Serum autophagy-related gene 5 level in stroke patients: correlation with CD4+ T cells and cognition impairment during a 3-year follow-up

Abstract Autophagy-related gene (ATG) 5 regulates blood lipids, chronic inflammation, CD4+ T-cell differentiation, and neuronal death and is involved in post-stroke cognitive impairment. This study aimed to explore the correlation of serum ATG5 with CD4+ T cells and cognition impairment in stroke patients. Peripheral blood was collected from 180 stroke patients for serum ATG5 and T helper (Th) 1, Th2, Th17, and regulatory T (Treg) cell detection via enzyme-linked immunosorbent assays and flow cytometry. The Mini-Mental State Examination (MMSE) scale was completed at enrollment, year (Y)1, Y2, and Y3 in stroke patients. Serum ATG5 was also measured in 50 healthy controls (HCs). Serum ATG5 was elevated in stroke patients compared to HCs (P<0.001) and was positively correlated to Th2 cells (P=0.022), Th17 cells (P<0.001), and Th17/Treg ratio (P<0.001) in stroke patients but not correlated with Th1 cells, Th1/Th2 ratio, or Treg cells (all P>0.050). Serum ATG5 (P=0.037), Th1 cells (P=0.022), Th17 cells (P=0.002), and Th17/Treg ratio (P=0.018) were elevated in stroke patients with MMSE score-identified cognition impairment vs those without cognition impairment, whereas Th2 cells, Th1/Th2 ratio, and Treg cells were not different between them (all P>0.050). Importantly, serum ATG5 was negatively linked with MMSE score at enrollment (P=0.004), Y1 (P=0.002), Y2 (P=0.014), and Y3 (P=0.001); moreover, it was positively related to 2-year (P=0.024) and 3-year (P=0.012) MMSE score decline in stroke patients. Serum ATG5 was positively correlated with Th2 and Th17 cells and estimated cognitive function decline in stroke patients.

Application of DynaCT combined with 3D iGuide puncture technique to microwave ablation of lung cancer / 中国胸心血管外科临床杂志

@#Objective    To investigate the feasibility and safety of DynaCT microwave ablation (MWA) guided by 3D iGuide puncture technology for lung cancer. Methods    The clinical data of 19 patients with primary or metastatic lung cancer who underwent DynaCT MWA from June 2019 to December 2020 in our hospital were retrospectively analyzed, including 15 males and 4 females with an average age of 64.9±11.7 years. The technical success rates, adverse reactions and complications, postoperative hospital stay, and local therapeutic efficacy were recorded. Results    Technical success rate was 100.0%. The mean time required to target and place the needle was 15.7±3.7 min and the mean ablation time was 5.7±1.6 min. Thirteen patients underwent biopsy synchronously before the ablation, and 10 (76.9%) patients had positive pathological results. The main adverse reactions were pain (7/19, 36.8%), post-ablation syndrome (4/19, 21.1%) and cough (2/19, 10.5%). The minor complications were pneumothorax (6/19, 31.6%), hemorrhage (5/19, 26.3%), pleural effusion (2/19, 10.5%) and cavity (1/19, 5.3%). Three patients had moderate pneumothorax and received closed thoracic drainage. The median hospitalization time after ablation was 2.0 (2.0, 3.0) d, and no patient died during the perioperative period. The initial complete ablation rate was 89.5% (17 patients) and the incomplete ablation rate was 10.5% (2 patients) at 1-month follow-up, and no local progression was observed. Conclusion    DynaCT MWA of lung cancer under the guidance of 3D iGuide system is safe and feasible with a high short-term local control rate, but the long-term efficacy remains to be further observed.

