A study on factors associated with age of Alzheimer's disease onset / 中华流行病学杂志

Objective: To understand the distribution characteristics of age of Alzheimer's disease (AD) onset and influencing factors. Methods: Based on the follow-up data of Alzheimer's Disease Neuroimaging Initiative from 2005 to 2022, participants with normal cognition (CN) or mild cognitive impairment (MCI) at baseline survey, and those with progression to AD during follow-up period were selected as study subjects. Univariate analysis and multiple linear regression analysis were performed to explore the associations of gender, race, number of ApoE ε4 genes carried, family history, years of education and marital status with the age of AD onset. Results: A total of 405 participants, with an average age of (74.0±6.9) years at baseline survey, progressed to AD during follow up period. The age of AD onset was (76.6±7.5) years, and age of onset in men was about 1.9 years later than women. Multiple linear regression analysis showed that for each increase in ApoE ε4 gene number, the age of AD onset was about 0.344 years earlier. The age of AD onset was 4.007 years earlier for those with MCI at baseline survey compared with those with CN. Years of education were not significantly associated with the age of onset of AD (P>0.05). Conclusion: Those who carry ApoE ε4 gene, and have MCI at baseline survey might have earlier age of AD onset.

Transition rules of cognitive frailty and influencing factors in the elderly in China / 中华流行病学杂志

Objective: To understand the transition rules of cognitive frailty and its influencing factors in the elderly in China and provide evidence for the early intervention of cognitive frailty. Methods: Data were retrospectively collected from China Health and Retirement Longitudinal Study with 3 round consecutive survey (2011, 2013, 2015) and the state of the subjects were classified into four categories: robust-normal cognitive, cognitive impairment, physical frailty, and cognitive frailty. A multi-state Markov model was established to explore the transition rules of cognitive frailty and its influencing factors. Results: A total of 3 470 older adults were included, and 350 (10.09%) had cognitive frailty at baseline. After two years, the probability of cognitive frailty in the cognitive impairment population was higher than that in people with physical frailty (31.6% vs. 7.6%). Persons with cognitive frailty were more likely to become physical frailty (29.7% vs. 15.6%). Being women (HR=1.599, 95%CI: 1.058-2.417), comorbidity (HR=3.035, 95%CI: 1.090-8.450), and depression (HR=1.678, 95%CI: 1.153-2.441) were the risk factors associated with cognitive frailty in the elderly, while being educated (HR=2.367, 95%CI: 1.567-3.575) was a protective factor for the transition of cognitive frailty to physical frailty. Conclusions: The prevalence of cognitive frailty is relatively high in the elderly in China. Those with cognitive impairment have a higher probability of cognitive frailty. Gender, education level, comorbidity, and depression are the main influencing factors for the occurrence and transition of cognitive frailty.

Research on predicting the risk of mild cognitive impairment in the elderly based on the joint model / 中华流行病学杂志

