Treg cell-derived osteopontin promotes microglia-mediated white matter repair after ischemic stroke.

The precise mechanisms underlying the beneficial effects of regulatory T (Treg) cells on long-term tissue repair remain elusive. Here, using single-cell RNA sequencing and flow cytometry, we found that Treg cells infiltrated the brain 1 to 5 weeks after experimental stroke in mice. Selective depletion of Treg cells diminished oligodendrogenesis, white matter repair, and functional recovery after stroke. Transcriptomic analyses revealed potent immunomodulatory effects of brain-infiltrating Treg cells on other immune cells, including monocyte-lineage cells. Microglia depletion, but not T cell lymphopenia, mitigated the beneficial effects of transferred Treg cells on white matter regeneration. Mechanistically, Treg cell-derived osteopontin acted through integrin receptors on microglia to enhance microglial reparative activity, consequently promoting oligodendrogenesis and white matter repair. Increasing Treg cell numbers by delivering IL-2:IL-2 antibody complexes after stroke improved white matter integrity and rescued neurological functions over the long term. These findings reveal Treg cells as a neurorestorative target for stroke recovery.

D3EGFR: a webserver for deep learning-guided drug sensitivity prediction and drug response information retrieval for EGFR mutation-driven lung cancer.

As key oncogenic drivers in non-small-cell lung cancer (NSCLC), various mutations in the epidermal growth factor receptor (EGFR) with variable drug sensitivities have been a major obstacle for precision medicine. To achieve clinical-level drug recommendations, a platform for clinical patient case retrieval and reliable drug sensitivity prediction is highly expected. Therefore, we built a database, D3EGFRdb, with the clinicopathologic characteristics and drug responses of 1339 patients with EGFR mutations via literature mining. On the basis of D3EGFRdb, we developed a deep learning-based prediction model, D3EGFRAI, for drug sensitivity prediction of new EGFR mutation-driven NSCLC. Model validations of D3EGFRAI showed a prediction accuracy of 0.81 and 0.85 for patients from D3EGFRdb and our hospitals, respectively. Furthermore, mutation scanning of the crucial residues inside drug-binding pockets, which may occur in the future, was performed to explore their drug sensitivity changes. D3EGFR is the first platform to achieve clinical-level drug response prediction of all approved small molecule drugs for EGFR mutation-driven lung cancer and is freely accessible at https://www.d3pharma.com/D3EGFR/index.php.

lncCPSET1 acts as a scaffold for MLL2/COMPASS to regulate Bmp4 and promote the formation of chicken primordial germ cells.

Primordial germ cells (PGCs) are the ancestors of female and male germ cells. Recent studies have shown that long non-coding RNA (lncRNA) and histone methylation are key epigenetic factors affecting PGC formation; however, their joint regulatory mechanisms have rarely been studied. Here, we explored the mechanism by which lncCPSET1 and H3K4me2 synergistically regulate the formation of chicken PGCs for the first time. Combined with chromatin immunoprecipitation (CHIP) sequencing and RNA-seq of PGCs transfected with the lncCPSET1 overexpression vector, GO annotation and KEGG enrichment analysis revealed that Wnt and TGF-ß signaling pathways were significantly enriched, and Fzd2, Id1, Id4, and Bmp4 were identified as candidate genes. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) showed that ASH2L, DPY30, WDR5, and RBBP5 overexpression significantly increased the expression of Bmp4, which was up-regulated after lncCPSET1 overexpression as well. It indicated that Bmp4 is a target gene co-regulated by lncCPSET1 and MLL2/COMPASS. Interestingly, co-immunoprecipitation results showed that ASH2L, DPY30 and WDR5 combined and RBBP5 weakly combined with DPY30 and WDR5. lncCPSET1 overexpression significantly increased Dpy30 expression and co-immunoprecipitation showed that interference/overexpression of lncCPSET1 did not affect the binding between the proteins in the complexes, but interference with lncCPSET1 inhibited DPY30 expression, which was confirmed by RNA immunoprecipitation that lncCPSET1 binds to DPY30. Additionally, CHIP-qPCR results showed that DPY30 enriched in the Bmp4 promoter region promoted its transcription, thus promoting the formation of PGCs. This study demonstrated that lncCPSET1 and H3K4me2 synergistically promote PGC formation, providing a reference for the study of the regulatory mechanisms between lncRNA and histone methylation, as well as a molecular basis for elucidating the formation mechanism of PGCs in chickens.

