Resibufogenin suppresses human hepatocellular carcinoma cell proliferation, migration and invasion in vitro / 药学学报

This manuscript aims to investigate the effects of resibufogenin on the proliferation, migration and invasion of human hepatocellular carcinoma cells and its related mechanisms. MTT assay was used to determine the inhibitory effect of resibufogenin on the growth of four hepatocellular carcinoma cells in vitro. Wound-healing assay and Transwell assay were used to evaluate the migration and invasion ability of resibufogenin on MHCC-97H cells. Western blot assay was used to detect the expression of migration and invasion related proteins in MHCC-97H cells treated with different concentrations of resibufogenin. The results showed that resibufogenin significantly inhibited the proliferation of hepatocellular carcinoma cells in vitro. The half maximal inhibitory concentration (IC50) values on MHCC-97H, HepG2, SK-Hep-1 and Huh-7 cells were 0.55 ± 0.06, 2.83 ± 0.24, 5.25 ± 0.49, 14.89 ± 2.28 μmol·L-1, respectively. Resibufogenin also suppressed the migration and invasion of MHCC-97H cells in a concentration-dependent manner. The protein expression of integrin α2, integrin α6, integrin β1, N-cadherin, matrix metalloproteinase 2 (MMP2) and transcription factor Twist in MHCC-97H cells were decreased significantly with the increase of the concentration of resibufogenin, while the protein expression of E-cadherin increased. In addition, we found that p-PI3K/PI3K and p-AKT/AKT ratios were significantly reduced after treatment with resibufogenin. In conclusion, resibufogenin can inhibit the proliferation, migration and invasion of hepatocellular carcinoma MHCC-97H cells in vitro, which is related to the regulation of intracellular migration and invasion protein expression and PI3K/AKT signaling pathway.

Study of the effects of long-term outcomes of autologous peripheral blood stem cell reinfusion in patients with decompensated cirrhosis / 中华肝脏病杂志

Objective: Autologous peripheral blood stem cells (PBSC) derived from bone marrow can promote liver regeneration and improve the liver function of patients, but there are few studies on its effect on the long-term outcomes in patients with decompensated cirrhosis. Based on previous work, this study observed the clinical outcomes of PBSC treatment in patients with decompensated cirrhosis for 10 years, in order to provide more data support for the safety and efficacy of stem cells in clinical applications. Methods: Data of patients with decompensated liver cirrhosis who completed PBSC treatment in the Department of Gastroenterology of the First Affiliated Hospital of Air Force Military Medical University from August 2005 to February 2012 were included. The follow-up endpoint was death or liver transplantation, and patients who did not reach the follow-up endpoint were followed-up for at least 10 years. The patients with decompensated liver cirrhosis who met the conditions for PBSC treatment but did not receive PBSC treatment in our hospital during the same period were used as controls. Results: A total of 287 cases with decompensated liver cirrhosis had completed PBSC treatment, and 90 cases were lost to follow-up within 10 years after surgery. A total of 151 cases with complete survival follow-up data were included in the control group. There were no statistically significant differences in baseline information such as gender, age, etiological composition and liver function score between the two groups. The 10-year survival rate was higher in PBSC than control group (37.56% vs. 26.49%, P<0.05). Cholinesterase, albumin, international normalized ratio, Child-Turcotte-Pugh score, model for end-stage liver disease score, and other indicators were gradually recovered within 3 months to 1 year after PBSC treatment, and stabilized at a more desirable level in the long-term after follow-up for up to 10 years. There was no statistically significant difference in the incidence of liver cancer between the two groups (25.22% vs.31.85%, P=0.267). The age of onset of hepatocellular carcinoma was later in PBSC than control group [(56.66±7.21) years vs. (52.69±8.42) years, P<0.05]. Conclusions: This long-term observational follow-up study of more than ten years confirms that PBSC treatment can bring long-term benefits to patients with decompensated cirrhosis, with good long-term safety, thus providing more data support on the safety and efficacy of stem cells for clinical applications.

Role of intercellular junctions in the biological behavior of SP cells of multiple myeloma / 药学实践杂志

Objective To observe the effects of the intercellular gap junction (GJIC) composed of connexin 43(Cx43) in mesenchymal stem cells (MSCs) from different sources and their signals on the biological behavior of multiple myeloma (MM) lateral population cells (SP cells), and to explore its possible mechanism. Methods Mesenchymal stem cells (MSCs) from different sources were isolated and cultured. SP cells of MM cell line RPMI 8266 were sorted by flow cytometry. RT-PCR and Western blot were used to detect the expression of Cx43 gene and protein in MSCs, RPMI 8266 and SP cells from different sources. The effects of MSCs from different sources on SP cell cycle, Cx43 protein expression, colony formation ability in vitro, stem cell related gene expression, cytokine secretion and drug resistance were observed. Results There was no significant difference in morphology and phenotype between MM-MSCs and ND-MSCs. Both MM-MSCs and RPMI 8266 cells expressed a higher level of Cx43. Co-culture with MM-MSCs induced more SP cells to enter G0 phase (P<0.001). The expressions of c-myc, Kif4 and Sox2 genes in SP cells were significantly up-regulated, while the expression of Oct-4 gene was down-regulated. After adding α-GA, c-myc, Kif4 and Sox2 were down-regulated in varying degrees, but there was no significant difference. The expression of Cx43 was up-regulated by (31.00±2)% and (39.00±2)%, respectively. The colony formation ability in vitro was up-regulated, and the addition of α-GA could partially inhibit this effect. A small amount of c-myc, Kif4, Sox2 and Oct-4 genes were expressed in RPMI 8266. These genes were significantly up-regulated in SP cell subpopulation. MM-MSCs secreted high levels of interleukin (IL)-6. After co-culture with SP cells, the expressions of IL-6, IL-10 and TGF-β in the supernatant of MM-MSCs were up-regulated (P=0.0072, P=0.037). bFGF and IL-17 had no significant change. After adding α-GA, the levels of IL-6, IL-10 and TGF-β in the supernatant decreased. MM cells were sensitive to bortezomib (BTZ) induced apoptosis, but SP cells were less sensitive. Co-culture with MM-MSCs significantly reduced BTZ-mediated apoptosis. The addition of α-GA partially restored the sensitivity of MM cells to bortezomib. Conclusion MM-MSCs and multiple myeloma SP cells up-regulate the expression of Cx43 protein, form more GJIC, and promote the proliferation and drug resistance of SP cells by changing the cytokine secretion profile of MSCs, which may be one of the reasons for the recurrence of MM.

