BACKGROUND:Promoting skin wound healing is a huge challenge facing global public health.To promote faster and higher-quality wound healing,it is necessary to explore more advantageous dressings to address this problem.OBJECTIVE:To investigate the hemostatic properties of acellular dermal matrix hydrogel and its effect on skin wound healing.METHODS:(1)Acellular dermal matrix hydrogel was prepared,and the differences in microscopic morphology and main components between it and acellular dermal matrix were analyzed.(2)Acellular dermal matrix hydrogel and chitosan hydrogel were used to cover the femoral artery puncture site of rats,and the bleeding quality and coagulation time were recorded.Acellular dermal matrix hydrogel and chitosan hydrogel were mixed with rat anticoagulated blood,and the coagulation index within 30 minutes was detected.(3)A full-thickness skin defect model with a diameter of 12 mm was made on the back of 18 SD rats,and they were randomly divided into 3 groups,with 6 rats in each group:the model group used PBS to clean the wound,and the control group and the experimental group used chitosan hydrogel and acellular dermal matrix hydrogel to cover the wound,respectively.The hydrogel dressing was changed every day,and the treatment was continued for 14 days,and the wound healing was observed.On day 3 after modeling,immunofluorescence staining of inducible nitric oxide synthase(M1 macrophages)and CD206(M2 macrophages)was performed on the wound surface.On day 14 after modeling,hematoxylin-eosin staining,Masson staining,and CD31 immunohistochemical staining were performed on the wound surface.RESULTS AND CONCLUSION:(1)Scanning electron microscopy revealed that the acellular dermal matrix hydrogel had a porous structure,and the Fourier transform infrared spectrum showed that it had the same main components as the acellular dermal matrix.(2)Both acellular dermal matrix hydrogel and chitosan hydrogel had obvious hemostatic ability in vivo.In the in vitro coagulation experiments,the coagulation index of acellular dermal matrix hydrogel was significantly higher than that of chitosan hydrogel.(3)In the rat skin full-thickness defect model,both acellular dermal matrix hydrogel and chitosan hydrogel could improve the wound healing rate.Hematoxylin-eosin and Masson staining results showed that acellular dermal matrix hydrogel could reduce the infiltration of inflammatory cells in the center of the wound.Both acellular dermal matrix hydrogel and chitosan hydrogel could decrease scar width and increase collagen deposition rate.CD31 immunohistochemical staining results showed that both hydrogels could promote angiogenesis in the wound site.Immunofluorescence staining results showed that both hydrogels could reduce the proportion of M1 macrophages and increase the proportion of M2 macrophages,and the effect of acellular dermal matrix hydrogel was stronger than that of chitosan hydrogel.(4)The results show that the acellular dermal matrix hydrogel has good hemostatic properties and the ability to promote wound healing.

BACKGROUND:Promoting skin wound healing is a huge challenge facing global public health.To promote faster and higher-quality wound healing,it is necessary to explore more advantageous dressings to address this problem.OBJECTIVE:To investigate the hemostatic properties of acellular dermal matrix hydrogel and its effect on skin wound healing.METHODS:(1)Acellular dermal matrix hydrogel was prepared,and the differences in microscopic morphology and main components between it and acellular dermal matrix were analyzed.(2)Acellular dermal matrix hydrogel and chitosan hydrogel were used to cover the femoral artery puncture site of rats,and the bleeding quality and coagulation time were recorded.Acellular dermal matrix hydrogel and chitosan hydrogel were mixed with rat anticoagulated blood,and the coagulation index within 30 minutes was detected.(3)A full-thickness skin defect model with a diameter of 12 mm was made on the back of 18 SD rats,and they were randomly divided into 3 groups,with 6 rats in each group:the model group used PBS to clean the wound,and the control group and the experimental group used chitosan hydrogel and acellular dermal matrix hydrogel to cover the wound,respectively.The hydrogel dressing was changed every day,and the treatment was continued for 14 days,and the wound healing was observed.On day 3 after modeling,immunofluorescence staining of inducible nitric oxide synthase(M1 macrophages)and CD206(M2 macrophages)was performed on the wound surface.On day 14 after modeling,hematoxylin-eosin staining,Masson staining,and CD31 immunohistochemical staining were performed on the wound surface.RESULTS AND CONCLUSION:(1)Scanning electron microscopy revealed that the acellular dermal matrix hydrogel had a porous structure,and the Fourier transform infrared spectrum showed that it had the same main components as the acellular dermal matrix.