OBJECTTo investigate the therapeutic effect of microencapsulated porcine retinal pigmented epithelial cells (RPE-M) transplantation on rat model of Parkinson's disease (PD).

METHODSPrimary porcine RPE cells were harvested by enzyme digestion and expanded in culture medium. Determine the levels of dopamine (DA) and homovanillic acid (HVA) by high performance liquid chromatography electrochemical (HPLC) assay, and the levels of brain-derived neurotrophic factor (BDNF) and glial-derived neurotrophic factor (GDNF) were detected by ELISA. Alginate-polylysine-alginate (APA) microencapsulated cells were produced by using a high voltage electrostatic system. PD rat model was established by unilateral injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle (MFB). After that, the RPE-M was transplanted into the corpus striatum of PD rat, and then the rotation test scores were recorded and biochemical changes of the corpus striatum were tested.

RESULTSThe levels of DA, HVA, BDNF and GDNF secreted by RPE were stable in the RPE culture supernatant and were not changed by the microencapsulation. Eighty-three percent rats developed PD by unilateral lesion of 6-OHDA in the MFB. The RPE-M transplantation had therapeutic effect on 33% PD rats.

CONCLUSIONPorcine RPE cells grow actively in vitro and could secrete DA, HVA, BDNF, and GDNF constantly, which does not be affected by the passage culture and the APA miroencapsulation. RPE-M transplantation of may be a curative therapy for PD.

Adrenergic Agents ; toxicity ; Animals ; Brain-Derived Neurotrophic Factor ; metabolism ; Cell Transplantation ; methods ; Cells, Cultured ; Disease Models, Animal ; Dopamine ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Epithelial Cells ; metabolism ; transplantation ; Glial Cell Line-Derived Neurotrophic Factor ; metabolism ; Male ; Oxidopamine ; toxicity ; Parkinson Disease ; etiology ; surgery ; Rats ; Rats, Sprague-Dawley ; Retina ; cytology ; Swine ; anatomy & histology ; Time Factors ; Transplantation, Heterologous ; methods ; Tyrosine 3-Monooxygenase ; metabolism

OBJECTIVETo construct recombinant lentiviral vectors for gene delivery of the glial cell line-derived neurotrophic factor (GDNF), and evaluate the neuroprotective effect of GDNF on lactacystin-damaged PC12 cells by transfecting it into bone marrow stromal cells (BMSCs).

METHODSpLenti6/V5-GDNF plasmid was set up by double restriction enzyme digestion and ligation, and then the plasmid was transformed into Top10 cells. Purified pLenti6/V5-GDNF plasmids from the positive clones and the packaging mixture were cotransfected to the 293FT packaging cell line by Lipofectamine2000 to produce lentivirus, then the concentrated virus was transduced to BMSCs. Overexpression of GDNF in BMSCs was tested by RT-PCR, ELISA and immunocytochemistry, and its neuroprotection for lactacystin-damaged PC12 cells was evaluated by MTT assay.

RESULTSVirus stock of GDNF was harvested with the titer of 5.6 x 100,000 TU/mL. After transduction, GDNF-BMSCs successfully secreted GDNF to supernatant with higher concentration (800 pg/mL) than BMSCs did (less than 100 pg/mL). The supernatant of GDNF-BMSCs could significantly alleviate the damage of PC12 cells induced by lactacystin (10 micromol/L).

CONCLUSIONOverexpression of lentivirus-mediated GDNF in the BMSCs cells can effectively protect PC12 cells from the injury by the proteasome inhibitor.

Acetylcysteine ; analogs & derivatives ; pharmacology ; Animals ; Bone Marrow Cells ; cytology ; metabolism ; Cells, Cultured ; Culture Media, Conditioned ; metabolism ; DNA, Recombinant ; Genetic Therapy ; methods ; Genetic Vectors ; Glial Cell Line-Derived Neurotrophic Factor ; genetics ; metabolism ; Lentivirus ; genetics ; Neurons ; drug effects ; Neuroprotective Agents ; metabolism ; PC12 Cells ; drug effects ; Plasmids ; genetics ; Protease Inhibitors ; pharmacology ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Stromal Cells ; Transduction, Genetic ; methods

OBJECTIVETo evaluate the effect of Zhuanggu Jianxi Decoction (, ZGJXD) on interleukin-1 β (IL-1 β)-induced degeneration of chondrocytes (CDs) as well as the activation of caveolin-p38 mitogen-activated protein kinase (MAPK) signal pathway, investigating the possible molecular mechanism that ZGJXD treats osteoarthritis.

