Objective: To understand the influence of chronic diseases on the risk of impaired activities of daily living (ADL) of the elderly. Methods: Baseline data of 10 501 elderly individuals recruited by the Chinese Longitudinal Healthy Longevity Survey in 2002 were used, and follow up for this population was conducted until 2014. Cox Proportional Hazard Model was used to estimate the hazards ratios (HR) for the associations between five kinds of chronic diseases, the number of chronic diseases and the risk of ADL impairment in different age groups of the elderly. Results: Hypertension increased the risk of ADL impairment in the elderly of all age groups, which increased the ADL impaired risk by 43% (HR=1.43, 95%CI: 1.14-1.79) in group aged 65-74 years, 21% (HR=1.21, 95%CI: 1.02-1.43) in group aged 75-89 years and 20% (HR=1.20, 95%CI: 1.02-1.43) in group aged 90-105 years, respectively. Diabetes and cerebrovascular disease increased the ADL impaired risk by 102%(HR=2.02, 95%CI: 1.29-3.17), and 79% (HR=1.79, 95%CI: 1.24-2.58) in group aged 65-74 years, respectively. 'Suffering from one chronic disease' increased the ADL impaired risk by 13% (HR=1.13, 95%CI: 1.02-1.25), and suffering from two or more chronic diseases increased the ADL impaired risk by 25% (HR=1.25, 95%CI: 1.13-1.40) in all the age groups. Suffering from two or more chronic diseases increased the ADL impaired risk by 50% (HR=1.50, 95%CI: 1.21-1.87) in group aged 65-74 years and 17% (HR=1.17, 95%CI: 1.01-1.38) in groups aged 75-89 years. Conclusions: Hypertension was one of the most important risk factors for the impaired ADL in the elderly population in all age groups. Hypertension, diabetes, cerebrovascular disease or comorbidity increased the risk of impaired ADL in group aged 65-74 years.
Activities of Daily Living ; Aged ; Aged, 80 and over ; China ; Chronic Disease ; Cohort Studies ; Humans ; Longitudinal Studies ; Risk Factors

The neurochemical features of the nitrergic and peptidergic innervation of the porcine esophagus were investigated by means of immunohistochemical methods combined with vagotomy. Neuronal cell bodies in both the submucosal and the myenteric plexus (MP) were detected immunoreactivities for nNOS, VIP, GAL, NPY, PACAP, L-ENK, SP, 5-HT and CB, while CGRP- and SOM-immunoreactive (ir) somata were not encountered. In addition, nNOS- and CB-ir myenteric neurons constituted the separate enteric subpopulations.Double immunostainings with a general neuronal marker (PGP9.5 ) and the specific markers, such as nNOS, VIP and SP revealed (1)nNOS-ir myenteric neurons in the porcine esophagus accounted for a higher percentage (63 % ) of all esophageal intrinsic PGP9.5-ir neurons in comparison of VIP-ir (36%) and SP-ir populations (28%); (2) An increasing rostrocaudal gradient in the number of myenteric neurons per ganglion as well as a significantly higher number of enteric ganglia within both plexuses in the abdominal segment; ( 3 ) The densest nerve fibers within the esophageal musculature were VIP-/GAL-/NPY-ir, some of which also co-expressed nNOS and/or PACAP immunoreactivity. The number of L-ENK- and/or SP-ir fibers was significantly higher in lamina muscularis mucosae ( LMM ) than in tunica muscularis externa (TME). In contrast to reports in other species, CGRP-ir fibers within the porcine esophagus constituted a very limited population and were extrinsic; (4) Vagotomy experiments revealed an obvious decrease of PACAP-and 5-HT-ir nerve fibers within the MP,suggesting that these fibers originate from the vagal nerve, while these nNOS- and/or VIP-/GAL-/NPY-ir fibers innervating both the TME and the LMM did not appear to be significantly affected by the vagotomy procedure, possibly being the intrinsic origin.

