Prevalence and influencing factors of cognitive frailty among Chinese older adults: A systematic review and meta-analysis.

AIMS: Cognitive frailty refers to the coexistence of physical frailty and cognitive impairment in older adults, without a concurrent diagnosis of Alzheimer's disease or other dementias. This review aims to evaluate the prevalence of CF subtypes and identify influencing factors among Chinese older adults. METHODS: The following databases were searched: PubMed/Medline, Embase, Cochrane Library, WOS, PsycINFO and CNKI et al (1 January 2001 to 20 October 2022). The risk of bias was assessed using the Agency for Healthcare Research and Quality Evidence-based Practice Center Methods Guide. Stata 17.0 software was used to pool the prevalence of cognitive frailty, and the pooled odds ratio and 95% CI of the influencing factors were calculated. RESULTS: The meta-analysis (56 studies and 80,320 participants) revealed the following prevalence rates: CF (18.9%), reversible CF (19.5%), potentially reversible CF (17.5%), CF in community-dwelling older adults (14.3%), CF in nursing homes (22.7%) and CF in older inpatients (25.2%). Influential factors identified included age, gender, education, nutrition, depression, exercise, sleep and comorbidity. CONCLUSIONS: The prevalence of CF among Chinese older adults is notably high, and it probably underestimates the prevalence of reversible cognitive frailty. It is crucial to encourage adherence to healthy behaviours, as it can effectively reduce and delay the onset of cognitive frailty.

Individualized Traditional Chinese Medicine treatment antibiotics for recurrent urinary tract infections: a multicenter, randomized controlled study.

OBJECTIVE: To systematically assess the effects of individualized Chinese medicines on recurrent urinary tract infections (rUTIs). METHODS: This study recruited 230 adult female patients in the remission phase of rUTIs from five hospitals in China. The patients were randomly allocated to two groups: an individualized Chinese medicine group (n = 114) and a control group (n = 116). Patients in the Chinese medicine group received individualized Chinese herbs, which were evaluated for syndrome differentiation. Patients in the control group received antibiotic treatment combined with a Chinese medicine placebo. The duration of treatment was three courses of four weeks each, with a three-month subsequent follow-up. UTI recurrence rate, Traditional Chinese Medicine (TCM) syndrome scores, 36-item Short Form Survey (SF-36) score, and urine secretory immunoglobulin A (SIgA) were measured and analyzed before and after treatment in each group. RESULTS: Patients from the Chinese medicine group exhibited significant decreases in both short- and long-term UTI recurrence rates compared with the control group (P < 0.05). The changes in TCM syndrome scores between the Chinese medicine and control groups were significant (P < 0.05). The changes in the average SF-36 quality-of-life scores in the Chinese medicine group were also significantly higher than those in the control group after treatment (P < 0.05). The Chinese medicine group also demonstrated a significant increase in urine SIgA expression. CONCLUSION: Taken together, compared to the often-used long-term antimicrobial prophylaxis during the remission stage of rUTIs, treating patients with an individualized Chinese medicine decoction by syndrome differentiation could effectively reduce the recurrence rate, improve the patients' TCM syndrome scores and quality of life, and enhance immunity, which in turn helps to prevent antibiotic resistance.

TRIM40 ameliorates diabetic retinopathy through suppressing inflammation via Reelin/DAB1 signaling disruption: A mechanism by proteasomal degradation of DAB1.

Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus. Reelin, an extracellular matrix protein, and its effector protein Disabled1 (DAB1) have been linked to cellular events and retinal development. However, whether and how Reelin/DAB1 signaling causes DR remains to be investigated. In our study, significantly increased expression of Reelin, very low density lipoprotein receptor (VLDLR), ApoE receptor 2 (ApoER2) and phosphorylated DAB1 in retinas of streptozotocin (STZ)-induced DR mouse model was observed, along with enhanced expression of proinflammatory factors. Similar results are confirmed in high glucose (HG)-treated human retinal pigment epithelium cell line ARPE-19. Surprisingly, dysregulated tripartite motif-containing 40 (TRIM40), an E3 ubiquitin ligase, is found to be involved in DR progression by bioinformatic analysis. We observe a negative correlation between TRIM40 and p-DAB1 protein expression levels under HG conditions. Importantly, we find that TRIM40 over-expression markedly ameliorates HG-induced p-DAB1, PI3K, p-protein B kinase (AKT) and inflammatory response in HG-treated cells, but dose not affect Reelin expression. Of note, Co-IP and double immunofluorescence identify an interaction between TRIM40 and DAB1. Furthermore, we show that TRIM40 enhances K48-linked polyubiquitination of DAB1, thereby promoting DAB1 degradation. Finally, promoting TRIM40 expression by intravenous injection of the constructed adeno-associated virus (AAV-TRIM40) markedly ameliorates DR phenotypes in STZ-treated mice, as indicated by the decreased blood glucose and glycosylated hemoglobin (HbAlc) levels, and increased hemoglobin contents. Additionally, diabetes-related elevation of acellular capillaries was also meliorated in mice over-expressing TRIM40. The electroretinogram (ERG) deficits were strongly rescued in mice receiving AAV-TRIM40 injection. Moreover, AAV-TRIM40 attenuates the inflammation and p-DAB1 expression in retinal tissues of STZ-treated mice. Collectively, our findings disclose a mechanism through which TRIM40 limits DAB1 stability under physiological conditions and reveals TRIM40 as a potential therapeutic target for the intervention of Reelin/DAB1 signaling, contributing to DR treatment.

