Changes in depressive symptoms before and after the first stroke: A longitudinal study from China Family Panel Study (CFPS).

OBJECTIVES: The study sought to examine the impact of longitudinal changes in depressive symptoms in middle-aged adults before and after their first stroke, and the impact of different ages. METHODS: The study monitored middle-aged patients with a first stroke in the China Family Panel Study (CFPS) survey from 2016 to 2020. This study examined longitudinal changes in depressive symptoms in middle-aged adults and their controls before and after stroke using multilevel models, and also explored factors influencing middle-aged adults at the time of their respective stroke and depressive symptoms using conditional regression models and stepwise regression models, respectively. A chi-square test was used to determine whether long-term changes in depressive symptoms in patients before and after stroke could be attributed to changes in a single depressive symptom. RESULTS: The study identified 582 first-time stroke patients and 5522 controls from a population of 17,588 participants. Middle-aged populations may have an increased risk of depressive symptoms after a first stroke compared to older populations. First-time stroke victims showed increased severity of depressive symptoms in both the two years before and the two years after stroke when depressive symptoms were assessed. Differences in the presentation of a single depressive symptom were most pronounced in sleep-related symptoms. CONCLUSIONS: The link between first stroke and changes in the trajectory of increased depressive symptoms is complex and bidirectional. Age is an important factor influencing changes in depressive symptoms, some attention should be paid to the middle-aged population. Special attention should also be paid to sleep-related symptoms in the long-term care of patients.

Association between internal migration experience and depressive symptoms: analysis of PSID data.

BACKGROUND: Depression is on the rise globally. Additionally, the United States has a high level of population mobility. The main aim of this study was to provide a reference for improving the mental health of internal migrants by investigating the relationship between internal migration experience and depressive symptoms. METHODS: We analysed data from the Panel Study of Income Dynamics (PSID). We included PSID data from the 2005 to 2019 waves in which all respondents were asked about their internal migration experience and depressive symptoms. This study included 15,023 participants. T tests, chi-square tests, multiple logistic regression methods were performed and fixed effects model. RESULTS: In the sample, the prevalence of depressive symptoms was 4.42%. The risk of depression in internal migrants was 1.259 times (OR = 1.259, 95% CI = (1.025-1.547, p < 0.05) that of nonmigrants. Internal migration experience was significantly positively associated with female depressive episodes (OR = 1.312, 95% CI = 1.010-1.704, p < 0.05) and increased risk of becoming depressed at a young age (OR = 1.304, 95% CI = 1.010-1.684, p < 0.05). The association between internal migration experience and depressive symptoms was more significant for participants who might move (OR = 1.459, 95% CI = 1.094-1.947, p < 0.05). In addition, different internal migratory causes are associated with depressive symptoms to varying degrees. CONCLUSIONS: Our findings highlight the need for greater policy attention to mental health inequalities between Internal migrants and those who never move away from their hometown in the United States. Our study provides a foundation for further research.

CTRP9 mitigates vascular endothelial cell injury in patients with hypertensive heart disease by inhibiting PI3K/Akt/mTOR axis.

OBJECTIVE: To investigate the mechanism of factor-alpha-related protein 9 (CTRP9) in mitigating the vascular endothelial cell (VEC) injury in patients with hypertensive heart disease (HHD) by the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) axis. METHODS: 43 patients with HHD admitted to our hospital from February 2018 to February 2019 were included in the study group, and another 39 healthy controls from the same period were the reference group. The total protein of transfected VECs was detected by western blotting, and the proliferation rate of the VECs was determined by Cell Counting Kit-8 (CCK-8). The levels of CTRP9, high sensitivity C-reactive protein (hs-CRP), thrombomodulin (TM), and von Willebrand factor (vWF) were detected by ELISA. The mechanism of CTRP9 in alleviating VEC injury in HHD patients by inhibiting the PI3K/Akt/mTOR axis was analyzed. RESULTS: The two groups did not differ in terms of their general data (P>0.05). The CTRP9 level in the study group was higher than in the reference group (P<0.001). Study group had higher levels of endothelin-1 (ET-1), hs-CRP, TM, vWF (P<0.001), and markedly lower phospho-PI3K (p-PI3K) and phospho-protein kinase B (p-AKT) protein levels (P<0.05). Compared to the reference group, the proliferation capacity of trophoblast cells in the study group was sharply decreased (P<0.05). The study group had lower phosphorylation levels of PI3K, Akt, and mTOR proteins than the reference group (P<0.05). Phosphorylation of Akt occurred at 15 min and reached its peak at 30 min. A drastically reduced invasion capacity of VECs was observed in the study group compared to the reference group (P<0.05). CONCLUSIONS: CTRP9 mitigates VEC injury in patients with HHD by inhibiting the PI3K/Akt/mTOR axis.

