Fluorinated BPA derivatives enhanced 10B delivery in tumors.

Boron neutron capture therapy (BNCT) is an emerging approach for treating malignant tumors with binary targeting. However, its clinical application has been hampered by insufficient 10B accumulation in tumors and low 10B concentration ratios of tumor-to-blood (T/B) and tumor-to-normal tissue (T/N). Herein, we developed fluorinated BPA derivatives with different fluorine groups as boron delivery agents for enabling sufficient 10B accumulation in tumors and enhancing T/B and T/N ratios. Our findings demonstrated that fluorinated BPA derivatives had good biological safety. Furthermore, fluorinated BPA derivatives showed improved 10B accumulation in tumors and enhanced T/B and T/N ratios compared to the clinical boron drug fructose-BPA (f-BPA). In particular, in B16-F10 tumor-bearing mice, fluorinated BPA derivatives met the requirements for clinical BNCT even at half of the clinical dose. Thus, fluorinated BPA derivatives are potentially effective boron delivery agents for clinical BNCT in melanoma.

Medical insurance benefits and health inequality: evidence from rural China.

Alleviating health inequality among different income groups has become a significant policy goal in China to promote common prosperity. Based on the data from the China Health and Retirement Longitudinal Study (CHARLS) covering the period from 2013 to 2018, this study empirically examines the impact of Integrated Medical Insurance System (URRBMI) on the health and health inequality of older adult rural residents. The following conclusions are drawn: First, URRBMI have elevated the level of medical security, reduced the frailty index of rural residents, and improved the health status of rural residents. Second, China exhibits "pro-rich" health inequality, and URRBMI exacerbates health inequality among rural residents with different incomes. This result remains robust when replacing the frailty index with different health modules. Third, the analysis of influencing mechanisms indicates that the URRBMI exacerbate inequality in the utilization of medical services among rural residents, resulting in a phenomenon of "subsidizing the rich by the poor" and intensifying health inequality. Fourth, in terms of heterogeneity, URRBMI have significantly widened health inequality among the older adult and in regions with a higher proportion of multiple-tiered medical insurance schemes. Finally, it is suggested that China consider establishing a medical financing and benefit assurance system that is related to income and age and separately construct a unified public medical insurance system for the older adult population.

Serum neurofilament light chain and inflammatory cytokines as biomarkers for early detection of mild cognitive impairment.

To investigate the association between serum neurofilament light chain (NfL) levels, inflammatory cytokines, and cognitive function to assess their utility in the early detection of mild cognitive impairment (MCI). We conducted a cross-sectional study involving 157 community-dwelling individuals aged 55 years and above, categorized into healthy controls, MCI, and probable Alzheimer's disease (AD). Serum levels of NfL, inflammatory cytokines, and AD pathology markers were measured using enzyme-linked immunosorbent assay (ELISA). Correlations between these biomarkers and cognitive function were analyzed, and the diagnostic performance of the cognitive assessment scales and serum biomarker concentrations was evaluated using receiver operating characteristic (ROC) curve analysis. Serum NfL levels were significantly elevated in MCI and probable AD groups compared to healthy controls. Positive correlations were found between serum NfL and inflammatory cytokines IL-1ß, IL-6, and Aß40. Combining serum NfL with p-tau217 and the Boston Naming Test significantly enhanced the predictive accuracy for MCI. However, combining serum NfL with inflammatory markers did not improve MCI prediction accuracy. Elevated serum NfL is associated with cognitive impairment and inflammatory markers, suggesting its potential as a peripheral serum biomarker for MCI detection. The combination of serum NfL with p-tau217 and cognitive tests could offer a more accurate prediction of MCI, providing new insights for AD treatment strategies.

Does the increase in health insurance benefits have different effects on the health of middle-aged and older people individuals in rural areas? Analysis based on quantile difference-in-differences method.

