-cad mRNA levels were reduced,meanwhile HIF-1α and PHD2 protein expression were upregulated but E-cad and p120 protein expression were downregulated(all with P<0.05).After montelukast sodium intervention,the number of eosinophils and monocytes and CFD expression were significantly decreased in the lungs of Mon group,the contents of lactate and pyruvate were basically restored to normal,and the mRNA and protein expression of HIF-1α,PHD2,p120 and E-cad were effectively improved.Conclusion Montelukast sodium could alleviate the airway inflammatory responses in the lungs of asthmatic mice by regulating the PHD2/HIF-1α signaling pathway.

Background The association between occupational physical activity (OPA) and cardiometabolic risk factors remains controversial, potentially due to differences in the associations between OPA and various cardiometabolic indicators, as well as the lack of a clearly defined optimal OPA range for multiple-indicator synergistic benefits. Objective To investigate the relationship between OPA and cardiometabolic risk factors in individuals at high risk of cardiovascular disease (CVD) in Hubei Province, and to explore an optimal OPA range for multi-indicator improvements. Methods Data were derived from the Hubei Province dataset of the China Health Evaluation And Risk Reduction Through Nationwide Teamwork from 2015 to 2023, including 19028 high-risk CVD individuals. OPA (metabolic equivalent·h·d⁻¹, MET·h·d⁻¹) was assessed using the China Kadoorie Biobank physical activity questionnaire, anthropometric measurements (height, weight, waist circumference) and cardiometabolic indicators (blood pressure, fasting blood glucose, lipid profiles) were measured. Multivariate logistic regression was used to analyze the association between logOPA quartiles (Q1-Q4) and abnormal cardiometabolic indicators, while restricted cubic spline (RCS) models were employed to explore their dose-response relationships. Subgroup and interaction analyses were also conducted by gender. Results The median OPA of all participants was 12.86 MET·h·d⁻¹ (male: 14.40 MET·h·d⁻¹, female: 11.14 MET·h·d⁻¹). After adjusting for confounders, compared with the Q1 group, logOPA in the Q4 group was associated with 20% (OR=0.80, 95%CI: 0.72, 0.89), 14% (OR=0.86, 95%CI: 0.78, 0.96), and 13% (OR=0.87, 95%CI: 0.79, 0.95) reduction in the risk of abdominal obesity, low high-density lipoprotein cholesterol (HDL-C), and metabolic syndrome (MS), respectively, and 33% (OR=1.33, 95%CI: 1.18, 1.49), 33% (OR=1.33, 95%CI: 1.18, 1.50), and 38% (OR=1.38, 95%CI: 1.21, 1.57) increase in the risk of high total cholesterol (TC), high low-density lipoprotein cholesterol (LDL-C), and high non-HDL-C, respectively. Similar trends were observed in males and females, with significant positive associations of logOPA with high TC and high non-HDL-C in males (P_interaction<0.05). The risk of low HDL-C decreased rapidly when logOPA was more than 2.213 (OPA>9.14 MET·h·d⁻¹), showing an inverted L-shaped trend. The risk of high TC, high LDL-C, and high non-HDL-C increased beyond logOPA thresholds of 3.244, 2.476, and 3.377 (OPA >25.64, 11.89, and 29.28 MET·h·d⁻¹), respectively, showing a J-shaped trend. However, logOPA exhibited a U-shaped nonlinear dose-response relationship with blood pressure and fasting blood glucose abnormalities (P_non-linear<0.05) , with minimal risks at logOPA 2.969 and 2.372 (OPA of 19.47 and 10.72 MET·h·d⁻¹). Conclusion OPA exhibits heterogeneous dose-response patterns across cardiometabolic indicators. Integrating the inverted L-, J-, and U-shaped association patterns, we suggest an optimal OPA range of 9.14−25.64 MET·h·d⁻¹ for multiple cardiometabolic indicators in total individuals at high-risk of CVD, with ranges of 9.61−31.34 MET·h·d⁻¹ for males and 8.97−22.87 MET·h·d⁻¹ for females. These findings provide critical evidence for developing OPA interventions strategies targeting high-risk population for CVD.

