Antibacterial activity of pimaradienoic acid from Eleutherococcus trifoliatus (L.) S. Y. Hu.

Purpose: To investigate the antibacterial activity of pimaradienoic acid, a natural product isolated from Eleutherococcus trifoliatus. Methods: Pimaradienoic acid was purified from E. trifoliatus and tested against three Gram-positive bacteria. Minimum inhibitory concentrations (MICs) were determined, and bacterial growth curves were measured. Scanning electron microscopy (SEM) was used to observe morphological changes in bacteria after drug treatment. Results: Pimaradienoic acid exhibited concentration-dependent inhibition of the growth of the three bacteria tested. The MIC and bacterial growth dynamics results indicated that pimaradienoic acid had potent antibacterial activity. SEM revealed that pimaradienoic acid disrupted the bacterial membrane, leading to cell death. Conclusions: Pimaradienoic acid has significant antibacterial activity against Gram-positive bacteria, suggesting its potential as a novel antimicrobial agent.

Characteristics of motor and non-motor symptoms in patients with rapid eye movement sleep behavior disorder and early Parkinson disease / 中华行为医学与脑科学杂志

Objective:To investigate the motor and non-motor symptoms and polysomnographic features in patients with rapid eye movement sleep behavior disorder (RBD), early Parkinson's disease (PD) with and without RBD.Methods:Patients with idiopathic RBD (IRBD) and early PD were collected from the clinics in West China Hospital of Sichuan University from August 2020 to May 2021.All the patients were divided into 3 groups including IRBD group (67 cases), PD with RBD (PD+ RBD) group (19 cases), and PD without RBD (PD-RBD) group (22 cases). Unified Parkinson's disease rating scale part 3 (UPDRS-Ⅲ), Hoehn-Yahr(H-Y) stage, Epworth sleepiness scale (ESS), REM sleep behavior disorder questionnaire-Hong Kong (RBDQ-HK), 17-item Hamilton depression scale(HAMD-17), mini-mental state examination(MMSE), Sniffin’Sticks olfactory function test, visual analogue scale (VAS), and scale for outcomes in Parkinson's disease-AUT(SCOPA-AUT) were used to assess the motor and non-motor symptoms including sleepiness, RBD, depression, cognitive function, olfactory function, pain and autonomic function respectively.All patients were performed to the polysomnography (PSG) examination.One-way ANOVA, Krukal-Wallis test, χ2 test and Fisher accurate test were used to analyze the data of motor and non-motor symptoms and sleep parameters among the 3 groups accordingly. Results:There were statistically significant differences in motor symptoms among the three groups ( F=57.009, P<0.05), and the scores of UPDRS Ⅲ and H-Y stage were higher in the PD+ /- RBD group than those in the IRBD group(both P<0.05). However, there was no significant difference in motor symptoms between PD+ RBD group and PD-RBD group ( P>0.05). There were no significant differences in the scores of ESS, MMSE, olfactory function test and VAS (all P>0.05). But the HAMD-17 score was significantly higher in the PD+ RBD group(2(1, 9)) than that in the IRBD group (0(0, 3)( P<0.05). The SCOPA-AUT scores of autonomic function were significant differences in the three groups, mainly in the digestive system, urinary system, and sexual function ( P<0.05). Notably, the IRBD group (8(4, 14)) and PD+ RBD group (11(7, 14)) had higher scores of SCOPA-AUT compared with PD-RBD group (4(4, 5.75)(all P<0.05), especially in the digestive dysfunction(all P<0.05). The PD+ RBD group(3.47±1.17) had higher scores of sexual function compared with IRBP group(1.78±0.60)( P<0.05), and the urinary system scores also higher than PD-RBD group( P<0.05). The PD-RBD group(21.30 (6.10, 34.00)/h) had a significantly higher oxygen desaturation index in REM sleep compared with that of IRBD group(5.90(2.70, 16.73)/h) ( P<0.05). Conclusions:Early PD with RBD has more severe non-motor symptoms, especially depression and autonomic dysfunction.RBD can be related with the earlier and more widely autonomic dysfunction.

SPERT gene silencing inhibits the growth of human colon cancer xenograft tumor in nude mice via p38MAPK/HSP27 signaling pathway.