(2)Both acellular dermal matrix hydrogel and chitosan hydrogel had obvious hemostatic ability in vivo.In the in vitro coagulation experiments,the coagulation index of acellular dermal matrix hydrogel was significantly higher than that of chitosan hydrogel.(3)In the rat skin full-thickness defect model,both acellular dermal matrix hydrogel and chitosan hydrogel could improve the wound healing rate.Hematoxylin-eosin and Masson staining results showed that acellular dermal matrix hydrogel could reduce the infiltration of inflammatory cells in the center of the wound.Both acellular dermal matrix hydrogel and chitosan hydrogel could decrease scar width and increase collagen deposition rate.CD31 immunohistochemical staining results showed that both hydrogels could promote angiogenesis in the wound site.Immunofluorescence staining results showed that both hydrogels could reduce the proportion of M1 macrophages and increase the proportion of M2 macrophages,and the effect of acellular dermal matrix hydrogel was stronger than that of chitosan hydrogel.(4)The results show that the acellular dermal matrix hydrogel has good hemostatic properties and the ability to promote wound healing.

Objective: To identify the latent profile characteristics and associated factors of family intergenerational transmission of proactive health behaviors in overweight and obesity junior high school students, so as to provide a reference for promoting active health in adolescents. Methods: From October to December 2024, a stratified cluster random sampling method was employed to select 4 932 junior high school students with overweight and obesity from 18 junior high schools of three cities representing the eastern (Yantai), central (Zibo), and western (Zaozhuang) regions of Shandong Province. Latent profile analysis was used to explore the heterogeneity of family intergenerational transmission among those students. Univariate analysis and multiple Logistic regression analysis were conducted to identify factors associated with different profiles and to examine the influence of profile membership on junior high school students proactive health levels. Results: The intergenerational transmission of health behaviors in junior high school students could be classified into 3 latent profiles:the moderate modeling dysfunctional group (5.88%, n =290), the low modeling advantage deficient group (41.79%, n =2 061), and the high modeling functional harmonious group ( 52.33 % n =2 581). Univariate analysis showed that gender, urban/rural area, region location, paternal/maternal education level, family economic status, and only child status were significantly associated with the classification of latent profiles of intergenerational transmission in families of overweight and obesity junior high school students ( χ 2=7.63-165.22, all P <0.05). Multiple Logistic regression analysis revealed that, using the moderate modeling dysfunctional group as the reference, male students ( OR =0.71) and those residing in coastal cities ( OR =0.74) were less likely to belong to the low modeling advantage deficient group (both P <0.05); students with moderate family economic status were more likely to belong to the low modeling advantage deficient group ( OR =1.72， P <0.05). Conversely, students living in urban areas ( OR =1.43), those with fathers ( OR =2.53) or mothers ( OR =2.48) having a college degree or above, and those with moderate ( OR =3.89) or good ( OR =2.42) family economic status were more likely to be classified into the high modeling functional harmonious group (all P < 0.05 ). Using the low modeling advantage deficient group as the reference, residing in coastal cities ( OR =1.26), living in urban residence ( OR =1.14), having parents (father or mother) with a college education or above ( OR =1.91, 2.33), moderate or good family economic status ( OR = 2.27 , 3.17), and being an only child ( OR =1.19) were associated with a higher probability of belonging to the high modeling functional harmonious group (all P < 0.05 ). There was a statistically significant difference in active health behaviors among students across different latent profiles of family intergenerational transmission ( F =494.79, P <0.01). Conclusions The heterogeneity of family intergenerational transmission is associated the level of proactive health behaviors among junior high school students. Therefore, precision interventions should be implemented based on different categories of family intergenerational transmission, so as to strengthen the efficacy of intergenerational transmission of health behaviors and promote proactive health among junior high school students.