Efficacy difference of antipsychotics in Alzheimer's disease and schizophrenia: explained with network efficiency and pathway analysis methods.

Approximately 50% of Alzheimer's disease (AD) patients will develop psychotic symptoms and these patients will experience severe rapid cognitive decline compared with those without psychosis (AD-P). Currently, no medication has been approved by the Food and Drug Administration for AD with psychosis (AD+P) specifically, although atypical antipsychotics are widely used in clinical practice. These drugs have demonstrated modest efficacy in managing psychosis in individuals with AD, with an increased frequency of adverse events, including excess mortality. We compared the differences between the genetic variations/genes associated with AD+P and schizophrenia from existing Genome-Wide Association Study and differentially expressed genes (DEGs). We also constructed disease-specific protein-protein interaction networks for AD+P and schizophrenia. Network efficiency was then calculated to characterize the topological structures of these two networks. The efficiency of antipsychotics in these two networks was calculated. A weight adjustment based on binding affinity to drug targets was later applied to refine our results, and 2013 and 2123 genes were identified as related to AD+P and schizophrenia, respectively, with only 115 genes shared. Antipsychotics showed a significantly lower efficiency in the AD+P network than in the schizophrenia network (P < 0.001) indicating that antipsychotics may have less impact in AD+P than in schizophrenia. AD+P may be caused by mechanisms distinct from those in schizophrenia which result in a decreased efficacy of antipsychotics in AD+P. In addition, the network analysis methods provided quantitative explanations of the lower efficacy of antipsychotics in AD+P.

Trophectoderm grade is associated with the risk of placenta previa in frozen-thawed single-blastocyst transfer cycles.

STUDY QUESTION: Do obstetric and perinatal complications vary according to different blastocyst developmental parameters after frozen-thawed single-blastocyst transfer (SBT) cycles? SUMMARY ANSWER: Pregnancies following the transfer of a blastocyst with a grade C trophectoderm (TE) were associated with an increased risk of placenta previa compared to those with a blastocyst of grade A TE. WHAT IS KNOWN ALREADY: Existing studies investigating the effect of blastocyst morphology grades on birth outcomes have mostly focused on fetal growth and have produced conflicting results, while the risk of obstetric complications has rarely been reported. Additionally, growing evidence has suggested that the appearance of TE cells could serve as the most important parameter for predicting implantation and live birth. Given that the TE ultimately develops into the placenta, it is plausible that this independent predictor may also impact placentation. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study at a tertiary-care academic medical center included 6018 singleton deliveries after frozen-thawed SBT cycles between January 2017 and December 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: Singleton pregnancies were grouped into two groups according to blastocyst developmental stage (Days 5 and 6), four groups according to embryo expansion (Stages 3, 4, 5, and 6), three groups according to inner cell mass (ICM) quality (A, B, and C), and three groups according to TE quality (A, B, and C). The main outcomes included pregnancy-induced hypertension, preeclampsia, gestational diabetes mellitus, preterm premature rupture of membrane, placenta previa, placental abruption, placenta accreta, postpartum hemorrhage, preterm birth, low birth weight, small for gestational age, and birth defects. Multivariate logistic regressions were performed to evaluate the effect of blastocyst developmental stage, embryo expansion stage, ICM grade, and TE grade on measured outcomes adjusting for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE: No association was found between blastocyst developmental stage and obstetric or perinatal outcomes both before and after adjusting for potential confounders, and similar results were found with regard to embryo expansion stage and ICM grade. Meanwhile, the incidence of placenta previa derived from a blastocyst with TE of grade C was higher compared with those derived from a blastocyst with TE of grade A (1.7%, 2.4%, and 4.0% for A, B, and C, respectively, P = 0.001 for all comparisons). After adjusting for potential covariates, TE grade C blastocysts had 2.81 times the likelihood of resulting in placenta previa compared to TE grade A blastocysts (adjusted odds ratio 2.81, 95% CI 1.11-7.09). No statistically significant differences were detected between any other measured outcomes and TE grades both before or after adjustment. LIMITATIONS, REASONS FOR CAUTION: The study is limited by its retrospective, single-center design. Additionally, although the sample size was relatively large for the study group, the sample size for certain subgroups was relatively small and lacked adequate power, particularly the ICM grade C group. Therefore, these results should be interpreted with caution. WIDER IMPLICATIONS OF THE FINDINGS: The study extends our knowledge of the potential downstream effect of TE grade on placental abnormalities. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Key Research and Development Program of China (2023YFC2705500, 2023YFC2705501, 2023YFC2705505, 2019YFA0802604); National Natural Science Foundation of China (82130046, 82320108009, 82371660, 32300710); Shanghai leading talent program, Innovative research team of high-level local universities in Shanghai (SHSMU-ZLCX20210201, SHSMU-ZLCX20210200, SHSMU-ZLCX20180401), Shanghai Jiaotong University School of Medicine Affiliated Renji Hospital Clinical Research Innovation Cultivation Fund Program (RJPY-DZX-003), Science and Technology Commission of Shanghai Municipality (23Y11901400), Shanghai's Top Priority Research Center Construction Project (2023ZZ02002), and Three-Year Action Plan for Strengthening the Construction of the Public Health System in Shanghai (GWVI-11.1-36). The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Effects of SARS-COV-2 infection during the frozen-thawed embryo transfer cycle on embryo implantation and pregnancy outcomes.