Objective: To construct and compare the dynamic prediction models of the risk of mild cognitive impairment (MCI) in the elderly based on six different cognitive function scales. Methods: Based on longitudinal data from the Alzheimer's Disease Neuroimaging Initiative from 2005 to 2020, Mini-mental state examination (MMSE), functional activities questionnaire (FAQ), Alzheimer's disease assessment scale-cognitive (ADAS-Cog) 11, ADAS-Cog13, ADAS delayed word recall (ADASQ4), and Rey auditory verbal learning test (RAVLT)_immediate were used as longitudinal cognitive function evaluation indicators to assess the longitudinal changes in cognitive function. The joint model was used to analyze association between indicators variation trajectory and survival outcome MCI, and construct the risk prediction model of MCI in the elderly, the linear mixed model was constructed the longitudinal sub-model which described the evolution of a repeated measure over time, a proportional hazards model was constructed the survival sub-model, and the two sub-models were connected through the correlation parameter (α). The areas under the receiver operator characteristic curve (AUC) were used to evaluate the predictive efficacy of the model in the follow-up period of (t, t+Δt). The starting point t was selected at the 30th, 42nd, and 54th month, and the Δt was selected as 15 and 21 months. Based on the prediction model, an example of the research object was selected for dynamic individual predictions of the risk of MCI. Results: Finally, 544 older adults (aged 60 years and above) with normal baseline cognitive status were included, of which 119 cases (21.9%) had MCI during the follow-up process were regarded as the case group, and 425 cases remained normal as the control group. The joint model suggests that the longitudinal trajectories of the six evaluation indicators are all related to the risk of MCI (P<0.001). The risk of MCI decreased by 32.3% (HR=0.677, 95%CI: 0.541-0.846) and 10.8% (HR=0.892, 95%CI: 0.865-0.919) for each one-point increase of MMSE and RAVLT_immediate longitudinal scores. The risk of MCI increased by 53.2% (HR=1.532, 95%CI: 1.393-1.686), 36.2% (HR=1.362, 95%CI: 1.268-1.462), 23.2% (HR=1.232, 95%CI: 1.181-1.285), and 85.1% (HR=1.851, 95%CI:1.629-2.104) for each one-point increase of FAQ, ADAS-Cog11, ADAS-Cog13, and ADASQ4 longitudinal scores. AUC results show that RAVLT_immediate (0.760 2) and ADASQ4 (0.755 8) have higher average prediction efficiency, followed by ADAS-Cog13 (0.743 7), ADAS-Cog11 (0.715 3), FAQ (0.700 8) and MMSE (0.629 5). ADASQ4 joint model was used to provide a dynamic individual prediction of the risk of MCI. The average probability of MCI after five years of follow-up and ten years of follow-up in the example individuals were 8% and 40%, respectively. Conclusions: The RAVLT_immediate and ADASQ4 scales, which are only for memory tests, have high accuracy in predicting the risk of MCI. Using the RAVLT_immediate and ADASQ4 scales as longitudinal cognitive function evaluation indicators to construct a joint model, the results can provide a basis for realizing MCI risk prediction for the elderly.

Non-coding RNAs in viral myocarditis / 生物工程学报

Viral myocarditis (VMC) is a disease characterized by inflammation of myocardial cells caused by viral infection. Since the pathogenesis mechanism of VMC has not been fully elucidated, the diagnosis and treatment of this disease remains extremely challenging. Non-coding RNAs (ncRNAs) are a class of RNAs that do not encode proteins. An increasing number of studies have shown that ncRNAs are involved in regulating the occurrence and development of VMC, thus providing potential new targets for the treatment and diagnosis of VMC. This review summarizes the possible roles of ncRNAs in the pathogenesis and diagnosis of VMC revealed recently.

Comprehensive benefits of agroforestry snail control forests in Eryuan County, Yunnan Province / 中国血吸虫病防治杂志

Objective To investigate the efficiency of various agroforestry systems for snail control in plateau hilly schistosomiasis-endemic areas of Yunnan Province, so as to provide insights into the construction of agroforestry schistosomiasis control projects in plateau hilly regions. Methods The pilot areas of snail control forests with various agroforestry systems were built in snail-breeding farmlands in Eryuan County, Yunnan Province in 2010, and the economic benefits and snail control effect were investigated in 2018. In addition, a fuzzy comprehensive evaluation model was created to screen the agroforestry system with high comprehensive benefits. Results A total of 14 types of pilot areas of snail control forests with various agroforestry systems were built. Economic benefit analysis showed that the“walnut + garlic”pattern had the best economic benefit, with annual economic benefits of 270 000 Yuan/hm2, followed by the“walnut + chili”pattern (annual economic benefits of 120 000 Yuan/hm2) and the “walnut + vegetables”pattern (annual economic benefits of 105 000 Yuan/hm2). No snails were detected in 8 types of the agroforestry systems, including the“walnut + chili”pattern, the“walnut + tobacco”pattern and the“walnut + garlic”pattern; however, there were snail found with various densities in other types of systems. Fuzzy comprehensive evaluation showed that the“walnut + garlic”pattern had the best comprehensive control effect, followed by the“walnut + chili”pattern and the“walnut + tobacco” pattern, while the pure grassland pattern showed no effect on snail control. Conclusions The agroforestry system is a preferential approach of forestry schistosomiasis control in plateau hilly schistosomiasis-endemic areas, which not only achieves snail control effects, but also promotes economic development and ecological construction in poor hilly areas.