METHODSSerum pharmacology was applied in the present study, where ZGJXD was orally administrated to New Zealand rabbits and then ZGJXD containing serum (ZGJXD-S) was collected for following in vitro experiments. CDs were isolated aseptically from New Zealand rabbits and then cultured in vitro. Upon IL-1 β stimulation, the degeneration of CDs was verified by inverted microscope, toluidine blue stain and type II collagen immunocytochemistry. After IL-1 β-stimulated CDs were intervened with blank control serum, ZGJXD-S, together with or without SB203580 (a specific inhibitor of p38 MAPK) for 48 h, caveolin-1 protein expression and the phosphorylation level of p38 were determined by Western blotting, and the mRNA expression of IL-1 β, tumor necrosis factor α (TNF-α), matrix metalloproteinase 3 (MMP-3) and MMP-13 were examined by real-time polymerase chain reaction.

RESULTSIL-1 β stimulation induced degeneration of CDs, increased caveolin-1 expression and p38 phosphorylation, up-regulated the mRNA level of IL-1 β, TNF-α, MMP-3 and MMP-13. However, the IL-1 β-induced activation of caveolin-p38 signaling and alteration in the expression of p38 downstream target genes were suppressed by ZGJXD-S and/or SB203580 in CDs.

CONCLUSIONZGJXD can prevent CDs degeneration via inhibition of caveolin-p38 MAPK signal pathway, which might be one of the mechanisms that ZGJXD treats osteoarthritis.

Animals ; Base Sequence ; Blotting, Western ; Caveolins ; metabolism ; Chondrocytes ; drug effects ; enzymology ; metabolism ; DNA Primers ; Drugs, Chinese Herbal ; pharmacology ; Gene Expression Profiling ; Interleukin-1beta ; physiology ; MAP Kinase Signaling System ; Male ; RNA, Messenger ; genetics ; Rabbits ; p38 Mitogen-Activated Protein Kinases ; genetics ; metabolism

OBJECTIVETo observe the association between baseline pulse pressure (PP) level and new-onset cardio-cerebrovascular events in diabetic population.

METHODSPhysical examination data between July 2006 to October 2007 from a total of 101 510 employees of Kailuan Group were reviewed, 8306 subjects with a fasting plasma glucose level of ≥ 7.0 mmol/L or with confirmed diabetes diagnosis and were enrolled in this prospective cohort study. Subjects were followed up for 38-53 (48.1 ± 3.1) months and the cardio-cerebrovascular events were obtained every six months, association between baseline PP and new-onset cardio-cerebrovascular events in the diabetic population were analyzed.

RESULTS(1) Incidences of total cardio-cerebrovascular events in the PP groups were 3.4%, 2.8%, 4.5%, 6.4%, respectively. Incidences of cerebral infarction events and myocardial infarction were 2.1%, 1.6%, 2.9%, 3.9% and 1.1%, 0.7%, 1.0%, 1.7%, respectively. (2) Multivariate Cox's proportional hazards regression analysis indicated that baseline PP group was the risk factor for total cardio-cerebrovascular events, cerebral infarction events and myocardial infarction, and the risk for all the events of the PP ≥ 60 mm Hg (1 mm Hg = 0.133 kPa) group was increasing. The values of RR(95%CI) were 1.88 (95%CI 1.34-2.65, P < 0.01), 1.92 (95%CI 1.23-2.99, P < 0.01) and 1.52 (95%CI 0.82-2.81, P > 0.05) after adjust the other factors.(3) In line with increasing level of baseline PP, age, BMI, SBP, DBP, HDL-C, and hs-CRP levels significantly increased in this diabetic population (P < 0.01 or P < 0.05).

CONCLUSIONThe level of high baseline PP is a risk factor for new-onset cardio-cerebrovascular events in diabetic population.

Adult ; Aged ; Aged, 80 and over ; Blood Pressure ; physiology ; Cardiovascular Diseases ; etiology ; Diabetes Mellitus ; physiopathology ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Prospective Studies ; Young Adult

OBJECTIVEThis study aimed to investigate the depression status among high-risk pregnancy women, and to analyze its relevant social and psychological factors.

METHODSA total of 42 high-risk pregnancy women and 40 normal pregnancy women in a teaching hospital in Harbin city were followed up at time points of 32 - 36 weeks pregnancy, one week before labor, one week postpartum, and six weeks postpartum, respectively. During follow-up, the basic situation, social psychosocial factors of pregnancy women were collected and the depression of pregnancy women was measured by self-designed questionnaire and self-rating depression scale. The Edinburgh Postnatal Depression Scale (EPDS) was applied at timepoint of one week postpartum. Single factor analysis and the unconditional multivariate logistic regression were applied for analyzing the on the related social-psychosocial factors among high-risk pregnancy women.