Objective The study aimed to investigate whether montelukast sodium could alleviate airway inflammatory responses in asthmatic mice by affecting the PHD2/HIF-1α pathway.Methods An allergic asthma model was established by ovalbumin(OVA)induction,and 18 female BALB/c mice were randomly divided into a control group(Con group),an asthma group(OVA group),and an asthma group with montelukast sodium intervention(30 mg/kg montelukast sodium by oral administration 1 h before OVA challenge,Mon group).HE staining was used to analyze the pathological changes in the lungs of mice.Blood cell analyzer and kits were used to determine the number of inflammatory cells and the levels of cytokines,the content of lactic acid and pyruvic acid in the lungs,respectively.RT-PCR and Western blot were used to detect the mRNA and protein expression of HIF-1α,PHD2,E-cad and p120 in the lungs of mice.Results Compared with the Con group,there was a significant increase in the number of eosinophils,lymphocytes,neutrophils and monocytes,the levels of IL-5,IL-13,complement factor D(CFD)and contents of lactate and pyruvate in the lungs of mice in the OVA group.Lung HIF-1α,PHD2,p120 and E-cad mRNA levels were reduced,meanwhile HIF-1α and PHD2 protein expression were upregulated but E-cad and p120 protein expression were downregulated(all with P<0.05).After montelukast sodium intervention,the number of eosinophils and monocytes and CFD expression were significantly decreased in the lungs of Mon group,the contents of lactate and pyruvate were basically restored to normal,and the mRNA and protein expression of HIF-1α,PHD2,p120 and E-cad were effectively improved.Conclusion Montelukast sodium could alleviate the airway inflammatory responses in the lungs of asthmatic mice by regulating the PHD2/HIF-1α signaling pathway.

Objective:To carry out the scoping review on the form, function and application effect of decision aids for breast reconstruction of breast cancer patients, so as to provide reference for domestic research on decision aids for breast reconstruction.Methods:According to the scoping review framework, literature was systematically searched on Web of Science, PubMed, Cochrane Library, Embase, Scopus, CINAHL, China National Knowledge Infrastructure, Wanfang Data, VIP, and China Biology Medicine disc. The retrieval period was from the establishment of the database to January 19, 2024.Results:A total of 14 articles were included, including 8 randomized controlled trials (RCT), four quasi-experimental studies, one qualitative study, and one prospective cohort study. The main forms of decision aids included web-based software programs, mobile applications (APP), decision support groups, or decision support manuals. The evaluation of intervention effectiveness mainly involved indicators such as patient decision regret, decision conflict, satisfaction, acceptance, and patient-reported outcomes.Conclusions:Breast reconstruction decision aids have a certain positive impact on improving patient satisfaction, decision quality, and patient-reported outcomes, but most studies have not examined their long-term effects. The research on decision aids for breast reconstruction in China is still in its infancy. It is suggested that future research should draw on relevant foreign studies to develop and advance high quality and diversified decision aids, and promote their clinical applications.

Objective To investigate the risk factors for myocardial injury after Nano-Knife surgery in patients with pancreatic cancer, and to establish a nomogram model for risk prediction. Methods A retrospective analysis was performed for the clinical data of 92 patients with pancreatic cancer who underwent Nano-Knife surgery in The Fifth Affiliated Hospital of Zhengzhou University from September 2020 to November 2021, with serum cardiac troponin I > 0.03 ng/mL within 3 days after surgery as the diagnostic criteria for myocardial injury, the patients were divided into myocardial injury group with 51 patients and non-myocardial injury group with 41 patients. Related baseline data were collected for all patients, including age, sex, body mass index, American Society of Anesthesiologists classification, smoking history, alcohol abuse history, and preoperative comorbidities. The Mann-Whitney U test was used for comparison of continuous data between groups, and the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups. Univariate and multivariate logistic regression analyses were used to screen out the variables with statistical significance, and the factors screened out were used to establish a nomogram for predicting the risk of myocardial injury after Nano-Knife surgery in patients with pancreatic cancer. The receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC) were used to evaluate the discriminatory ability and clinical utility of the model. Results Compared with the non-myocardial injury group, the myocardial injury group had a significantly longer ablation time ( χ 2 =7.410, P =0.006), a significantly greater number of probes ( χ 2 =6.130, P =0.047), and a significantly higher proportion of patients with preoperative hypertension ( χ 2 =12.124, P < 0.001) or chronic kidney disease ( χ 2 =12.829, P < 0.001). The univariate logistic regression analysis showed that tumor diameter, ablation time, surgical procedure, number of probes, history of hypertension, and history of chronic kidney disease were associated with the development of myocardial injury (all P < 0.05), and the multivariate logistic regression analysis showed that tumor diameter (odds ratio [ OR ]= 3.94, 95% confidence interval [ CI ]: 1.09-14.18, P =0.036), ablation time ( OR =4.15, 95% CI : 1.30-13.27, P =0.016), surgical procedure ( OR =6.92, 95% CI : 1.92-25.07, P =0.003), and history of hypertension ( OR =4.07, 95%CI: 1.12-14.77, P =0.034) were independent risk factors for myocardial injury after Nano-Knife surgery in patients with pancreatic cancer. An AUC of 0.859 showed that the nomogram had good discriminatory ability and clinical utility. Conclusion There is a relatively high incidence rate of myocardial injury after Nano-Knife surgery in patients with pancreatic cancer. Preoperative hypertension, tumor diameter > 4 cm, and ablation time > 1 hour are independent risk factors for myocardial injury, and the surgical procedure of Nano-Knife surgery and bypass anastomosis can increase the risk of myocardial injury. The nomogram has a good effect in predicting the risk of myocardial injury.