Objective: To explore the association between the consumption of chemical fertilizers and the risk of low birth weight (LBW), to provide references for prevention programs on LBW and to improve the birth outcomes. Methods: Stratified multivariate logistic regression method was used in this study involving 153 preterm LBW infants, 179 term LBW infants and 204 normal control infants that were randomly selected from the birth monitoring data between October 2007 and September 2012 in Pingding county, Shanxi province. Associations between the risk of LBW and maternal exposure to chemical fertilizers during pregnancy were identified. A normal control group was set up to compare results between preterm and term LBW groups. Results: Totally, 18 749 infants were born between 2007 and 2012, with the total incidence rates of LBW as 48.5‰, preterm LBW as 19.4‰, and term LBW as 29.1‰. Concerning the case control study on preterm LBW, after adjustment for confounding factors, the risk of preterm LBW appeared 2.51 (95%CI: 1.05-5.99) times higher in villages with annual consumption of chemical fertilizer ≥100 tons than those villages that using chemical fertilizer less than 50 tons. No significant statistical associations were found between the amounts of household chemical fertilizer consumption and the risks of preterm LBW. Regarding the case control study on term LBW, after adjustment for confounding factors, in villages with ≥100 tons annual consumption of chemical fertilizers, the risk of term LBW was 4.03 (95%CI: 1.63-9.92) times of the risk in villages where the annal use of chemical fertilizers was less than 50 tons. There was no significant association between household consumption of chemical fertilizers and the risk of term LBW. Conclusions: Maternal exposure to chemical fertilizers during pregnancy was associated with the risk of LBW. Our findings suggested that the amount of chemical fertilizer consumption in rural areas seemed also associated with the risks of other adverse pregnancy outcomes. Women should avoid the chance of exposure to chemical fertilizers during pregnancy and the consumption of chemical fertilizers should be carefully managed.
Adult ; Case-Control Studies ; Environmental Exposure/adverse effects* ; Female ; Fertilizers/adverse effects* ; Humans ; Infant ; Infant, Low Birth Weight ; Infant, Newborn ; Maternal Exposure ; Pregnancy ; Premature Birth/epidemiology* ; Random Allocation ; Risk Factors

Abstract: Objective To clarify the long-term evolution of hepatitis B virus (HBV) quasi-species in HBsAg asymptomatic carriers in Long'an county, Guangxi. Methods ELISA was used to detect serological markers of HBV. Viral loads were measured by real time PCR. HBV DNA was extracted from serum by kits. The whole HBV genome was amplified using nested PCR and amplicons were sequenced by next-generation sequencing (NGS). These sequences from NGS were analyzed by the software like Mega. Results Serum samples were collected from 9 HBsAg asymptomatic carriers in Longan County，Guangxi at 4 different time points in 2004, 2007, 2013, 2019 or 2020. A total of 23 serum samples and 309 full-length gene quasi-species sequences were obtained, with an average amount of (0.18±0.07) G sequencing data for each sample. Genotype of 55.54%(5/9) the studied subjects underwent genotype conversion during the long-term evolution process of HBV quasi-species, and the genotyping results of the phylogenetic tree in the PreS/S region are in perfect agreement with the results of the whole genome analysis; recombinant B/C, I/C were found; the Sn ranged from 0 to 0.37 and the genetic diversity ranged from 0 to 0.11, respectively. A total of 21 special single nucleotide/amino acid mutations (7 in the S region, 2 in the X region, 3 in the PreC region and 9 in the BCP region) and 6 deletion mutations were detected, multiple mutations were found and no drug resistant mutations were found; 77.8%(7/9) of the HBV strains carried by the subjects in 2004 had double mutations at nt1 762(A→T) and 1 764(G→A) and a stop mutation at nt1 896(G→A); HBV mutations can be restored from the mutant type to the wild type and (or) vice versa without antiviral drug pressure, and The evolution rate of HBV genome was 2.03×10-5~3.50×10-3.Conclusion HBV genotype, recombinants, genetic complexity and diversity of HBV quasi-species can change over time during in natural infection. The transformation between HBV mutation type and wild type reduces the value of predicting clinical outcomes by genetic types and related mutations to some extent. The HBV genome evolution rate of asymptomatic carriers of HBsAg in Long'an County is very high.