Malignant peritoneal mesothelioma.

Malignant peritoneal mesothelioma (MPM) is a rare, life-threatening malignant tumor. We present a report of a rare case of a 67-year-old male patient with MPM and severe abdominal pain, bloating, and bloody ascites as manifestations. The diagnosis was confirmed by cytology of ascites aspiration fluid and further verified by laparoscopic exploratory biopsy. The characteristics of signs and clinical manifestations in this case are less common. As everyone knows, asbestos exposure is usually associated with pleural mesothelioma, but only 6%-10% of malignant mesothelioma cases originate from the peritoneum, which is far less than pleural mesothelioma. Generally, its non-specificity provides a huge challenge to medical professionals in its diagnosis, and this is also the main reason for delayed diagnosis. Patients should be vigilant, even though no clear risk factor is observed.

Gestational diabetes mellitus decreased umbilical cord blood polyunsaturated fatty acids: a meta-analysis of observational studies.

BACKGROUND: Polyunsaturated fatty acid (PUFA) is important for the development of the fetal brain, and the retina. Gestational diabetes mellitus (GDM) may influence maternal and fetal fatty acid metabolism, in turn affecting fetal growth and development. In several studies, maternal and fetal PUFA metabolic differences have been reported between mothers with and without GDM, but not in other studies. Thus, the aim of this meta-analysis (registration number: CRD42020220448) was to compare levels of linoleic acid (LA), α-linolenic acid (ALA), arachidonic acid (AA), docosahexaenoic acid (DHA), and total n-3 and n-6 PUFA between mothers with and without GMD and their fetuses. METHODS: We performed a meta-analysis of observational studies on maternal and fetal fatty acid metabolism, published until May 2021. In addition, we performed subgroup analysis depending on the analyzed tissues (plasma/serum, erythrocyte membrane, or placenta) and the expression modes of fatty acids (concentration or percentage). RESULTS: We included 24 observational studies involving 4335 maternal datasets and 12 studies involving 1675 fetal datasets in the meta-analysis. Levels of AA, DHA, and n-6 and n-3 PUFA were lower in the cord blood of mothers with GDM than in controls (P  <  0.05). Compared to that in controls, in erythrocyte membranes, the percentages of AA, DHA, and n-6 and n-3 PUFA in total fatty acid were lower in mothers with GDM (P  <  0.05), but in plasma/serum, the percentages of AA, DHA, and n-6 PUFA in total fatty acid were higher in mothers with GDM (P  <  0.05). CONCLUSIONS: GDM appears to influence the transfer of PUFAs from mothers to fetuses. The percentage of PUFAs in maternal plasma/serum was higher, and that in erythrocyte membranes was lower in mothers with GDM compared to those with normal glucose tolerance.

Apigenin suppresses TGF-ß1-induced cardiac fibroblast differentiation and collagen synthesis through the downregulation of HIF-1α expression by miR-122-5p.