Changes of viral DNA load in the early stages of antiviral treatment in varicella zoster virus-induced acute retinal necrosis / 中华眼底病杂志

Objective:To observe the changes of varicella zoster virus (VZV)-DNA load in aqueous humour samples in VZV-induced acute retinal necrosis (ARN) in the early stages of antiviral treatment.Methods:A retrospective observational clinical study. From April 2016 to April 2018, 24 patients with 24 eyes of VZV-induced ARN who were diagnosed by Department of Ophthalmology, Eye and ENT Hospital of Fudan University and received complete aqueous humor sampling were included in the study. Among them, there were 13 males with 13 eyes, 11 females with 11 eyes; 12 left eyes and 12 right eyes; the age was 52.0±9.5 years old (39-71 years old). The time from the onset of ocular symptoms to the diagnosis of ARN was 16.6±6.1 days (7-30 days). Best-corrected visual acuity (BCVA) and ultra-wide-field fundus imaging were performed in all affected eyes. The BCVA examination was carried out using the Snellen visual acuity chart, which was converted into the logarithm of the minimum angle of resolution (logMAR) visual acuity. All patients were given intravitreal injection of 40 mg/ml ganciclovir 0.1 ml (including 4 mg of ganciclovir), 2 times a week, until the active necrotizing retinal lesions subsided, at most after the diagnosis 4 weeks, with a maximum of 9 injections. The follow-up period was 12.8±5.6 months. The aqueous humor samples were collected at presentation and 4, 7, 14, 21, 28 days after the initiation of antiviral therapy, and the VZV-DNA load was detected by real-time quantitative polymerase chain reaction. A plateau phase and a logarithmic reduction phase of the DNA load changes were observed after antiviral treatment began. Wilcoxon rank sum test was used to compare and analyze the differences in BCVA between the eyes at baseline and last follow-up.Results:The mean viral load at presentation was 8.6×10 7±1.3×10 8 copies/ml. The initial plateau phase last for an average of 7.4±2.4 days. In the following logarithmic reduction phase, the mean slope of the decline in viral load was -0.13±0.04 log/day, and the expected time for half reduction of the initial viral load was 2.5±0.7 days. After 28 days antiviral treatment, the viral load decreased to 1.7×10 5±1.8×10 5 copies/ml. In the course of the disease, rhegmatogenous retinal detachment occurred in 16 eyes. Before treatment and at the last follow-up, the logMAR BCVA of the affected eye was 1.1±0.6 and 0.8±0.7, respectively. The results of correlation analysis showed that the logMAR BCVA at the last follow-up was correlated with the initial VZV-DNA load ( r=0.467, P=0.033). Conclusion:The VZV-DNA load in the aqueous humor of eyes with VZV-induced ARN is significantly decreased after antiviral treatment, which is closely related to the clinical process of ARN.

Therapeutic effect of exposed bone cement in treatment of infectious bone and soft tissue defect / 中华显微外科杂志

Objective:To evaluate the therapeutic effect of exposed bone cement in treatment of infectious bone and soft tissue defect by comparison with routine bone cement therapy.Methods:A retrospective analysis was carried out in 27 patients who had been treated from January 2016 to January 2020. Of the 27 patients, 12 were treated by exposed bone cement filling for bone defect at the first stage, followed by flap and bone grafting at the second stage. Other 15 patients were treated by routine bone cement filling and flap repair at the first stage, followed by bone grafting at the second stage. Regular dressing change was carried out after surgery. All patients entered follow-up by out-patient review for wound condition and X-ray. Infection rate of bone and soft tissue, time of bone union, flap survive rate and complication were compared between the 2 groups.Results:The follow-up lased for 9-24(16.5±3.9 ) months. The bone defects were all healed. The treatment time of bone defects in the group of exposed bone cement was 25-34(28.5±2.8) weeks. The treatment time of bone defect in the routine cement group was 25-36(29.6±3.4 )weeks. There was no statistical difference between the 2 groups( P<0.05). Two cases in each group had failed in infection control after bone cement implantation. With further debridement, cleaning and other treatment, the infection was under control. All flaps in the 2 groups survived. In the group of exposed bone cement, there were 3 flaps splitting, 2 hemorrhage(effusion) and 1 partial flap necrosis, In the routine bone cement group, there were 4 wound dehiscence, 8 hemorrhage(effusion) and 3 partial flaps necrosis. There was no significant difference in flap complications between the 2 groups( P>0.05). The healing of bone defect was evaluated by Samantha X-ray score, the scores of the 2 groups were 5.41±0.67 and 5.40±0.63, respectively, with no statistical significance. The Paley's approach was used to grade the bone healing and the function of adjacent joints. Paley bone defect healing evaluation results weve all excellent. Joint function assessment were as follow: in the group of exposed bone cement, 6 cases were excellent and 3 were good; in routine bone cement group: 6 cases were in excellent and 5 in good. There was no significant statistical difference. Conclusion:Compared with a routine bone cement treatment, the exposed bone cement in the treatment of infectious bone defects saw a fewer flap splitting and fewer hemorrhage/effusion, without an increase in bone and soft tissue infection. This procedure could be considered for further trials in the treatment of a composite defects of infected bone and soft tissue.