Spectrum-effect Relationship of Anti-hepatoma Activity from 3 Kinds of Genus Paris Based on Cluster Analysis and Grey Relational Analysis / 中国实验方剂学杂志

Objective::To study the spectrum-effect relationship between HPLC fingerprints and anti-hepatoma activity of Paris polyphylla var. yunnanensis, P. forrestii and P. vietnamensis, and to elucidate its effective substance. Method::HPLC was used to establish the fingerprint of three extracts from the plant. The mobile phase was consisted of acetonitrile (A)-water (B) for gradient elution (0-10 min, 20%A; 10-20 min, 20%-25%A; 20-30 min, 25%-30%A; 30-40 min, 30%-35%A; 40-50 min, 35%-40%A; 50-60 min, 40%A; 60-75 min, 40%-45%A; 75-80 min, 45%-60%A), and the flow rate was 0.9 mL·min-1. The UV detection wavelength was 203 nm. Thiazolyl blue tetrazolium bromide (MTT) array was used to detect the inhibitory effects of three extracts on the proliferation of HepG2 cells, and the half inhibitory concentration (IC50) was calculated. Cluster analysis and grey relational analysis were used to analyze the data of spectrum and efficacy, and to find out the components that contributed a lot to the anti-liver cancer effect. Result::A total of 11 common peaks were identified as common peaks among HPLC fingerprints of three kinds of Paris. After treated 72 h, P. forrestii has the highest inhibitory effect on the HepG2 cells, the IC50 of P. forrestii, P. polyphylla var. yunnanensis and P. vietnamensis were 148.33, 178.87, 208.09 mg·L-1, respectively. According to the grey relational analysis, the common peaks 1-10 from P. polyphylla var. yunnanensis had great correlation to anti-tumor effect, and the common peaks 1-7 for P. forrestii, the common peaks 1-4, 6-10, N1 for P. vietnamensis, all the correlation degrees with IC50 were >0.7.Cluster analysis of variables in each Paris showed that peaks with correlation degree >0.7 could cluster with IC50. Conclusion::The established HPLC fingerprint method is reliable with good reproducibility. The peaks 1-4, 6 and 7 from three kinds of Paris have the greatest contribution to the anti-hepatoma effect.

Progress in prevention and treatment of enterovirus 71 infection / 中华微生物学和免疫学杂志

Enterovirus 71 (EV71) is a major pathogen causing severe hand, foot and mouth disease (HFMD) in infants under five years old. It can cause central nervous system damageand even death in severe cases. Considering the high mortality and disability rate of HFMD, this review focused on the most recent developments in vaccines and treatments against EV71 infection.

Determination and Analysis of Heavy Metals of Paridis Rhizoma from Different Localities and Pieces / 中国实验方剂学杂志

