Weidiao-3 Mixture Improves the Clinical Efficacy of Immunotherapy for Advanced Gastric Cancer by Regulating Intestinal Flora / 中国医学科学院学报

Objective To investigate the effects of Weidiao-3(WD-3)Mixture on the clinical efficacy of immunotherapy for advanced gastric cancer and the intestinal flora.Methods Fifty-one patients with advanced gastric cancer treated in Wuxi Traditional Chinese Medicine Hospital from January 2020 to December 2021 were randomized into a WD-3 group(immunotherapy + WD-3 Mixture,one dose per day)(n=25)and a gastric cancer(GC) group(only immunotherapy)(n=26)according to the admission time.Ten healthy volunteers were included as the healthy control group.The Karnofsky score and the Quality of Life Questionnare-Core score were evaluated before and after treatment,and the clinical efficacy was compared after treatment.After treatment,the stool samples were collected for 16SrRNA gene high-throughput sequencing and targeted metabolomics.The α and β diversity and structure of the intestinal flora and the content of short-chain fatty acids were compared between groups.Results The quality of life in both groups improved after treatment and was better in the WD-3 group than in the GC group(P=0.035).The dry mouth(P=0.038)and altered taste(P=0.008)were mitigated in the WD-3 group after treatment,and the reflux(P=0.001)and dry mouth(P=0.022)were mitigated in the GC group after treatment.After treatment,the WD-3 group outperformed the GC group in terms of dysphagia(P=0.047)and dry mouth(P=0.045).The WD-3 group was superior to the GC group in terms of objective remission rate and disease control rate,with prolonged median progression-free survival and median overall survival(P=0.039,P=0.043).The α and β diversity indexes of the intestinal flora showed no significant differences between WD-3 and GC groups(all P>0.05).At the phylum level,WD-3 and GC groups had lower relative abundance of Firmicutes(P=0.038,P=0.042)and higher relative abundance of Proteobacteria(P=0.016,P=0.015)than the healthy control group.The relative abundance of Actinomycetes in the GC group was lower than that in the healthy control group(P=0.035)and the WD-3 group(P=0.046).At the genus level,the GC group had lower relative abundance of Bifidobacteria and Coprococcus than the healthy control group and the WD-3 group(all P<0.001).LEfSe revealed the differences in the relative abundance of 6 intestinal bacterial taxa between the WD-3 group and the GC group.At the genus level,Saccharopolyspora had higher relative abundance in the WD-3 group than in the healthy control group and only existed in the WD-3 group.The content of isobutyric acid and isovaleric acid in the WD-3 group was higher than that in the healthy control group(P=0.037,P=0.004).Conclusion WD-3 Mixture may increase the relative abundance of Bifidobacteria and Coprococcus and the content of isobutyric acid and isovaleric acid to alter the intestinal microecology,thereby improving the efficacy of immunotherapy for gastric cancer.

A double-blind, randomized, placebo- and positive-controlled phase III trial of 1% benvitimod cream in mild-to-moderate plaque psoriasis / 中华医学杂志(英文版)

BACKGROUND@#Benvitimod cream, a novel synthetic small molecule, was effective in treating mild-to-moderate plaque psoriasis. We conducted a phase III clinical trial to assess the efficacy and safety of benvitimod cream in patients with mild-to-moderate plaque psoriasis.@*METHODS@#We randomly assigned 686 patients (2:1:1) to receive 1% benvitimod cream, 0.005% calcipotriol ointment or placebo twice a day for 12 weeks. The primary efficacy end points were the percentage of patients with a 75% or greater reduction from baseline in the psoriasis area and severity index (PASI 75) score and with a score of 0 or 1 in static physician's global assessment (sPGA) at week 12.@*RESULTS@#The results showed that 50.4% of patients in the benvitimod group achieved PASI 75, which was significantly higher than that in the calcipotriol (38.5%, P < 0.05) and placebo (13.9%, P < 0.05) groups. The proportion of patients achieving an sPGA score 0 or 1 was 66.3% in the benvitimod group and 63.9% in the calcipotriol group, which were both significantly higher than that in the placebo group (34%, P < 0.05). In the long-term follow-up study, 50.8% of patients experienced recurrence. After retreatment with 1% benvitimod, 73.3% of patients achieved an sPGA score of 0 or 1 again at week 52. Adverse events included application site irritation, follicular papules, and contact dermatitis. No systemic adverse reactions were reported.@*CONCLUSION@#During this 12-week study, benvitimod cream was demonstrated with high effectiveness and safety in patients with mild-to-moderate plaque psoriasis.@*TRIAL REGISTRATION@#Chinese Clinical Trial Registry (ChiCTR), ChiCTR-TRC-13003259; http://www.chictr.org.cn/showprojen.aspx?proj=6300.