Analysis of inflammatory characteristics and changes of small airway function in patients with eosinophil and neutrophil asthma / 中国综合临床

Obsjective To analyze the inflammation characteristics and changes of small airway function in patients with eosinophil and neutrophil asthma, and provide evidence for individualized treatment of asthma. Methods:Using a cross-sectional study, 46 patients with eosinophilic asthma and 42 patients with neutrophilic asthma confirmed by cytology of induced sputum were recruited from July 1, 2017 to June 30, 2019 at the respiratory Department of Respiratory Medicine,Jinshan Branch of the Sixth People's Hospital of Shanghai. Patients were divided by asthma category into eosinophilic asthma group and neutrophilic asthma group.The severity of acute attack, the score of asthma control test (ACT) and the concentration of serum C-reactive protein (CRP) were compared between the two groups The fraction of exhaled nitric oxide (FeNO), related cytokines(interleukin-4(IL-4), interleukin-5(IL-5), interleukin-13(IL-13), interleukin-17(IL-17) and interferon γ(IFN-γ)) in peripheral blood and induced sputum supernatant and lung function indicators (forced exhalation volume in one second (FEV1)% percent predicted (%pred), maximal mid-expiratory flow (MMEF)% pred, forced expiratory flow (FEF) 75% pred, forced expiratory flow at 50% of FVC exhaled (FEF50%) pred were detected. Independent sample t-test was used for the comparison between measurement data groups comforming to normal distritution, rank sum test was used for the comparison between measurement data groups not conforming to normal distribution, and χ 2 test was used for the comparison of counting data. Results:There were no significant differences in the general data and ACT scores between the two groups (all P>0.05). The ratio of severe and critical degree (52.38%(22/42)), uncontrolled and partially controlled patients (59.52%(25/42)), CRP level (24.6(7.1, 35.0) mg/L) in neutrophil asthma group were higher than those in eosinophilic asthma group(30.43% (14/46), 36.96% (17/46), and 8.5 (2.0, 12.0) mg/L, respectively) (χ 2=4.37, χ 2=4.48, Z=4.76; P=0.036, P=0.034, P<0.001). The concentration of FeNO was higher in eosinophilic asthma group (76(54,93) ppb) than that in neutrophil asthma group(27(15,41) ppb),and the differences was statistically significant ( Z=6.52, P<0.001). The values of FEV1% pred ((56.13±21.51)%), MMEF% pred ((62.03±23.97)%), FEF75% pred ((54.42±20.49)%), FEF50% pred ((66.89±26.47)%) in neutrophil asthma group were lower than those in eosinophilic asthma group ((68.53±29.81)%, (72.16±23.05)%, (65.38±25.46)% and (79.86±27.61)%), and the difference between the two groups was statistically significant( t values were 2.25, 2.02, 2.21, 2.24; P values were 0.027, 0.046, 0.030, 0.027). The concentrations of serum IL-4((49.42±24.46) ng/L), IL-5((104.89±43.91) ng/L) and IL-4((44.49±19.12) ng/L), IL-5((95.45±28.58) ng/L) in induced sputum supernatant were higher than neutrophilic asthma group((32.29±14.19), (50.35±22.30), (33.33±15.08), (55.61±26.41) ng/L). The difference between the two groups was statistically significant ( t values were 4.06, 7.44, 3.02, 6.77, P values were <0.001, <0.001, 0.003, <0.001). In eosinophilic asthma group, the concentrations of serum IL-13 ((76.18±20.62) ng/L), IL-17 ((31.32±9.32) ng/L), IFN-γ ((18.27±5.56) ng/L) and IL-13((71.08±20.08) ng/L), IL-17((26.29±6.70) ng/L), and IFN-γ((17.61±5.94) ng/L) in induced sputum supernatant were lower than those in neutrophilic asthma group((153.83±44.53 ) ng/L, (55.27±18.89) ng/L, (26.46±10.08) ng/L, (120.32±28.41) ng/L, (44.99±12.66) ng/L, (23.91±7.66) ng/L). The difference between the two groups was statistically significant ( t values were 10.33, 7.43, 4.66,9.31,8.54,4.33, respectively; all P<0.001). Conclusion:Eosinophilic asthma and neutrophil asthma have different inflammation, small airway function characteristics and different response to treatment. The small airway function changes in early stage of neutrophil asthma are more obvious.