In the context of healthy aging, enhancing health performance is an intrinsic requirement for the development and reform of the health insurance system. This paper mainly discusses the health effects of increasing medical insurance benefits on people with different levels of health. So this paper utilizes multiple rounds of data from the China Health and Retirement Longitudinal Study (CHARLS) and employs the quantile difference-in-differences method to systematically investigate the impact effects of the integration of urban and rural residents' health insurance on the frailty levels of rural middle-aged and older people individuals. The research findings are as follows: Firstly, the integration of urban and rural resident health insurance has mitigated the frailty level of rural older people individuals, with a more pronounced impact on those with poorer health statuses. Secondly, in terms of heterogeneity analysis, the health performance effects of the urban-rural health insurance integration policy are more significant among the older people population and in the western regions. Thirdly, the integration of urban and rural resident health insurance primarily improves health by reducing the burden of medical expenses, with a greater impact on the older people population with poorer health statuses. Based on the research findings, we recommend addressing the disparities in healthcare benefits across various insurance systems, alleviating the financial burden of healthcare for impoverished individuals, and consistently improving the coordination of healthcare insurance policies for both urban and rural residents.

The impact of endovascular stents types on perioperative outcomes of ruptured abdominal aortic aneurysms: a single-center experience.

Introduction: Ruptured abdominal aortic aneurysm (rAAA) represents a critically urgent vascular surgical condition, and endovascular aneurysm repair (EVAR) is a clinically effective treatment option. This study aims to investigate whether the type of intravascular graft used for ruptured abdominal aortic aneurysms has an impact on perioperative outcomes of EVAR. Methods: A retrospective analysis was conducted on patients who underwent EVAR for ruptured abdominal aortic aneurysm at a single medical center from 2019 to 2022. Patients who required simultaneous stent implantation in the renal arteries or visceral arteries, as well as those with ruptured aneurysms located in the para-renal, supra-renal, or thoracoabdominal regions, were excluded from the analysis. Additionally, patients who underwent open surgery during the initial procedure or converted to open repair were excluded. The primary endpoint was perioperative mortality rate. Other study outcomes included perioperative complications, reoperation rates, and length of hospital stay. Characteristics and corresponding outcomes of patients receiving different endovascular stent treatments were compared using SPSS software. Results: A total of 58 patients received treatment with two types of endovascular stents: Gore Excluder (n = 29) and Microport Hercules (n = 29). The number of other endografts was too small for statistical analysis. Compared to patients treated with Hercules, those treated with Excluder had a significantly increased likelihood of concomitant coronary atherosclerosis (P = 0.009) and potentially higher creatinine levels (P = 0.014). Additionally, Excluder was more commonly used in patients with shorter aneurysm necks (P < 0.001). There was a statistically significant difference in overall mortality between the two groups (Hercules 27.6%, Excluder 6.9%, P = 0.037). Furthermore, patients who received Excluder treatment had lower mortality rates in subgroups of non-alcohol users (P = 0.028), non-diabetic patients (P = 0.027), and patients with dispersed thrombosis at the proximal neck (P = 0.046). In the multivariate analysis, the type of stent used (OR 0.06, 95% CI 0.00-1.31) and the occurrence of intraoperative complications (OR 20.70, 95% CI 1.14-76.70) in patients with rAAA was identified as an independent risk factor for perioperative mortality. Conclusion: Our study suggests that the management of intraoperative complications may be a modifiable factor that can improve outcomes. Patients receiving Excluder treatment demonstrated better performance in EVAR for single-center rAAA patients compared to other endovascular stents, and this difference warrants further investigation.

Tailoring therapeutics via a systematic beneficial elements comparison between photosynthetic bacteria-derived OMVs and extruded nanovesicles.

Photosynthetic bacteria (PSB) has shown significant potential as a drug or drug delivery system owing to their photothermal capabilities and antioxidant properties. Nevertheless, the actualization of their potential is impeded by inherent constraints, including their considerable size, heightened immunogenicity and compromised biosafety. Conquering these obstacles and pursuing more effective solutions remains a top priority. Similar to extracellular vesicles, bacterial outer membrane vesicles (OMVs) have demonstrated a great potential in biomedical applications. OMVs from PSB encapsulate a rich array of bioactive constituents, including proteins, nucleic acids, and lipids inherited from their parent cells. Consequently, they emerge as a promising and practical alternative. Unfortunately, OMVs have suffered from low yield and inconsistent particle sizes. In response, bacteria-derived nanovesicles (BNVs), created through controlled extrusion, adeptly overcome the challenges associated with OMVs. However, the differences, both in composition and subsequent biological effects, between OMVs and BNVs remain enigmatic. In a groundbreaking endeavor, our study meticulously cultivates PSB-derived OMVs and BNVs, dissecting their nuances. Despite minimal differences in morphology and size between PSB-derived OMVs and BNVs, the latter contains a higher concentration of active ingredients and metabolites. Particularly noteworthy is the elevated levels of lysophosphatidylcholine (LPC) found in BNVs, known for its ability to enhance cell proliferation and initiate downstream signaling pathways that promote angiogenesis and epithelialization. Importantly, our results indicate that BNVs can accelerate wound closure more effectively by orchestrating a harmonious balance of cell proliferation and migration within NIH-3T3 cells, while also activating the EGFR/AKT/PI3K pathway. In contrast, OMVs have a pronounced aptitude in anti-cancer efforts, driving macrophages toward the M1 phenotype and promoting the release of inflammatory cytokines. Thus, our findings not only provide a promising methodological framework but also establish a definitive criterion for discerning the optimal application of OMVs and BNVs in addressing a wide range of medical conditions.