Colorectal cancer is one of the most common gastrointestinal malignancies and is also a disease of genetic heterogeneity. Our previous studies have shown that SPERT (sprermatid-associated protein) gene may be an underlying oncogene that is associated with the progression of the disease in colorectal cancer patients, and SPERT gene silencing can inhibit the proliferation of colorectal tumor cells and promote cell apoptosis. Here, we use the stably transfected human colorectal cancer cell line RKO to construct an animal xenograft model and study the effect of SPERT gene silencing on animal xenografts. The results showed that SPERT gene silencing can inhibit tumor growth in animals. In addition, through signaling pathway analysis, we found that the p38MAPK/HSP27 signaling pathway may be the molecular mechanism by which SPERT gene silencing inhibits the growth of xenograft tumors in nude mice. Combined with previous data, SPERT gene silencing has the same inhibitory effect on tumor growth in vitro and in vivo. These data suggest that SPERT gene may be a potential target for the treatment of colorectal cancer in clinic.

Value of anti-neutrophil cytoplasmic antibody in assessing the severity of bronchiolitis obliterans in children / 中国当代儿科杂志

OBJECTIVE@#To study the value of anti-neutrophil cytoplasmic antibody (ANCA) in assessing the severity of bronchiolitis obliterans (BO) in children.@*METHODS@#A prospective analysis was performed on 59 children who were diagnosed with BO from June 2009 to October 2014. ELISA was used to measure the concentrations of myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)-ANCA in serum. According to the results of ELISA, the children were divided into three groups: double-negative ANCA (n=22), single-positive ANCA (n=17), and double-positive ANCA (n=20). The three groups were compared in terms of the scores of BO risk factors, clinical symptoms, chest high-resolution computed tomography (HRCT), and lung pathology on admission, as well as the changes in the expression level of ANCA and the scores of clinical symptoms and chest HRCT over time.@*RESULTS@#Compared with the double-negative ANCA group, the double-positive ANCA group had a significantly higher score of BO risk factors (P0.05). The single-positive ANCA and double-positive ANCA groups still had a significantly higher score of clinical symptoms than the double-negative ANCA group (P<0.05).@*CONCLUSIONS@#The expression level of ANCA is correlated with the severity of BO in children and thus has certain clinical significance in disease evaluation.

shRNA­induced knockdown of the SPERT gene inhibits proliferation and promotes apoptosis of human colorectal cancer RKO cells.

Colorectal cancer is the third most common type of cancer and the fourth leading cause of cancer­related deaths worldwide. Although several genes have been identified to contribute to the pathogenesis of colorectal cancer, there are still many genes with unidentified functions in colorectal cancer. This study aimed to investigate the effect of shRNA­induced knockdown of the SPERT gene on the proliferation and apoptosis of human colorectal cancer RKO cells. SPERT was screened based on the TCGA dataset, and SPERT expression, cell growth, proliferation and apoptosis were detected in shSPERT­ and shCtrl­transfected RKO cells. In addition, the SPERT­related biological pathways were detected using a PathScan® Signaling Antibody Array Kit. We detected lower SPERT expression in shSPERT­transfected RKO cells than in shCtrl­transfected cells at both the translational and transcriptional levels (P<0.05), and an MTT assay revealed a clear­cut decrease in the proliferation of shSPERT­transfected RKO cells relative to shCtrl­transfected RKO cells (P<0.01). A Caspase­Glo® 3/7 assay detected an increase in the caspase­3/7 activity and the number of apoptotic cells in the shSPERT­transfected RKO cells than in the shCtrl­transfected cells (P<0.01), and flow cytometry detected a higher apoptotic rate in the shSPERT­transfected RKO cells than in the shCtrl­transfected cells (20.65±0.26 vs. 5.93±0.06%, respectively, P<0.01). Elevated levels of phosphorylated p44/42 MAPK (ERK1/2), Akt, Bad, HSP27, p38 MARK and Chk2, and elevated PARP and caspase­3 expression levels were detected in shSPERT­transfected RKO cells compared with the shCtrl­transfected cells (P<0.05). The results of the current study demonstrated that knockdown of SPERT suppresses colorectal cancer cell growth and promotes apoptosis. SPERT may serve as an oncogene and may be a potential target for the treatment of colorectal cancer.