Role of microRNA-150 in proliferation, migration and invasion of conjunctival mucosa-associated lymphoid tissue lymphoma / 第二军医大学学报

Objective To observe the expression of microRNA-150 (miR-150) in conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma, so as to investigate its mechanism in proliferation, migration and invasion of conjunctival MALT lymphoma. Methods The expressions of ;m'P-150 and Cbl-b, a possible downstream molecule of miR-150, were measured by qPCR in MALT lymphoma tissues and precancerous tissues collected from 3 patients with conjunctival MALT lymphoma in Changzheng Hospital of Second Military Medical University. Then, we transfected miR-150 inhibitor and negative control into human multiple myeloma cell lines RPM1 8226 by cell transfection. CCK-8 assay and flow cytometry (FCM) method were used to investigate the role of miR-150 in the proliferation and apoptosis of RPM1 8226 cells. Transwell assay was used to analyze the effect of miR-150 on the migration and invasion of RPMI 8226 cells. Western blotting analysis was used to examine the regulation of miR150 on Cbl-b expression in RPMI 8226 cells. Results The expression of miR-150 was significantly increased in the conjunctival MALT lymphoma tissues compared with precancerous tissues (P< 0. 05,P< 0. 01). Compared with negative control group, the proliferation of RPMI 8226 cells was significantly repressed (P< 0. 01), the apoptosis was significantly increased (P< 0. 01), and the migration and invasion were significantly decreased (P< 0. 05,P< 0. 01) after transfection of miR-150 inhibitor. The expression of Cbl-b was significantly up-regulated in MALT lymphoma tissues, and was significantly increased after inhibiting miR-150 expression. Conclusion Up-regulated miR-150 can promote the proliferation, migration and invasion of lymphoma cells and is involved in the generation of conjunctival MALT lymphoma, which may be mediated by inhibiting its downstream target gene Cbl-b.

Immune effects of different forms of vaccines of meningococcus serogroup B outer membrane protein 0315 / 中国免疫学杂志

Objective:To evaluate preliminarily immunocompetence and immunoprotection of a NMB0315 nucleic acid vaccine,a recombinant protein vaccine and a nucleic acid vaccine plus a recombinant protein vaccine against Neisseria meningitidis serogroup B in mice, and to provide reliable experimental basis for further exploration of the effective immunization methods and pathways of NMB0315 vaccine. Methods:The NMB0315 nucleic acid vaccine [ pcDNA3. 1 (+)/NMB0315 ] and recombinant protein vaccine(pET-30a/NMB0315)were prepared. Female BALB/c mice were inoculated with a NMB0315 DNA vaccine followed by boosting with recombinant protein NMB0315 through intramuscular and intraperitoneal immunization respectively. Next, humoral immunologic response and cellullar immunologic response were detected in female BALB/c mice by ELISA. The survival rate of BALB/c mice was used to evaluate immunoprotection of the vaccines in mice. Results:Specific IgG,IgG1,IgG2a,and sIgA,induced by the NMB0315 DNA vaccine(pNMB0315-CpG),protein NMB0315 vaccine(rNMB0315-FA),NMB0315 DNA vaccine prime-protein boost at week 8, were detected by indirect ELISA,the A450 values were up to(0. 505±0. 042,0. 513±0. 022,0. 342±0. 017,0. 250±0. 015),(0. 823± 0. 061,0. 807±0. 045,0. 596±0. 027,0. 450±0. 028)and(0. 694±0. 053,0. 711±0. 032,0. 455±0. 021,0. 386±0. 024)respectively, which was significantly higher than the PBS control(P<0. 05). The antibody level of protein vaccine was significantly higher than the nucleic acid vaccine group and combined immunization group ( P<0. 05 ) . The stimulation index and IFN-γ level of combined immunization group were significantly higher than the protein vaccine group and nucleic acid vaccine group(P<0. 05). The bactericidal titer of nucleic acid vaccine group, protein vaccine group and combined immunization group reached 1 :64, 1 :128 and 1 :128 respectively,and the protection rates were 70%,95% and 80% respectively. The IgG2a/IgG1 ratios of the nucleic acid vaccine group, the recombinant protein vaccine group and the combined immunization vaccine group were all less than 1 at week 2, 4, 6, 8. Conclusion:The humoral immunity effects( including mucosal immune) induced by the NMB0315 vaccines form high to low were as follows:the recombinant protein vaccine group, the combined immunization vaccine group, the nucleic acid vaccine;and the cellular immune effects from high to low were as follows:the combined immunization vaccine group, the nucleic acid vaccine group, the recombinant protein vaccine group;The protection effects induced by the NMB0315 vaccines in BALB/c mice within 72 hours from high to low were as follows:the recombinant protein vaccine group, the combined immunization vaccine group, the nucleic acid vaccine group.