Extraction and identification of exosomes from three different sources of human ovarian granulosa cells and analysis of their differential miRNA expression profiles.

OBJECTIVE: As important functional cells in the ovary, ovarian granulosa cells are involved in the regulation of oocyte growth and development and play an important role in the study of female fertility preservation. Based on the importance of granulosa cell functionalism, in this study, we analyzed the exosome secretion capacity of human ovarian granulosa cells (SVOG/KGN-cell line, PGC-primary cells) and the differences in their miRNA expression. METHODS: Cells were identified by hematoxylin-eosin staining (HE) and FSHR immunofluorescence staining; CCK8 and colony-forming assay were performed to compare cell proliferation capacity; exosomes were extracted and identified by ultra-high speed centrifugation, transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blot analysis (WB), and the expression profile of each cellular exosomal miRNA was analyzed by miRNA high-throughput sequencing. RESULTS: The proliferative abilities of the three granulosa cells differed, but all had the ability to secrete exosomes. In the exosomes of SVOG, KGN, and PGC cells, 218, 327, and 471 miRNAs were detected, respectively. When compared to the exosomal miRNAs of PGC cells, 111 miRNAs were significantly different in SVOG, and 70 miRNAs were washed two significantly different in KGN cells. These differential miRNA functions were mainly enriched in the cell cycle, cell division/differentiation, multicellular biogenesis, and protein binding. CONCLUSION: Human ovarian granulosa cells of different origins are capable of secreting exosomes, but there are still some differences in their exosomes and exosomal miRNAs, and experimental subjects should be selected rationally according to the actual situation.

Latent classes of symptom trajectories among major depressive disorder patients in China.

OBJECTIVE: This study aimed to understand the long-term symptom trajectories of Chinese patients with major depressive disorder (MDD) using piecewise latent growth modeling and growth mixture modeling. The investigation also aimed to identify the baseline characteristics indicative of poorer treatment outcomes. METHODS: A total of 558 outpatients with MDD were assessed using a sequence of surveys. The Hamilton Rating Scale for Depression (HRSD), Hamilton Anxiety Rating Scale (HAMA), and Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) were used to evaluate baseline depression, anxiety, and cognitive function. Depression symptom severity was subsequently measured at the 1-month, 2-month, 6-month, 1-year, and 2-year follow-ups. RESULTS: Results indicated three depressive symptomology trajectories, including (a) severe, improving class (12.72 %), (b) partially responding, later deteriorating class (6.09 %), and (c) moderate, improving class (81.18 %). Logistic regression analyses showed that a history of cardiovascular disease (CVD) increased the odds of belonging to the partially responding, later deteriorating class, whereas higher baseline depression increased the odds of belonging to the severe, improving class compared to the moderate, improving class. Patients who experienced less depression relief during the first month of treatment had a lower probability of belonging to the moderate, improving class. LIMITATIONS: Participant attrition in this study may have inflated the estimated rate of treatment-resistant patients. CONCLUSIONS: The burden of CVD and poorer initial treatment response are plausible risk factors for poorer treatment outcomes, highlighting targets for intervention in Chinese MDD patients.

Regional population and social welfare from the perspective of sustainability: Evaluation indicator, level measurement, and interaction mechanism.