AIM: To optimize an orthopedic non-muscle invasive bladder cancer (NMIBC) model in nude mouse by comparing four different ways of cellular transplantation, and to evaluate the efficacy of drug by bladder instillation, so as to provide a stable and efficient animal model for the treatment of bladder cancer. METHODS: After disruption of bladder mucosa by dilute acid-alkali or silver nitrate, T24 cells were instilled into the nude mouse bladder. T24 cells were injected directly into the bladder with mechanical injury of bladder mucosa. T24 cells were injected into the bladder wall. On the 14th day after making models, the nude mice were sacrificed. And the bladder mass and histopathological changes of tumor (including bladder) was observe to confirm the formation of orthopedic bladder cancer. The dynamic changes of orthopedic bladder cancer were observed after injecting T24 cells into the bladder wall. Gemcitabine was used to verify the applicability of the model of injecting T24 cells into the bladder wall in vivo. RESULTS: No tumor was found in the bladder after intravesical instillation of T24 cells with dilute acid-alkali or silver nitrate treatment. With mechanical injury of bladder mucosa, all nude mice had tumors after injection T24 cells. But the number of tumors varied and often occurred at multiple sites. The tumor was found in the bladder of all nude mice by injecting T24 cells into bladder wall, and there was only one tumor. The tumor showed slow linear growth within 15 days and rapid linear growth from day 18 to 31. In vivo efficacy evaluation, gemcitabine 150 mg/kg intravesical perfusion could significantly inhibit the growth of NMIBC in nude mice replicated by direct injection of T24 cells into the bladder wall, and the tumor inhibition rate was 97.1%. CONCLUSION: The orthotopic NMIBC model can not be established with the bladder mucosa injuried by dilute acid-alkali or silver nitrate treatment. The number and size of orthotopic bladder cancer are different by mechanical injury of bladder mucosa. Injection of T24 cells into the bladder wall of nude mouse can successfully establish the orthotopic NMIBC model, which can be used for the evaluation of NMIBC therapeutic drugs.

Objective:To investigate the effect of digoxin on bleomycin-induced pulmonary fibrosis in mice, and investigate its possible mechanism through in vitro and in vivo experiments. Methods:① In vivo experiment: 60 C57/BL6J mice were randomly divided into control group, pulmonary fibrosis model group (model group), pirfenidone (300 mg/kg) group, digoxin 1.0 mg/kg and 0.2 mg/kg groups, with 12 mice in each group. The pulmonary fibrosis model of mice was reproduced by single intratracheal infusion of bleomycin (5 mg/kg). The control group was given the same amount of sterile normal saline. From the next day after modeling, each group was received corresponding drugs by intragastric administration once a day for 28 days. Control group and model group were given the same amount of normal saline. The mice were sacrificed and the lung tissue was collected to detect the lung coefficient. After hematoxylin-eosin (HE) and Masson staining, the lung tissue morphology and collagen changes were observed under light microscope. Immunohistochemistry was used to detect the positive expressions of α-smooth muscle actin (α-SMA) and extracellular matrix (ECM) collagen (COL-Ⅰ and COL-Ⅲ) in lung tissue. The protein expressions of ECM fibronectin (FN), transforming growth factor-β (TGF-β) and phosphorylation of Smad3 (p-Smad3) in lung tissue were detected by Western blotting. ② In vitro experiment: human embryonic lung fibroblast-1 (HFL-1) cells were cultured and divided into blank control group, fibroblast activation model group (model group), pirfenidone (2.5 mmol/L) group and digoxin 100 nmol/L and 50 nmol/L groups when cell density reached 70%-90%. After 3-hour treatment with corresponding drugs, except blank control group, the other groups were treated with TGF-β for 48 hours to