Elusive Protein-Glycosphingolipid Interactions Revealed by Membrane Anchor-Assisted Native Mass Spectrometry.

Interactions between glycan-binding proteins (GBPs) and glycosphingolipids (GSLs) present in cell membranes are implicated in a wide range of biological processes. However, studying GSL binding is hindered by the paucity of purified GSLs and the weak affinities typical of monovalent GBP-GSL interactions. Native mass spectrometry (nMS) performed using soluble model membranes is a promising approach for the discovery of GBP ligands, but the detection of weak interactions remains challenging. The present work introduces MEmbrane ANchor-assisted nMS (MEAN-nMS) for the detection of low-affinity GBP-GSL complexes. The assay utilizes a membrane anchor, produced by covalent cross-linking of the GBP and a lipid in the membrane, to localize the GBP on the surface and promote GSL binding. Ligands are identified by nMS detection of intact GBP-GSL complexes (MEAN-nMS) or using a catch-and-release (CaR) strategy, wherein GSLs are released from GBP-GSL complexes upon collisional activation and detected (MEAN-CaR-nMS). To establish reliability, a library of purified gangliosides incorporated into nanodiscs was screened against human immune lectins, and the results compared with affinities of the corresponding ganglioside oligosaccharides. Without a membrane anchor, nMS analysis yielded predominantly false negatives. In contrast, all ligands were identified by MEAN-(CaR)-nMS, with no false positives. To highlight the potential of MEAN-CaR-nMS for ligand discovery, a natural library of GSLs was incorporated into nanodiscs and screened against human and viral proteins to uncover elusive ligands. Finally, nMS-based detection of GSL ligands directly from cells is demonstrated. This breakthrough paves the way for shotgun glycomics screening using intact cells.

(-)-α-Bisabolol inhibits D-Gal-induced HSF cellular senescence in vitro and prevents skin aging in vivo by reducing SASP.

Objectives: To study the anti-aging effect of (-)-α-bisabolol ((-)-α-bis) on the skin and preliminarily clarify its mechanism. Materials and Methods: Human skin fibroblasts (HSF) were induced senescence by D-Galactose. Senescence ß-galactosidase staining was utilized to evaluate the senescence of HSF. TNF-α, IL-6, IL-8, IL-1ß, CCL-2, CCL-5, and MMP-9 in senescence-as-sociated secretory phenotype (SASP) were detected by RT-qPCR. Meanwhile, aged BALB/c mice were applied topically with 0.5% and 2%(-)-α-bis gel for 30 days continuously to evaluate anti-aging parameters on the skin such as surface measurement, the Trans Epidermal Water Loss (TEWL), and skin barrier index of dorsal skin. Then, HE staining, Masson staining, and IHC were applied to measure epidermal thickness, collagen fiber content in the dermis, and content of dermal collagen I, respectively. Last, SOD, MDA, and HYP contents of the back skin tissue of mice were also detected. Results: (-)-α-Bis reduced the expression of senescence-associated ß-galactosidase (SA-ß-gal) and expression levels of SASP in HSF cells stimulated by D-Gal (P<0.05). Mice aged 9 months were applied locally with (-)-α-bis gel to improve skin aging, the TEWL and skin barrier index of dorsal skin, and ameliorate the epidermal thickness and contents of dermal collagen fibers and collagen I (P<0.05). Furthermore, (-)-α-bis up-regulated the mRNA expression levels of elastin and collagen III effectively (P<0.05). Conclusion: (-)-α-Bis can delay the senescence of HSF cells by reducing the expression of SA-ß-gal and SASP factors in vitro. Improved skin barrier function as well as SASP is responsible for the delay of skin aging in vivo.

Patients with High Baseline Neutrophil-to-Lymphocyte Ratio Exhibit Better Response to Filgotinib as Treatment for Rheumatoid Arthritis.

INTRODUCTION: High baseline neutrophil-to-lymphocyte ratio (NLR) in rheumatoid arthritis (RA) has been associated with positive responses to biologic tumor necrosis factor inhibition and negative responses to conventional synthetic disease-modifying antirheumatic drug (csDMARD) triple therapy. Datasets from three randomized clinical trials in patients with RA were used to test the hypothesis that baseline NLR is associated with improved clinical response to filgotinib in methotrexate (MTX)-naïve or MTX-experienced RA populations. METHODS: Patients from FINCH 1 (inadequate response to MTX, MTX-IR; NCT02889796), FINCH 2 (inadequate response to biologic DMARDs; NCT02873936), and FINCH 3 (MTX-naïve; NCT02886728) were classified as baseline NLR-High or baseline NLR-Low based on a previously published cut point of 2.7. In total, 3365 patients were included across the three studies. Differences in clinical outcomes and patient-reported outcomes (PROs) were determined using linear-regression models. RESULTS: Control-arm patients (placebo + MTX/placebo + csDMARD) classified as NLR-High exhibited worse continuous clinical and PRO responses at week 12 across clinical trials compared to NLR-Low patients. In contrast, NLR-High patients who received FIL 200 mg + MTX/csDMARD exhibited consistently better responses after 12 weeks compared to NLR-Low patients across clinical trials, clinical endpoints, and PROs. These trends were most prominent among the MTX-IR population. CONCLUSION: The 2.7 baseline NLR cut point could be used to enrich for patients most likely to benefit from the addition of filgotinib to background MTX/csDMARD. Use of baseline NLR as part of therapeutic decision-making would not require additional diagnostics and could contribute to improved outcomes for patients with RA. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02889796; NCT02873936; NCT02886728.

Rheumatoid arthritis is a disease that results in swollen and painful joints. There is currently no method to determine which treatment will work best for an individual patient. However, there may be identifying markers found in the blood that could indicate how a patient will respond to treatment. One of these possible markers is a ratio of two types of white blood cells, neutrophils and lymphocytes, which are part of the body's immune system and help the body detect and fight infection and other diseases. This ratio is referred to as the neutrophil-to-lymphocyte ratio. The current study evaluated whether the neutrophil-to-lymphocyte ratio at the beginning of treatment was associated with rheumatoid arthritis treatment outcomes. Blood test results were used from 3365 patients receiving filgotinib (a medicine used to treat rheumatoid arthritis) or other therapies as part of the FINCH clinical trials. Patients were classified as having a high or low neutrophil-to-lymphocyte ratio at the start of treatment. Patients receiving filgotinib over 24 weeks who had a high neutrophil-to-lymphocyte ratio showed less disease activity than patients whose ratio was low. This study provides support for the use of the neutrophil-to-lymphocyte ratio as a way to help determine whether a patient would benefit from filgotinib as part of their rheumatoid arthritis treatment and may help improve rheumatoid arthritis treatment outcomes.

Construction of ecological security pattern in combination with landslide sensitivity: A case study of Yan'an City, China.

The ecological security pattern can harmonize the relationship between natural environmental protection and socio-economic development. This study proposes a regional ecological security pattern optimization framework by integrating theory and practice with landslide sensitivity and landscape structure. Using Yan'an City as an example, this study optimizes the landscape layout of preliminary ecological sources. The landslide sensitivity index is generated using the information value model and then used to adjust the ecological resistance surface. The Minimum Cumulative Resistance (MCR) approach is used to extract ecological corridors, locate ecological nodes utilizing circuit theory, and outline crucial ecological control areas. The results demonstrate: (1) the ecological sources are primarily composed of forestlands, with a total area of 2,352.2400 km2, concentrated in the southwest, central, and southeast regions. The optimal landscape granularity for the source patches is 600 m. (2) Yan'an is divided into four landslide sensitivity level zones: extremely high, high, medium, and low, with the overall landslide sensitivity of the region being high. (3) The highest ecological resistance is observed in built-up land and the lowest in forestland. The total number of ecological corridors is 26, avoiding most of the highly sensitive areas of landslides. (4) The number of ecological pinch points is 61, while the ecological barrier points amounted to 54. The critical ecological control areas consist mainly of cropland, forestland, and grassland, and differentiated restoration strategies are proposed to address their unique characteristics. The findings of the research can offer scientific guidance for the practice of ecological security protection in geohazard-prone areas.

Preadsorbed Chymotrypsin Modulated the Composition of Protein Corona and Immunological Response.

It is well-known that proteins after administration into biological environments adsorb on the surface of nanoparticles (NPs). The biological identity could be determined by protein corona, but whether and how the preadsorbed molecules impact the composition of the corona and immunological response have rarely been reported. Here, the effects of preadsorbed chymotrypsin (Chy) on forming protein corona and subsequent immunological response are reported. We find that preadsorbed Chy on the surface of AuNPs results in a protein corona with enriched immunoglobulins and reduced human serum albumin protein, which further affect the polarization of macrophages into specific phenotypes. Our study suggests that the protein surrounding the nanoparticles could affect the protein corona and immunological response, which may direct the preparation of multifunctional nanomedicine for future studies.

The difference in core-surface temperature indicates the prognosis of heart failure patients.

Aim: To evaluate the difference between core temperature and surface temperature (ΔT) as an index for the prognosis of heart failure (HF). Patients & methods: Core temperature and surface temperature were measured in 253 patients with HF. The association of ΔT with prognostic indicators of HF was analyzed. Results: Patients with ΔT ≥2°C were more likely to have lower left ventricular ejection fraction and lower estimated glomerular filtration rate, higher levels of troponin T, brain natriuretic peptide and procalcitonin, and high blood urea nitrogen/creatinine ratio. The risk of death increased by 32% for a 1°C increase in ΔT and was 4.36-times higher in the ΔT ≥2°C group than in the ΔT <2°C group. Conclusion: ΔT may be used to predict the prognosis of patients with HF.

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Evaluation of ß2-microglobulin in the condition and prognosis of psoriasis patients.

BACKGROUND: Numerous studies have linked the inflammatory pathway in psoriasis and metabolic disease, while no specific marker defined it. It is worth exploring the association of ß2-microglobulin (ß2M) in psoriasis severity and comorbidities. OBJECTIVES: To investigate the correlation between blood ß2M level and psoriasis severity, to explore the inflammatory factors influencing the occurrence of psoriasis comorbidities such as arthritis, diabetes, and hypertension. METHODS: Ninety-seven psoriasis patients were analyzed in the cohort retrospective study during 12 weeks. RESULTS: Significantly higher levels of blood ß2M and ESR were observed in the group that patients' PASI ≥10 than in the group that PASI <10. Blood ß2M level had strong significantly positive correlations with the PASI in Pearson's correlation analysis. In the model that systemic inflammatory factors to find psoriasis comorbidity risk factors, logistic regression analysis showed that blood ß2M level was the significant risk factor associated with diabetes and hypertension. High-sensitivity C-reactive protein (hsCRP) was the significant risk factor associated with arthritis. CONCLUSIONS: Patients with a severer psoriasis tended to have higher blood ß2M levels and severer inflammatory state. In the systemic inflammation indexes, the level of blood ß2M affected the risk of hypertension and diabetes, and hsCRP affected the risk of arthritis in patients with psoriasis.

A rare case report of endometrial adenosarcoma in the cesarean scar diverticulum.

Background: Endometrial adenosarcoma is an unusual type of uterine tumor that features a seemingly benign epithelial component, paired with a low-grade sarcomatous component, usually similar in appearance to endometrial stromal sarcoma. To our knowledge, no image of endometrial adenocarcinoma in the cesarean scar diverticulum has been reported previously. Case Description: We present a rare case of endometrial adenocarcinoma located in the cesarean scar diverticulum of a 44-year-old patient. The patient was admitted to our hospital complaining of irregular vaginal bleeding that had lasted for over two months. Both B-ultrasound and magnetic resonance imaging confirmed a mass at the junction of the corpus uteri and cervix. After the initial curettage failed to confirm the disease, a hysteroscopy was subsequently performed. Upon further pathological analysis, a diagnosis of endometrial adenosarcoma was confirmed. The patient underwent hysterectomy and salpingo-oophorectomy. The patient was discharged home four days after the surgery and remained recurrence-free for one year after follow-up. Conclusions: Hysteroscopy can serve as a valuable diagnostic tool to identify the lesion in this unique scenario, particularly when curettage fails to diagnose this uncommon condition. We hope that this case would bring awareness of this potential scenario, enabling clinicians in the future to identify similar cases more readily.

The Benefit of the Optimized Formula of Yinxieling in Psoriasis Vulgaris via Regulation on Autophagy Based on microRNA Expression Profile and Network Pharmacology Analysis.

Background: Psoriasis is a widespread chronic, immune-mediated skin disease with frequent recurrences, and is extremely harmful to the physical and mental health of patients, causing enormous suffering and exerting considerable economic burdens on the health care system as a whole. In more than a decade of clinical use, the optimized formula of Yinxieling (PSORI-CM01) has consistently demonstrated its effectiveness for treating psoriasis. However, its underlying mechanism remains largely unexplored. Methods: The network pharmacology analysis was conducted to predict the mechanism and protective effect of PSORI-CM01 in treating psoriasis. Subsequently, we collected blood samples from 21 patients with psoriasis as part of a randomized, double-blind, and double-dummy clinical trial for microRNA expression profiling. Finally, it was experimentally confirmed that PSORI-CM01 improved psoriasis by regulating miR-20a-3p and miR-3184-3p expression. Results: As a result of the network pharmacology analysis, PSORI-CM01 improved psoriasis through the regulation of autophagy, cellular apoptosis, cellular proliferation, and anti-inflammatory processes. In the target-miRNA regulatory network, these key targets were mainly associated with the regulation of hsa-miR-20a-3p, hsa-miR-155-5p, has-miR-3184-3p, hsa-miR-328-3p and hsa-miR-124-3p. Based on the microRNA expression profiling results, the PSORI-CM01 treatment group exhibited five up-regulated genes and 16 down-regulated genes compared with the healthy control group. In particular, miR-20a-3p and miR-3184-3p were the primary differentially expressed microRNAs, and they were significantly enriched in the signaling pathways involving autophagy, apoptosis, proliferation, and anti-inflammation. Further experiments confirmed that PSORI-CM01 effectively regulates miR-20a-3p and miR-3184-3p, resulting in increased autophagy. Conclusion: We demonstrated by combining network pharmacology and clinical studies of miRNA expression profiles in PBMCs that PSORI-CM01 effectively modulated miR-20a-3p and miR-3184-3p, leading to an increase in autophagy and a decrease in keratinocyte proliferation.

Ocular surface changes in moderate-to-severe acne vulgaris.

AIM: To investigate ocular surface disorders and tear function changes in patients with acne vulgaris and explore the potential relationship between acne vulgaris and dry eye. METHODS: This cross-sectional study included right eyes of 53 patients with acne vulgaris and 54 healthy controls. The participants completed the Ocular Surface Disease Index (OSDI) questionnaire. The following ocular surface-related parameters were measured: tear meniscus height (TMH), noninvasive tear breakup time (NIBUT), Schirmer I test (SIT), lipid layer thickness (LLT) score of the tear film, meibum score, meibomian gland orifice obstruction score, the ratio of meibomian gland loss, conjunctival hyperemia score, and corneal fluorescein staining (CFS) score. RESULTS: The stability of the tear film decreased in acne vulgaris patients. In the acne group, the TMH and NIBUT were lower, whereas the OSDI, meibum score, meibomian gland orifice obstruction score, ratio of meibomian gland loss, and conjunctival hyperemia score were higher compared with controls (P<0.05). There were no significant differences in the CFS score, SIT, or LLT score between the groups (P>0.05). In two dry eye groups, the TMH, NIBUT, and LLT score were lower in the acne with dry eye (acne-DE) group, and the meibum score, meibomian gland orifice obstruction score, ratio of meibomian gland loss and conjunctival hyperemia score in the acne-DE group were higher (P<0.05). There were no significant differences between OSDI, SIT, and CFS score (P>0.05). CONCLUSION: Patients with moderate-to-severe acne vulgaris are more likely to experience dry eye than those without acne vulgaris. Reduced tear film stability and meibomian gland structure dysfunction are more pronounced in patients with moderate-to-severe acne and dry eye.

Is pharmacologic venous Thromboprophylaxis necessary for patients undergoing minimally invasive surgery for endometrial Cancer? A systematic review and Meta-analysis.

OBJECTIVE: Given the low incidence of venous thromboembolism (VTE) in endometrial cancer patients undergoing minimally invasive surgery, coupled with the existing uncertainties within guidelines regarding pharmacologic thromboprophylaxis in this area, there is an urgent need for a comprehensive literature review. This review aims to evaluate the necessity of pharmacologic VTE prophylaxis in these patients. METHODS: PubMed, Embase, Cochrane Central Register of Controlled Trials, International Clinical Trials Registry Platform, and ClinicalTrials.gov were systematically searched from inception to March 10, 2024. The analysis was performed using R version 4.2.3. RESULTS: Seven studies involving 3931 endometrial cancer patients were included in the analysis. Meta-analysis results revealed that within 30 days postoperatively, the incidence of VTE was 0.51% (5 out of 990) in the pharmacologic prophylaxis group and 0.70% (7 out of 995) in the mechanical prophylaxis group, with a relative risk (RR) of 1.14 (95% CI 0.19-6.95), indicating no significant difference between the groups. Additionally, within the same timeframe, the incidence of VTE was 0.37% (4 out of 1083) in the extended pharmacologic prophylaxis group and 1.14% (4 out of 352) in the non-extended pharmacologic prophylaxis group, yielding an RR of 0.41 (95% CI 0.11-1.54), again showing no significant difference between the groups. CONCLUSIONS: Our study indicates that routine pharmacological VTE prophylaxis may not be imperative for endometrial cancer patients undergoing minimally invasive surgery, as mechanical prophylaxis alone seems to be efficacious. However, it is crucial to acknowledge that a subset of high-risk patients may derive benefit from pharmacological prophylaxis or even extended regimens. Nonetheless, the absence of a validated risk prediction model for identifying such patients underscores the need for further research in this area. PROTOCOL REGISTRATION: CRD 42024516595.

Genomic correlation, shared loci, and causal relationship between insomnia and psoriasis: a large-scale genome-wide cross-trait analysis.

Psoriasis and insomnia have co-morbidities, however, their common genetic basis is still unclear. We analyzed psoriasis and insomnia with summary statistics from genome-wide association studies. We first quantified overall genetic correlations, then ascertained multiple effector loci and expression-trait associations, and lastly, we analyzed the causal effects between psoriasis and insomnia. A prevalent genetic link between psoriasis and insomnia was found, four pleiotropic loci affecting psoriasis and insomnia were identified, and 154 genes were shared, indicating a genetic link between psoriasis and insomnia. Yet, there is no causal relationship between psoriasis and insomnia by two-sample Mendelian randomization. We discovered a genetic connection between insomnia and psoriasis driven by biological pleiotropy and unrelated to causation. Cross-trait analysis indicates a common genetic basis for psoriasis and insomnia. The results of this study highlight the importance of sleep management in the pathogenesis of psoriasis.

Leveraging Electronic Health Records to Assess Residential Mobility Among Veterans in the Veterans Health Administration.

BACKGROUND: Residential mobility, or a change in residence, can influence health care utilization and outcomes. Health systems can leverage their patients' residential addresses stored in their electronic health records (EHRs) to better understand the relationships among patients' residences, mobility, and health. The Veteran Health Administration (VHA), with a unique nationwide network of health care systems and integrated EHR, holds greater potential for examining these relationships. METHODS: We conducted a cross-sectional analysis to examine the association of sociodemographics, clinical conditions, and residential mobility. We defined residential mobility by the number of VHA EHR residential addresses identified for each patient in a 1-year period (1/1-12/31/2018), with 2 different addresses indicating one move. We used generalized logistic regression to model the relationship between a priori selected correlates and residential mobility as a multinomial outcome (0, 1, ≥2 moves). RESULTS: In our sample, 84.4% (n=3,803,475) veterans had no move, 13.0% (n=587,765) had 1 move, and 2.6% (n=117,680) had ≥2 moves. In the multivariable analyses, women had greater odds of moving [aOR=1.11 (95% CI: 1.10,1.12) 1 move; 1.27 (1.25,1.30) ≥2 moves] than men. Veterans with substance use disorders also had greater odds of moving [aOR=1.26 (1.24,1.28) 1 move; 1.77 (1.72,1.81) ≥2 moves]. DISCUSSION: Our study suggests about 16% of veterans seen at VHA had at least 1 residential move in 2018. VHA data can be a resource to examine relationships between place, residential mobility, and health.

The most recent progress of baicalein in its anti-neoplastic effects and mechanisms.

Problems, such as toxic side effects and drug resistance of chemoradiotherapy, target therapy and immunotherapy accompanying the current anti-cancer treatments, have become bottlenecks limiting the clinical benefit for patients. Therefore, it is urgent to find promising anti-cancer strategies with higher efficacy and lesser side effects. Baicalein, a flavonoid component derived from the Chinese medicine scutellaria baicalensis, has been widely studied for its remarkable anti-cancer activity in multiple types of malignancies both at the molecular and cellular levels. Baicalein exerts its anti-tumor effects by inhibiting angiogenesis, invasion and migration, inducing cell apoptosis and cell cycle arrest, as well as regulating cell autophagy, metabolism, the tumor microenvironment and cancer stem cells with no obvious toxic side effects. The role of classic signaling pathways, such as PI3K/AKT/mTOR, MAPK, AMPK, Wnt/ß-catenin, JAK/STAT3, MMP-2/-9, have been highlighted as the major targets for baicalein exerting its anti-malignant potential. Besides, baicalein can regulate the relevant non-coding RNAs, such as lncRNAs, miRNAs and circ-RNAs, to inhibit tumorigenesis and progression. In addition to the mentioned commonalities, baicalein shows some specific anti-tumor characteristics in some specific cancer types. Moreover, the preclinical studies of the combination of baicalein and chemoradiotherapy pave the way ahead for developing baicalein as an adjunct treatment with chemoradiotherapy. Our aim is to summary the role of baicalein in different types of cancer with its mechanisms based on in vitro and in vivo experiments, hoping providing proof for baicalein serving as an effective and safe compound for cancer treatment in clinic in the future.

The synergistic effect of high temperature and relative humidity on non-accidental deaths at different urbanization levels.

Numerous studies have examined the impact of temperature on mortality, yet research on the combined effect of temperature and humidity on non-accidental deaths remains limited. This study investigates the synergistic impact of high temperature and humidity on non-accidental deaths in China, assessing the influence of urban development and urbanization level. Utilizing the distributed lag nonlinear model (DLNM) of quasi-Poisson regression, we analyzed the relationship between Wet Bulb Globe Temperature (WBGT) and non-accidental deaths in 30 Chinese cities from 2010 to 2016, including Guangzhou during 2012-2016. We stratified temperature and humidity across these cities to evaluate the influence of varying humidity levels on deaths under high temperatures. Then, we graded the duration of heat and humidity in these cities to assess the impact of deaths with different durations. Additionally, the cities were categorized based on gross domestic product (GDP), and a vulnerability index was calculated to examine the impact of urban development and urbanization level on non-accidental deaths. Our findings reveal a pronounced synergistic effect of high temperature and humidity on non-accidental deaths, particularly at elevated humidity levels. The synergies of high temperature and humidity are extremely complex. Moreover, the longer the duration of high temperature and humidity, the higher the risk of non-accidental death. Furthermore, areas with higher urbanization exhibited lower relative risks (RR) associated with the synergistic effects of heat and humidity. Consequently, it is imperative to focus on damp-heat related mortality among vulnerable populations in less developed regions.

Potato oxidized hydroxypropyl starch/pectin-based indicator film with Clitoria ternatea anthocyanin and silver nanoparticles for monitoring chilled beef freshness.

Potato oxidized hydroxypropyl starch (POHS)/pectin (P) functional and smart beef freshness indicator films were prepared using butterfly pea (Clitoria ternatea) anthocyanin (BA) and silver nanoparticles (AgNPs). BA exhibited significant pH-responsive color changes. BA and AgNPs were evenly distributed within a polymer matrix to create a compatible film with POHS/P. The films containing BA and AgNPs had good UV resistance and maintained strong mechanical strength, barrier properties, and color stability. The color of the indicator film changed from purple to green when exposed to ammonia, with the 1 % POHS/P/BA/AgNPs film showing the most sensitive response. The films also demonstrated strong antibacterial and antioxidant properties. The freshness of beef was monitored using 1 % POHS/P/BA/AgNPs films and was identified as sub-fresh and spoiled on days 4 and 7, respectively. The relationship between the color change of the indicator label and the freshness of chilled beef was established: purple for fresh meat, blue for less fresh meat, and green for spoiled meat. Thus, the new POHS/P/BA/AgNPs film can serve as a smart packaging material to indicate food freshness and extend shelf life. These results suggest that POHS/P/BA/AgNPs films have significant potential as an active and smart food packaging material.

Splenectomy as a part of cytoreductive surgery in ovarian cancer: systematic review and meta-analysis.

OBJECTIVE: The role of splenectomy on cytoreductive surgery in patients with ovarian cancer remains controversial. We conducted this meta-analysis to evaluate the safety and impact of survival outcome of splenectomy in patients with ovarian cancer. METHODS: In this meta-analysis we analyzed studies published in PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), International Clinical Trials Registry Platform (ICTRP), and Clinical Trials. gov that appeared in our search from inception to November 10, 2023. RESULT: This meta-analysis included 10 studies, totaling 6297 patients, comprising one prospective and nine retrospective analyses. The results indicated no significant disparity in overall survival and mortality (OR 1.14, 95% CI 0.69 to 1.87, p=0.62) between the splenectomy cohort and the no splenectomy (required) cohort. Furthermore, relative to the no splenectomy (required) cohort, the splenectomy group showed a heightened incidence of overall post-operative complications (odds ratio (OR) 1.66, 95% CI 1.65 to 2.61, p=0.03), an extended duration of hospitalization (mean difference (MD) 2.88 days, 95% CI 2.09 to 3.67), an increased interval from surgery to the initiation of adjuvant chemotherapy (MD 4.44 days, 95% CI 2.41 to 6.07, p<0.0001), and a greater probability of undergoing reoperation (OR 4.7, 95% CI 1.91 to 11.55, p=0.0007). However, concerning the occurrence of specific post-operative complications such as anastomotic leakage (OR 0.97, 95% CI 0.33 to 2.84, p=0.95), pancreatic fistula (OR 3.25, 95% CI 0.63 to 16.7, p=0.16), abdominal abscess (OR 1.75, 95% CI 0.25 to 12.33, p=0.57), sepsis (OR 1.46, 95% CI 0.77 to 2.77, p=0.25), and thrombotic events (OR 1.82, 95% CI 0.93 to 3.57, p=0.08), no significant differences were observed between the two cohorts. CONCLUSION: Splenectomy does not impact the overall survival and mortality of patients with ovarian cancer. Thus, it can be considered an acceptably safe procedure to obtain optimal cytoreduction. However, caution should be taken when selecting patients for splenectomy because it is associated with an increased incidence of overall post-operative complications, prolonged hospital stays, delayed initiation of adjuvant chemotherapy, and an increased probability of requiring subsequent surgical interventions.

Functional disability and receipt of informal care among Chinese adults living alone with cognitive impairment.

BACKGROUND: Adults with cognitive impairment are prone to living alone in large numbers but receive relatively little attention. This study aimed to evaluate whether living alone with cognitive impairment was associated with a higher burden of functional disability but lack of informal care. METHODS: 982 observations of adults living alone with cognitive impairment and 50,695 observations of adults living with others and with normal cognition were identified from 4 waves (2011/2012, 2013, 2015, and 2018) of the China Health and Retirement Longitudinal Study (CHARLS). A matched comparator was selected using propensity score matching (1:2). Functional disability included disability in Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL), and mobility. The time of receiving informal care was measured in monthly hours. RESULTS: Adults living alone with cognitive impairment demonstrated significantly higher odds ratio of ADL disability (OR = 1.59, 95 % CI: 1.30, 1.95), IADL disability (OR = 1.19, 95 % CI: 1.00, 1.44), mobility disability (OR = 1.38, 95 % CI: 1.12, 1.70), but received fewer hours of informal care (ß = -127.7 h per month, standard error = 25.83, P < 0.001), compared to the adults living with others and with normal cognition. CONCLUSIONS: This study highlights the high burden of functional disability but low coverage of informal care among Chinese adults living alone with cognitive impairment and calls for more resources to be allocated to this vulnerable subpopulation to improve the functional health and to increase the provision of long-term care services.

Vitamin D supplementation during pregnancy and the role of maternal prenatal depression.

BACKGROUND: The current study sought to investigate the correlation between vitamin D supplementation in pregnant women with vitamin D deficiency in early pregnancy and the incidence of prenatal depression prior to delivery. METHODS: This is a retrospective, single-center study that was conducted at a tertiary hospital in Chengdu, China. We conducted an analysis on pregnant women who were initially diagnosed with vitamin D deficiency at 12-14 weeks of gestation. After starting vitamin D supplementation at a dose of 800 IU daily from 14 weeks onwards, we measured both their vitamin D concentration and depression scores again during median gestational week 39 prior to delivery. RESULTS: The study cohort comprised 1365 women who had been diagnosed with vitamin D deficiency at 12-14 weeks of gestation between November 1st, 2021 to November 1st, 2022. 537 pairs were matched based on a propensity score to control for other confounding factors. After propensity score matching, the baseline vitamin D levels were made consistent between the groups (P = 0.512). The incidence of depression in patients in vitamin D deficiency group following vitamin D supplementation was significantly higher than insufficiency group and reached statistical significance (P < 0.001). Additionally, we observed that serum 25-(OH) D concentration achieving insufficiency status after supplementation was 59.12%. CONCLUSION: Our study indicates that daily supplementation of 800IU of vitamin D can improve the depressive symptoms of individuals who are vitamin D deficiency during early pregnancy but achieve vitamin D insufficiency after supplementation during prenatal period.

Causal associations between psoriasis, eczema, urticaria, and mental illness: A bidirectional Mendelian randomization study of the European population.

Observational studies have reported a relationship between multiple common dermatoses and mental illness. To assess the potential bidirectional causality between 3 skin disorders (psoriasis, eczema, and urticaria) and 4 psychiatric disorders (bipolar disorder, schizophrenia, major depressive disorder, and anxiety) in the European population, we used Mendelian randomization (MR) analysis, which provides definitive evidence for causal inference. Eligible single nucleotide polymorphisms were screened for dermatological and psychiatric disorders using a genome-wide association study database. We conducted bidirectional, 2-sample MR analysis using instrumental variables related to psoriasis, eczema, and urticaria as exposure factors, and bipolar disorder, schizophrenia, major depression, and anxiety as outcomes. Reverse MR analysis with bipolar disorder, schizophrenia, major depression, and anxiety as exposure and psoriasis, eczema, and urticaria as outcomes were also performed, and the causality was analyzed using inverse-variance weighting (IVW), MR-Egger, and weighted median methods. To thoroughly assess causality, sensitivity analyses were conducted using the IVW, MR-PRESSO, and MR-Egger methods. The results showed that bipolar disorder increased the incidence of psoriasis (odds ratio = 1.271, 95% confidence interval = 1.003-1.612, P = .047), heterogeneity test with Cochran Q test in the IVW showed P value > .05, (P = .302), the MR-Pleiotropy and MR-PRESSO (outlier methods) in the multiplicity test showed P value > .05, (P = .694; P = .441), and MR-Pleiotropy evidence showed no apparent intercept (intercept = -0.060; SE = 0.139; P = .694). Major depression increased the risk of eczema (odds ratio = 1.002, 95% confidence interval = 1.000-1.004, P = .024), heterogeneity test showed P value > .05, (P = .328), multiplicity detection showed P value > .05, (P = .572; P = .340), and MR-Pleiotropy evidence showed no apparent intercept (intercept = -0.099; SE = 0.162; P = .572). Sensitivity analyses of the above results were reliable, and no heterogeneity or multiplicity was found. This study demonstrated a statistically significant causality between bipolar disorder and psoriasis, major depression, and eczema in a European population, which could provide important information for physicians in the clinical management of common skin conditions.