BACKGROUND: Apigenin can reduce cardiomyocyte hypertrophy by downregulating hypoxia inducible factor-1 alpha (HIF-1α) expression. However, its effects on cardiac fibroblasts (CFs) and its exact inhibitory molecular mechanisms on HIF-1α remain unclear. PURPOSE: This study aims to examine the effects of apigenin on cell proliferation and differentiation, microRNA-122-5p (miR-122-5p) expression, and HIF-1α-mediated Smad signaling pathway in transforming growth factor beta 1 (TGF-ß1)-stimulated CFs and cardiac fibrosis and to investigate the relationship between miR-122-5p and HIF-1α. METHODS: The TGF-ß1-stimulated CFs, the combination of TGF-ß1-stimulated and miR-122-5p mimic-transfected CFs, the combination of TGF-ß1-stimulated and miR-122-5p inhibitor-transfected CFs, and the isoproterenol-induced cardiac fibrotic mice were used and treated with or without apigenin. The recombinant lentiviruses overexpressing HIF-1α vector and miR-122-5p mimic were co-transfected to observe their interaction. Related mRNA and protein expressions and myocardial collagen were determined. The luciferase reporter gene that contains HIF-1α wild type or mutant type 3'-UTR was used, and the luciferase activity was determined to verify the direct link between miR-122-5p and HIF-1α. RESULTS: In the TGF-ß1-stimulated CFs, apigenin treatment increased the miR-122-5p and Smad7 expressions and decreased the HIF-1α, α-smooth muscle actin, collagen Ⅰ/Ⅲ, Smad2/3, and p-Smad2/3 expressions. Similar and inverse results were observed in the miR-122-5p mimic- and inhibitor-transfected CFs, respectively. Moreover, the miR-122-5p mimic could antagonize the effects of TGF-ß1 in the TGF-ß1 and miR-122-5p mimic-combined CFs, and the miR-122-5p inhibitor could enhance the effects of TGF-ß1 in the TGF-ß1 and miR-122-5p inhibitor-combined CFs. In the two aforementioned cell models, the addition of apigenin could further enhance the effects of miR-122-5p mimic and partially reverse the effects of miR-122-5p inhibitor. After treatment of HIF-1α-transfected CFs with miR-122-5p mimic, the HIF-1α expression decreased. Further study confirmed that HIF-1α was a direct target of miR-122-5p. Apigenin also decreased the myocardial collagen accumulation in cardiac fibrotic mice. CONCLUSION: Apigenin could suppress the differentiation and collagen synthesis of TGF-ß1-stimulated CFs and mouse cardiac fibrosis, and its mechanisms were related to the increment of miR-122-5p expression and subsequent downregulation of HIF-1α expression via direct interaction, which might finally result in the decrements of Smad2/3 and p-Smad2/3 expressions and increment of Smad7 expression.

SIRT3 protects endothelial cells from high glucose-induced senescence and dysfunction via the p53 pathway.

Hyperglycemia induces endothelial cells (ECs) dysfunction and vascular complications by accelerating ECs senescence. It also induces downregulation of sirtuins (SIRTs). However, the molecular mechanism involved in the regulation of ECs senescence by SIRT3 remains unclear. Here, we showed that high glucose (HG) decreased the expression level of SIRT3 in human umbilical vein endothelial cells (HUVECs), increased the proportion of cells expressing senescence-associated galactosidase (SA-gal), and HG damaged the cell's ability to form tubule networks on Matrigel. However, transfection with adenoviral construct including SIRT3 significantly inhibited HG-induced SA-gal activity, decreased p53 acetylation level at the site Lys 320 (k320), and overexpression of SIRT3 antagonized high glucose-induced angiogenic dysfunction. Our results suggested a possible molecular mechanism involving HG-SIRT3-p53 in ECs senescence.

[Case analysis and control strategy of imported malaria in Qingcheng District, Qingyuan City from 2011 to 2016].

OBJECTIVE: To understand the characteristics of imported malaria cases in Qingcheng District, Qingyuan City and explore the strategies and priorities in prevention and control, so as to provide the evidence for improving the diagnosis, treatment and management of imported malaria. METHODS: The data of imported malaria as well as the case epidemiological investigations were collected and retrospectively analyzed for the species composition, original countries, population distribution, regional distribution, onset situation, diagnosis, treatment, etc. in Qingcheng District from 2011 to 2016. RESULTS: The number of imported malaria cases was 13 from 2011 to 2016. All the patients were confirmed by laboratory, and of which, 9 patients infected with Plasmodium falciparum, 1 with P. vivax, 1 with P. ovale and 2 with mixed infections (P. vivax and P. falciparum). The yearly incidence of imported malaria presented an uptrend. The infection sources of all the patients were from African countries, and the exported labor workers and travelers for business from malaria endemic areas were the high risk population. The reported time was mainly January, February, November and December (11/13, 84.62%). All the patients were male, and the majority of them (12/13, 2.31%) were 21-60 years old. The median time from onset to seeing a doctor was 2.5 days and the median time from seeing a doctor to being diagnosed was 1.9 day. Six patients (46.15%) were diagnosed as other diseases at the first visit to a doctor, and one patient died of falciparum malaria because of delayed diagnosis. CONCLUSIONS: The incidence of overseas imported malaria presents an uptrend in Qingcheng District. It is necessary to further strengthen the professional training in medical staff to improve the diagnosis and treatment of malaria cases. It is also necessary to strengthen the multisectoral cooperation, establish the surveillance in the high risk population, etc.