Effect of methylene blue on hydrogen peroxide-induced apoptosis in macrophages through mitochondria-dependent pathway in mice / 中华麻醉学杂志

Objective To evaluate the effect of methylene blue (MB) on hydrogen peroxide (H2O2)-induced apoptosis in macrophages through mitochondria-dependent pathway in mice.Methods Mouse peritoneal macrophage line RAW264.7 cells were cultured in DMEM culture medium containing 10％ fetal bovine serum.Cells were divided into 6 groups (n =24 each) using a random number table method:control group (group C),H2O2 group,prophylactic different concentrations of MB groups (MB1,2 groups) and therapeutic different concentrations of MB groups (MB3.4 groups).H2O2 50 μmol/L was added to the culture medium in group H2O2.MB was added to the culture medium with the final concentrations of 0.1 μmol/L (in MB1 and MB3 groups) and 1.0 μmol/L (in MB2 and MB4 groups) at 30 min before adding H2O2 in MB1.2 groups and 30 min after adding H2O2 in MB3.4 groups.At 24 h of culture or incubation in each group,the cell survival rate was measured by methyl thiazolyl tetrazolium assay,the activity of reactive oxygen species (ROS) in cells was determined with the fluorescent probe,the lactate dehydrogenase (LDH) activity in supernatant was detected by spectrophotometry,the activity of superoxide dismutase (SOD) in cells was detected by colorimetric method,mitochondrial membrane potential (MMP) was measured using rhodamine 123 staining,the content of ATP was determined by an ATP bioluminescent method,the expression of pro-caspase-3 and spliceosomes P20 protein and P 18 protein was detected by Western blot,and cell apoptosis was detected using flow cytometry.Results Compared with group C,the cell survival rate,SOD activity and contents of MMP and ATP were significantly decreased,the ROS activity and activity of LDH in supernatant were increased,the expression of pro-caspase-3 and spliceosomes P20 protein and P18 protein was up-regulated,and early and late apoptosis rates were increased in the other five groups (P＜0.05).Compared with group H2O2,the cell survival rate,SOD activity and contents of MMP and ATP were significantly increased,the ROS activity and activity of LDH in supernatant were decreased,the expression of pro-caspase-3 and spliceosomes P20 protein and P18 protein was down-regulated,and early and late apoptosis rates were decreased in MB1-4 groups (P＜0.05).Compared with group MB1,the cell survival rate was significantly decreased,and the expression of caspase-3 spliceosome P 18 was down-regulated in group MB2,and the cell survival rate and SOD activity were significantly decreased,and the activity of ROS was increased in group MB3 (P＜0.05).Compared with group MB4,the expression of caspase-3 spliceosome P 18 was significantly down-regulated,early and late apoptosis rates were decreased,and the activity of ROS was increased in group MB2,and the activity of ROS was significantly increased in group MB3 (P＜0.05).Conclusion The mechanism by which MB attenuates H2O2-induced oxidative damage to macrophages is related to inhibiting cell apoptosis in macrophages through mitochondria-dependent pathway in mice.

Calpain inhibitors ameliorate muscle wasting in a cachectic mouse model bearing CT26 colorectal adenocarcinoma.

Cancer-related cachexia involves increased protein breakdown through various proteolytic pathways, including the ubiquitin-proteasome pathway (UPP). We hypothesized that a calcium- and calpain-dependent pathway might play a crucial role during the proteolytic procedure, and that pathway interventions would ameliorate cancer cachexia in vivo. After being inoculated with CT26 adenocarcinoma cell culture subcutaneously, BALB/c mice developed cachexia in 12 days. They were then administered with different types of calpain inhibitors individually or in combination for 7 consecutive days. Eighteen healthy mice were also assessed as a control group. Changes in body weight, gastrocnemius muscle mass, tumor volume, food intake, survival time, and serum nutritional markers were monitored. Also measured were the levels of calpains, E3 ubiquitin ligases, and apoptosis-associated markers in gastrocnemius muscle. Our study showed that the intraperitoneal administration of calpain inhibitors significantly improved tumor-free body weight and gastrocnemius muscle mass in all treatment groups. Treatment with calpain inhibitors also ameliorated cachexia-associated negative effects in metabolic profiles and increased survival time in most of the tumor-bearing mice compared with the cachexia controls. Furthermore, calpain inhibitors reduced the calpain activity and the expression of MuRF-1 and atrogin-1 in all treatment groups, while increasing the level of cleaved caspase-3 and BAX and lowering the level of BCL-2 in some groups. These results justify further evaluation of calpain inhibitors both alone and in combination with other candidate agents as a potential new therapeutic strategy for treating cancer cachexia.