STUDY QUESTION: Does severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the frozen-thawed embryo transfer (FET) cycle affect embryo implantation and pregnancy rates? SUMMARY ANSWER: There is no evidence that SARS-CoV-2 infection of women during the FET cycle negatively affects embryo implantation and pregnancy rates. WHAT IS KNOWN ALREADY: Coronavirus disease 2019 (COVID-19), as a multi-systemic disease, poses a threat to reproductive health. However, the effects of SARS-CoV-2 infection on embryo implantation and pregnancy following fertility treatments, particularly FET, remain largely unknown. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study, included women who underwent FET cycles between 1 November 2022 and 31 December 2022 at an academic fertility centre. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women who tested positive for SARS-CoV-2 during their FET cycles were included in the COVID-19 group, while those who tested negative during the same study period were included in the non-COVID-19 group. The primary outcome was ongoing pregnancy rate. Secondary outcomes included rates of implantation, biochemical pregnancy, clinical pregnancy, early pregnancy loss, and ongoing pregnancy. Multivariate logistic regression models were applied to adjust for potential confounders including age, body mass index, gravidity, vaccination status, and endometrial preparation regimen. Subgroup analyses were conducted by time of infection with respect to transfer (prior to transfer, 1-7 days after transfer, or 8-14 days after transfer) and by level of fever (no fever, fever <39°C, or fever ≥39°C). MAIN RESULTS AND THE ROLE OF CHANCE: A total of 243 and 305 women were included in the COVID-19 and non-COVID-19 group, respectively. The rates of biochemical pregnancy (58.8% vs 62.0%, P = 0.46), clinical pregnancy (53.1% vs 54.4%, P = 0.76), implantation (46.4% vs 46.2%, P = 0.95), early pregnancy loss (24.5% vs 26.5%, P = 0.68), and ongoing pregnancy (44.4% vs 45.6%, P = 0.79) were all comparable between groups with or without infection. Results of logistic regression models, both before and after adjustment, revealed no associations between SARS-CoV-2 infection and rates of biochemical pregnancy, clinical pregnancy, early pregnancy loss, or ongoing pregnancy. Moreover, neither the time of infection with respect to transfer (prior to transfer, 1-7 days after transfer, or 8-14 days after transfer) nor the level of fever (no fever, fever <39°C, or fever ≥39°C) was found to be related to pregnancy rates. LIMITATIONS, REASONS FOR CAUTION: The retrospective nature of the study is subject to possible selection bias. Additionally, although the sample size was relatively large for the COVID-19 group, the sample sizes for certain subgroups were relatively small and lacked adequate power, so these results should be interpreted with caution. WIDER IMPLICATIONS OF THE FINDINGS: The study findings suggest that SARS-CoV-2 infection during the FET cycle in females does not affect embryo implantation and pregnancy rates including biochemical pregnancy, clinical pregnancy, early pregnancy loss, and ongoing pregnancy, indicating that cycle cancellation due to SARS-CoV-2 infection may not be necessary. Further studies are warranted to verify these findings. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Key Research and Development Program of China (2023YFC2705500, 2019YFA0802604), National Natural Science Foundation of China (82130046, 82101747), Shanghai leading talent program, