Demographic and clinical factors associated with immune reconstitution in HIV/HBV co-infected and HIV mono-infected patients: a retrospective cohort study.

OBJECTIVES: To describe the clinical characteristics and factors associated with CD4 T-cell count and CD4/CD8 ratio restoration in HIV mono-infected and HIV/HBV co-infected individuals, and to explore liver and renal functional changes in both groups. METHODS: A retrospective cohort study was performed including 356 HIV/HBV co-infected and 716 HIV mono-infected participants who initiated antiretroviral therapy (ART) during 2013-2017 in Beijing Youan Hospital, China. Demographic and clinical characteristics were compared between the two groups, using χ2 and Mann-Whitney non-parametric tests. Bivariate and multivariate Cox regression models were used to test their association. RESULTS: Baseline HIV viral load and ART regimen were found to be significantly associated with CD4 T-cell restoration among HIV-infected participants, whereas baseline HIV viral load was the only significant factor associated with CD4 T-cell restoration in HIV/HBV co-infected participants. The final model showed that baseline HIV viral load and ART regimen were significantly associated with CD4/CD8 ratio restoration among HIV-infected participants, while baseline HIV viral load was the significant factor. Liver and renal functions were similar at the endpoint (P > 0.05). CONCLUSIONS: Baseline HIV viral load count was found to be the key factor affecting immune restoration in both HIV and HIV/HBV individuals. Future multi-wave prospective studies are needed to clarify the potential biological mechanism.

Relationships of Hypnotics with Incident Dementia and Alzheimer's Disease: A Longitudinal Study and Meta-Analysis.

BACKGROUND: Evidence describing the association between hypnotics use and dementia risk is conflicting. It is unknown if the controversy is related to the type or dose of hypnotics or if hypnotics affect different populations. OBJECTIVES: We sought to derive lessons learned and future projections based on evidence from longitudinal studies. MEASUREMENTS: In the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort, 1,543 older adults without dementia (mean age = 73.3 years, female = 45%) were followed for four years. The association between hypnotics and the risk of Alzheimer's disease (AD) was investigated using Cox proportional hazards regressions. Next, electronic databases were searched until March 2022 to conduct the evidence synthesis of the associations of hypnotics with incident risk of dementia. RESULTS: In the ADNI cohort, ever use of hypnotics was associated with an increased risk of AD (hazard ratio = 1.96, 95% confidence intervals = 1.23-3.11, p < 0.01). This association was significant for benzodiazepines and Z-drugs but not for melatonin. The association was stronger in long-term (more than one year) users and those with high cumulative doses. A meta-analysis of 26 longitudinal studies with 3,942,018 participants revealed a correlation between the use of hypnotics and the risk of dementia (relative risk = 1.23, 95% confidence intervals = 1.13-1.33, p < 0.001, median risk difference = 4%). It is a linear dose-response relationship, if a person takes the daily recommended dose for 100 days, their risk of developing dementia increases by 5% relative to non-users. According to subgroup analyses, neither association was significant among patients with a history of insomnia. CONCLUSIONS: Individuals who use hypnotics, especially high-dose or long-term users, are at a higher risk of dementia and AD. The main issue with conclusion credibility is heterogeneity.

Lattice distortion enabling enhanced strength and plasticity in high entropy intermetallic alloy.

Intermetallic alloys have traditionally been characterized by their inherent brittleness due to their lack of sufficient slip systems and absence of strain hardening. However, here we developed a single-phase B2 high-entropy intermetallic alloy that is both strong and plastic. Unlike conventional intermetallics, this high-entropy alloy features a highly distorted crystalline lattice with complex chemical order, leading to multiple slip systems and high flow stress. In addition, the alloy exhibits a dynamic hardening mechanism triggered by dislocation gliding that preserves its strength across a wide range of temperatures. As a result, this high-entropy intermetallic circumvents precipitous thermal softening, with extensive plastic flows even at high homologous temperatures, outperforming a variety of both body-centered cubic and B2 alloys. These findings reveal a promising direction for the development of intermetallic alloys with broad engineering applications.

[Surveillance of human soil-transmitted nematodiasis in Jurong City from 2016 to 2020].