Effect of methylene blue preconditioning on ischemia-reperfusion injury in isolated rat lungs / 中华麻醉学杂志

Objective To evaluate the effect of methylene blue(MB)preconditioning on ischemi-a-reperfusion(I∕R)injury in isolated rat lungs. Methods Eighteen pathogen-free healthy male Sprague-Dawley rats, aged 3 months, weighing 240-320 g, were divided into 3 groups(n=6 each)using a ran-dom number table: sham operation group(group Sham), lung I∕R group(group I∕R)and methylene blue preconditioning group(group MB). A model of isolated lung I∕R injury was established in pentobarbi-tal sodium-anesthetized rats. MB 2 mg∕kg was intraperitoneally injected at 2 h before stopping perfusion in group MB. Isolated lungs were perfused for 20 min, followed by 45-min ischemia, and then reperfused for 60 min in I∕R and MB groups. At 60 min of reperfusion, the activity of lactic dehydrogenase(LDH)in the perfusate was detected, wet weight(W)and dry weight(D)was determined, W∕D ratio was calcu-lated, and the levels of malondialdehyde(MDA), ATP, reactive oxygen species(ROS)and superoxide dismutase(SOD)were measured in lung tissues. Mitochondria and cytoplasm were isolated from lung tis-sues for determination of mitochondrial membrane potential(MMP), degree of mitochondrial swelling and content of cytochrome C(Cyt c)in cytoplasm. Apoptotic cells in lung tissues were detected using TUNEL, and apoptotic index was calculated. Results Compared with group Sham, the activity of LDH in perfu-sate, W∕D ratio, levels of ROS, MDA and Cyt c in cytoplasm and apoptosis index were significantly in-creased, the degree of mitochondrial swelling was aggravated, and the content of ATP and MMP were de-creased in I∕R and MB groups, and the SOD activity was significantly decreased in group I∕R(P<005). Compared with group I∕R, the activity of LDH in perfusate, W∕D ratio, levels of ROS, MDA and Cyt c in cytoplasm and apoptosis index were significantly decreased, the degree of mitochondrial swelling was attenu-ated, and the activity of SOD, content of ATP and MMP were increased in group MB(P<005). Con-clusion Methylene blue preconditioning can reduce I∕R injury in isolated rat lungs, and the mechanism may be related to improving mitochondrial function and inhibiting cell apoptosis.

Relationship between TLR4/NF-κB signaling pathway and propofol-induced inhibition of endotoxin-induced release of TNF-α from alveolar macrophages of rats / 中华麻醉学杂志

Objective To evaluate the relationship between Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling pathway and propofol-induced inhibition of endotoxin-induced release of tumor necrosis factor-alpha (TNF-α) from alveolar macrophages (AMs) of rats.Methods AMs extracted from adult male Sprague-Dawley rats were cultured and inoculated in 6-well plates (1 × 106 cells/well)and in 96-well plates (1×104 cells/well).The cells were divided into 5 groups (n=18 each) using a random number table:control group (group C),dimethyl sulfoxide group (group D),lipopolysaccharide (LPS) group (group L),propofol group (group P) and LPS plus propofol group (group L+P).The cells were continuously cultured with phosphate buffer solution in group C.Dimethyl sulfoxide was added at the final concentration of 5 mg/ml in group D.LPS was added at the final concentration of 1 μg/ml in group L.Propofol was added at the final concentration of 25 μmol/L (4.46 μg/ml) in group P.LPS and propofol were added at the final concentration of 1 μg/ml and 25 μmol/L (4.46 μg/ml),respectively,in group L+P.At 24 h of culture or incubation,the cell viability was detected by CCK-8 assay,the morphological changes of cells were observed using Wright's staining,the concentration of TNF-α in the supernatant was determined by enzyme-linked immunosorbent assay,and TLR4 expression and NF-κB activities were measured by Western blot.Results Compared with group C,the cell viability and concentration of TNF-α in the supernatant were significantly increased,the expression of TLR4 was up-regulated,and the activity of NF-κB was enhanced in L and L+P groups (P＜0.05),and no significant change was found in the parameters mentioned above in D and P groups (P＞0.05).Compared with group L,the cell viability and concentration of TNF-α in the supernatant were significantly decreased,the expression of TLR4 was down-regulated,and the activity of NF-κB was weakened (P＜0.05),the morphological changes of cells were significantly attenuated,and the number of pseudopodia was reduced in group L+P.Conclusion The mechanism by which propofol inhibits endotoxin-induced release of TNF-α from AMs is related to inhibited activation of TLR4/NF-λB signaling pathway in rats.

Percutaneous microwave ablation combined with synchronous transcatheter arterial chemoembolization for the treatment of colorectal liver metastases: results from a follow-up cohort.