Risk factors analysis of central airway stenosis after lung transplantation / 器官移植

Objective To investigate the risk factors of central airway stenosis after lung transplantation. Methods Clinical data of 155 recipients undergoing lung transplantation in Wuxi People's Hospital Affiliated to Nanjing Medical University from July 2016 to December 2017 were retrospectively analyzed. According to the incidence of central airway stenosis following lung transplantation, all recipients were divided into the stenosis group (n=36) and control group (n=119). The incidence of central airway stenosis after lung transplantation was summarized. The risk factors of central airway stenosis after lung transplantation were assessed by univariate and multivariate logistic regression analyses. Results Among 155 lung transplant recipients, 36 cases (23.2%) developed central airway stenosis. The average incidence time was (53±13) d after lung transplantation. Univariate analysis demonstrated that bilateral lung transplantation, grade 3 primary graft dysfunction (PGD), airway fungal infection, long cold ischemia time, long mechanical ventilation time and long intensive care unit (ICU) stay were the risk factors for central airway stenosis after lung transplantation (all P < 0.05). Multivariate analysis showed that airway fungal infection, long cold ischemia time and long mechanical ventilation time were the independent risk factors for central airway stenosis after lung transplantation (all P < 0.05). Conclusions Airway fungal infection after lung transplantation, long cold ischemia time and long mechanical ventilation time probably lead to central airway stenosis after lung transplantation. Active preventive measures and intimate monitoring should be taken to improve the quality of life of the recipients after lung transplantation.

Effect of Xiao Qinglongtang on IL-33/ST2 Signaling Pathway in Mice with Allergic Rhinitis / 中国实验方剂学杂志

ObjectiveTo investigate the therapeutic effect of Xiao Qinglongtang （XQLT） on ovalbumin （OVA）-induced allergic rhinitis （AR） in mice and its effect on the interleukin-33 （IL-33）/suppression of tumorigenicity 2 （ST2） signaling pathway. MethodSeventy-two female BALB/c mice of SPF grade were randomly divided into a control group， a model group， a positive control group （loratadine， 2.05 mg·kg-1）， and low-， medium-， and high-dose （5.005，10.01，20.02 g·kg-1） XQLT groups. All mice except for those in the control group were sensitized by intraperitoneal injection of OVA solution， and the AR model was induced by intranasal drops of OVA solution. Thirty minutes before local intranasal drops， drugs were administered once， and mice in the control group and the model group received phosphate buffered saline （PBS） at 20 mL·kg-1 for 7 days. After the last intranasal drop of OVA solution， the times of sneezing and nasal rubbing of mice within 10 min was recorded. After drug administration for 7 days， blood samples were collected， and nasal bones of mice were decalcified for the preparation of pathological sections. The content of OVA-specific immunoglobulin E （OVA-sIgE）， interleukin-4 （IL-4）， interleukin-5 （IL-5）， and interleukin-13 （IL-13） was detected by enzyme-linked immunosorbent assay （ELISA） kits. Hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Giemsa staining were used to observe the pathological changes， goblet cell hyperplasia， and eosinophil infiltration of nasal mucosa， respectively. Western blot was used to detect the expression levels of IL-33， ST2， and IL-1 receptor accessory protein （IL-1RAP） in nasal mucosa. ResultCompared with the control group， the model group showed increased times of sneezing and nasal rubbing （P<0.01）， edema and thickening of nasal mucosa， goblet cell hyperplasia and eosinophil infiltration， increased serum levels of OVA-sIgE， IL-4， IL-5 and IL-13 （P<0.01）， and increased protein expression of IL-33， ST2， and IL-1RAP in nasal mucosa （P<0.05，P<0.01）. After drug administration， compared with the model group， the high-dose XQLT group showed reduced times of sneezing and nasal rubbing （P<0.01）， improved pathological conditions of nasal mucosa， reduced serum levels of OVA-sIgE， IL-4， IL-5， and IL-13 （P<0.01）， and declining protein expression of IL-33， ST2， and IL-1RAP in nasal mucosa （P<0.05，P<0.01）. ConclusionXQLT has a therapeutic effect on OVA-sensitized AR mice， and the mechanism may be related to the regulation of the IL-33/ST2 signaling pathway and Th2 inflammatory cytokine to reduce Th2 inflammatory response and alleviate nasal mucosal injury.

Epidemiological investigation on a visceral leishmaniasis case in Zhengzhou City of Henan Province / 中国血吸虫病防治杂志

Objective To perform an epidemiological investigation on a case with visceral leishmaniasis in Zhengzhou City, Henan Province, and to identify the source of infection, so as to illustrate the transmission chain and assess the risk of local leishmaniasis transmission. Methods The medical data were collected from a case with visceral leishmaniasis in Zhengzhou City, and the patient’s bone marrow smears were detected by microscopy. Serum anti-Leishmania antibody test and PCR assay were performed among high-risk residents and all dogs in the village where the patient lived. Sandflies were captured using light traps and artificial traps, and the captured female Phlebotomus chinensis was subjected to PCR assay. The internal transcribed spacer 1 (ITS1) gene was amplified with a nested PCR assay using the genomic DNA extracted from visceral leishmaniasis patients, positive dogs and sandflies, and the sequences were aligned with those download from NCBI. In addition, a phylogenetic tree was created based on the ITS1 gene. Results The visceral leishmaniasis patient had recurrent irregular fever, reduced complete blood counts, low hemoglobin, and a large number of Leishmania amastigotes in bone marrow smears, and was therefore diagnosed as visceral leishmaniasis. Both rk39 rapid diagnostic test and PCR assay tested negative among 324 residents living neighboring the patient’s residence, while 21.39% (43/201) dogs were positive for rk39 rapid diagnostic test and 13.93% (28/201) positive for PCR assay. There were 17 female Ph. chinensis tested positive for Leishmania (0.82%) by PCR assay, and the ITS gene sequences from visceral leishmaniasis patients, positive dogs and sandflies shared a 100% homology with L. infantum. The Leishmania species was therefore characterized as L. infantum. Conclusions L. infantum infection occurs in visceral leishmaniasis patients, dogs and sandflies in Zhengzhou City, indicating a complete transmission chain and a high transmission risk of visceral leishmaniasis by L. infantum. Intensified control measures are required to prevent local transmission of leishmaniasis in Zhengzhou City.