Key to regional sustainable development are the development and interplay of population dynamics and social welfare, each playing a significant role. As a representative region with demographic characteristics such as negative population growth and large labor outflow, the development and interaction between population and social welfare in Nanchong deserve in-depth exploration. This article takes the development of population and social welfare in Nanchong as the research object, and constructs an evaluation indicator system of population and social welfare through research backtracking, and uses entropy method and coupling coordination model to measure the development level and interactive effect of population and social welfare in Nanchong from 2010 to 2021. The research results show that: Firstly, the comprehensive evaluation results of population in Nanchong shows a linear upward trend, which indicates the stable positive effect of population structure and distribution, the gradual improvement effect of population quality effectively compensate for the weakening effect of population quantity, thus achieving the positive development of population. Secondly, the comprehensive evaluation results of social welfare in Nanchong shows an exponential upward trend, which indicates the social welfare has maintained a rapid growth momentum in various dimensions and the long-term positive effects have completely absorbed the negative effects, thus achieving the positive development of social welfare. Thirdly, during the sample period, the population and social welfare in Nanchong consistently maintained a high level of interaction strength, with factors diffusing and integrating. On this basis, the diffusion theory is used as an empirical reference to construct three interactive mechanisms between the population and social welfare in Nanchong and the implications are inferred from the empirical results.

Pan-Cancer Single-Nucleus Total RNA Sequencing Using snHH-Seq.

Tumor heterogeneity and its drivers impair tumor progression and cancer therapy. Single-cell RNA sequencing is used to investigate the heterogeneity of tumor ecosystems. However, most methods of scRNA-seq amplify the termini of polyadenylated transcripts, making it challenging to perform total RNA analysis and somatic mutation analysis.Therefore, a high-throughput and high-sensitivity method called snHH-seq is developed, which combines random primers and a preindex strategy in the droplet microfluidic platform. This innovative method allows for the detection of total RNA in single nuclei from clinically frozen samples. A robust pipeline to facilitate the analysis of full-length RNA-seq data is also established. snHH-seq is applied to more than 730 000 single nuclei from 32 patients with various tumor types. The pan-cancer study enables it to comprehensively profile data on the tumor transcriptome, including expression levels, mutations, splicing patterns, clone dynamics, etc. New malignant cell subclusters and exploring their specific function across cancers are identified. Furthermore, the malignant status of epithelial cells is investigated among different cancer types with respect to mutation and splicing patterns. The ability to detect full-length RNA at the single-nucleus level provides a powerful tool for studying complex biological systems and has broad implications for understanding tumor pathology.

Characterization of human pluripotent stem cell differentiation by single-cell dual-omics analyses.

In vivo differentiation of human pluripotent stem cells (hPSCs) has unique advantages, such as multilineage differentiation, angiogenesis, and close cell-cell interactions. To systematically investigate multilineage differentiation mechanisms of hPSCs, we constructed the in vivo hPSC differentiation landscape containing 239,670 cells using teratoma models. We identified 43 cell types, inferred 18 cell differentiation trajectories, and characterized common and specific gene regulation patterns during hPSC differentiation at both transcriptional and epigenetic levels. Additionally, we developed the developmental single-cell Basic Local Alignment Search Tool (dscBLAST), an R-based cell identification tool, to simplify the identification processes of developmental cells. Using dscBLAST, we aligned cells in multiple differentiation models to normally developing cells to further understand their differentiation states. Overall, our study offers new insights into stem cell differentiation and human embryonic development; dscBLAST shows favorable cell identification performance, providing a powerful identification tool for developmental cells.

A transdermal drug delivery system based on dissolving microneedles for boron neutron capture therapy of melanoma.

Boron neutron capture therapy (BNCT) is a promising therapy for malignant tumors that requires selective and high concentrations of 10B accumulation in tumor cells. Despite ongoing developments in novel boron agents and delivery carriers, the progress and clinical application of BNCT is still restricted by the low 10B accumulation and tumor-to-normal tissue (T/N) ratio. Herein, a dissolving microneedle-based transdermal drug delivery system was specifically designed for BNCT in a mouse model of melanoma. By incorporating fructose-BPA (F-BPA) into PVA microneedle tips, this system successfully delivered sufficient F-BPA into the melanoma site after the application of only two patches. Notably, the T/N ratio achieved through the treatment combining PVA/F-BPA MNs with BNCT (PVA/F-BPA MNs-BNCT) surpassed 93.16, signifying a great improvement. Furthermore, this treatment approach effectively inhibited tumor growth and significantly enhanced the survival rate of the mice. In brief, our study introduces a novel, simple, and efficient administration strategy for BNCT, opening new possibilities for the design of nanomedicine for BNCT.

Proinflammatory phenotype in major depressive disorder with adulthood adversity: In line with social signal transduction theory of depression.

BACKGROUND: The social signal transduction theory of depression proposes that life stress can be transformed into inflammatory signals, and ultimately lead to the development of major depressive disorder (MDD). The hypotheses of this study were: (1) The pro-inflammatory effect of life stress was only seen in patients with MDD, but not in healthy controls (HCs); (2) Inflammation can mediate the relationship between life stress and depressive symptoms. METHODS: This study included 170 MDD patients and 196 HCs, and 13 immune-inflammatory biomarkers closely related to MDD were measured, principal component analysis (PCA) was adopted to extract the inflammatory index. Life stress was assessed by Life Event Scale (LES), a total score of >32 points on the LES was considered as adulthood adversity (AA). Path analyses were used to explore the relationship among adulthood stress, inflammatory index, and severity of depression. RESULTS: Among MDD patients, α2M, CXCL-1, IL-1ß, and TLR-1 levels were higher in patients with AA than non-AA group (all FDR-adjusted P values <0.05), meanwhile, the levels of CCL-2 and IL-18 were lower. Path analyses suggested that pro- and anti-inflammatory index could mediate the association between AA and severity of depression in MDD patients. CONCLUSION: This study found that inflammatory signals can mediate the relationship between adulthood adversity and depression, however, the causal relationship need to be further confirmed. These findings shed light on further understanding the theory of social signal transduction in MDD and provide clues for stress management and controlling inflammation strategies in depression. CLINICAL TRIALS: NCT02023567.

Case report: Anxiety and depression as initial symptoms in a patient with acute hypoxia and patent foramen ovale.

The prevalence of patent foramen ovale (PFO) is 15-35% among adults. The role of right-to-left shunting through the PFO, anxiety, depression, and hypoxemia in the systemic circulation remains poorly understood. Herein, we present the case of a 52-year-old woman with no heart or lung disease, who was admitted due to anxiety for 5 months and had symptom exacerbation with dizziness for 4 days and presented with cyanosis. She was noted to have acute hypoxemia, with an oxygen saturation of 94.48% on room air, and arterial blood gas showed an oxygen tension of 65.64 mmHg. Agitated saline contrast echocardiography showed right-to-left shunting due to PFO. Arteriovenous fistula, pneumonia, pulmonary embolism, pulmonary hypertension, congestion peripheral cyanosis, ischemic peripheral cyanosis, and methemoglobin were excluded. Additionally, the patient improved by taking Paroxetine, Oxazepam, and Olanzapine. Her oxygen tension returned to 90.42 mmHg, and her symptoms resolved. In the case of severe anxiety and depression, right-to-left shunting through the PFO may cause acute systemic hypoxemia via a flow-driven mechanism, occasionally manifesting as cyanosis. When anxiety improved, hypoxia also improved. Thus, the treatment of anxiety and depression seems effective in improving hypoxemia. Notably, this is a rare report, and we hope to draw the attention of psychosomatic specialists, psychiatrists, and clinicians to seek the relationship between anxiety appearing as acute stress and PFO. This may be a new therapeutic method for treating severe anxiety disorder.

Effect of Paxlovid on Tacrolimus Concentration in Perioperative Kidney Transplant Patients Infected With COVID-19: A Case Report.

Paxlovid, as a new drug, received emergency approval for the treatment of COVID-19 in China; there is very little experience with kidney transplantation patients taking tacrolimus with perioperative COVID-19 infection. We discontinued tacrolimus on the day of using Paxlovid, and we chose to frequently monitor the concentration of tacrolimus and creatinine early in the course of treatment by enzyme multiplied immunoassay technique (EMIT) and liquid chromatography-mass spectrometry (LC-MS/MS). The results show varying degrees of elevation of creatinine levels in 3 patients, and EMIT may overestimate the true concentration of tacrolimus metabolites compared with LC-MS/MS. All the data comply with the Helsinki Congress and the Declaration of Istanbul.

Effect of night shift work on metabolic syndrome in adults who suffered from earthquake stress in early life.