Objective:To analyze and determine heavy metal content in Paridis Rhizoma from different genus and localities,in order to provide a reference for selecting cultivation areas and establishing the quality standard of Paridis Rhizoma of heavy metals content. Method:Microwave digestion method combined with inductively coupled plasma atomic emission spectrometry method (ICP-AES) method were applied to determine the contents of 6 heavy metals,i.e. As,Cu,Hg,Cd,Pb and Cr in 39 samples of Paridis Rhizoma of different genus and localities in Yunnan Province. Cluster analysis,statistical analysis and principal component analysis (PCA) were used to compare the differences of heavy metals contents in different localities and species. Result:The contents of six heavy metals in Paridis Rhizoma met the ISO international standard of Heavy Metal Limit of Traditional Chinese Medicine-traditional Chinese Medicinal Materials. Under the limited value standard of Green Trade Standards of Importing Medicinal Plants and Preparations,the over-standard rate of heavy metal As was 15.4%,the excess rate of Cd was 5.1%,and the excess rate of Pb was 2.6%. The contents of Cu and Hg conformed to relevant requirements. Cluster analysis,statistical analysis and principal component analysis showed that for the same variety,differences in producing places had significant effects on heavy metal content,while differences in species had little effects. Conclusion:The results of this study indicated that the heavy metal content of Paris planted in and around Dali basically conformed to relevant standards. The differences of heavy metal content in Paris were mainly regional differences,which provided a theoretical basis for standardizing the cultivation of medicinal materials and formulating the limit standards of heavy metals for Paridis Rhizoma.

Effect of sitagliptin on cardiomyocyte pyroptosis induced by type 2 diabe-tes mellitus and underlying mechanism / 中国病理生理杂志

AIM:To explore the effect of sitagliptin (SLT) on cardiomyocyte pyroptosis induced by type 2 dia-betes mellitus (T2DM) and the underlying mechanism. METHODS:The T2DM rat model was established by high-fat diet and intraperitoneal injection of streptozotocin (35 mg/kg). The model rats were treated with SLT at 3, 10 and 30 mg/kg and nicotinamide [NAM; an non-specific inhibitor of sirtuin (SIRT) family] at 500 mg/kg for 4 weeks. Fasting blood glu-cose was measured, and the tissue proteins were determined by the methods of Western blot and immunochemistry. RE-SULTS:Compared with control group, the pyroptosis of cardiomyocytes and NLRP3 expression were significantly induced, while the protein level of SIRT3 was downregulated by T2DM (P<0.05). SLT inhibited the pyrpotosis of diabetic rat car-diomyocytes, downregulated the expression of NLRP3, and upregulated the expression of SIRT3 in a dose-dependent man-ner (P<0.05). All the function of SLT (30 mg/kg) was reversed by the treatment with NAM (500 mg/kg). Compared with control group, the pyroptosis of cardiomyocytes and NLRP3 expression were significantly induced, while the protein level of SIRT3 was not regulated by NAM (500 mg/kg). CONCLUSION:SLT exerts the inhibitory effect on the pyropto-sis of cardiomyocytes induced by diabetes, and the mechanism is related to the SIRT3/NLRP3 signaling pathway.