RESULTSThe age of high-risk pregnancy women was (31.0±5.6), and the age of normal pregnancy women was (30.5±3.8) (t=0.169, P>0.05). The results showed that the depression rate in high-risk pregnancy women was 45.2% (19/42), which was 25.0% (10/40) in normal pregnancy women, the difference was significant (χ2=3.671, P=0.045). The depression rates at different time points were 30.9% (13/42), 42.9% (18/42), 23.8% (10/42), 26.2% (11/42) in high-risk pregnancy women respectively, and 25.0% (10/40), 15.0% (6/40), 20.0% (8/40), 17.5% (7/40) in the control group respectively, the difference of the depression rates among groups at one week before labor was significant (χ2=7.680, P<0.01), the difference among groups at 32-36 weeks pregnancy (χ2=0.133, P=0.80), at one week postpartum (χ2=0.174, P=0.79) and at six weeks postpartum (χ2=0.903, P=0.43) were not significant. At one week postpartum and six weeks postpartum periods, the EPDS depression rate were 12.5% (4/32), 30.4% (7/23) in case group respectively, 8.3% (3/36), 22.9% (8/35) in control group respectively, the difference were not significant (χ2=0.319, 0.416, P=0.573, 0.519). There were significantly associations between the depression mood of one week before labor and the depressive symptoms of six weeks postpartum in both groups (r=0.824, 0.677, both P values were <0.05). The risk factors for maternal depression among high-risk pregnancy women were not ready for production (OR=2.73, P<0.01) and fearing of childbirth safety (OR=2.89, P<0.01).

CONCLUSIONThe depression date of high-risk pregnancy was high, especially at the time point one week before labor. Risk factors of maternal depression among high-risk pregnancy were "not ready for production" and "fear of childbirth safety".

Adult ; China ; epidemiology ; Cohort Studies ; Depression ; epidemiology ; psychology ; Depression, Postpartum ; epidemiology ; psychology ; Female ; Humans ; Logistic Models ; Postpartum Period ; psychology ; Pregnancy ; Pregnancy Complications ; epidemiology ; psychology ; Pregnancy, High-Risk ; psychology ; Risk Factors

Aimed to solve the issues of pesticide residue, heavy metal contents and harmful elements in the productive process of Chinese herbal medicines, the research team built the technical regulations for production of pollution-free Chinese herbal medicines. This regulation included the environment of production area, the process of production, quality of products etc., which were the key steps controlled the quality of Chinese herbal medicines. The environment of production area was selected according to the ecological factors which were stipulated by Ecological Suitability Regionalization of Chinese herbal medicines (second edition). The quality of air should be attain the one or two levels of GB/T3095-2012 standard values. The cultivation soils should reach to the one or two levels of GB15618 and NY/T391 standard values. The quality of irrigation water should accord with the stipulation of GB5084-2005. Aimed to the production of Chinese herbal medicines, disease-resistant and superior varieties which were suitable to the local stations should be selected, and the breeding of superior seeds and seedlings should be strengthened. Additionally, rational fertilizer application of pollution-free Chinese herbal medicines should be conformed to the principles, requirements, and the kinds of fertilizers allowed or limited for use, which were stipulated by the standard of DB13/T454. Furthermore, the plant protection policy of priority to prevention and synthetical prevention should be followed; improving ecological environment and strengthening cultivation management should be served as the basics. Agricultural measures, and biological and physical control strategies should be preferred to use; and high toxicity, residue pesticide and its mixture should be inhibited; the use of chemical pesticides should be minimized and then to decrease contamination and residue. Additionally, the quality of products should be reached to the standard of pollution-free Chinese herbal medicines; high toxicity and detection rate of pesticide residues and the contents of heavy metal and harmful elements (e.g. plumbum, cadmium, mercury, arsenic and cuprum) should accord with the common criteria of pollution-free Chinese herbal medicines. Application of technical regulations for production of pollution-free Chinese herbal medicines guarantees significantly social, economic and ecological benefits.

Objective In recent years, the incidence of invasive pulmonary aspergillosis (IPA) in non-neutropenic patients has been increasing. Most previous studies have focused on the diagnosis and treatment of IPA in severely immunocompromised patients. The purpose of this study was to investigate the clinical characteristics of IPA in non-neutropenic patients. Methods We enrolled 183 IPA patients (including 46 proven IPA cases and 137probable IPA cases) admitted to our hospital from 2008 to 2018, after excluding possible IPA cases and neutropenic cases. The clinical and laboratory data were collected and analyzed. Results In this study, 164 (89.6%) patients had underlying diseases and risk factors, among which chronic obstructive pulmonary disease and prolonged steroid treatment were the most common. Cough (79.8%), dyspnea (71.0%), sputum (68.9%)and fever (61.2%) were the common symptoms. Chest CT findings were mainly consolidation (45.9%), nodule (32.8%), ground-glass opacity (29.0%) and cavity (26.8%). The halo sign (8.2%) and air crescent sign (7.1%) were relatively rare. The mean numbers of leucocyte and neutrophils were 14.6×10⁹/L and 10.2×10⁹/L, respectively. Positive rates of sputum culture and bronchoalveolar lavage fluid culture were 32.5% and 35.1%, respectively. Positive rates of galactomannan (GM) antigen test in serum and bronchoalveolar lavage fluid samples were 55.2% and 77.1%, respectively. Transthoracic needle biopsy and transbronchial lung biopsy were associated with positive rates of 45.3% and 20.6%, respectively. Conclusion The clinical and imaging features of IPA in non-neutropenic patients are atypical. Compared with sputum culture and GM antigen test in serum, alveolar lavage fluid GM test has higher sensitivity which can assist in definitive diagnosis.