With numerous advancements in novel biochemical techniques, our knowledge of the role of RNAs in the regulation of cellular physiology and pathology has grown significantly over the past several decades. Nevertheless, detailed information regarding RNA processing, trafficking, and localization in living cells has been lacking due to technical limitations in imaging single RNA transcripts in living cells with high spatial and temporal resolution. In this review, we discuss tech-niques that have shown great promise for single RNA imaging, followed by highlights in our recent work in the development of molecular beacons (MBs), a class of nanoscale oligonucleotide-probes, for detecting individual RNA transcripts in living cells. With further refinement of MB design and development of more sophisticated fluorescence microscopy techniques, we envision that MB-based approaches could promote new discoveries of RNA functions and activities.

We have previously described a novel artificial NFEV β-secretase (BACE1) cleavage site, which when introduced into the amyloid-β precursor protein (APP), significantly enhances APP cleavage by BACE1 in in vitro and cellular assays. In this study, we describe the identification and characterization of a single chain fragment of variable region (scFv), specific to the EV neo-epitope derived from BACE1 cleavage of the NFEV-containing peptide, and its conversion to IgG1. Both the scFv displayed on phage and EV-IgG1 show exquisite specificity for binding to the EV neoepitope without cross-reactivity to other NFEV containing peptides or WT-APP KMDA cleavage products. EV-IgG1 can detect as little as 0.3 nmol/L of the EV peptide. EV-IgG1 antibody was purified, conjugated with alkaline phosphatase and utilized in various biological assays. In the BACE1 enzymatic assay using NFEV substrate, a BACE1 inhibitor MRK-3 inhibited cleavage with an IC(50) of 2.4 nmol/L with excellent reproducibility. In an APP_NFEV stable SH-SY5Y cellular assay, the EC(50) for inhibition of EV-Aβ peptide secretion with MRK-3 was 236 nmol/L, consistent with values derived using an EV polyclonal antibody. In an APP_NFEV knock-in mouse model, both Aβ_EV40 and Aβ_EV42 peptides in brain homogenate showed excellent gene dosage dependence. In conclusion, the EV neoepitope specific monoclonal antibody is a novel reagent for BACE1 inhibitor discovery for both in vitro, cellular screening assays and in vivo biochemical studies. The methods described herein are generally applicable to novel synthetic substrates and enzyme targets to enable robust screening platforms for enzyme inhibitors.
Amino Acid Sequence ; Amyloid Precursor Protein Secretases ; antagonists & inhibitors ; chemistry ; genetics ; Amyloid beta-Protein Precursor ; Animals ; Antibodies ; pharmacology ; Brain Chemistry ; drug effects ; Disease Models, Animal ; Enzyme Inhibitors ; pharmacology ; Enzyme-Linked Immunosorbent Assay ; Gene Knock-In Techniques ; Humans ; Inhibitory Concentration 50 ; Mice ; Molecular Sequence Data ; Single-Chain Antibodies ; pharmacology