Changes of T Lymphocyte Subsets and Immunoglobulin in Peripheral Blood of Patients with ALL and N-ALL before and after Treatment and their Value for Monitoring of Disease and Evaluation of Prognosis / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To study the changes of T lymphocyte subsets and immunoglobulin in peripheral blood of patients with acute lymphoblastic leukemia (ALL) and non-acute lymphocytic leukemia (N-ALL) before and after treatment and their value for monitoring of disease and evaluation of prognosis.</p><p><b>METHODS</b>One hundred and six cases of leukemia were selected in our hospital, including 48 cases of ALL (ALL group) and 58 cases of N-ALL (N-ALL group); 54 peoples of normal physical examination were selected as the normal control group in the same period. The IgA, IgG and IgM levels of peripheral blood were detected, and the absolute value of T lymphocyte subsets was determined by cell slide method. According to whether the patients' status was improved or not by treatment, the 106 patients were divided into the unimproved group (55 cases including 25 ALL, 30 N-ALL) and improved group (51 cases including 23 ALL, 28 N-ALL).</p><p><b>RESULTS</b>The levels of IgA, IgG and IgM in 106 cases of leukemia were significantly lower than those in the control group (all P<0.05), and the CD3level, CD3CD4/CD3CD8ratio and the absolute value of CD3CD4T cells in the peripheral blood were significantly lower than those in the control group(all P<0.05); the absolute value of CD3CD8T cells showed no significant difference in comparison with the control group (P >0.05). After treatment, IgA,IgG and IgM levels in the improved group were significantly higher than those before therapy (all P<0.05), while their levels were not significantly different from that in the control group (all P>0.05); the CD3level, CD3CD4/CD3CD8ratio and the absolute value of CD3CD4T cells in the peripheral blood were significantly higher than those before therapy (all P<0.05), while those were not significantly different from the control group (all P>0.05). Compared with levels before treatment, the levels of above mentioned indicators in the unimproved group after treatment were not significantly different (all P>0.05); and the CD3level, CD3CD4/CD3CD8ratio and the absolute value of CD3CD4T cells were significantly lower than those in the control group (all P<0.05), and the absolute value of CD3CD8T cells were higher than that in the control group (P<0.05).</p><p><b>CONCLUSION</b>After the treatment, the T lymphocyte subsets (CD3, CD3CD4T cells) and immunoglobulin (IgA, IgG, IgM) levels in peripheral blood of patients with ALL and N-ALL have been improved significantly, and the detection of these indexes is helpful for disease monitoring and prognosis evaluation.</p>

Role of SIRT3 in dysfunction of energy metabolism induced by deoxycho-lic acid in human colon NCM460 cells / 中国病理生理杂志

AIM: To investigate the effect of deoxycholic acid (DCA) on the energy metabolism in human normal colon epithelial NCM460 cells.METHODS: NCM460 cells was treated with DCA at 10, 30 and 100 μmol/L for 5 d, or DCA at 100 μmol/L for 3, 5 and 7 d.After treated with DCA at 100 μmol/L for 3 d, the cells were treated with resveratrol, the activator of sirtuin 3 (SIRT3), for the next 4 d.Adenosine triphosphate (ATP) production in the mitochondria and lactate acid level were detected.The protein expression of SIRT3 was determined by Western blot.RESULTS: DCA inhibited the ATP production, increased lactate acid level, and downregulated the protein expression of SIRT3 in a dose-and time-dependent manner.Resveratrol at 10 μmol/L reversed the effects of DCA on the NCM460 cells.CONCLUSION: DCA induces the dysfunction of energy metabolism in NCM460 cells, and the mechanism may be related with SIRT3.

Protective Effect of Pyrola decorata H. Andres on β-amyloid Protein- induced Cytotoxicity in PC12 Cells / 医药导报

Objective To investigate protective activity against Aβ25-35-induced cytotoxicity in PC12 cells of different extracts and ursolic acid, which were isolated from pyrola decorata. Methods Aβ25-35-induced cytotoxicity in PC12 cells was established as the model in vitro. The cultured PC12 cells were divided into blank control group, DMSO control group, model control group, different extract groups of pyrola decorate and ursolic acid(UA) group. The different extract groups included ether extract (PE), acetidin extract (AE), n-butanol extract (BE), the water extract (WE), 50% ethanol extract (HEE). MTT assay was used to test the optimum concentration, and the number of viable cells in culture medium was measured by ELISA at 490 nm wavelength. Results The cell viabilities in different extracts groups(PE, AE, BE, WE, HEE) were respectively 89.3%, 77.2%, 79. 2%, 75. 1% ,74. 0% at the concentration of 5. 0 mg ? mL-1 . Moreover, ursolic acid showed the best neuroprotective activity (88.9%) at the concentration of 500 μg?L-1 . Compared with model control group, the survival rate of each group was remarkably increased, and the protective activities of PE and UA were more significant among them. Conclusion Different polar extracts of pyrola decorata and isolated ursolic acid have neuroprotective effects on Aβ25-35-induced cytotoxicity in PC12 cells in certain degrees.