The influence of urea and nitrate nutrients on the bioavailability and toxicity of nickel to Prorocentrum donghaiense (Dinophyta) and Skeletonema costatum (Bacillariophyta).

Nitrogen nutrients and nickel(Ni) are ubiquitous in aquatic environments, and they are important for primary production of ocean ecosystem. This study examined the interaction of nitrogen nutrients (specifically urea and nitrate) and Ni on chlorophyll (Chl a) concentration and photosynthesis parameters values of Prorocentrum donghaiense and Skeletonema costatum. The data presented here indicate that low concentration of Ni for P. donghaiense and S. costatum can enhance both Chl a concentration and photosynthesis parameters values when grown in urea containing environment. Despite this increase there was also an observed depression in both species tested when incubated in high concentration of Ni for P. donghaiense and S. costatum regardless of incubating in urea or nitrate. Additionally, EC50 values of Chl a and Fv/Fm for Ni at different time intervals were calculated in this study. These observations indicated that the Ni tolerance was higher in P. donghaiense as compared to S. costatum. The Ni tolerance of P. donghaiense incubated in urea was higher than that incubating in nitrate. The same phenomenon was not observed in S. costatum, which indicated that the influence of urea was dependent on the species investigated. Thus, urea input could impact Ni bioavailability and toxicity, and then affect the biodynamics thereafter.

Age-related changes of brain iron load changes in the frontal cortex in APPswe/PS1ΔE9 transgenic mouse model of Alzheimer's disease.

Alzheimer's disease (AD) as a neurodegenerative brain disorder is a devastating pathology leading to disastrous cognitive impairments and dementia, associated with major social and economic costs to society. Iron can catalyze damaging free radical reactions. With age, iron accumulates in brain frontal cortex regions and may contribute to the risk of AD. In this communication, we investigated the age-related brain iron load changes in the frontal cortex of 6- and 12-month-old C57BL/6J (C57) and APPswe/PS1ΔE9 (APP/PS1) double transgenic mouse by using graphite furnace atomic absorption spectrometry (GFAAS) and Perls' reaction. In the present study, we also evaluated the age-related changes of DMT1 and FPN1 by using Western blot and qPCR. We found that compared with 6-month-old APP/PS1 mice and the 12-month-old C57 mice, the 12-month-old APP/PS1 mice had increased iron load in the frontal cortex. The levels of DMT1 were significantly increased and the FPN1 were significantly reduced in the frontal cortex of the 12-month-old APP/PS1 mice than that in the 6-month-old APP/PS1 mice and 12-month-old C57 mice. We conclude that in AD damage occurs in conjunction with iron accumulation, and the brain iron load associated with loss control of the brain iron metabolism related protein DMT1 and FPN1 expressions.

Differentiation of rat dermal papilla cells into fibroblast-like cells induced by transforming growth factor ß1.

BACKGROUND: The origin of wound-healing fibroblasts is still debated. Dermal papilla cells (DPCs), which are an important population of stem cells for the regeneration of hair follicles, play a considerable role in cutaneous wound healing. Based on the plasticity of DPCs in wound healing, we hypothesized that DPCs may contribute to the fibroblast population of wound repair. OBJECTIVE: To explore the possibility of differentiation of DPCs into fibroblasts induced by transforming growth factor ß1 (TGF-ß1). METHODS: The fourth passage DPCs were treated with TGF-ß1 (10 ng/mL) for 4 days, and a series of methods was used to observe morphologic changes under an inverted phase contrast microscope, to validate the messenger ribonucleic acid expression change in α-smooth muscle actin (α-SMA) and vimentin by quantitative real-time reverse transcriptase polymerase chain reaction (QRT-PCR), to analyze the expression of α-SMA and vimentin protein by flow cytometry, and to semiquantitatively measure the expression of fibroblast-specific protein 1 (FSP1) by Western blot. RESULTS: DPCs treated with TGF-ß1 presented fibroblast-like changes in morphology and immunocytochemistry. The effects of TGF-ß1 on α-SMA and vimentin in DPCs were detected on both the transcriptional and the posttranscriptional levels. The results showed that TGF-ß1 significantly downregulated α-SMA expression and enhanced the expression of vimentin at all times tested. Further study revealed that TGF-ß1 could gradually promote the expression of FSP1 in a time-dependent manner. CONCLUSION: DPCs experienced the changes in molecular marker expression in response to TGF-ß1, which may be a key source of fibroblasts in wound healing.