Objective: To describe the characteristics of newly reported HIV/AIDS cases via non-marital or non-commercial heterosexual transmission and to find out the relative factors in Hangzhou, from 2015 to 2017. Methods: Data were collected through the national HIV/AIDS comprehensive control and prevention data system. Study subjects would include those reported HIV/AIDS cases who were residents of Hangzhou and were infected via non-marital heterosexual transmission, between January 1, 2015 and December 31, 2017. Demographic characteristics and behavioral information were collected. χ(2) test was used to compare different characteristics of the non-married heterosexual transmission subjects. Logistic regression was used to assess factors that associated with non-marital but non-commercial HIV heterosexual transmission with SPSS. 20 software used to analyze statistically. Results: Non-marital HIV heterosexual transmission accounted for 38.03% (1 393/3 663) of the total new reported HIV/AIDS cases in 2015-2017. Out of the 1 393 HIV/AIDS cases, those infected through non-marital but non-commercial heterosexual transmission accounted for 50.83% (708/1 393), and those through non-martial commercial transmission was accounted for 49.17% (685/1 393). Male to female ratio was 3.51 ∶ 1 (1 084/309). Male HIV cases reported that their major way of infection was via non-marital commercial transmission (670/1 084, 61.81%), while female patients reported the way was via non-marital non-commercial (294/309, 95.1%). Results from multivariate logistic analysis showed that the related risk factors and ORs for non-marital but non-commercial transmission appeared as: female (aOR=48.25, 95%CI: 26.94- 88.44),<30 year olds (aOR=2.43, 95%CI: 1.31-4.51), 30-39 year olds (aOR=1.92, 95%CI: 1.11- 3.33), 40-49 year olds (aOR=1.80, 95%CI: 1.08-3.00), married or unmarried (vs. divorced or widowed, aOR=1.57, 95%CI: 1.10-2.24; aOR=1.78, 95%CI: 1.15-2.78), high school and above of education level (vs. primary school and under of education level, aOR=1.82, 95%CI: 1.18-2.80), administrative officers or employee (vs. farmers, aOR=2.03, 95%CI: 1.04-1.91). Number of non- marital partners less than 5 (vs. number of non-marital partners more than 5, aOR=10.65, 95%CI: 6.41-17.42). Conclusions: HIV/AIDS cases with non-marital heterosexual transmission accounted for considerable proportion regarding the HIV transmission in Hangzhou from 2015 to 2017. Differences were found in the following factors as non-marital and non-commercial heterosexual transmission with diverse gender, age, marital status, educational level and occupation among of the HIV/AIDS patients.
Female ; HIV ; HIV Infections/transmission* ; Heterosexuality ; Humans ; Male ; Risk Factors ; Sexual Behavior/psychology* ; Sexual Partners ; Single Person

Circadian disruption is being increasingly recognized as a critical factor in the development and progression of Parkinson’s disease (PD). This review aims to provide an in-depth overview of the relationship between circadian disruption and PD by exploring the molecular, cellular, and behavioral aspects of this interaction. This review will include a comprehensive understanding of how the clock gene system and transcription–translation feedback loops function and how they are diminished in PD. The article also discusses the role of clock genes in the regulation of circadian rhythms, as well as the impact of clock gene dysregulation on mitochondrial function, oxidative stress, and neuroinflammation, including the microbiota-gut-brain axis, which have all been proposed as being crucial mechanisms in the pathophysiology of PD. Finally, this review highlights potential therapeutic strategies targeting the clock gene system and circadian rhythm for the treatment of PD.

This case report describes the diagnosis and endodontic therapy of maxillary fused second and third molars, using cone-beam computed tomography (CBCT). A 31-year-old Chinese male, with no contributory medical or family/social history, presented with throbbing pain in the maxillary right molar area following an unsuccessful attempted tooth extraction. Clinical examination revealed what appeared initially to be a damaged large extra cusp on the buccal aspect of the distobuccal cusp of the second molar. However, CBCT revealed that a third molar was fused to the second molar. Unexpectedly, the maxillary left third molar also was fused to the second molar, and the crown of an unerupted supernumerary fourth molar was possibly also fused to the apical root region of the second molar. Operative procedures should not be attempted without adequate radiographic investigation. CBCT allowed the precise location of the root canals of the right maxillary fused molar teeth to permit successful endodontic therapy, confirmed after 6 months.
Adult ; Cone-Beam Computed Tomography ; methods ; Follow-Up Studies ; Fused Teeth ; diagnostic imaging ; Humans ; Image Processing, Computer-Assisted ; methods ; Imaging, Three-Dimensional ; methods ; Male ; Maxilla ; Molar ; abnormalities ; Molar, Third ; abnormalities ; Pulpitis ; diagnostic imaging ; Root Canal Therapy ; Tooth Root ; abnormalities ; Tooth, Supernumerary ; diagnostic imaging ; Tooth, Unerupted ; diagnostic imaging