Silicate Ions Derived from Calcium Silicate Extract Decelerate Ang II-Induced Cardiac Remodeling

BACKGROUND@#Pathological cardiac hypertrophy is one of the main activators of heart failure. Currently, no drug can completely reverse or inhibit the development of pathological cardiac hypertrophy. To this end, we proposed a silicate ion therapy based on extract derived from calcium silicate (CS) bioceramics for the treatment of angiotensin II (Ang II) induced cardiac hypertrophy. @*METHODS@#In this study, the Ang II induced cardiac hypertrophy mouse model was established, and the silicate ion extract was injected to mice intravenously. The cardiac function was evaluated by using a high-resolution Vevo 3100 small animal ultrasound imaging system. Wheat germ Agglutinin, Fluo4-AM staining and immunofluorescent staining was conducted to assess the cardiac hypertrophy, intracellular calcium and angiogenesis of heart tissue, respectively. @*RESULTS@#The in vitro results showed that silicate ions could inhibit the cell size of cardiomyocytes, reduce cardiac hypertrophic gene expression, including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and b-myosin heavy chain (b-MHC), decrease the content of intracellular calcium induced by Ang II. In vivo experiments in mice confirmed that intravenous injection of silicate ions could remarkably inhibit the cardiac hypertrophy and promote the formation of capillaries, further alleviating Ang II-induced cardiac function disorder. @*CONCLUSION@#This study demonstrated that the released silicate ions from CS possessed potential value as a novel therapeutic strategy of pathological cardiac hypertrophy, which provided a new insight for clinical trials.

Current Situation and Influencing Factors of Delay in Seeking Medical Treatment Among Residents in Rural Areas of Sichuan Province / 中国医学科学院学报

Objective To understand the current situation and explore the influencing factors of delay in seeking medical treatment for common symptoms of residents in the rural areas of Sichuan province. Methods In July 2019,multi-stage random sampling was carried out in Zigong city,Sichuan province,and the data were collected by face-to-face questionnaire interview.The residents who had lived at hometown for more than half a year in the past year and had seen a doctor in the most recent month were surveyed.Logistic regression was adopted to predict the influencing factors of delay in seeking medical treatment. Results A total of 342 subjects were enrolled,and the incidence of delay in seeking medical treatment was 13.45%(46/342).Compared with the young and middle-aged(<65 years)people,the elderly(≥65 years)people were more likely to have delay in seeking medical treatment (OR=2.187,95%CI=1.074-4.457,P=0.031).The rural residents who gave higher score of the overall quality of township health centers were less likely to have delay in seeking medical treatment (OR=0.854,95%CI=0.735-0.992,P=0.039). Conclusions The occurrence of delay in seeking medical treatment for common symptoms of rural residents in Sichuan province is low.Age and the overall quality evaluation of township health centers affect the occurrence of delay in medical treatment among the rural residents in Sichuan province.Efforts should be made to improve the awareness of disease prevention among the elderly in rural areas.The investment in health resources in township health centers should be increased to strengthen the introduction and training of talents.These measures can improve the health services in township health centers,guide residents to make timely use of health resources,and reduce the occurrence of delay in seeking medical treatment.

Processing Magnoliae Officinalis Cortex with ginger juice: process optimization based on AHP-CRITIC weighting method and composition changes after processing / 中国中药杂志

The weight coefficients of appearance traits, extract yield of standard decoction, and total content of honokiol and magnolol were determined by analytic hierarchy process(AHP), criteria importance though intercrieria correlation(CRITIC), and AHP-CRITIC weighting method, and the comprehensive scores were calculated. The effects of ginger juice dosage, moistening time, proces-sing temperature, and processing time on the quality of Magnoliae Officinalis Cortex(MOC) were investigated, and Box-Behnken design was employed to optimize the process parameters. To reveal the processing mechanism, MOC, ginger juice-processed Magnoliae Officinalis Cortex(GMOC), and water-processed Magnoliae Officinalis Cortex(WMOC) were compared. The results showed that the weight coefficients of the appearance traits, extract yield of standard decoction, and total content of honokiol and magnolol determined by AHP-CRITIC weighting method were 0.134, 0.287, and 0.579, respectively. The optimal processing parameters of GMOC were ginger juice dosage of 8%, moistening time of 120 min, and processing at 100 ℃ for 7 min. The content of syringoside and magnolflorine in MOC decreased after processing, and the content of honokiol and magnolol followed the trend of GMOC>MOC>WMOC, which suggested that the change in clinical efficacy of MOC after processing was associated with the changes of chemical composition. The optimized processing technology is stable and feasible and provides references for the modern production and processing of MOC.