BACKGROUND: The purpose of this study was to retrospectively evaluate the therapeutic efficacy and safety of ultrasound-guided percutaneous microwave ablation (MWA) combined with synchronous transcatheter arterial chemoembolization (TACE) in patients with colorectal liver metastases (CRLM). PATIENTS AND METHODS: A retrospective analysis was performed in 30 patients who were treated with ultrasound-guided percutaneous MWA combined with synchronous TACE for colorectal cancer liver metastases from November 2011 to December 2014 in Zhongshan Hospital, Fudan University. The response of the tumor to treatment was evaluated by follow-up computed tomography and/or magnetic resonance imaging. Local tumor control, procedure-related complications, and long-term survival data were analyzed. RESULTS: A total of 30 patients with 43 tumors ranging in size from 1.4 cm to 10.0 cm were analyzed. The patients' mean age was 61.6±10.3 years (range, 44.0-78.0 years). The median follow-up time was 26.5±10.4 months (range, 13.3-50.6 months). The complete ablation rate was 81.4% (35/43 lesions) for CRLM. Complete response was achieved in eight cases (26.7%), and partial response was achieved in 17 cases (56.7%) 1 month after the procedure. The objective response rate (complete response + partial response) was 83.4%. Progression-free survival and overall survival were 5.0 months and 11.0 months, respectively. The 12-month and 24-month survival rates were 46.7% and 25.4%, respectively. A total of 22 patients succumbed during follow-up due to tumor progression. No major complications or perioperative mortalities were recorded. CONCLUSION: Ultrasound-guided percutaneous MWA combined with synchronous TACE therapy is a safe and effective modality for patients with CRLM.

Combination Therapies in the Management of Large (≥ 5 cm) Hepatocellular Carcinoma: Microwave Ablation Immediately Followed by Transarterial Chemoembolization.

PURPOSE: To evaluate the safety and efficacy of microwave (MW) ablation combined with transarterial chemoembolization in a single stage for the treatment of large (≥ 5 cm) hepatocellular carcinoma (HCC). MATERIALS AND METHODS: From March 2013 to January 2015, 66 patients (54 men and 12 women; mean age, 54 y; range, 29-83 y) with 72 large HCC lesions were included in this study. Eighteen (27.3%) had Barcelona Clinic Liver Cancer class B disease, and 48 (72.7%) had class C disease. Seventy-nine percent of patients (n = 52) had hepatitis B virus infection. The average tumor size was 9.0 cm ± 3.9, ranging from 5 to 19 cm. MW ablation was performed under ultrasound guidance, immediately followed by chemoembolization. Local tumor response, progression-free survival (PFS), and overall survival (OS) were assessed. RESULTS: The technique was successfully performed in all patients. Complete response (CR) was achieved in 28 cases (42.4%), and partial response (PR) was achieved in 34 cases (51.5%) at 1 month after the procedure. The objective response rate (ie, CR plus PR) was 93.9%. Median PFS and OS times were 9 months and 21 months, respectively. The 6-, 12-, and 18-month OS rates were 93.9%, 85.3%, and 66.6%, respectively. Hemorrhage was detected in three patients and arteriovenous fistula in two patients after MW ablation; all were promptly treated with embolization. There were no liver abscesses, bile-duct injuries, or other major procedure-related complications. CONCLUSIONS: MW ablation immediately followed by chemoembolization is safe and effective in the treatment of large HCC lesions.

Efficacy of locally administered dexamethasone for prevention of low back pain after labor epidural analgesia / 中华麻醉学杂志

Objective To evaluate the efficacy of locally administered dexamethasone for prevention of low back pain after labor epidural analgesia.Methods Two hundred nulliparous parturients who required labor epidural analgesia,of ASA physical status Ⅰ or Ⅱ,were randomly divided into 2 groups (n =100 each) using a random number table:control group (group C) and dexamethasone group (group D)).In group D,lidocaine 4 ml and dexamethasone 1 ml (5 mg) were injected around the puncture site.In group C,lidocaine 4 ml and normal saline 1 ml were injected around the puncture site.Epidural puncture was performed after local administration.According to the results of epidural puncture,each group was further divided into two subgroups:single puncture group (Cs subgroup,Ds subgroup) and repetitive puncture group (Cr subgroup,Dr subgroup).The patients were followed up for 72 h,and the development of low back pain was recorded.Results Compared to group C,the incidence of low back pain was significantly decreased,and pain was reduced in group D.The incidence of low back pain was significantly lower in Ds group than in Cs group,and in Dr group than in Cr group.Conclusion Locally administered dexamethasone 5 mg is helpful in reducing low back pain after labor epidural anesthesia.