OBJECTIVE: To observe the pressure pain threshold (PPT), skin conductance (SC) and blood perfusion (BP) of the sensitized acupoints in patients with knee osteoarthritis (KOA), and explore the mechanism of acupuncture at the sensitized acupoints for treating diseases. METHODS: Eleven healthy subjects and 11 unilateral KOA patients were recruited from July 2020 to March 2021 in this study. The PPT, SC and BP of control acupoints in healthy controls, and non-sensitized and sensitized acupoints in KOA patients were measured and compared between baseline and after manual acupuncture (MA) treatment. RESULTS: Before MA treatment, lower PPT was observed at the sensitized acupoints compared with non-sensitized and control acupoints (P<0.05). After MA treatment, PPT at the sensitized acupoints increased significantly in KOA patients (P<0.05). Before MA treatment, there was no statistical difference in SC and BP among control, non-sensitized and sensitized acupoints (P>0.05). Compared with the control and non-sensitized acupoints, there were significant increases of SC and BP in sensitized acupoints of KOA patients after MA treatment (P<0.05 or P<0.01). CONCLUSION MA at sensitized acupoints could elevate PPT of KOA patients, which may be associated with the increment of SC and BP.
Humans ; Acupuncture Points ; Pain Threshold ; Osteoarthritis, Knee/therapy* ; Acupuncture ; Acupuncture Therapy ; Pain

BACKGROUNDData on the epidemiology of hypertension in Chinese non-dialysis chronic kidney disease (CKD) patients are limited. The aim of the present study was to investigate the prevalence, awareness, treatment, and control of hypertension in the non-dialysis CKD patients through a nationwide, multicenter study in China.

METHODSThe survey was performed in 61 tertiary hospitals in 31 provinces, municipalities, and autonomous regions in China (except Hong Kong, Macao, and Taiwan). Trained physicians collected demographic and clinical data and measured blood pressure (BP) using a standardized protocol. Hypertension was defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, and/or use of antihypertensive medications. BP < 140/90 mmHg and < 130/80 mmHg were used as the 2 thresholds of hypertension control. In multivariate logistic regression with adjustment for sex and age, we analyzed the association between CKD stages and uncontrolled hypertension in non-dialysis CKD patients.

RESULTSThe analysis included 8927 non-dialysis CKD patients. The prevalence, awareness, and treatment of hypertension in non-dialysis CKD patients were 67.3%, 85.8%, and 81.0%, respectively. Of hypertensive CKD patients, 33.1% and 14.1% had controlled BP to < 140/90 mmHg and < 130/80 mmHg, respectively. With successive CKD stages, the prevalence of hypertension in non-dialysis CKD patients increased, but the control of hypertension decreased (P < 0.001). When the threshold of BP < 130/80 mmHg was considered, the risk of uncontrolled hypertension in CKD 2, 3a, 3b, 4, and 5 stages increased 1.3, 1.4, 1.4, 2.5, and 4.0 times compared with CKD 1 stage, respectively (P < 0.05). Using the threshold of < 140/90 mmHg, the risk of uncontrolled hypertension increased in advanced stages (P < 0.05).

CONCLUSIONSThe prevalence of hypertension Chinese non-dialysis CKD patients was high, and the hypertension control was suboptimal. With successive CKD stages, the risk of uncontrolled hypertension increased.

Adult ; Aged ; Awareness ; Female ; Humans ; Hypertension ; complications ; epidemiology ; therapy ; Male ; Middle Aged ; Prevalence ; Renal Insufficiency, Chronic ; complications

Objective: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. Methods: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. Results: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). Conclusion An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.
Aged ; Asian Continental Ancestry Group ; Blood Glucose/analysis* ; China/epidemiology* ; Cohort Studies ; Diabetes Mellitus/blood* ; Female ; Glucose Tolerance Test ; Glycated Hemoglobin A/analysis* ; Glycemic Index ; Humans ; Male ; Middle Aged ; Uric Acid/blood*