DJ1 Ameliorates AD-like Pathology in the Hippocampus of APP/PS1 Mice / 生物医学与环境科学（英文）

OBJECTIVE@#To explore whether the protein Deglycase protein 1 (DJ1) can ameliorate Alzheimer's disease (AD)-like pathology in Amyloid Precursor Protein/Presenilin 1 (APP/PS1) double transgenic mice and its possible mechanism to provide a theoretical basis for exploring the pathogenesis of AD.@*METHODS@#Adeno-associated viral vectors (AAV) of DJ1-overexpression or DJ1-knockdown were injected into the hippocampus of 7-month-old APP/PS1 mice to construct models of overexpression or knockdown. Mice were divided into the AD model control group (MC), AAV vector control group (NC), DJ1-overexpression group (DJ1 +), and DJ1-knockdown group (DJ1 -). After 21 days, the Morris water maze test, immunohistochemistry, immunofluorescence, and western blotting were used to evaluate the effects of DJ1 on mice.@*RESULTS@#DJ1 + overexpression decreased the latency and increased the number of platform traversals in the water maze test. DJ1 - cells were cured and atrophied, and the intercellular structure was relaxed; the number of age spots and the expression of AD-related proteins were significantly increased. DJ1 + increased the protein expression of Nuclear factor erythroid 2-related factor 2 (NRF2), heme oxygenase-1 (HO-1), light chain 3 (LC3), phosphorylated AMPK (p-AMPK), and B cell lymphoma-2 (BCL-2), as well as the antioxidant levels of total superoxide dismutase (T-SOD), total antioxidant capacity (T-AOC), and Glutathione peroxidase (GSH-PX), while decreasing the levels of Kelch-like hydrates-associated protein 1 (Keap1), mammalian target of rapamycin (mTOR), p62/sequestosome1 (p62/SQSTM1), Caspase3, and malondialdehyde (MDA).@*CONCLUSION@#DJ1-overexpression can ameliorate learning, memory, and AD-like pathology in APP/PS1 mice, which may be related to the activation of the NRF2/HO-1 and AMPK/mTOR pathways by DJ1.

Relationship Between Maternal Negative Emotions and Feeding Patterns of Infants Aged 0-6 Months in Remote Rural Areas of Sichuan Province / 中国医学科学院学报

Objective To investigate the status of exclusive breastfeeding and bottle feeding in remote rural areas of Sichuan province and explore the relationship between negative emotions of mothers and feeding patterns of infants.Methods Multistage cluster sampling was employed to select the infants aged 0-6 months and their mothers in remote rural areas of Sichuan province.A self-designed questionnaire was used to collect the demographic characteristics of mothers and infants and the basic family information.The Chinese version of Depression Anxiety Stress scale was used to evaluate mothers' negative emotions,and the Breastfeeding Self-efficacy scale to assess the confidence level of mothers' behavior of adhering to exclusive breastfeeding.Results Totally 723 pairs of infants and their mothers were included.The exclusive breastfeeding and bottle feeding rates were 34.16% (247/723) and 57.54% (416/723),respectively.Mothers with depression tendency were less likely to adopt exclusive breastfeeding (OR=0.532,95%CI=0.291-0.974,P=0.041) and more likely to adopt bottle feeding (OR=1.877,95%CI=1.054-3.344,P=0.033).Further subgroup analysis of breastfeeding self-efficacy showed that in the group of low self-efficacy,the mothers with depression tendency were less likely to adopt exclusive breastfeeding (OR=0.461,95%CI=0.236-0.902,P=0.024) and more likely to adopt bottle feeding (OR=1.968,95%CI=1.047-3.701,P=0.036) than the mothers without depression tendency.In the group of high self-efficacy,mothers' depression,anxiety,and stress tendency had no significant correlation with infant feeding patterns (all P>0.05).Conclusions The mothers in the remote rural areas of Sichuan province are more likely to employ bottle feeding than exclusive breastfeeding.The mothers with stronger depression tendency demonstrate lower possibility of exclusive breastfeeding and higher possibility of bottle feeding.Breastfeeding self-efficacy may affect the association between maternal depression and infant feeding patterns.