Rosiglitazone and imidapril alone or in combination alleviate muscle and adipose depletion in a murine cancer cachexia model.

Rosiglitazone (RGZ) and imidapril improve cancer cachexia via different mechanisms. Therefore, we hypothesized that combination therapy of RGZ+imidapril would further attenuate cancer cachexia in vivo. After injection with colon-26 adenocarcinoma for 9 days, BALB/c mice were randomly divided into the following four treatment groups for 7 days (n = 8 per group): (1) placebo, (2) RGZ, (3) imidapril, and (4) RGZ+imidapril. Eight healthy control animals were also assessed. Body weight, tumor volume, gastrocnemius muscle and epididymal adipose mass, serum metabolic markers and cytokines, and the expression of nuclear factor-κB and two E3 ubiquitin ligases, atrogin-1 and MuRF-1, were measured. From days 14 to 16, all treatments significantly reduced tumor volume (P < 0.05). From days 10 to 16, improvements in the tumor-free body weight were observed in the RGZ and RGZ+imidapril groups. In addition, significant improvements in both gastrocnemius muscle and epididymal adipose mass were observed in all treatment groups (all, P < 0.05). Furthermore, all treatments significantly increased tumor necrosis factor alpha levels as compared to those observed in the healthy control animals (P < 0.001). Insulin levels significantly increased in the placebo group as compared to those in the healthy control group (P < 0.05), which were reduced in all the treatment groups (P < 0.05). Finally, whereas all treatments significantly reduced atrogin-1 levels as compared to the placebo group (all, P < 0.05), significant reductions in MuRF-1 levels were only observed in the RGZ and RGZ+imidapril groups (both, P < 0.05). Thus, all three treatments reduce tumor growth and alleviate cancer cachexia; however, synergistic effects of RGZ+imidapril combination therapy were not observed.

Regulatory effects of IFN-γ on Treg cells from HIV/AIDS patients receiving HAART for one year / 中华微生物学和免疫学杂志

Objective To investigate the regulatory effects of IFN-γon Treg cells from HIV/AIDS patients receiving highly active antiretroviral therapy (HAART) for one year.Methods Thirty HIV/A1DS patients whose CD4+T cells were below 350/μ1 were recruited for HAART therapy.Blood samples were collected at the time points of 0,24,48 weeks after HAART.PBMCs were isolated and randomly divided into two culture groups.One group was cultured directly in medium and another group was co-cultured with IFN-γ (40 pg/ml).The supernatants and cells were separated after 5 days of culture for analysis.The concentrations of IL-12 and CD4+CD25+Foxp3 Treg cells were measured by ELISA and flow cytometry,respectively.Results The levels of IL-12 in the supernatants from the culture without IFN-γ at time points of 0,24,48 weeks after HAART were lower than those from the co-cultured group [(37.02±12.76) vs (41.79± 15.02),t=2.336,P=0.03; (41.76±17.01) vs (47.2±14.26),t=2.702,P=0.014; (48.01± 11.84) vs (53.44± 11.30),t =3.14,P =0.003].The percentages of CD4+ CD25 + Foxp3 Treg cells in CD4+ T cells from the direct-cultured group were higher than those from the co-cultured group at the three time points [(10.41±1.10)％ vs (2.40±1.11)％,t=13.89,P=0.000; (8.33±2.03)％ vs (1.99± 0.86)％,t=12.93,P=0.000; (5.65±1.55)％ vs (1.32±0.73)％,t=10.61,P=0.000].Moreover,the results within the same group at the time points of 0,24,48 weeks upon HAART were also significantly different.Conclusion With the interference of HAART,IL-12 levels were increased,while CD4+CD25+ Foxp3 Treg cells were decreased in patients with HIV/AIDS.IFN-γ plays an important role in this process.

Treatment of cancer cachexia in mice by combination of dsRNA-dependent protein kinase inhibitor and medroxyprogesterone acetate.