At present, enteral nutrition is well used in the management of patients with severe acute pancreatitis, and feeding intolerance is a common phenomenon in patients with severe acute pancreatitis during the process of enteral nutrition. Through literature review, this article summarizes the timing, route, preparation type of enteral nutrition in patients with severe acute pancreatitis and the influencing factors, prevention and treatment measures of enteral nutrition feeding intolerance at home and abroad, so as to provide a reference for the prevention of enteral nutrition feeding intolerance in patients with severe acute pancreatitis.

Objective:To analyze the value of low dose enteral nutrition (EN) in treatment of septic shock combined with acute gastrointestinal injury Ⅲ (AGI Ⅲ).Methods:Clinical data of septic shock patients combined with AGI Ⅲ admitted at our hospital were analyzed.Patients were divided into two groups according to the nutrition therapy they received:treatment group (EN,n =41) and control group (no EN,n =46).The mortality and ICU hospital stays were collected.The intestinal barrier,inflammatory cytokines,and oxidative stress were evaluated before and after EN treatment.Results:For patients in the treatment group,the dosages of EN ranged from 200 to 410 kcal/d,with the median dose of 350 kcal/d.No significant differences were found on death rates between the two groups (24.4％vs 32.6％,P =0.398).Patients in the treatment group had shorter ICU hospital stays than those of the control group (11.8 ± 3.7 vs 16.2 ± 5.3,P ＜0.01).After one week EN treatment,patients in the treatment group had lower levels of CRP,IL-6,TNF-α,diamine oxidase,endotoxin and D-lactate than those of the control group (P ＜ 0.05).Conclusion:For septic shock patients combined with AGI Ⅲ,low dose EN can improve the intestinal barrier function and systemic inflammatory responses.

OBJECTIVETo investigate the suitable transfection condition of human epidermal cells (hECs) with human epidermal growth factor (EGF) gene by adenovirus vector (Ad-hEGF) and its effects on the biological characteristics of hECs.

METHODShECs were isolated from deprecated human fresh prepuce tissue of circumcision by enzyme digestion method and then sub-cultured. hECs of the third passage were used in the following experiments. (1) Cells were divided into non-transfection group and 5, 20, 50, 100, 150, and 200 fold transfection groups according to the random number table (the same grouping method below), with 3 wells in each group. Cells in non-transfection group were not transfected with Ad-hEGF gene, while cells in the latter six groups were transfected with Ad-hEGF gene in multiplicities of infection (MOI) of 5, 20, 50, 100, 150, and 200 respectively. The morphology of the cells was observed with inverted phase contrast microscope, and expression of green fluorescent protein of the cells was observed with inverted fluorescence microscope at transfection hour (TH) 24, 48, and 72. (2) Another three batches of cells were collected, grouped, and treated as above, respectively. Then the transfection rate of Ad-hEGF gene was detected by flow cytometer (n=3), the mass concentration of EGF in culture supernatant of cells was detected by enzyme-linked immunosorbent assay (n=6), and the proliferation activity of cells was detected by cell counting kit 8 (CCK8) and microplate reader (n=6) at TH 24, 48, and 72, respectively. (3) Cells were collected and divided into non-transfection group and transfection group, with 6 wells in each group. Cells in non-transfection group were cultured with culture supernatant of cells without transfection, while cells in transfection group were cultured with culture supernatant of cells which were transfected with Ad-hEGF gene in the optimum MOI (50). CCK8 and microplate reader were used to measure the biological activity of EGF secreted by cells on culture day 1, 3, and 5. (4) Cells were collected and divided into non-transfection group and transfection group, with 12 wells in each group. Cells in non-transfection group were not transfected with Ad-hEGF gene, while cells in transfection group were transfected with Ad-hEGF gene in the optimum MOI (50). The expression levels of cytokeratin 14 (CK14) and CK19 of cells were measured by immunofluorescence staining at TH 24. (5) Cells were collected, grouped, and treated as in (4), with 6 wells in each group. At post scratch hour (PSH) 0 (immediately after scratch), 12, 24, and 48, the migration distance of cells was observed and measured with inverted phase contrast microscope. Data were processed with analysis of variance of factorial design, analysis of variance for repeated measurement, and LSD test.