establish fibroblast activation model. The expressions of α-SMA, FN and p-Smad3 proteins and the phosphorylations of phosphatidylinositol-3-kinase (PI3K)/Akt pathway proteins PI3K and Akt (p-PI3K, p-Akt) were detected by Western blotting. Results:① In vivo, compared with the control group, the alveolar structure of mice in the model group was significantly damaged, a large number of inflammatory cells infiltrated, collagen deposition in the lung interstitium was increased, the deposition of ECM in the lung tissue was also increased, and the expressions of α-SMA, FN, TGF-β and p-Smad3 protein were increased, indicating that the model of bleomycin-induced pulmonary fibrosis in mice was successfully prepared. Compared with the model group, digoxin significantly inhibited airway inflammation and collagen fiber deposition, reduced ECM deposition, and decreased the protein expressions of α-SMA, FN, TGF-β and p-Smad3, while the effect was better than that of the pirfenidone group, and the digoxin 1.0 mg/kg group had a better effect except FN [α-SMA ( A value): 5.37±1.10 vs. 9.51±1.66, TGF-β protein (TGF-β/GAPDH): 0.09±0.04 vs. 0.33±0.23, p-Smad3 protein (p-Smad3/GAPDH): 0.05±0.01 vs. 0.20±0.07, all P < 0.01]. ② In vitro, compared with the blank control group, the expressions of FN, α-SMA, p-Smad3 and PI3K/Akt signaling proteins in the model group were increased, indicating that the fibroblast activation model induced by TGF-β was successfully reproduced. Compared with the model group, digoxin significantly inhibited fibroblast activation, and decreased the expressions of FN, α-SMA, p-Smad3, and PI3K/Akt pathway proteins, moreover, the effect was better than that of the pirfenidone group, and decreased FN, SMA and p-Akt protein expressions were more obvious in digoxin 100 nmol/L group [FN protein (FN/GAPDH): 0.21±0.15 vs. 0.88±0.22, α-SMA protein (α-SMA/GAPDH): 0.20±0.01 vs. 0.50±0.08, p-Akt protein (p-Akt/GAPDH): 0.30±0.01 vs. 0.65±0.10, all P < 0.01]. Conclusion:Digoxin could suppress the pulmonary fibrosis in mice induced by bleomycin, which might be associated with the regulation of fibroblast activation via suppressing PI3K/Akt signaling pathway in a dose-dependent manner.

In case/control gene expression data, differential expression (DE) represents changes in gene expression levels across various biological conditions, whereas differential co-expression (DC) represents an alteration of correlation coefficients between gene pairs. Both DC and DE genes have been studied extensively in human diseases. However, effective approaches for integrating DC-DE analyses are lacking. Here, we report a novel analytical framework named DC&DEmodule for integrating DC and DE analyses and combining information from multiple case/control expression datasets to identify disease-related gene co-expression modules. This includes activated modules (gaining co-expression and up-regulated in disease) and dysfunctional modules (losing co-expression and down-regulated in disease). By applying this framework to microarray data associated with liver, gastric and colon cancer, we identified two, five and two activated modules and five, five and one dysfunctional module(s), respectively. Compared with the other methods, pathway enrichment analysis demonstrated the superior sensitivity of our method in detecting both known cancer-related pathways and those not previously reported. Moreover, we identified 17, 69, and 11 module hub genes that were activated in three cancers, which included 53 known and three novel cancer prognostic markers. Random forest classifiers trained by the hub genes showed an average of 93% accuracy in differentiating tumor and adjacent normal samples in the TCGA and GEO database. Comparison of the three cancers provided new insights into common and tissue-specific cancer mechanisms. A series of evaluations demonstrated the framework is capable of integrating the rapidly accumulated expression data and facilitating the discovery of dysregulated processes.