Data mining of medical rule in Lingnan TCM masters for treating Allergic rhinitis / 国际中医中药杂志

Objective:To analyze the characteristics of prescription about Lingnan Traditional Chinese Medicine (TCM) masters for Biqiu treatment based on data mining, so as to provide reference for the clinical practice and patent drug research and development of rhinorrhea in Lingnan district.Methods:By searching journal documents and medical records in CNKI, VIP, Wanfang, Chinese BioMedical Database (SinoMed) and Duxiu Data Retrieval Platform, we selected the articles and famous TCM medical records that met the criteria on the TCM medical rules of treating Biqiu. We screened database in strict accordance with inclusion and exclusion criteria and extracted prescription information from medical cases. The software Ancient and Modern Consilia Cloud Platform (V 1.5) was used for data mining analysis and medical case standardization, and SPSS Clementine 12.0 software were used to conduct frequency statistics, association analysis and cluster analysis of drugs in medical cases. Results:A total of 31 articles and 42 medical cases including 73 prescriptions were screened. The frequency results showed that there were 40 kinds of high frequency TCMs (frequency more than 5), mainly including drugs for benefiting the qi and strengthening the spleen, medicine to relieve cold and promote nasal passages, which was the same as the frequency statistics of the effects of herbal medicine. Seven drug groups were obtained by cluster analysis. The results of rule analysis showed that 16 association rules for drug pairs and 18 association rules for 3 TCMs pairs were obtained.Conclusions:While treating allergic rhinitis, Lingnan medical doctors focus on tonifying spleen qi, dispersing wind and cold, and promoting the nasal passages, which reflect the treatment theory of cultivating earth and generating gold, and attacking and tonifying. Lingnan medical doctors commonly used Guangdong medicinal herbs, which have distinct regional characteristics. The data mining methods can comprehensively summarize and explore the potential rules of Lingnan prominent practitioners' treatment of allergic rhinitis, and provide reference for guiding the treatment of congested nose and congested nose in TCM.

Research on the mechanism of bufalin inhibiting migration and invasion of human prostate cancer PC3 cells / 药学学报

In this study, we investigated the inhibitory effects of bufalin on proliferation, migration and invasion of PC3 cells in vitro, and preliminarily explored the molecular mechanism of epithelial-mesenchymal transformation (EMT) inhibited by bufalin. The viability of PC3 cells was evaluated by MTT assay, and the migration and invasion abilities of PC3 cells were detected by wound healing and Transwell assay. Western blot was used to detect the expression of EMT and integrin family proteins. The results showed that the half maximal inhibitory concentration (IC50) value of bufalin against PC3 cells was 0.26 ± 0.03 μmol·L-1. After bufalin treatment, the migration rate of PC3 cells slowed down (P < 0.05), the number of PC3 cells passing through the microporous membrane decreased (P < 0.05), which indicated that bufalin could inhibit the proliferation, migration and invasion of PC3 cells in a concentration-dependent manner. We found that bufalin could affect the expression of EMT-related proteins,including up-regulation of E-cadherin and down-regulation of N-cadherin, β-catenin, matrix metalloproteinase 9 (MMP9), matrix metalloproteinase 2 (MMP2), c-myc and Snail. Bufalin also inhibited the expression of integrin family proteins, including integrin α2 (ITGA2), integrin β1 (ITGB1), integrin β3 (ITGB3), integrin β5 (ITGB5), Yes-associated protein/transcriptional coactivator with a PDZ-binding motif (YAP/TAZ) and integrin-linked kinase (ILK). In addition, bufalin could also inhibit the protein expression level of phospho-focal adhesion kinase (p-FAK)/FAK, phospho-steroid receptor coactivator (p-Src)/Src and phospho-protein kinase B (p-Akt)/Akt. These results suggested that bufalin might inhibit the proliferation, metastasis and invasion of prostate cancer PC3 cells through the FAK/Src/phosphoinositide 3-kinase (PI3K)/Akt pathway. Therefore, bufalin provides reference value for the development of therapeutic drugs for prostate cancer.

Research progress of malperfusion syndrome in acute type A aortic dissection / 中华胸心血管外科杂志

Acute aortic dissection type A(AADA) has a critical condition and high mortality. One of the most severe complications is malperfusion syndrome. AADA with malperfusion syndrome affects almost all vascular beds, including the brain, coronary artery, viscera, limb branches, and so on. The incidence and severity of malperfusion vary from organ to organ. Clinically, malperfusion must be diagnosed and treated in time. At present, there is no consensus on the clinical management strategy of AADA complicated with malperfusion syndrome. In this review, we discussed the related research progress of AADA involved with malperfusion syndrome to provide some guidance for clinical practice.