Objective: To examine the role of night shift work on the risk of metabolic syndrome (MetS) in adults suffered from earthquakes prenatally or as infants and to analyse the effect of stress on factors that influence MetS in this population. Methods: We included 870 subjects from 2014 to 2015. All subjects work as miners for the Kailuan Mining Group and were born were living in Tangshan. Participants were classified into two groups on basis of their work schedules: day shift and night shift. They were further classified into the prenatal exposure group, the infancy exposure group, and the control group based on their age during the Tangshan earthquake. This study was conducted 38 years after the earthquake. Participants' general demographic data, smoking and drinking habits, as well as work schedules were collected. All participants' sleep status was assessed with the Pittsburgh Sleep Quality Index. The measurement of all subjects' waist circumference and blood pressure was made, and triglycerides, fasting blood glucose, high-density lipoproteins, and low-density lipoproteins were measured by collecting blood samples. The definition of MetS was made after the guidelines for preventing and controlling type 2 diabetes in China (2017 Edition). Results: A total of 187 (21.5%) workers were determined to have MetS. The incidence of MetS was greatly higher in night shift workers who were exposed to an earthquake during infancy than in day shift workers (χ2 = 8.053, p = 0.005). A multivariate logistic regression analysis displayed male participants had a higher risk develop MetS than female participants (p = 0.042, OR = 0.368, 95% CI = 0.140, 0.965). Current smokers (p = 0.030, OR = 1.520, 95%CI = 1.042, 2.218) and participants who sleep fewer than 7 h per night (p = 0.015, OR = 1.638, 95%CI = 1.101, 2.437) had a higher risk of MetS. Prenatal earthquake stress was also a risk element for MetS (p = 0.012, OR = 1.644, 95%CI = 1.115, 2.423). Conclusion: The risk of MetS is significantly higher in night shift workers exposed to earthquake stress during infancy than day shift workers. Earthquake exposure during pregnancy is an independent risk factor for MetS. Smoking and sleeping less than 7 h have a higher risk of MetS than the control group.

Early non-response as a predictor of later non-response to antipsychotics in schizophrenia: a randomized trial.

BACKGROUND: It remains a challenge to predict the long-term response to antipsychotics in patients with schizophrenia who do not respond at an early stage. This study aimed to investigate the optimal predictive cut-off value for early non-response that would better predict later non-response to antipsychotics in patients with schizophrenia. METHODS: This multicenter, 8-week, open-label, randomized trial was conducted at 19 psychiatric centers throughout China. All enrolled participants were assigned to olanzapine, risperidone, amisulpride, or aripiprazole monotherapy for 8 weeks. The positive and negative syndrome scale (PANSS) was evaluated at baseline, week 2, week 4, and week 8. The main outcome was the prediction of nonresponse. Nonresponse is defined as a < 20% reduction in the total scores of PANSS from baseline to endpoint. Severity ratings of mild, moderate, and severe illness corresponded to baseline PANSS total scores of 58, 75, and 95, respectively. RESULTS: At week 2, a reduction of < 5% in the PANSS total score showed the highest total accuracy in the severe and mild schizophrenia patients (total accuracy, 75.0% and 80.8%, respectively), and patients who were treated with the risperidone and amisulpride groups (total accuracy, 82.4%, and 78.2%, respectively). A 10% decrease exhibited the best overall accuracy in the moderate schizophrenia patients (total accuracy, 84.0%), olanzapine (total accuracy, 79.2%), and aripiprazole group (total accuracy, 77.4%). At week 4, the best predictive cut-off value was < 20%, regardless of the antipsychotic or severity of illness (total accuracy ranging from 89.8 to 92.1%). CONCLUSIONS: Symptom reduction at week 2 has acceptable discrimination in predicting later non-response to antipsychotics in schizophrenia, and a more accurate predictive cut-off value should be determined according to the medication regimen and baseline illness severity. The response to treatment during the next 2 weeks after week 2 could be further assessed to determine whether there is a need to change antipsychotic medication during the first four weeks. TRIAL REGISTRATION: This study was registered on Clinicaltrials.gov (NCT03451734).

Ecological correlation between short term exposure to particulate matter and hospitalization for mental disorders in Shijiazhuang, China.