Targeting PDE4 as a promising therapeutic strategy in chronic ulcerative colitis through modulating mucosal homeostasis

Phosphodiesterase-4 (PDE4) functions as a catalyzing enzyme targeting hydrolyzation of intracellular cyclic adenosine monophosphate (cAMP) and inhibition of PDE4 has been proven to be a competitive strategy for dermatological and pulmonary inflammation. However, the pathological role of PDE4 and the therapeutic feasibility of PDE4 inhibitors in chronic ulcerative colitis (UC) are less clearly understood. This study introduced apremilast, a breakthrough in discovery of PDE4 inhibitors, to explore the therapeutic capacity in dextran sulfate sodium (DSS)-induced experimental murine chronic UC. In the inflamed tissues, overexpression of PDE4 isoforms and defective cAMP-mediating pathway were firstly identified in chronic UC patients. Therapeutically, inhibition of PDE4 by apremilast modulated cAMP-predominant protein kinase A (PKA)-cAMP-response element binding protein (CREB) signaling and ameliorated the clinical symptoms of chronic UC, as evidenced by improvements on mucosal ulcerations, tissue fibrosis, and inflammatory infiltrations. Consequently, apremilast maintained a normal intestinal physical and chemical barrier function and rebuilt the mucosal homeostasis by interfering with the cross-talk between human epithelial cells and immune cells. Furthermore, we found that apremilast could remap the landscape of gut microbiota and exert regulatory effects on antimicrobial responses and the function of mucus in the gut microenvironment. Taken together, the present study revealed that intervene of PDE4 provided an infusive therapeutic strategy for patients with chronic and relapsing UC.

The safety and efficacy of microwave ablation in the treatment of lung cancer: A clinical analysis of single center / 中国胸心血管外科临床杂志

@#Objective    To evaluate the safety and efficacy of microwave ablation (MWA) in the treatment of lung tumors. Methods    The clinical data of 31 patients with lung neoplasms treated with MWA from January 2019 to August 2020 in a single center were retrospectively analyzed. There were 17 males and 14 females at an age of 63.4±10.4 years. The characteristics of the lesions, technical success rate, technical efficiency, local progression rate, adverse reactions and complications were recorded in detail. Results    There were 39 target lesions with an average diameter of 20.2±10.6 mm. A total of 36 MWA procedures were completed. The initial technical success rate was 84.6% (33/39), and the technical efficiency was 92.3% (36/39). The median postprocedure hospital stay was 2.0 (2.0, 3.0) d. A total of 12.9% (4/31) of the patients had local progression, and the local control rate was 87.1%. The main adverse reactions were pain (12/36, 33.3%), cough (6/36, 16.7%), post-ablation syndrome (6/36, 16.7%) and pleural effusion (3/36, 8.3%). The main complications were pneumothorax (11/36, 30.6%), hemorrhage (8/36, 22.2%), cavitation (2/36, 5.6%) and pulmonary infection (1/36, 2.8%). The median follow-up time was 13.0 (8.0, 18.0) months. No patient died during the follow-up. Conclusion    MWA is safe and effective in the treatment of lung tumors with controllable complications. Successive researches with large sample, and medium and long-term follow-ups are needed to explore the significance of combined therapies.