External fixation combined with Prontosan management for open fractures complicated with multidrug-resistant bacterial infection / 中华创伤骨科杂志

Objective:To access the efficacy of external fixation combined with Prontosan management for open fractures complicated with multidrug-resistant bacterial infection.Methods:A retrospective analysis was conducted of the data of 22 patients with open fracture complicated by multidrug-resistant bacterial infection who had been admitted to Department of Orthopedic Trauma and Microsurgery, Zhongnan Hospital of Wuhan University from January 2015 to January 2020. According to whether the Prontosan management was used or not, the patients were divided into 2 groups.The Protosan group [9 males and 3 females with an age of (44.6±13.1) years] were subjected to external fixation, vacuum sealing drainage(VSD) or conventional dressing changes, and at the same time Protosan management to flush the wound or Prontosan gel to change dressings.The control group[6 males and 4 females with an age of (45.1±11.7) years] were subjected to external fixation plus VSD or conventional dressing changes. Skin flaps or skin grafts were used to repair the wound immediately after the wound infection was controlled in both groups. The time for negative culture of the bacteria on the wound surface, number of debridement, survival of the skinflaps or grafts, and fracture union were recorded and compared between the 2 groups.Results:There was no significant difference in the preoperative general data between the 2 groups which were comparable( P>0.05).All patients were followed up for 10 to 24 months (mean, 14.5 months).In the Prontosan group, the number of debridement was 2.0 (2.0, 3.0) times, significantly fewer than that in the control group [4.0 (3.0, 4.0) times]; the time for negative bacterial culture (8.3±2.2) d, significantly shorter than that in the control group [(14.2±3.1) d]; the fracture union time (5.5±1.1) months, significantly shorter than that in the control group [(6.5 ±1.1) months]; the Samantha X-ray score at 6 months after operation 6.0 (5.0,6.0) points, significantly higher than that in the control group [5.2(4.5,5.5) points] (all P<0.05). Skin flaps or grafts survived in all the patients without any nonunion or chronic osteomyelitis. Conclusion:In the external fixation of open fractures complicated with multidrug-resistant bacterial infection, combination with Prontosan management can effectively control infection and promote granulation, early wound healing and fracture union.

Astragaloside IV Attenuates Polymicrobial Sepsis-Induced Cardiac Dysfunction in Rats via IKK/NF-κB Pathway / 中国结合医学杂志

OBJECTIVE@#To evaluate the protective effects of Astragaloside IV (AST) in a rat model of myocardial injury induced by cecal ligation and puncture (CLP).@*METHODS@#The model of sepsis-induced cardiac dysfunction was induced by CLP. Using a random number table, 50 specific pathogen free grade of Sprague Dawley rats were randomized into 5 groups: the sham group (sham), the model group (CLP, 18 h/72 h) and AST group (18 h/72 h). Except the sham group, the rats in other groups received CLP surgery to induce sepsis. CLP groups received intragastric administration with normal saline after CLP. AST groups received intragastric administration with AST solution (40 mg/kg) once a day. The levels of inflammatory mediators and oxidative stress markers in the serum of the septic rats were determined via enzyme-linked immunosorbent assay (ELISA) at different time point, such as interleukin 6 (IL-6), IL-10, high mobility group box-1 protein B1 (HMGB-1), superoxide dismutase (SOD), and malondialdehyde (MDA). Cardiac function was determined by echocardiography. Moreover, changes in myocardial pathology were evaluated using hematoxylin and eosin staining. The levels of lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) were analysed to determine the status of CLP-induced myocardium. In addition, the apotosis of myocardial cells was analysed by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL). The protein levels of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), IκB kinase α (IKKα), nuclear factor kappa B p65 (NF-κB p65) were detected by Western blot analysis. Moreover, survival rate was investigated.@*RESULTS@#AST improved the survival rate of CLP-induced rats by up to 33.3% (P<0.05). The cardioprotective effect of AST was observed by increased ejection fraction, fractional shortening and left ventricular internal diameter in diastole respectively (P<0.01 or P<0.05). Subsequently, AST attenuated CLP-induced myocardial apoptosis and the ratio of Bcl-2/Bax in the myocardium, as well as the histological alterations of myocardium (P<0.01 or P<0.05); the generation of inflammatory cytokines (IL-6, IL-10, HMGB-1) and oxidative stress markers (SOD, MDA) in the serum was significantly alleviated (P<0.01 or P<0.05). On the other hand, AST markedly suppressed CLP-induced accumulation of IKK-α and NF-κB p65 subunit phosphorylation (P<0.01 or P<0.05).@*CONCLUSIONS@#AST plays a significant protective role in sepsis-induced cardiac dysfunction and survival outcome. The possible mechanism of cardioprotection is dependent on the activation of the IKK/NF-κB pathway in cardiomyocytes.