Gene Expression Profiling ; Gene Regulatory Networks ; Humans ; Microarray Analysis ; Neoplasms/genetics*

Objective:To investigate the effect of Fuzheng-Peiyuan recipe assisted modified VAD program on M protein, myeloma cells and immune function in patients with multiple myeloma (MM). Methods:A total of 96 patients with MM from January 2017 to May 2019 in our hospital were selected as the research objects, and they were divided into two groups according to the random number table method, with 48 patients in each group. The control group was given a modified VAD regimen (vincristine + adriamycin + dexamethasone), and the observation group was given Fuzheng-Peiyuan recipe as an auxiliary VAD regimen. Both groups were treated for 3 cycles. The clinical efficacy, TCM syndrome score, bone pain score, blood creatinine, hemoglobin, blood calcium, M protein, myeloma cells, immune function [Interleukin-2 (IL-2), Interferon-gamma (INF-γ), Interleukin-4 (IL-4), Interleukin-10 (IL-10)] levels and adverse reactions of the two groups were recorded and compared before and after treatment. Results:The total effective rate of the observation group was 81.3% (39/48), and the control group was 62.5% (30/48). The difference between the two groups was statistically significant ( χ2=4.174, P=0.041). The scores of TCM syndromes ( t=4.674, 13.328) and bone pain scores ( t=4.505, 11.398) in the observation group were significantly lower than those in the control group ( P<0.01) at 1 and 3 cycles after treatment; SCr ( t=4.452, 10.039), blood calcium ( t=4.578, 4.155) in the observation group were significantly lower than those in the control group ( P<0.01); HbAlc levels ( t=5.290, 8.871) in the observation group was significantly higher than that of the control group ( P<0.01); M protein ( t=11.145, 33.812), myeloma cells ( t=6.415, 19.731) in the observation group were significantly lower than those in the control group ( P<0.01); serum IL-2 ( t=4.922, 8.789), INF-γ ( t=5.610, 8.886) in the observation group were significantly higher than those in the control group ( P<0.01); IL-4 ( t=4.709, 6.784), IL-10 ( t=5.287, 12.823) in the observation group were significantly lower than those in the control group ( P<0.01). During the treatment, the incidence of adverse reactions in the observation group was 41.7% (20/48) and that in the control group was 62.5% (30/48). The difference between the two groups was statistically significant ( χ2=4.174, P=0.041). Conclusion:Fuzheng-Peiyuan recipe assisted in improving the VAD regimen in the treatment of MM has a significant clinical effect, which can relieve the clinical symptoms of patients and reduce the degree of bone pain, and promote the reduction of myeloma cells in patients, improve their immune function, and improve the tolerance of chemotherapy.

Objective: To determine the level of Soluble Suppression of Tumorigenicity-2 (sST2) in patients with heart failure(HF) and atrial fibrillation (AF), and to explore its diagnostic and prognostic value in patients with HF and AF. Methods: A prospective cohort study was carried out to investigate the data of 185 HF patients who were hospitalized between January 2018 and June 2018 in department of cardiology or department of cardiac care unit in TEDA International Cardiovascular Hospital. And according to whether they had atrial fibrillation before admission, we categorized patients into: HF with sinus rhythm (HF-SR, n=90) and HF with AF(HF-AF, n=95). Meanwhile, 40 healthy controls were collected. Baseline data of HF-SR and HF-AF groups and plasma sST2 levels in different ejection fraction groups were compared. Plasma sST2 level was determined by enzyme-linked immunosorbent assay(ELISA). Statistical methods such as nonparametric test and Spearman correlation analysis were used. The receiver operating characteristic curve was applied to evaluate the diagnostic value of sST2 in HF-SR and HF-AF groups. And by using the COX risk model, Multi-factor COX analysis was used to analyze the prognosis of patients. Results: Compared with healthy controls, the median (P₂₅, P₇₅) of Plasma sST2 levels in HF patients increased remarkably [32.93 (20.31-51.39) ng/mL vs 15.99(7.97-22.69) ng/mL, Z=-4.373, P<0.001]. Patients with HF-AF group had significantly higher test results [39.86 (27.20-59.21)] ng/mL than HF-SR group [24.74 (14.83-44.11)] ng/mL, Z=-6.783, P<0.001].In the HFmrEF and HFpEF subgroups, the plasma sST2 level of patients in the HF-AF group was higher than that in the HF-SR group (Z=-2.381, P=0.017; Z=-3.701, P<0.001).Spearman correlation analysis showed that, in HF-AF patients, plasma sST2 level was positively correlated with diastolic blood pressure, Hypertension, New York Association (NYHA) cardiac function