Transdermal delivery of Chinese herbal medicine extract using dissolvable microneedles for hypertrophic scar treatment

Hypertrophic scars are unfavorable skin diseases characterized by excessive collagen deposition. Although systemic treatments exist in clinic to manage hypertrophic scars, they pose significant side effects and tend to lose efficacy over prolonged applications. Traditional Chinese medicine (TCM) offers as a promising candidate to treat pathological scars. A large number of TCMs have been studied to show anti-scarring effect, however, the natural barrier of the skin impedes their penetration, lowering its therapeutic efficacy. Herein, we reported the use of dissolvable hyaluronic acid (HA) microneedles (MNs) as a vehicle to aid the transdermal delivery of therapeutic agent, a model TCM called shikonin for the treatment of hypertrophic scars. Here, shikonin was mixed with HA to make MNs with adequate mechanical strength for skin penetration, making its dosage controllable during the fabrication process. The therapeutic effect of the shikonin HA MNs was studied

Protective role of berberine on ulcerative colitis through modulating enteric glial cells-intestinal epithelial cells-immune cells interactions

Ulcerative colitis (UC) manifests as an etiologically complicated and relapsing gastrointestinal disease. The enteric nervous system (ENS) plays a pivotal role in rectifying and orchestrating the inflammatory responses in gut tract. Berberine, an isoquinoline alkaloid, is known as its anti-inflammatory and therapeutic effects in experimental colitis. However, little research focused on its regulatory function on ENS. Therefore, we set out to explore the pathological role of neurogenic inflammation in UC and the modulating effects of berberine on neuro-immune interactions. Functional defects of enteric glial cells (EGCs), with decreased glial fibrillary acidic protein (GFAP) and increased substance P expression, were observed in DSS-induced murine UC. Administration of berberine can obviously ameliorate the disease severity and restore the mucosal barrier homeostasis of UC, closely accompanying by maintaining the residence of EGCs and attenuating inflammatory infiltrations and immune cells overactivation. , berberine showed direct protective effects on monoculture of EGCs, bone marrow-derived dendritic cells (BMDCs), T cells, and intestinal epithelial cells (IECs) in the simulated inflammatory conditions. Furthermore, berberine could modulate gut EGCs-IECs-immune cell interactions in the co-culture systems. In summary, our study indicated the EGCs-IECs-immune cell interactions might function as a crucial paradigm in mucosal inflammation and provided an infusive mechanism of berberine in regulating enteric neurogenic inflammation.

Immunologic mechanisms of Yinhua Pinggan granule and San-ao decoction against influenza virus / 中国中药杂志

This paper aimed to investigate the effect of Yinhua Pinggan granule and San-ao decoction on the immunologic mechanisms of influenza viral pneumonia mice , in order to study the activity of the combined administration of different formulas on influenza A/H1N1 virus. The model of pneumonia was established in mice through nasal dropping influenza virus, and then divided randomly into five groups: normal control group, influenza virus model group, oseltamivir control group, Yinhua Pinggan granule group, and San-ao decoction group. The animals were put to death at the 5th day after gavage administration with the corresponding drugs. The contents in mice serum of TNF-α, IL-6 and IFN-γ were respectively measured by ELISA. The mRNA expressions of TLR3/7, MyD88, JNK, p38MAPK and NF-κB p65 in lung tissues were respectively detected by RT-PCR. The protein expressions of JNK, p38MAPK and NF-κB p65 in lung tissues were determined by immunohistochemical analysis, respectively. According to the results, Yinhua Pinggan granule and San-ao decoction could significantly decrease the levels of TNF-α and IL-6, increase the level of IFN-γ in mice serum of lung tissues, significantly reduce the gene expressions of TLR3/7, MyD88, JNK, p38MAPK and NF-κB p65 in influenza virus-infected mice lung tissues, and significantly reduce the protein expressions of JNK, p38MAPK and NF-κB p65 in lung tissues. Furthermore, the regulatory effect of Yinhua Pinggan granule was superior to that of San-ao decoction. In conclusion, Yinhua Pingan granule and San-ao decoction have the therapeutic effect on pneumonia mice infected by H1N1 virus . The anti-influenza mechanisms of Yinhua Pinggan granule and San-ao decoction may be the results of interactions by regulating the immunologic function of influenza virus-infected mice and TLR3/7 signaling pathway with multiple links of the gene and protein expressions. Moreover, the combined administration of warm-natured and cold-natured Yinhua Pinggan granule with the effects of detoxification and exhalation has a better effect than the single administration of warm-natured San-ao decoction.