Renormalization of Thalamic Sub-Regional Functional Connectivity Contributes to Improvement of Cognitive Function after Liver Transplantation in Cirrhotic Patients with Overt Hepatic Encephalopathy

Objective@#The role of preoperative overt hepatic encephalopathy (OHE) in the neurophysiological mechanism of cognitive improvement after liver transplantation (LT) remains elusive. This study aimed to explore changes in sub-regional thalamic functional connectivity (FC) after LT and their relationship with neuropsychological improvement using resting-state functional MRI (rs-fMRI) data in cirrhotic patients with and without a history of OHE. @*Materials and Methods@#A total of 51 cirrhotic patients, divided into the OHE group (n = 21) and no-OHE group (n = 30), and 30 healthy controls were enrolled in this prospective study. Each patient underwent rs-fMRI before and 1 month after LT. Using 16 bilateral thalamic subregions as seeds, we conducted a seed-to-voxel FC analysis to compare the thalamic FC alterations before and after LT between the OHE and no-OHE groups, as well as differences in FC between the two groups of cirrhotic patients and the control group. Correction for multiple comparisons was conducted using the false discovery rate (p < 0.05). @*Results@#We found abnormally increased FC between the thalamic sub-region and prefrontal cortex, as well as an abnormally decreased FC between the bilateral thalamus in both OHE and no-OHE cirrhotic patients before LT, which returned to normal levels after LT. Compared with the no-OHE group, the OHE group exhibited more extensive abnormalities prior to LT, and the increased FC between the right thalamic subregions and right inferior parietal lobe was markedly reduced to normal levels after LT. @*Conclusion@#The renormalization of FC in the cortico-thalamic loop might be a neuro-substrate for the recovery of cognitive function after LT in cirrhotic patients. In addition, hyperconnectivity between thalamic subregions and the inferior parietal lobe might be an important feature of OHE. Changes in FC in the thalamus might be used as potential biomarkers for recovery of cognitive function after LT in cirrhotic patients.

Effect of neuregulin-1 on cardiac glucose metabolism in rats with experimental myocardial infarction / 中华心血管病杂志

Objective: To investigate the effect of neuregulin-1(NRG-1) on cardiac glucose metabolism in Sprague Dawley (SD) rats with experimental myocardial infarction (MI). Methods: Adult male SD rats were randomly divided into three groups: the sham-operated group, MI group, and MI+NRG1 group. The rat MI model was established via ligation of the left anterior descending coronary artery. Two weeks after operation, echocardiography was performed, MI rats with left ventricular ejection fraction (LVEF) between 0.3-0.5 were selected and randomly assigned to MI group and MI+NRG-1 group. Rats in MI+NRG-1 group were treated with recombinant human NRG-1β (100 μg/kg) via tail vein at 2 weeks after operation (twice per week for 6 weeks); while rats in sham-operated group and MI group received equal volume of physiological saline. By the end of administration, echocardiography and small animal positron emission tomography (PET) were performed to detect cardiac function and myocardial glucose uptake. Myocardial morphology and collagen volume fraction, cardiomyocyte apoptosis and reactive oxygen species (ROS) production were evaluated by histopathologic analysis. Myocardial pyruvate dehydrogenase (PDH) and citrate synthase (CS) activity, as well as ATP production were detected by commercial kits. The mRNA and protein expression levels of NRG-1, p-ErbB4, and key factors involved in glucose metabolism (including Glut-4, HK2, PDK4, PDH, CS) were detected by quantitative real-time PCR (qRT-PCR) and Western blot assay, respectively. Results: With the MI model successfully established, the left ventricular ejection fraction(LVEF) and left ventricular shortening fraction(LVFS) were significantly lower in MI group and MI+NRG-1 group than that in sham group (both P<0.01), while there was no significant difference between MI group and MI+NRG-1 group(all P>0.05). After 6 weeks of NRG-1β intervention, the LVEF and LVFS were significantly higher in MI+NRG-1 group than in MI group (both P<0.01). By the end of experiment, PET imaging showed that the mean standardized uptake value (SUVmean) were lower in MI+NRG-1 group than in the sham group (4.06±0.28 vs. 5.18±0.37, P<0.01), while significantly higher than that in MI group (4.06±0.28 vs.2.86±0.49, P<0.01). Histopathological analysis showed that compared with MI group, rats in MI+NRG-1 group exhibited significantly decreased left ventricle collagen volume fraction ((7.83±1.24) % vs. (18.31±3.58) %, P<0.01), cardiomyocyte apoptosis((37.98±4.26)% vs. (67.04±5.38)%, P<0.01), and DHE fluorescence intensity(0.057 28±0.007 06 vs. 0.076 94±0.008 46, P<0.01), indicating that NRG-1β could reduce ROS production. PDH activity, CS activity, and ATP production were significantly higher in MI+NRG-1 group than in MI group (all P<0.05). qRT-PCR demonstrated an upregulated Glut-4, HK2 and CS, but downregulated PDK4 mRNA expression in MI+NRG-1 group compared with MI group (all P<0.01). Western blot assay showed significantly higher protein expression of NRG-1, p-ErbB4, Glut-4, HK2, PDH, CS in MI+NRG-1 group than in MI group (all P<0.01). Conclusion: NRG-1 could improve glucose uptake and utilization in myocardium by activating phosphorylation of myocardial ErbB4 receptor in MI rats, thus providing a therapeutic option for improving energy metabolism after MI.