Convergent engineering of syntrophic Escherichia coli coculture for efficient production of glycosides.

Synthetic microbial coculture to express heterologous biosynthetic pathway for de novo production of medicinal ingredients is an emerging strategy for metabolic engineering and synthetic biology. Here, taking efficient production of salidroside as an example of glycosides, we design and construct a syntrophic Escherichia coli-E. coli coculture composed of the aglycone (AG) strain and the glycoside (GD) strain, which convergently accommodate biosynthetic pathways of tyrosol and salidroside, respectively. To accomplish this the phenylalanine-deficient AG strain was engineered to utilize xylose preferentially and to overproduce precursor tyrosol, while the tyrosine-deficient GD strain was constructed to consume glucose exclusively and to enhance another precursor UDP-glucose availability for synthesis of salidroside. The AG and GD strains in the synthetic consortium are obligatory cooperators through crossfeeding of tyrosine and phenylalanine and compatible in glucose and xylose mixture. Through balancing the metabolic pathway strength, we show that the syntrophic coculture was robust and stable, and produced 6.03 g/L of salidroside. It was the de novo production of salidroside for the first time in E. coli coculture system, which would be applicable for production of other important glycosides and natural products.

Routine proteinuria monitoring for bevacizumab in patients with gynecologic malignancies.

BACKGROUND: Proteinuria leading to nephrotic syndrome is a rare adverse event arising from treatment with bevacizumab. There is limited evidence to guide the frequency and appropriate test for monitoring for proteinuria. The purpose of this study was to determine the prevalence and severity of proteinuria during bevacizumab administration to patients with gynecologic malignancies, and to evaluate risk factors associated with this toxicity; a secondary objective was to evaluate the cost of routine proteinuria monitoring to assess for opportunities of cost containment that could change clinical practice. METHODS: A retrospective chart review was performed at an academic gynecologic oncology clinic. Women over 18 years of age with a diagnosed gynecologic malignancy were evaluated for the development of proteinuria while receiving bevacizumab treatment as measured by a urine protein-to-creatinine ratio. Patient and disease-specific risk factors were evaluated using logistic regression to determine correlations of risk factors to development of proteinuria. Cost assessment was performed using institution-specific data for urine laboratory tests. RESULTS: Eighty-nine patients were identified, and the overall prevalence of proteinuria of any grade was 35%. The mean number of bevacizumab cycles was 13 (2-64 cycles). The majority of patients experienced grade 1 proteinuria (70%, 62 patients). Grade 3 proteinuria was observed in two patients (2%). There was a trend toward increased bevacizumab cycles associated with increased grade proteinuria (p = 0.053), however there were no factors significantly associated with the development of proteinuria as measured by urine protein-to-creatinine ratio. CONCLUSION: Monitoring of urine protein-to-creatinine ratios with each cycle may be unnecessary due to the low prevalence of grade 3 proteinuria observed. Additionally, urine protein-to-creatinine ratios may not provide adequate assessment of proteinuria toxicity associated with bevacizumab therapy. Potential cost savings opportunities for the institution can be realized with a cost-reductive monitoring algorithm that will utilize less costly laboratory techniques for patients at high risk of developing proteinuria.