Effectiveness Evaluation Analysis on Berberine Tablets Combination with Metformin Treating Type 2 Diabetes / 现代医院

Objective To explore the clinical effect of Berberine tablets combination with Metformin treating type 2 diabetes (T2DM). Methods Of 80 cases of T2DM were randomly divided into control group and treatment group, 40 cases each group. The control group was given the treatment of Metformin, and the treatment group was given an additional treatment of Berberine tablets. After 3 months treatment, the indexes of blood sugar levels, HOMA-β, HOMA-IR and inflammatory factor were compared between the two groups. Results After treatment, the levels of FPG, 2hPG and HbA1c in the treatment group were all obviously lower than the control group (P＜0. 05). The indexes of HOMA-β and HOMA-IR in the treatment group were lower than the control group (P＜0. 05). And the levels of CRP, IL-6 and TNF-α in the treatment group were all lower than the control group (P＜0. 05). Conclusion The treatment of Berberine tablets combination with Metformin could alleviate inflammatory response, promote secretion of insulin βcell, increase cell insulin sensitivity and achieve a variety of hypoglycemic effect.

An analysis on knowledge, attitude and practice regarding antibiotics use among community residents in Hangzhou / 预防医学

Objective To assess the current status of knowledge, attitude and practice (KAP) towards antibiotic use among community residents in Hangzhou, and to explore the correlations among them. Methods A total of 449 permanent residents in Hangzhou were randomly selected using a multistage stratified random sampling method. Self-reported data on basic demographic factors, and relevant KAP information were collected by the questionnaire survey. Differences in KAP scores according to each demographic factor were assessed by the t test or ANOVA test, and AMOS 21.0 was used for the path analysis. Results Scores for knowledge, attitude and practice regarding antibiotic use were (6.17±2.45), (6.45±0.99) and (6.21±1.02) respectively. Results of the path analysis showed that education level and age had effects on the knowledge (coefficients: 0.57 and -0.38 respectively) . Age, gender and knowledge had effects on the attitude (coefficients: -0.27, 0.12 和 0.02 respectively), and attitudes, gender, monthly income and the level of education had effects on the practice (coefficients: 0.48、 0.37、 0.06 and 0.02 respectively) . Conclusion Community residents in Hangzhou lack relevant knowledge, and there are some irrational attitudes and practices regarding antibiotic use. There is a correlation between knowledge and attitudes, as well as between attitudes and practices, but the knowledge and practices are not correlated.

Gait characteristics of patients with sciatica / 医用生物力学

Objective To analyze and summarize the gait characteristics of patients with sciatica, so as to assist with diagnosis and evaluation for such patients in clinic. Methods Forty-three patients with lumbar disc herniation accompanied by siatica were fitted with portable gait analyzer, and required to walk at the self-selected comfortable speed for a distance of 120 m. Forty-three healthy subjects with matched age, gender and body mass index (BMI) were recruited as control. The gait data including 7 spatial-temporal parameters (single-support duration, double-support duration, ratio of single-support duration to double-support duration, duration of gait cycle, step speed, step frequency, step length) and 4 acceleration parameters (pulling acceleration, swing power, ground impact, foot fall) were collected to compare the gait differences between patients and healthy subjects, as well as between affected and healthy limbs of patients. Results The single-support duration, ratio of single-support duration to double-support duration, step speed, step frequency, step length and four acceleration parameters of patients with sciatica were obviously smaller than those of healthy subjects, while the double-support duration of patients with sciatica was increased. The affected limb of patients with sciatica showed a significant decrease in single-support duration, step frequency and all four acceleration parameters but increase in step length as compared to their healthy limbs. Conclusions Patients with sciatica have significant gait abnormalities due to their affected limbs, which influence their walking ability. Portable gait analyzer can be used for objectively characterizing the walking abnormalities of patients, so as to provide additional information for the clinical diagnosis and evaluation.