The associations between particulate matter (PM) and overall and specific mental disorders (MDs) are investigated using data from two general hospitals in Shijiazhuang, China, from January 2014 to December 2019. A longitudinal time series study, as one type of ecological study, is conducted using a generalized additive model to examine the relationship between short-term exposure to PM2.5, PM10, and daily hospital admissions for MDs, and further stratification by subtypes, age, and gender. A total of 10,709 cases of hospital admissions for MDs have been identified. The significant short-time effects of PM2.5 on overall MDs at lag01 and PM10 at lag05 are observed, respectively. For specific mental disorders, there are substantial associations of PM pollution with mood disorders and organic mental disorders. PM2.5 has the greatest cumulative effect on daily admissions of mood disorders and organic mental disorders in lag01, and PM 10 has the greatest cumulative effect in lag05. Moreover, the effect modification by sex or age is statistically significant, with males and the elderly (≥ 45 years) having a stronger effect. Short-term exposure to PM2.5 and PM10can be associated with an increased risk of daily hospital admissions for MDs.

[Mechanism of Liuwei Dihuang Pills in treatment of mice with diminished ovarian reserve based on proteomics].

This study aims to investigate the efficacy and possible mechanism of Liuwei Dihuang Pills in the treatment of diminished ovarian reserve(DOR) by using proteomic techniques. Firstly, cyclophosphamide(60 mg·kg~(-1)) combined with busulfan(6 mg·kg~(-1)) was injected intraperitoneally to establish the mouse model of DOR. After drug injection, the mice were continuously observed and the success of modeling was evaluated by the disturbance of the estrous cycle. After successful modeling, the mice were administrated with the suspension of Liuwei Dihuang Pills by gavage for 28 days. At the end of the gavage, four female mice were selected and caged together with males at a ratio of 2∶1 for the determination of the pregnancy rate. Blood and ovary samples were collected from the remaining mice on the next day after the end of gavage. Hematoxylin-eosin(HE) staining and transmission electron microscopy(TEM) were then employed to observe the morphological and ultrastructural changes in the ovaries. The serum levels of hormones and oxidation indicators were measured by enzyme-linked immunosorbent assay. Quantitative proteomics techniques were used to compare the ovarian protein expression before and after modeling and before and after the intervention with Liuwei Dihuang Pills. The results showed that Liuwei Dihuang Pills regulated the estrous cycle of DOR mice, elevated the serum levels of hormones and anti-oxidation indicators, promoted follicle development, protected the mitochondrial morphology of ovarian granulosa cells, and increased the litter size and survival of DOR mice. Furthermore, Liuwei Dihuang Pills negatively regulated the expression of 12 differentially expressed proteins associated with DOR, which were mainly involved in lipid catabolism, inflammatory response, immune regulation, and coenzyme biosynthesis. These differentially expressed proteins were significantly enriched in sphingolipid metabolism, arachidonic acid metabolism, ribosomes, ferroptosis, and cGMP-PKG signaling pathway. In summary, the occurrence of DOR and the treatment of DOR with Liuwei Dihuang Pills are associated with multiple biological pathways, mainly including oxidative stress response, inflammatory response, and immune regulation. "Mitochondria-oxidative stress-apoptosis" is the key to the treatment of DOR by Liuwei Dihuang Pills. YY1 and CYP4F3 may be the key upstream targets that trigger mitochondrial dysfunction and ROS accumulation, and the metabolism of arachidonic acid is the main signaling pathway of drug action.

Association between peripheral orexin A/B levels and depression with childhood trauma.

BACKGROUND: Orexin dysfunction has previously been demonstrated to be associated with depression. However, no studies reported the different effects of orexin A/B on depression with and without childhood trauma (CT). In this study，we assessed the correlation between expression of orexin A/B and depression severity in major depressive disorder (MDD) patients and healthy controls. METHODS: A total of 97 MDD patients and 51 healthy controls were recruited in this study. According to the total scores of childhood trauma questionnaire (CTQ), the MDD patients were further divided into two subgroups, MDD with CT and MDD without CT. The 17-item Hamilton Depression Scale (HAMD-17), and plasma orexin A and orexin B concentrations were measured in all participants using enzyme-linked immunosorbent assay. RESULTS: Orexin B plasma levels were significantly higher in MDD patients with CT and without CT than that in the healthy control group (P < 0.05), whereas there was no statistical difference between the two depression groups. After adjusting age and BMI for covariates, the LASSO regression revealed significant association between the plasma orexin B levels and the total scores of HAMD (ß = 3.348), CTQ (ß = 2.005). There was no difference in plasma orexin A levels among three groups (P > 0.05). CONCLUSIONS: Although peripheral orexin B levels are associated with the depression, rather than orexin A, CT appear to play a role in the association between orexin B levels and depression. China Clinical Trial Registration Center (Registration No.: ChiCTR2000039692).