Downregulation of cannabinoid receptor 1 from neuropeptide Y interneurons in the basal ganglia of patients with Huntington's disease and mouse models.

Cannabinoid receptor 1 (CB(1) receptor) controls several neuronal functions, including neurotransmitter release, synaptic plasticity, gene expression and neuronal viability. Downregulation of CB(1) expression in the basal ganglia of patients with Huntington's disease (HD) and animal models represents one of the earliest molecular events induced by mutant huntingtin (mHtt). This early disruption of neuronal CB(1) signaling is thought to contribute to HD symptoms and neurodegeneration. Here we determined whether CB(1) downregulation measured in patients with HD and mouse models was ubiquitous or restricted to specific striatal neuronal subpopulations. Using unbiased semi-quantitative immunohistochemistry, we confirmed previous studies showing that CB(1) expression is downregulated in medium spiny neurons of the indirect pathway, and found that CB(1) is also downregulated in neuropeptide Y (NPY)/neuronal nitric oxide synthase (nNOS)-expressing interneurons while remaining unchanged in parvalbumin- and calretinin-expressing interneurons. CB(1) downregulation in striatal NPY/nNOS-expressing interneurons occurs in R6/2 mice, Hdh(Q150/Q150) mice and the caudate nucleus of patients with HD. In R6/2 mice, CB(1) downregulation in NPY/nNOS-expressing interneurons correlates with diffuse expression of mHtt in the soma. This downregulation also occludes the ability of cannabinoid agonists to activate the pro-survival signaling molecule cAMP response element-binding protein in NPY/nNOS-expressing interneurons. Loss of CB(1) signaling in NPY/nNOS-expressing interneurons could contribute to the impairment of basal ganglia functions linked to HD.

Thymic stromal lymphopoietin (TSLP)-induced polyclonal B-cell activation and autoimmunity are mediated by CD4+ T cells and IL-4.

The cytokine thymic stromal lymphopoietin (TSLP) functions as a regulator of bone marrow B-cell development and a key initiator of allergic inflammation. In the current study, we show that mature B cells, derived from transgenic mice with systemically elevated levels of TSLP (K5-TSLP mice), exhibit markedly enhanced mitogenic responses in vitro and that this enhanced responsiveness leads to polyclonal B-cell activation and development of autoimmune hemolytic anemia in vivo. In contrast, B cells derived from K5-TSLP mice lacking CD4(+) T cells failed to show polyclonal activation. Furthermore, neither mature B-cell activation nor hemolytic anemia occurred in IL-4-deficient K5-TSLP mice. Consistent with these findings, activation of mature B cells occurred independently of B-cell intrinsic TSLP signals. Taken together, our results demonstrate that systemic alterations in TSLP, through induction of IL-4 from CD4(+) T cells and other cell types, functions as an important factor in peripheral B-cell homeostasis and promotion of humoral autoimmunity.

[Development of glipizide push-pull osmotic pump controlled release tablets by using expert system and artificial neural network].

The purpose of this study is to develop glipizide push-pull osmotic pump (PPOP) tablets by using a formulation design expert system and an artificial neural network (ANN). Firstly, the expert system for the formulation design of osmotic pump of poor water-soluble drug was employed to design the formulation of glipizide PPOP, taking the dissolution test results of Glucotrol XL as the goal. Then glipizide PPOP was prepared according to the designed formulations and the in vitro dissolution was carried out. And in vivo evaluation was carried out between the samples which were similar to Glucotrol XL and the Glucotrol XL in Beagle dogs. The range of the factors of formulation and procedure, which could influence the drug release, was optimized using artificial neural network. Finally, the design space was found. It was found that the target formulation which was similar to Glucotrol XL in dissolution test could be obtained in a short period by using the expert system. The samples which were similar to Glucotrol XL were bio-equivalent to the Glucotrol XL in Beagle dogs. The design space of the key parameter coating weight gain was 9.5%-12.0%. It could be concluded that a well controlled product of glipizide PPOP was developed since the dissolution test standard of our product was more strict than that of Glucotrol XL.