Expression of Vitamin D receptor in the myocardium of mice with viral myocarditis / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the dynamic expression and role of vitamin D receptor (VDR) in the myocardium of mice with viral myocarditis (VMC).</p><p><b>METHODS</b>One hundred and twenty 4-week-old male BALB/c mice were selected and assigned into control (n=40) and experimental groups (n=80). The mice in the experimental group were injected intraperitoneally with Coxsackievirus B3 to establish the model of VMC, while the mice in the control group were injected intraperitoneally with an equal volume of DMEM solution. Fifteen mice in the experimental group and ten mice in the control group were sacrificed at 3, 7, 14, or 28 days after injection, and the myocardial specimens were obtained. The dynamic expression of VDR in the myocardium was determined by the immunohistochemical technique. The pathological changes in the myocardium were examined using hematoxylin and eosin staining.</p><p><b>RESULTS</b>In the experimental group, the mice had significantly increased expression of VDR after virus injection (P<0.01); the expression of VDR reached the peak at 7 days after injection, and then declined gradually; the expression of VDR remained high at 28 days after injection. At 3, 7, 14, and 28 days after injection, the expression of VDR in the experimental group was significantly higher than that in the control group (P<0.01). Moreover, in the experimental group, the changes in the pathological score of the myocardium were in accordance with the changes in the expression of VDR; the expression level of VDR in the myocardium was positively correlated with the pathological changes in the myocardium in the experimental group (P<0.01).</p><p><b>CONCLUSIONS</b>VDR may be involved in the inflammatory-immune process in the pathogenesis of VMC.</p>

Cellular toxicity and anti-tumor efficacy of iRGD modified doxorubixin loaded sterically stabilized liposomes / 药学学报

iRGD-modified sterically stabilized liposomes loaded doxorubicin (iRGD-SSL-DOX) were prepared and their cellular toxicity and anti-tumor efficacy were evaluated, comparing to doxorubixin loaded sterically stabilized liposomes (SSL-DOX) and RGD modified doxorubixin loaded sterically stabilized liposomes (RGD-SSL-DOX). The iRGD peptide, with both tumor targeting and cell penetrating functions, was conjugated to DSPE-PEG-NHS and DSPE-PEG-iRGD was obtained. DSPE-PEG-RGD was gained in the same way. iRGD-SSL-DOX, RGD-SSL-DOX and SSL-DOX were prepared by ammonium sulfate gradient method. The size and zeta potential of the liposomes were characterized by dynamic laser light scattering. The cellular toxicity study was done on B16 melanoma cell line and the anti-tumor efficacy study was carried on B16 cell line bearing C57BL/6 mice. The results showed that the particle sizes of liposomes were all around 90-100 nm. DOX entrapment efficiency was above 95%. The formulations were with good preparation reproducibility. iRGD-SSL-DOX showed no significant difference in B16 cellular toxicity with SSL-DOX and RGD-SSL-DOX, but the anti-tumor efficacy on B16 melanoma bearing C57BL/6 mice was significantly better than that of SSL-DOX, similar as that of RGD-SSL-DOX. Therefore, iRGD modified liposomes loaded DOX would be a promising drug delivery system for tumor therapy.