Inhibitor of dsRNA-dependent protein kinase (PKRI) and medroxyprogesterone acetate (MPA) improve cancer cachexia via different mechanisms. We aimed to compare these two drugs, alone or in combination, in cancer cachexia in mice. Forty male BABL/c mice aged 6-8 weeks were randomly divided into PKRI, MPA, PKRI+MPA, placebo, and healthy control groups. The first 4 groups were injected with colon-26 adenocarcinoma and fed for 12 days and then treated with PKRI and MPA alone or in combination for 7 days. Body weight, tumor volume, wet weight of gastrocnemius muscle, serum levels of nutritional markers and cytokines were measured. The tumor growth (volume and weight) of mice treated with PKRI, MPA alone or PKRI+MPA was slower than that of placebo group. Wet weight of gastrocnemius muscle was significantly higher in PKRI and PKRI+MPA-treated than in placebo animals (P<0.01). All tumor-bearing mice had a significantly lower level of blood glucose, higher level of serum triglyceride and lower level of serum albumin compared with healthy control (P<0.001). However, PKRI, MPA and PKRI+MPA groups had a significant higher level of blood glucose and lower level of serum triglyceride compared with placebo group (P<0.001). All tumor bearing mice had a significant higher level of serum TNF-α, IL-1 and IL-6 compared with healthy control (P<0.001). Serum level of TNF-α and IL-6 was significantly lower in PKRI and PKRI+MPA-treated than in placebo animals (P<0.01). PKRI alone and combination therapy with PKRI and MPA reduce tumor growth and may alleviate cachexia.

Clinical characteristics of bronchiolitis obliterans in pediatric patients / 中华儿科杂志

<p><b>OBJECTIVE</b>To analyze the clinical characteristics, image findings, laboratory examination, the therapeutic methods and clinical outcomes of bronchiolitis obliterans (BO) in pediatric patients.</p><p><b>METHOD</b>Twenty-six pediatric patients with BO were reported. All data were collected from cases who were hospitalized in the Department of Pediatrics, First Affiliated Hospital of Guangzhou Medical College from June 1(st), 2009 to the April 30(th), 2011, and infectious agents, clinical manifestations, risk factors, changes in imageology, laboratory examination, therapeutic methods and treatment responses were analyzed.</p><p><b>RESULT</b>The ranges of age at onset was 4.5 months-8 years in 26 cases (18 boys and 8 girls). The course of disease was (6.2 ± 3.5) months. The period of followed-up ranged from 2 to 24 months. The common clinical characteristics were persistent wheezing of different severity (26 cases, 100%), cough (24 cases, 92%), intolerance to exercise (22 cases, 85%), short of breath (21 cases, 81%), retraction (20 cases, 77%), wheezy phlegm (16 cases, 62%), keeping with crackles (10 cases, 38%), cyanosis around the mouth (3 cases, 12%) and no clubbed fingers (toes). In 18 cases the etiology was detected, mycoplasma (11 cases, 42%), respiratory syncytial virus (4 cases, 15%), parainfluenza virus (2 cases, 8%), influenza virus A (2 cases, 8%) and influenza virus B (2 cases, 8%), human bocavirus (HBoV) (1 case, 4%). There were 8 cases (31%) with combined infection. Chest X-ray in 10 cases indicated changes suggestive of bronchopneumonia (38%), in only 1 case there was an image of interstitial pneumonia disease (4%). All the patients were diagnosed by high-resolution computerized tomography (HRCT). All cases were demonstrated to have air retention, poor blood perfusion in lung, just like "Westemark sign" with HRCT. In 19 cases antineutrophil cytoplasmic antibody (ANCA) was determined and 10 patients (53%) were positive for P-ANCA, and 8 cases (42%) were positive for C-ANCA. All patients received oral corticosteroid and low doses azithromycin. In 13 cases (50%) the treatment effectively reduced the severity of disease and the frequency of cough and wheezing. The average number of days for symptom improvement was (7.1 ± 4.8) days.</p><p><b>CONCLUSION</b>Respiratory infection plays an important role in BO in children. The chronic and persistent wheezing, cough, intolerance to exercises, short breath, retraction were the main clinical manifestations. But these symptoms are non-specific. Chest X-ray can not provide enough information for diagnosis. Classical "Westemark sign" with HRCT is an important sign. ANCA with a high positive rate (approximately 50%) suppose immuno-lesion in BO. Oral corticosteroid and methotrexate may relieve clinical symptoms.</p>

Dynamics of IL-2 and IL-7 levels during Highly active antiretroviral therapy and their significance / 中国医师杂志

Objective The objective of this study was to investigate the course of certain common gamma cytokines ( IL-2 and IL-7 ) and their role on the control of the viral infection in a short term antiviral therapy.Methods A total of 35 adults with chronic HIV infection,responding to combined antiretroviral therapy (cART) guideline criteria were enrolled in this one year follow-up study.After signing an informed consent,20 ml blood were collected from each patient at base line,week 0,week 24 and week 48.1 ml serum collected from each patient was kept at -80 * C until use.Serum concentration of IL-2 and IL-7 was determined using ELISA kit from ebioscience Beijing.CD4 and CD8 cells were counted and quantified using flux cytometry,and serum HIV RNA was quantified using real time PCR.Results All patients had a mean baseline IL-2 level [ (9.67 ± 2.6 ) pg/ml ]lower than the controls [ ( 27.36 ± 5.05 ) pg/ml ].After treatment for 48 weeks,IL-2 increased[ ( 19.8 ± 3.3 ) pg/ml ].However,the mean baseline 1L-7 [ ( 81.74± 20.47 ) pg/ml ]in patients was higher than controls [ ( 2.06 ± 1.52 ) pg/ml ].After treatment for 48 weeks,IL-7 decreased [ (8.36 ± 2.16)pg/ml ].IL-2 showed a significant increase and positive correlation with CD4 cells after HAART initiation (0week:R =0.21,P =0.063,24week:R =0.24,P =0.033,48week:R =0.19,P =0.103; IL-7 showed a significant decrease after HAART initiation but it did not show correlation with CD4 cells.We noted there was a negative correlation between IL-2 and CD4 count in HAART baseline (R =0.28,P =0.012 ),but no correlation between IL-7 and CD4 count from 6 month after HAART.IL-2 showed negative correlation with HIV RNA ( R =- 0.17,P =0.032),but IL-7 showed a relationship with the HIV RNA Conclusions The increase of IL-2 coupled with the decrease of IL-7 revealed a partial restoration of immune response during HAART.However,the absence of relationship with HIV RNA suggested that these cytokines might not be directly involved in the reduction of viral load.

Combined treatment with GH, insulin, and indomethacin alleviates cancer cachexia in a mouse model.

Cancer-induced cachexia involves weight loss, catabolic activity, and inflammation. We have evaluated the effects of various treatments (GH, insulin (INS), indomethacin (IND), and all possible combinations) on cancer cachexia in a mouse model. BALB/c mice that were implanted with colon-26 adenocarcinoma developed cachexia in 9 days. Body weight, tumor volume, tumor-free weight, inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin 6 (IL6)), and nutritional markers (glucose (Glu), albumin, triglycerides (TGs)) of treatment and control groups were monitored. In the cachexia group, there was a significant decrease in tumor-free bodyweight by day 11. Treatment with GH+INS+IND significantly alleviated tumor-free bodyweight reduction and cachexia-induced changes in nutritional markers and cytokines, and prolonged survival time. GH+INS+IND treatment was more effective than other treatment combinations in elevating Glu and TGs, reducing TNF-α and IL6 levels, and prolonging survival time. In conclusion, GH+INS+IND alleviated cachexia symptoms in a murine model of cancer cachexia.

Protective effect of heme oxygenase-1 on lung injury induced by erythrocyte instillation in rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Intratracheal instillation of blood induces self-repaired acute lung injury. However, the mechanism of repair has been unclear. Heme-oxygenase (HO)-1, which catalyzes heme breakdown, acts as an inducible defense against oxidative stress and plays an important role in inflammation. The objective of this study was to test the role of HO-1 in lung injury caused by intratracheal instillation of red cells.</p><p><b>METHODS</b>Forty healthy, male Sprague-Dawley rats were randomly divided into five groups: normal group, saline group, erythrocyte group, erythrocyte+zinc-protoporphyrin (ZnPP, HO-1 inhibitor) group and saline+ZnPP group. At 2 days after intratracheal instillation of red cells, lung tissues and lavage samples were isolated for biochemical determinations and histological measurements.</p><p><b>RESULTS</b>Histological analysis revealed that administration of ZnPP worsened the acute lung injury induced by instilled erythrocytes. HO-1 was over-expressed in the erythrocyte group and in the erythrocyte + ZnPP group. Compared with the erythrocyte + ZnPP group, the levels of total protein, lactate dehydrogenase and tumor necrosis factor-alpha in the lavage were lower (P < 0.01), while the level of interleukin-10 was higher in the erythrocyte group (P < 0.01).</p><p><b>CONCLUSION</b>HO-1 protects against erythrocyte-induced inflammatory injury in lung.</p>