Immune effects of different forms of vaccines of meningococcus serogroup B outer membrane protein 0315 / 中国免疫学杂志

Objective:To evaluate preliminarily immunocompetence and immunoprotection of a NMB0315 nucleic acid vaccine,a recombinant protein vaccine and a nucleic acid vaccine plus a recombinant protein vaccine against Neisseria meningitidis serogroup B in mice, and to provide reliable experimental basis for further exploration of the effective immunization methods and pathways of NMB0315 vaccine. Methods:The NMB0315 nucleic acid vaccine [ pcDNA3. 1 (+)/NMB0315 ] and recombinant protein vaccine(pET-30a/NMB0315)were prepared. Female BALB/c mice were inoculated with a NMB0315 DNA vaccine followed by boosting with recombinant protein NMB0315 through intramuscular and intraperitoneal immunization respectively. Next, humoral immunologic response and cellullar immunologic response were detected in female BALB/c mice by ELISA. The survival rate of BALB/c mice was used to evaluate immunoprotection of the vaccines in mice. Results:Specific IgG,IgG1,IgG2a,and sIgA,induced by the NMB0315 DNA vaccine(pNMB0315-CpG),protein NMB0315 vaccine(rNMB0315-FA),NMB0315 DNA vaccine prime-protein boost at week 8, were detected by indirect ELISA,the A450 values were up to(0. 505±0. 042,0. 513±0. 022,0. 342±0. 017,0. 250±0. 015),(0. 823± 0. 061,0. 807±0. 045,0. 596±0. 027,0. 450±0. 028)and(0. 694±0. 053,0. 711±0. 032,0. 455±0. 021,0. 386±0. 024)respectively, which was significantly higher than the PBS control(P<0. 05). The antibody level of protein vaccine was significantly higher than the nucleic acid vaccine group and combined immunization group ( P<0. 05 ) . The stimulation index and IFN-γ level of combined immunization group were significantly higher than the protein vaccine group and nucleic acid vaccine group(P<0. 05). The bactericidal titer of nucleic acid vaccine group, protein vaccine group and combined immunization group reached 1 :64, 1 :128 and 1 :128 respectively,and the protection rates were 70%,95% and 80% respectively. The IgG2a/IgG1 ratios of the nucleic acid vaccine group, the recombinant protein vaccine group and the combined immunization vaccine group were all less than 1 at week 2, 4, 6, 8. Conclusion:The humoral immunity effects( including mucosal immune) induced by the NMB0315 vaccines form high to low were as follows:the recombinant protein vaccine group, the combined immunization vaccine group, the nucleic acid vaccine;and the cellular immune effects from high to low were as follows:the combined immunization vaccine group, the nucleic acid vaccine group, the recombinant protein vaccine group;The protection effects induced by the NMB0315 vaccines in BALB/c mice within 72 hours from high to low were as follows:the recombinant protein vaccine group, the combined immunization vaccine group, the nucleic acid vaccine group.

Rates of Intentional and Unintentional Nonadherence to Peritoneal Dialysis Regimes and Associated Factors.

With increasing emphasis on expanding home-based dialysis, there is a need to understand adherence outcomes. This study set out to examine the prevalence and predictors of nonadherence among patients undergoing peritoneal dialysis. A cross sectional sample of 201 peritoneal dialysis patients recruited between 2010-2011 from Singapore General Hospital completed measures of quality of life, medication beliefs, self-efficacy and emotional distress. Nonadherence rates were high; 18% for dialysis, 46% for medication and 78% for diet. Intentional nonadherence was more common for dialysis (p = .03), whereas unintentional nonadherence was more common for medication (p = .002). Multivariate models indicated significant associations for higher education (intermediate vs low OR = 3.18, high vs low OR = 4.70), lower environment quality of life (OR = 0.79), dialysis self-efficacy (OR = 0.80) with dialysis nonadherence; higher education (OR = 2.22), self-care peritoneal dialysis (OR = 3.10), perceived necessity vs concerns over medication (OR = 0.90), self-efficacy (OR = 0.76) with nonadherence to medication. The odds for nonadherence to diet were higher among patients who were younger (OR = 0.96), of Chinese ethnicity (OR = 2.99) and those reporting better physical health (OR = 1.30) and lower self-efficacy (OR = 0.49). Nonadherence is common in peritoneal dialysis. Self-efficacy and beliefs about medication are promising targets for interventions designed to improve adherence.

Effectiveness of a day care program in supporting patients on peritoneal dialysis and their caregivers.

PURPOSE: Physical inactivity and social isolation are major problems faced by peritoneal dialysis (PD) patients. Respite care is also an unmet need for their caregivers. The study aimed to evaluate the benefits of day care service for PD patients. METHOD: Khoo Teck Puat Hospital collaborated with St Luke's Eldercare (SLEC) to provide day care services for PD patients. The day care provided assistance with two PD exchanges and activities for patients to maintain health and improve social interaction. Outcome indicators included: (1) enrollment status, length of stay and peritonitis rate; (2) quality of life and mental status evaluations on patients and caregivers with the 12-item Short-Form Health Survey, Hospital Anxiety and Depression Scale and Zarit Burden Interview Short-Form 12; and (3) qualitative data collected via interviews with patients, caregivers, healthcare providers and SLEC staff. RESULTS: Sixty-four patients were referred, and 16 eventually participated. Mean age of participants was 67.2 (range 54-85) years. For patients who stayed >1 month (n = 9), length of stay was 205.0 days (58-428) and frequency of attendance was 2.9 (0.6-4.8) times/week. There were no peritonitis episodes while patients were in the program. Mental improvement was noticed for most patients and caregivers, but physical improvement was less obvious. Caregivers also felt less burden. CONCLUSIONS: Day care service is effective in alleviating the burden of caregivers and beneficial to patients with relatively good functional status. However, persuading patients and their caregivers to take up the program was a challenge.

Predicting technique and patient survival over 12 months in peritoneal dialysis: the role of anxiety and depression.

BACKGROUND: Emotional distress is common in dialysis patients, but its role on clinical outcomes for patients on peritoneal dialysis (PD) is uncertain. PURPOSE: To evaluate the effect of depression and anxiety on 1-year prognosis in PD patients. METHODS: A total of N = 201 PD patients (58.9 ± 12.59 years) completed the Hospital Anxiety Depression Scale and measures of social support at baseline and were followed up for CC technique and actuarial patient survival. RESULTS: Mortality and technique failure rates were 9.9 and 5.97 %, respectively. Carer-assisted PD, anxiety, comorbid burden and albumin were significant univariate predictors. Multivariate proportional hazard model to adjust for confounders indicated that anxiety remained significant with HR of 2.145 [95 % CI 1.03, 4.49, p = 0.043] for death/technique failure. CONCLUSION: Anxiety is an important predictor of actuarial and technique survival in PD. Effective treatment for symptoms of anxiety may represent an easily achievable means of improving the clinical outcome of PD patients.

Clinical Features of Adult/Adolescent Atopic Dermatitis and Chinese Criteria for Atopic Dermatitis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Atopic dermatitis (AD) is an inflammatory skin disease characterized by chronic recurrent dermatitis with profound itching. Most patients have personal and/or family history of atopic diseases. Several criteria have been proposed for the diagnosis of AD. Although the clinical features of childhood AD have been widely studied, there has been less large-scale study on adult/adolescent AD. The aim of this study was to investigate the clinical features of adult/adolescent patients with chronic symmetrical eczema/AD and to propose Chinese diagnostic criteria for adult/adolescent AD.</p><p><b>METHODS</b>A hospital-based study was performed. Forty-two dermatological centers participated in this study. Adult and adolescent patients (12 years and over) with chronic symmetrical eczema or AD were included in this study. Questionnaires were completed by both patients and investigators. The valid questionnaires were analyzed using EpiData 3.1 and SPSS 17.0 software.</p><p><b>RESULTS</b>A total of 2662 valid questionnaires were collected (1369 male and 1293 female). Of all 2662 patients, 2062 (77.5%) patients had the disease after 12 years old, while only 600 (22.5%) patients had the disease before 12 years old, suggesting late-onset eczema/AD is common. Two thousand one hundred and thirty-nine (80.4%) patients had the disease for more than 6 months. One thousand one hundred and forty-four (43.0%) patients had a personal and/or family history of atopic diseases. One thousand five hundred and forty-eight (58.2%) patients had an elevated total serum IgE and/or eosinophilia and/or positive allergen-specific IgE. Based on these clinical and laboratory features, we proposed Chinese criteria for adult/adolescent AD. Of all 2662 patients, 60.3% were satisfied with our criteria, while only 48.2% satisfied with Hanifin Rajka criteria and 32.7% satisfied with Williams criteria, suggesting a good sensitivity of our criteria in adult/adolescent AD patients.</p><p><b>CONCLUSION</b>Late-onset of eczema or AD is common. The clinical manifestations of AD are heterogeneous. We have proposed Chinese diagnostic criteria for adolescent and adult AD, which are simple and sensitive for diagnosis of adult/adolescent AD.</p>

Curcumin induces apoptosis by PTEN/PI3K/AKT pathway in EC109 cells / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To study the molecular mechanism of curcumin in human esophageal carcinoma cell line (EC109).</p><p><b>METHODS</b>EC109 cells were cultivated in vitro. When 80%-90% confluence was reached, they were treated with curcumin in different concentrations (15-120 µmol/L). The effects on cell proliferation were examined by CCK-8 colorimetry. The ultrastructure of EC109 cells were detected with transmission electron microscope(TEM). The cells apoptosis was observed with laser confocal microscope(LCM) by AnnexinV-FITC/PI double staining. The proteins level of PTEN, AKT, GSK3β and Caspase 3 were tested by flow cytometry(FCM) .</p><p><b>RESULTS</b>CCK-8 test showed that curcumin could inhibit the proliferation of EC109 cells in a time- and concentration-dependent manner. TEM and LCM examinations indicated that curcumin could make EC109 cells apoptosis. The data of FCM showed that curcumin could increase the expression of PTEN, GSK3β and Caspase 3, decreased the expression of AKT.</p><p><b>CONCLUSION</b>The effects of curcumin on inhibiting proliferation and promoting apoptosis of EC109 cells were related with increased expression of PTEN and inhibition of PI3K/AKT signaling pathway.</p>

The effects of curcumin on PTEN/PI3K/Akt pathway in Ec109 cells / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the inhibition effect of curcumin on the proliferation of the human esophageal carcinoma cell line Ec109 and its impact on PEN/PI3K/Akt signaling pathway.</p><p><b>METHODS</b>Esophageal carcinoma Ec109 cells were cultured in vitro conventionally and were treated with curcumin at different concentrations. The cell proliferation level was examined by MIT colorimetry, the ultrastructure of curcumin-treated Ec109 cells were detected with transmission electron microscope (TEM) and cell apoptosis was observed by FCM with AnnexinV-FITC/PI double staining. The protein levels of PTEN, Akt, GSK3P and Caspase 3 of curcumin-treated Ec109 cells were detected by Western blot.</p><p><b>RESULTS</b>MTT test showed that curcumin could inhibit the proliferation of Ec109 cells in a time and concentration-dependent manner. TEM examination indicated that curcumin could induce Ec109 cell apoptosis. FCM detection showed that Ec109 cell apoptotic rate increased significantly with the increase of drug concentration. On the other hand, curcumin could promote the expression of PTEN, GSK3beta and Caspase 3 yet reduce the expression of Akt.</p><p><b>CONCLUSION</b>Curcumin could obviously up-regulate the expression of PTEN, GSK3beta and Caspase 3, surpress PI3K/Akt signaling pathway and hence inhibit the proliferation of Ec109 cells.</p>

Pharmacological postconditioning with lactic acid and low dose edaravone could attenuate myocardial reperfusion injury through mitochondrial pathway / 中华心血管病杂志

<p><b>OBJECTIVE</b>To test the hypothesis that pharmacological postconditioning with lactic acid and low dose edaravone could mimic the upper trigger of mechanical postconditioning and relieve reperfusion injury through mitochondrial pathway.</p><p><b>METHODS</b>Rats were randomly divided into 6 groups (n = 18 each): sham, reperfusion/injury(I/R), postconditioning (IP), lactic acid (Lac, 60 µl), low dose edaravone (Eda, 3 µg/kg), and Lac+Eda. After 45 min myocardial ischemia, different drugs or saline were administrated around the infarct border according to different groups using micro syringe at the time of reperfusion. After 10 min reperfusion, right atrial plasma pH value was determined in all rats. Then the rats were sacrificed at 1, 6 and 24 h (n = 6 each), apoptotic index was measured by TUNEL, infarct area and ischemic area were measured through Evans blue-TTC double staining, mitochondrial absorbance, the contents of MDA and SOD in ischemic myocardium were detected by spectrophotometry, and the expression of apoptotic pathway molecules, such as Bcl-2, Bax and Cytochrome c (Cyt-c) , were detected by Western blot.</p><p><b>RESULTS</b>Right atrial plasma pH value was significantly lower, the content of MDA was significantly lower, and the content of SOD was significantly higher in IP and Lac+Eda groups than in I/R group (all P < 0.05). The mitochondrial absorbance in Lac+Eda group at all time points were all significantly higher than those in I/R group (all P < 0.05). The level of Bcl-2 in ischemic myocardium in Lac+Eda group was significantly higher than in I/R group (1.02 ± 0.19 vs.0.02 ± 0.01, P < 0.05), the level of Bax (0.38 ± 0.07 vs.2.40 ± 0.45, P < 0.05) and Cyt-c(0.78 ± 0.05 vs.6.54 ± 1.86, P < 0.05) were all lower than those in I/R group. The content of CK[(849 ± 228) vs.(1249 ± 211) U/L, P < 0.05] and CK-MB[(470 ± 266) vs. (966 ± 263) U/L, P < 0.05] in Lac+Eda group were all significantly lower than in I/R group, apoptotic index [(10.51 ± 1.52)% vs. (15.00 ± 1.90) %, P < 0.05] and infarct area [(27.12 ± 5.55)% vs. (45.66 ± 10.81)%, P < 0.05] in Lac+Eda group were all significantly lower than those in I/R group.</p><p><b>CONCLUSION</b>Pharmacological postconditioning with lactic acid and low dose edaravone could mimic the upper triggers of mechanical postconditioning and attenuate myocardial reperfusion injury through mitochondrial pathway.</p>

Evaluation of adherence and depression among patients on peritoneal dialysis.

INTRODUCTION: It is challenging for dialysis patients to maintain adherence to their medical regimen, and symptoms of depression are prevalent among them. Limited data is available about adherence and depression among patients receiving peritoneal dialysis (PD). This study aimed to examine the rates of treatment non-adherence and depression in PD patients. METHODS: A total of 20 PD patients (response rate 71.4%; mean age 64.4 ± 11.6 years) were assessed using the Beliefs about Medicines Questionnaire, Self Efficacy for Managing Chronic Disease Scale, Hospital Anxiety and Depression Scale (HAD) and Kidney Disease Quality of Life-Short Form. A self-reported adherence (PD exchanges, medication and diet) scale developed for the study was also included. Medical information (e.g. most recent biochemistry results) was obtained from chart review. RESULTS: The mean self-reported scores indicated an overall high level of adherence, although a significant proportion of patients were non-adherent. Among the latter, 20% of patients were non-adherent to medication and 26% to diet due to forgetfulness, while 15% and 26% of patients admitted to deliberate non-adherence to medication and diet, respectively. Treatment modality, employment, self-care status and self-efficacy were associated with overall adherence. Using a cutoff point of 8 for HAD depression and anxiety subscales, 40% of patients were found to be depressed and 30% had symptoms of anxiety. CONCLUSION: This is the first study to document treatment adherence and depression among PD patients in Singapore. Findings of high prevalence of depression and anxiety, and reports of poor adherence warrant development of intervention programmes.

The epidemiological study of work-related musculoskeletal disorders and related factors among automobile assembly workers / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the work-related musculoskeletal disorders among automobile assembly workers, to discusses the related risk factors and their relationship.</p><p><b>METHOD</b>The selected 1508 automobile assembly workers from a north car manufacturing company were regarded as the study object. The hazard zone jobs checklist, Nordic musculoskeletal symptom questionnaire (NMQ) and pain questionnaire were used to perform the epidemiological cross-sectional and retrospective survey and study for the General status, awkward ergonomics factors and related influencing factors, and musculoskeletal disorders of workers.</p><p><b>RESULTS</b>The predominant body sites of occurring WMSDs among automobile assembly workers were mainly low back, wrist, neck and shoulders, the predominant workshop section of occurring WMSDs were mostly concentrated in engine compartment, interior ornament, door cover, chassis and debugging section. The predominant body site of WMSDs among engine compartment and chassis section workers was low back, interior ornament workers were low back and wrist, door cover workers was wrist, chassis workers was low back, debugging workers were neck and low back. Neck musculoskeletal disorders had the trend with the increase of a body height; Smoking may increase the occurrence of musculoskeletal disorders.</p><p><b>CONCLUSION</b>The WMSDs appears to be a serious ergonomic proble assem among automobile assembly workers, predominant occurring site of WMSDs is with different workshop section, its characteristics is quite obvious, probably related to its existing awkward work position or activities. The worker height and smoking habits may be important factors which affect musculoskeletal disorders happen.</p>

Population pharmacokinetics of high-dose methotrexate administered in 329 children with acute lymphoblastic leukemia / 中国实验血液学杂志

The aim of this study was to investigate the population pharmacokinetic characteristics of high-dose methotrexate (HDMTX) administered in children with acute lymphoblastic leukemia (ALL) for individualizing methotrexate dose regimen with routine plasma concentration data. The data of 329 children with acute lymphoblastic leukemia administering HDMTX in hospital were collected from 2003 to 2006. Population pharmacokinetics model, parameters, inter-and intra-individual variation were estimated by nonlinear mixed effect modes (NONMEM) software. The effects of the covariates including sex, age, body weight, alkalization and hydration volumes as well as biochemical parameters on the clearance and apparent volume of distribution of methotrexate were explored and the final model was established. The results showed that according to one compartment open pharmacokinetic model with first-order absorption and first-order elimination used in the modeling procedure, the factor that significantly influenced the clearance and apparent volume of distribution of methotrexate was weight (p<0.05). The final model in this study was: CL=7.0 x [1 + 0.0218 x (WT-31.1)] x EXP (eta(CL)) (L/h); V=32.8 x [1 + 0.0288 x (WT-31.1)] x EXP (eta(V)) (L), where 31.1 (kg) was the average body weight of the population. The inter individual variation (CV) of CL and V were 19.4% and 31.0% respectively. It is concluded that the population pharmacokinetic model of HDMTX in children with ALL is established. The obtained final model and population pharmacokinetics parameters of methotrexate may be useful for individualization treatment.

Down-regulation of perlecan expression contributes to the inhibition of rat cardiac microvascular endothelial cell proliferation induced by hypoxia / 生理学报

Exposure of endothelial cells (ECs) to hypoxia leads to a decrease in EC proliferation. However, the mechanism by which hypoxia inhibits EC proliferation is unclear. Perlecan has been reported to play an important role in regulating EC proliferation. We hypothesized that perlecan was involved in the hypoxia-induced inhibition of EC proliferation. To test this hypothesis, rat cardiac microvascular ECs were cultured under normoxic or hypoxic conditions for 12 h and harvested for determination of perlecan mRNA expression using real-time reverse transcription-polymerase chain reaction (RT-PCR). The results showed that exposure of ECs to hypoxia for 12 h induced a decrease in perlecan mRNA expression (61.72%, P<0.05). Concomitantly, the down-regulation of endogenous perlecan induced by hypoxia or the neutralization of endogenous perlecan with anti-perlecan antibody significantly inhibited EC proliferation and responsiveness to basic fibroblast growth factor (bFGF), and decreased focal adhesion kinase (FAK) expression and extracellular signal-regulated kinase 1/2 (ERK1/2) activation. These data indicate that down-regulation of perlecan expression contributes to hypoxia-induced inhibition of rat cardiac microvascular EC proliferation by suppressing FAK-mediated and ERK1/2-dependent growth signals.