A patient with lung cancer metastatic to the fifth thoracic vertebra and spinal cord compression treated with percutaneous vertebroplasty and I-125 seed implantation.

Percutaneous vertebroplasty is a minimally invasive surgical technique for the treatment of spinal damage and pathological compression fractures. Iodine-125 (I-125) particles can inhibit the uncontrolled proliferation of tumor cells to achieve anti-tumor effects. We report treating a spinal cord compression and T5 metastatic lung cancer patient through percutaneous vertebroplasty and I-125 seed implantation. Three years of follow-up demonstrated that our surgical plan achieved a satisfactory clinical outcome with good postsurgical recovery of spinal column function and relieved the symptoms of spinal cord compression.

Attenuation of alpha1 collagen production with antisense ribonucleic acid in cultured hypertrophic scar fibroblasts.

BACKGROUND: It has been demonstrated that hypertrophic scar fibroblasts (HSFs) overexpress collagen messenger ribonucleic acid (mRNA) and protein, especially alpha1 collagen. Antisense nucleic acids are effective in inhibiting harmful or uncontrolled gene expression, suggesting that antisense ribonucleic acid (RNA) can effectively downregulate the expression of alpha1 collagen gene and attenuate the scars. AIMS: This study was conducted to observe the effect of recombinant plasmid pREP9-COL1 on alpha1 collagen expression in HSFs and clarify the prospect of antisense RNA on scar treatment. METHODS: The alpha1 collagen gene fragment including the region of 5' UTR to exon (229 bp) was cloned in the eukaryotic expression plasmid pREP9 in the antisense orientation relative to the RSV-LTR promoter to reconstruct the pREP9- COL1 plasmid. Then it was transferred into HSFs through lipofectamine. The expression of alpha1 collagen was examined by immunostaining, reverse-transcriptase polymerase chain reaction, and Western blots. RESULTS: The recombinant plasmid pREP9-COL1 with a correct sequence was constructed successfully; pREP9-COL1 consistently inhibited human alpha1 collagen gene expression at both mRNA and protein levels. CONCLUSIONS: Antisense RNA was effective in downregulating alpha1 collagen expression of HSFs. Therefore, this approach offered a prospect of scar treatment by attenuation of alpha1 collagen production with antisense RNA.

Effect of asiaticoside on hypertrophic scar in the rabbit ear model.

BACKGROUND: Previous observations suggested that asiaticoside had a possible antiscaring effect. However, the precise pathological mechanism still remain unknown. We questioned whether asiaticoside might alleviate the formation of hypertrophic scar by affecting the expression of Transform growth factor beta (TGF-beta)/Smad signaling. AIMS: To investigate the effect of asiaticoside on the expression of TGF-beta/Smad signaling in the rabbit ear model of hypertrophic scar and to clarify the mechanism of asiaticoside on the scar treatment. METHODS: The rabbit model with hypertrophic scar was created and applied topically with a low-dose (0.5%) or high-dose (1%) asiaticoside three times daily for 1, 2 or 3 months and then we examined the changes of macroscopic and histopathologic characteristics of scars, and the expression of TGF-beta(1) and Smad protein was studied by applying reverse transcription-polymerase chain reaction and western blotting. RESULT: Asiaticoside could remarkably alleviate the scar in the rabbit ear model. Western blotting showed that the asiaticoside could decrease TGF-beta(1) expression, and further study revealed that asiaticoside could remarkably enhance the expression of inhibitory Smad7, but it had no effect on the expression of Smad2. CONCLUSION: Asiaticoside suggested a possible antiscaring effect probably by enhancing the expression of inhibitive Smad7.

A genetic study of two calcium-independent cytosolic PLA2 genes in schizophrenia.

The present study detected 9 single nucleotide polymorphisms (SNPs) at the PLA2G4C and PLA2G6 loci among 240 Chinese parent-offspring trios of Han descent. Of these 9 SNPs, 5 showed highly polymorphic in the Chinese population. They were then applied as genetic markers to test the genetic association of these two calcium-independent cytosolic PLA2 genes with schizophrenia. The transmission disequilibrium test (TDT) showed that rs1549637 at the PLA2G4C locus was the only SNP associated with the illness (chi(2) = 5.63, P = 0.018). The global P-value was 0.082 for 1000 permutations with the TDT analysis. Neither the conditional on allele test nor the conditional on genotype test showed a disease association for the combination of these two genes. Because the PLA2G4C association is so weak, this initial finding should be interpreted with caution.