Research advances on the chemical components and pharmacological activities of Zanthoxyli Radix / 药学学报

Zanthoxyli Radix is a traditional Chinese medicine. It can be used for the treatment of wind-cold-dampness arthralgia, muscle and bone pain, fall fracture, hernia, sore throat, toothache and other diseases. Due to possessing many excellent and mild pharmacological properties, there are lots of reports about Zanthoxyli Radix worldwide. At present, more than 100 bioactive components have been extracted and purified from Zanthoxyli Radix. Nitidine chloride (NC), one of the most important alkaloids in Zanthoxyli Radix, has the activities of anti-tumor, anti-inflammation, anti-bacteria, etc. In this review, we summarize the chemical components of Zanthoxyli Radix, pharmacological activity and mechanism of action of NC to provide references for further research and utilization of Zanthoxyli Radix.

Research progress on posttransplant lymphoproliferative disease after lung transplantation / 器官移植

Posttransplant lymphoproliferative disease (PTLD) is a fatal complication after lung transplantation, which is intimately associated with age, immunosuppression level and Epstein-Barr virus (EBV) infection, etc. Reducing immunosuppression level, rituximab therapy and T cell immunotherapy are common treatments for PTLD. With the rapid development of lung transplantation in China, PTLD after lung transplantation has attracted widespread attention. This article reviews the risk factors, pathological types, clinical manifestations, diagnosis, treatment, prognosis and prevention of PTLD after lung transplantation, aiming to provide reference for early monitoring and management of the incidence and progression of PTLD.

Effectiveness of health education interventions targeting taeniasis and cysticercosis among primary school students in disease-elimination pilot areas of Henan Province / 中国血吸虫病防治杂志

Objective To compare the changes of knowledge, attitude and practice (KAP) related to taeniasis and cysticercosis among primary school students before and after health education interventions in disease-elimination pilot areas of Henan Province, so as to evaluate the effectiveness of health education interventions. Methods A primary school was selected from each of Dushu, Bowang and Yangji townships, Fangcheng County, Henan Province from 2017 to 2019; then, 2 to 3 classes were randomly selected from grade 4 to 6 in each primary school, and finally, all students in these classes were enrolled as study subjects. A thematic health education lecture pertaining to taeniasis and cysticercosis was given once each year by means of “health education in class”. The KAP towards taeniasis and cysticercosis was investigated among primary school students using selffilled structured questionnaires, and the changes of awareness of taeniasis and cysticercosis control knowledge and percentage of healthy behaviors formation were compared in primary school students among years and following various frequencies of health education interventions. Results More than 10 thousand person-time primary school students received health education interventions during the period from 2017 to 2019, and a total of 1 223 person-time primary school students were investigated during the 3-year study period, including 633 person-time men and 590 person-time women and 88.55% of primary school students at ages of 10 to 12 years. The proportion of households raising pigs and using dry toiliets decreased from 5.30% (24/453) and 18.10% (82/453) in 2017 to 3.60% (13/361) and 11.08% (40/361) in 2019, respectively. The awareness rate of taeniasis and cysticercosis control knowledge increased significantly from 0.22% (1/453) in 2017 to 62.59% (256/409) in 2018 and 76.73% (277/361) in 2019 (χ2 = 567.60, P < 0.001), and the awareness rate was 85.25% (104/122) among primary school students attending the thematic special health education courses for successive three times. The awareness rates of taeniasis and cysticercosis control knowledge were 0.44% (1/225), 58.00% (116/200) and 71.63% (149/208) among male students and 0 (0/338), 66.99% (140/209) and 83.66% (128/153) among female students from 2017 to 2019, and there was a significant difference in the awareness of taeniasis and cysticercosis control knowledge between male and female students in 2019 (χ2 = 7.14, P = 0.01). On-site teaching by doctors was the students’ favorite way to receive health education interventions (70.07%, 857/1 223), followed by watching health education videos (58.63%, 717/1 223) and seeing parasite specimens (48.9%, 598/1 223). The proportion of students’ families who used cutting boards for raw and cooked food separately increased from 7.28% (33/453) in 2017 to 47.37% (171/361) in 2019, was 67.21% (82/122) among students attending the health education courses for successive three times. The proportion of students who frequently washed their hands before meals and after using toilet increased from 71.96% (324/453) in 2017 to 89.47% (319/361) in 2019 and was 95.90% (117/122) among students attending the health education courses for successive three times. In addition, the percentage of students washing hands frequently in families using dry toilets was significantly lower in those who did not use dry toilets (χ2 = 9.21, P = 0.002), and the proportion of students with a habit of eating raw or undercooked meat decreased significantly from 35.76% (162/453) in 2017 to 6.65% (24/361) in 2019 (χ2 = 69.11, P < 0.01). Conclusion The thematic health education activity of “health education in class” contributes greatly to the increase in the awareness of taeniasis and cysticercosis control knowledge and the rate of healthy behaviors formation among primary school students in diseaseelimination pilot areas of Henan Province.

Construction and migration practice of " future hospital" information platform based on cloud architecture / 中华医院管理杂志

The " future hospital" information platform based on cloud architecture, through the deep integration of cloud computing, made full use of the high availability and strong scalability provided by the cloud computing platform, constructed an integrated hospital information platform, and realized the transformation and upgrading of the technical framework of hospital information platform in the era of big data, to meet the needs of homogeneous management and innovative service mode. In order to ensure the reliability of network transmission between cloud data center and hospital, and further ensure medical data security and patient privacy while using cloud computing, the " future hospital" information platform was migrated from the virtual private cloud(VPC)of public cloud to the local private cloud platform of the hospital, realized the hybrid cloud architecture mode of " future hospital" information platform with local proprietary cloud platform as the core and combined with public cloud VPC.