classification Ⅲ to Ⅳ, white blood count(WBC), and the level of Alanine Aminotransferase (ALT), Υ-glutamine transaminase (Υ-GT), B-type natriuretic peptide (BNP) (r>0, P<0.05).Also, there is a negative correlation between sST2, left ventricular ejection fraction (LVEF) and estimated Glomerular Filtration Rate (eGFR) (r<0, P<0.05). At ROC analysis, sST2 showed predictive value in both HF-AF and HF-SR group, with an optimal cut-off value of 25.33 ng/mL(AUC 0.872, 95%CI: 0.805-0.935, P<0.001, sensitivity 81.1%, specificity 87.5%) and 23.34 ng/mL(AUC 0.665, 95%CI: 0.570-0.761, P<0.001, sensitivity 55.6%, specificity 77.5%).The AUC of BNP and sST2 in differential diagnosis of HF-SR and HF-AF was 0.604 and 0.699, respectively, and the AUC of sST2 was higher than that of BNP. Multi-factor COX analysis indicated that plasma sST2 level, BNP, NYHA cardiac function grading could be risk factors for cardiac events in HF patients. Plasma sST2, left atrial diameter (LA-D), and associated cardiomyopathy are risk factors for cardiac events in patients with HF-AF. The incidence of cardiac events in HF patients with sST2≥20.31 ng/mL was significantly higher than that of patients with sST2<20.31 ng/mL (χ²=7.625, P=0.006). The incidence of cardiac events in HF-AF patients with plasma sST2≥39.86 ng/mL was significantly higher than that in patients with sST2<39.86 ng/mL (χ²=4.287, P=0.038). Conclusions The plasma sST2 level in patients with HF-AF is significantly higher than that both in HF-SR and healthy controls. The diagnostic value of plasma sST2 in patients with HF-AF is higher than that in patients with HF-SR. It is suggested that sST2 are more valuable for the differential diagnosis of HF-SR, HF-AF than BNP. HF-AF Patients with plasma sST2 ≥ 39.86 ng/mL are prone to cardiovascular events.

Objective To study the serotype distribution characteristics and genotypes of Salmo-nella strains isolated in Yunnan Province from 2015 to 2017. Methods Automatic microbiological identifi-cation system and mass spectrometer were used to identify Salmonella strains. Their serotypes were detected using the White-Kauffmann-Le Minor (WKL) scheme based on serological detection. Genotyping was car-ried out by referring to the molecular typing method of Salmonella serotype pulse field gel electrophoresis (PFGE) in PulsenetChina. Cluster analysis was performed with Bionumerics (7.6). Results A total of 408 strains of Salmonella were detected in food and patients in Yunnan Province form 2015 to 2017,belong-ing to 70 serotypes. Thirty-four Salmonella derby strains were detected in food,accounting for 19.10% of all Salmonella strains detected in food. Among the Salmonella strains detected in patients,71 were Salmonella enteritis and 67 were Salmonella typhimurium,accounting for 30.34% and 27.63%, respectively. Results of PFGE revealed that Salmonella derby and Salmonella typhimurium were polymorphic,and Salmonella en-teritis had obvious advantages PFGE band patterns. No obvious time or geographical aggregation was found in the PFGE bands of the three Salmonella species. Conclusion Seventy Salmonella serotypes had been iden-tified in Yunnan Province by 2017. Salmonella derby was the predominant serotype detected in food, while Salmonella enteritidis and Salmonella typhimurium were the predominant serotypes in patients. These three Salmonella species caused sporadic infections in Yunnan Province.

Objective To explore the value of virtual touch tissue quantification (VTQ ) in the diagnosis of pancreas early damage of patients with hyperuricemia(HUA) .Methods Sixty‐five cases of patients with normal glucose tolerance and HUA (HUA group) and 42 cases of patients with HUA and impaired glucose tolerance (IGT group) were included in the study ,and other 150 health subjects were taken as control group .After routine ultrasound examination ,the pancreas shear wave velocity values (Vs) of different groups were measured by VTQ technology ,and the results were analyzed .Results Compared with the control group ,the rate of the abnormai ultrasonogram of pancreas in IGT group showed obvious increasing trend but there was no significantly difference between the other groups(both P >0 0.5) .The Vs of the normal control group ,HUA group ,and IGT group were (1 2.1 ± 0 1.5)m/s ,(1 4.1 ± 0 1.3)m/s and (1 5.9 ± 0 1.5)m/s ,respectively .The Vs of HUA group and IGT group were higher than that of the control group (both P <0 0.5) ,and the Vs of IGT group was significantly higher than that of HUA group ( P <0 0.5) .Conclusions Hyperuricemia may cause pancreas damage ,and with the disease progress ,the pancreas damage became more serious ,and VTQ technology may play an important role on the diagnosis of pancreas early damage in HUA patients .