OBJECTIVE: To investigate the prevalence of soil-transmitted nematode human infections in Jurong City from 2016 to 2020, so as to provide the scientific evidence for formulating the control strategy. METHODS: During the period from 2016 to 2020, the permanent residents at ages of over 3 years living in Jurong City were selected as the study subjects. Stool samples were collected for the detection of soil-transmitted nematode eggs using the modified Kato-Katz thick smear method (two detections for one stool sample), and the species of hookworm was identified in stool-positive stool samples using the culture method. The prevalence and intensity of soil-transmitted nematode infections were calculated, and the change of the infection prevalence among years was examined using the Cochran-Armitage test for trend. RESULTS: A total of 10 011 people-time populations were detected for soil-transmitted nematode infections in Jurong City from 2016 to 2020, and 56 egg-positives were identified, with mean prevalence of 0.56%. The prevalence of soil-transmitted nematode human infections appeared a tendency towards a decline year by year in Jurong City (χ2trend = 5.15, P < 0.01). The mean prevalence of hookworm, Ascaris lumbricoides and Trichuris trichiura infections was 0.44%, 0.11% and 0.20% in Jurong City from 2016 to 2020, respectively, and individuals with hookworm infections accounted for 78.57% of all cases with soil-transmitted nematode infections. Single parasite (98.21%) and mild infection were pre-dominant in individuals with soil-transmitted nematode infections, and no multiple infections were seen after 2016. CONCLUSIONS: The prevalence of human soil-transmitted nematodiasis is low in Jurong City. Based on reinforcement of soil-transmitted nematodiasis surveillance, an increase in the health education investment is required to consolidate the control achievements.

AT-rich sequences flanking the 5'-end breakpoint of the 4977-bp deletion of human mitochondrial DNA are located between two bent-inducing DNA sequences that assume distorted structure in organello.

The 4977-bp deletion is the most common deletion among more than 90 large-scale deletions of human mitochondrial DNA (mtDNA) that are associated with aging and mitochondrial myopathies. The reason why the frequency of occurrence of this common deletion is so high in aged and myopathic human tissues is not clear. Since several studies proved that unusual DNA structures play very important roles in a number of recombination events, we hypothesized that some kind of unusual DNA structure may flank the breakpoints of the 4977-bp mtDNA deletion. We used two-dimensional (2-D) gel electrophoresis to assess the mobility abnormalities of the PCR-amplified DNA fragments encompassing the sequences of nucleotide position (np) 7901 to 9058 of human mtDNA. The results showed that the sequences of np 7901-8732 and np 8251-9058 exhibited retarded and increased mobilities, respectively, and that the sequence of np 8285-8676 showed normal mobility in the 2-D gel. This indicates that the 5'-end breakpoint of the 4977-bp deletion is located within the junction site of two flanking bent-inducing DNA sequences. We confirmed this notion by using osmium tetroxide (OsO4) to probe mtDNA in organello. The results showed that the two AT-rich sequences flanking the 5'-end breakpoint of the 4977-bp deletion are susceptible to OsO4 modification. These findings suggest that the DNA sequences of the 5'-end breakpoint of the common mtDNA deletion are rendered to assume a more distorted structure than B-DNA by these two flanking bent-inducing DNA sequences in organello and thereby render this region to be more vulnerable to attack by reactive oxygen species and free radicals.

Location of lectin UEA-I receptors in histological diagnosis of nasopharyngeal precancerous lesion.

Three kinds of lectins (UEA-I, ConA, PNA) were used to study normal, dysplastic, neoplastic nasopharyngeal epithelium by lectin affinitive histochemical method. UEA-I (ulex europeus agglutinin-I) displayed membrane distribution in normal squamous epithelium, but most of nasopharyngeal carcinoma cells were negative. Notably, severe dysplastic epithelium (precancerous lesion) exhibited a strong membranous and cytoplasmic affinity, which contrasted sharply with the normal epithelium and carcinoma cells. The statistically significant difference in the content and distribution of lectin UEA-I in these three groups suggest that UEA-I is a hopeful marker for diagnosing precancerous lesion of the nasopharynx. However, PNA and ConA are of less diagnostic value.

The unusual structures of the hot-regions flanking large-scale deletions in human mitochondrial DNA.