Oxidative stress in chronic hepatitis C patients / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>This study is aimed to investigate oxidative stress status in chronic hepatitis C (CHC) patients.</p><p><b>METHODS</b>52 CHC patients were divided into two groups according to the serum level of alanine aminotransferase (ALT): group A (elevated ALT group) and group B (normal ALT group). 20 healthy controls were included in this study. Serum levels of xanthine oxidase (XOD), malondialdehyde (MDA), oxidizided glutathione (GSSG), glutathione (GSH), glutathione peroxidase (GSH-Px), glutathione S-transferase (GST), glutathione reductase (GR) and vitamin C (Vc) were determined by enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>Serum levels of XOD, MDA, GST and GR increased in CHC patients compared with healthy controls. While, serum levels of GSH, GSH-Px and Vc decreased compared with healthy controls. Furthermore, serum levels of XOD, MDA, GSSG, GST and GR in group A were up-regulated compared with group B. Serum levels of GSH, GSH-Px and Vc in group A were down-regulated compared with group B. In CHC patients, serum ALT level positively correlated with serum levels of XOD, MDA, GSSG and GST, while, negatively correlated with serum levels of GSH, GSH-Px and Vc. Serum aspartate aminotransferase (AST) level positively correlated with serum levels of XOD, MDA, GSSG, GR and GST, while, negatively correlated with serum GSH-Px level in CHC patients. Serum gamma-glutamyl transpeptidase (GGT) level positively correlated with serum GR level and negatively correlated with serum GSH level in CHC patients. Serum alkaline phosphatase (AKP) level positively correlated with serum levels of MDA and GR in CHC patients. In CHC patients, serum XOD level was positively related with serum HCV RNA level.</p><p><b>CONCLUSION</b>Oxidative stress was increased in CHC patients. In CHC patients with elevated serum ALT level, oxidative stress usually became serious.</p>

Hypomethylation of TNF-alpha gene promoter in the patients with acute-on-chronic hepatitis B liver failure / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>The present study was designed to investigate the possible epigenetic alteration in the promoter of TNF-alpha in the patients with acute-on-chronic hepatitis B liver failure (ACHBLF).</p><p><b>METHODS</b>The methylation of TNF-alpha promoter in peripheral blood mononuclear cells (PBMCs) was measured by methylation specific PCR (MSP). The level of serum TNF-alpha was determined by enzyme-linked immunosorbent assay (ELISA). Model for End-stage Liver Disease (MELD) was performed for the evaluation of liver failure.</p><p><b>RESULTS</b>The serum level of TNF-alpha in patients with ACHBLF(44.9260 +/- 26.48523) was higher than that in CHB (18.92505 +/- 9.04461) and healthy controls (11.9172 +/- 5.04612) (P < 0.05). Moreover, the serum TNF-alpha level was significantly decreased in methylation group as compared to unmethylaiton group in patients with ACHBLF (P < 0.05). MELD was not significantly different between methylated and unmethylated group of ACHBLF patients (P > 0.05). In addition, the serum level of TNF-alpha was found to be positively correlated with serum total bilirubin (r = 0.891, P < 0.01) and MELD score (r = 0.792, P < 0.01), but to be negatively correlated with prothrombin activity (r = - 0.511, P < 0.05) in patients with ACHBLF.</p><p><b>CONCLUSION</b>The TNF-alpha methylation patten is stable for the liver failure, suggesting the effect of environment on methylation.</p>

The analysis of IL-10 and its methylation in the patients with acute on chronic liver failure / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate the effect of IL-10 and the methylation of its promoter in acute on chronic liver failure (ACLF).</p><p><b>METHODS</b>Patients were divided into three groups: 25 with ACLF, 25 with CHB, 10 healthy controls. Respectively detect the serum level of IL-10 via ELISA, and the methylation of IL-10 promoter via MSP, to analyze the difference among the three groups.</p><p><b>RESULTS</b>Both the ACLF group and the CHB group have significant increase in serum level of IL-10 compared with the control group (P < 0.05); the ACLF group's level is higher than the CHB group, however without statistical significance (P > 0.05). The serum level of IL-10 in ACLF group has no significant relativity with ALT and HBV-DNA( r = -0.022, r = 0.033, respectively; P > 0.05); has positive relativity with TBIL and MELD ( r = 0.566, r = 0.443, respectively; P < 0.05); and negative relativity with PTA (r = -0.581, P < 0.05). The distribution of the methylation of IL-10 promoter in ACLF group is significantly different from the other two.</p><p><b>CONCLUSION</b>The serum level of IL-10 in hepatitis patients is significantly higher and increases with the degree of liver failure. The promoter methylation may be important in the gene inactivation.</p>