RESULTS(1) At TH 24 and 48, morphology of cells in each transfection group and non-transfection group were similar. Compared with that in non-transfection group, the cell debris increased significantly in 200 fold transfection group at TH 72. At TH 24, 48, and 72, the expression of green fluorescent protein was not seen in cells of non-transfection group, whereas it increased in cells of transfection group over transfection time. (2) The transfection rate of Ad-hEGF gene of cells in each transfection group increased gradually over transfection time. At TH 72, the transfection rates of Ad-hEGF gene of cells in 50-200 fold transfection groups were all above 90%, while the transfection rates of Ad-hEGF gene of cells in non-transfection group, 5, and 20 fold transfection groups were (0.51±0.20)%, (62.44±6.23)%, and (75.00±5.43)% respectively, which were obviously lower than the rate in 50 fold transfection group [(93.12±2.55)%, with P values below 0.01]. The mass concentration of EGF in culture supernatant of cells in each transfection group increased gradually over transfection time. At TH 72, the mass concentration of EGF in culture supernatant of cells in 50 fold transfection group was obviously higher than that in each of the other groups (with P values below 0.01). The proliferation activity of cells in each group at TH 24 and 48 was similar (with P values above 0.05). At TH 72, the proliferation activity of cells in 200 fold transfection group was obviously lower than that in other groups (with P values below 0.05). (3) On culture day 1, the biological activity of EGF secreted by cells in two groups was similar (P>0.05). On culture day 3 and 5, the biological activity of EGF secreted by cells in transfection group were obviously higher than that in non-transfection group (with P values below 0.01). (4) At TH 24, the expression levels of CK14 and CK19 of cells in transfection group were higher than those in non-transfection group. (5) The width of scratch in two groups was nearly the same at PSH 0. At PSH 12-48, the migration distance of cells in transfection group was obviously longer than that in non-transfection group (with P values below 0.01).

CONCLUSIONSThe suitable range of MOI of hECs transfected with Ad-hEGF gene is 50-150, and 50 is the optimum. hECs transfected with Ad-hEGF gene with MOI 50 can effectively express the EGF gene and keep its good abilities of proliferation, differentiation, and migration, as well.

Adenoviridae ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; EGF Family of Proteins ; genetics ; metabolism ; Epidermis ; cytology ; Genetic Vectors ; Humans ; Keratins ; metabolism ; Male ; Transfection

OBJECTIVETo study the application of VSD in the treatment of severe necrotizing fasciitis in extremities of patients.

METHODSEight patients, suffering from severe necrotizing fasciitis, who had been traditionally treated with iodophor-soaked gauze for 21 to 365 days in other hospitals, were transferred to our institute because of the nonhealing wounds and systemic toxic symptoms induced by infection, from January 2011 to August 2013. After admission, surgical debridement was performed timely, and the necrotic tissue was collected during the operation for pathological observation after HE staining. After the operation, VSD was started with negative pressure ranging from -100 to -80 kPa, and the furacilin solution (0.2 g/L) and oxygen (2 L/min) were continuously infused into the wound during the treatment. Surgical debridement was performed repeatedly according to the wound condition followed by change of VSD dressings to continue VSD treatment. The wounds were closed by suturing or with autologous skin grafts after being covered by fresh granulation tissue. The times of surgical debridement, times of change of VSD materials, wound healing status, and length of stay in our institute were recorded. All patients were followed up for a long time. Results HE staining showed that there were diffuse necrotic adipose and fibrous connective tissues in the necrotic tissue, and the normal tissue structure disappeared accompanied by significant infiltration of inflammatory cells. The number of surgical debridement was 2 to 10 (3.9 +/- 2.8) times. The number of VSD materials change was 2 to 10 (4.0 +/- 2.9) times. Wounds were closed by suturing and healed in two patients; wounds in the other six patients were partially sutured, their residual wounds were healed by autologous skin grafting. The length of stay in our institute was 20 to 49 (33 +/- 10) days. All patients were discharged after recovery. Patients were followed up for 2 to 24 months, and their wounds were found to be in good condition without ulceration or recurrence.

CONCLUSIONSVSD can effectively remove the necrotic tissues and exudates from the fascial spaces and promote proliferation of granulation tissue. Therefore it serves as an effective approach to the treatment of severe necrotizing fasciitis in extremities.

Debridement ; Drainage ; Extremities ; surgery ; Fasciitis, Necrotizing ; surgery ; Granulation Tissue ; Humans ; Negative-Pressure Wound Therapy ; Oxygen ; Pressure ; Skin ; Skin Transplantation ; Ulcer ; Vacuum