Large-scale deletions of mitochondrial DNA (mtDNA) are common events that have been found to occur in human ageing and in patients with mitochondrial myopathies. The mechanisms by which these deletions occur remain unclear, but several mechanisms have been proposed, such as slipped-mispairing, illegitimate recombination, and oxidative reactions elicited by free radicals. In addition, the DNA topological stress and local DNA structures have been suggested as the important factors in eliciting the recombinational events. Upon examination of 128 breakpoints of human mtDNA deletions that have been published in the past 8 years, we found that these large-scale deletions often occur at some 'hot-regions'. We thus hypothesized that there exist unusual structures in these regions of human mtDNA that are important for eliciting the deletions. To test this hypothesis, we used PCR techniques to amplify the sequences of the so-called hot-regions and analysed the PCR products by two-dimensional gel electrophoresis. We found that the sequences of nucleotide position (np) 5221-5988, np 6928-7493, np 7901-8732 and np 15327-16228 exhibited retarded mobilities like bent DNA structures; np 5989-6750, np 13282-13653 and np 13282-14850 showed increased mobilities like anti-bent DNA structures. Moreover, except for the sequences of np 1175-1766 found in 12 S and 16 S rRNA genes exhibiting abnormal mobility like bent DNA structures, we did not observe significant mobility abnormalities in the np 499-5545 region where deletions rarely occurred. We thus conclude that these hot-regions assume some kinds of unusual DNA structures, which may render these regions more sensitive to the attack of free radicals or serve as recognition motifs for certain recombination machinery that is involved in the large-scale deletions of human mtDNA.

Age-dependent respiratory function decline and DNA deletions in human muscle mitochondria.

The electron transport activities of various respiratory enzyme complexes in the muscle mitochondria of subjects of different ages without known mitochondriopathies were investigated. The results showed that the activity of cytochrome c oxidase declined with age more drastically than the activities of other respiratory enzyme complexes. NADH-cytochrome c reductase activity decreased mildly with age, whereas succinate cytochrome c reductase activity did not show significant age-dependent changes. Deletions in the muscle mitochondrial DNA (mtDNA) by use of PCR techniques were investigated. Three different age-dependent deletions in the muscle mtDNA of old individuals were found. These were identified to have sizes of 4,977 bp (8470 to 13446), 6,063 bp (7,842 to 13,904) and 7,436 bp (8,649 to 16,084). The 4,977 bp deleted mtDNA (dmtDNA) started to appear in the muscle mtDNA of subjects over 36 years of age and was found to exist in the muscle of more than 70% of the study subjects over 60 years of age. The 6,063 bp dmtDNA was detected in the muscle of the subjects above 25 years of age and was present in the muscle of about 91% of the individuals above 60 years old. However, the 7,436 bp deletion was less prevalent and was only seen in the muscle mtDNA of about 47.2% of the study subjects that were above 60 years. Using a quantitative PCR method, we found that the proportion of the 7,436 bp-deleted mtDNA increased with age, although with notable individual differences. Some of the subjects were found to have multiple deletions in their muscle mtDNAs, but some others carried only a specific type of deletion. The frequency of occurrence of multiple deletions in the muscle mtDNA was significantly increased with the age of the study subjects. The age-dependent increase in the proportions of various deleted mtDNA molecules may cause deleterious effects on the expression of mitochondrial genes in the muscle of old humans. This may account, at least in part, for the age-dependent decline of respiratory functions in the mitochondria of a broad spectrum of human tissues. We suggest that deletions of mtDNA are early molecular events that are associated with and contribute to the ageing processes of the human.

nm23-H1 expression in nasopharyngeal carcinoma: correlation with clinical outcome.

The expression levels of nm23-H1 mRNA and its protein in human nasopharyngeal carcinoma (NPC) were detected to clarify the relationship between nm23-H1 and metastasis and prognosis of patients with NPC. nm23-H1 mRNA expression in fresh tissues from 78 patients with NPC was investigated by in situ hybridization and RT-PCR. Routine labeling streptavidin-biotin immuno-histochemistry with the nm23-H1 murine monoclonal antibody was employed to study the expression of nm23-H1 protein in paraffin-embedded specimens from 231 patients with NPC treated in our hospital. The clinical pathologic data and results of follow-up were collected. Comparisons between expression of nm23-H1 protein or mRNA and clinical outcome were performed using the chi2 test. Multivariate prognostic analyses were performed by the Cox regression model. We found that nm23-H1-negative tumors were associated with a higher incidence of lymph-node metastasis (84.2%) than nm23-H1-positive ones (32.8%, p < 0.01). The distant metastasis and loco-regional recurrence rates in the nm23-H1-negative group were 55.8% and 31.68%, respectively but only 17.2% and 11.5%, respectively, in the nm23-H1-positive group (p < 0.01). A significant association was found between expression of nm23-H1 protein and prognosis (p < 0.01). Expression of nm23-H1 protein indicated favorable prognosis, suggesting that the absence of nm23-H1 protein expression was significantly associated with lymph-node metastasis, recurrence and distant metastasis in NPC. Expression of the nm23-H1 gene may be valuable for assessing the prognosis of NPC.