Expression profiling of UBF, a novel member of UBC family / 中国应用生理学杂志

<p><b>UNLABELLED</b>From large-scale sequence of human fetal liver cDNA library, we have obtained a full-length cDNA from an EST after further sequencing. It has been demonstrated by the alignment comparison with data base available that it is a novel member of Ubc family and got the number from GeneBank: UBF-F1 AF 294842.</p><p><b>AIM AND METHODS</b>To demonstrate its authenticity, UBF was amplified from the total RNA of human fetal liver and HL-60 cell line using RT-PCR, and the PCR products were further sequenced and compared with the original UBF sequence. To evaluate the expression level and subcellular location of UBF in human multiple tissues, in situ hybridization was carried out on the frozen section of human fetal multiple tissues and HL-60 cell line with DIG-labeled UBF cDNA probes.</p><p><b>RESULTS</b>The experimental results of RT-PCR and sequencing showed that the sequence of RT-PCR products were the same as the original UBF. The experimental results of in situ hybridization showed that UBF was expressed widely by human multiple fetal tissues and the expression level were very high in HL-60 cells.</p><p><b>CONCLUSION</b>It is suggested that the special structure of UBF is authentic, and the expression profiling research of UBF shows that UBF is expressed widely by human multiple fetal tissues and the expression level is very high in HL-60 cells, implying that UBF plays the important function in the developing tissues and leukemia cells. It is also suggested that UBF may be functionally related with the nucleic-involving cellular activities based on the results of sub-cellular localizations.</p>

Screening of differentially expressed genes in the mouse hematopoietic stromal cells after long-term culture / 中国实验血液学杂志

Hematopoietic stromal cells, being the essential ingredient of the hematopoietic microenvironment, play very important roles in the control and regulation of self-renewal, proliferation and differentiation of hematopoietic stem cells (HSC) via complex interactions of cell-cell, cell-humoral and cell-extracellular matrix. Evidence from in vivo experiment has proved that HSC derived from normal mice could reconstitute hematopoiesis of mice with HSC defects but failed to reconstitute hematopoiesis of those mice with microenvironment defects, showing the importance of hematopoietic microenvironment in the maintenance of hematopoiesis in vivo. A well-known long-term culture (LTC) system established by Dexter demonstrated in another way that stromal cell layer in the system could support ex vivo hematopoiesis for several months, even more than one year under the optimal conditions. It, however, has not been demonstrated that what is the key elements and in which way the ex vivo hematopoiesis could be maintained for so long time. As the inventions for the large-scale screening methodologies the suppression subtractive hybridization (SSH) was chosen for the screening differentially expressed genes expressed by LTC cultured stromal cells but not by the uncultured bone marrow cells (BMC). mRNA extracted from both cultured adherent cells (tester) and BMC (driver) were hybridized according to the protocol provided by CLONTECH. Total of 130 clones differentially expressed by cultured cells were randomly picked up and 106 ESTs were obtained after sequencing. They represent 26 identical or similar genes and 7 novel genes after the bioinformatics analysis. 5 of the novel genes with the entire open reading frame, without functional clues, have been cloned into the mammalian expression vectors and the functions of them in the control of proliferation and differentiation of HSC will be further exploring. The most interesting discovery is that 3 novel genes have signal peptides, implying the potential discovery of novel growth factors as 80% known growth factors have signal peptides. Our experimental results suggest that: (a) based on the results of subtractive efficiency, the SSH could be a reliable method to screen differentially expressed genes; (b) gene expression may be regulated by multiple factors, even conditioning-dependent, in this experiment the genes expressed by bone marrow stromal cells are LTC-cultivation inducible; (c) it is possible to find interesting genes or special gene after relatively large-scale screen.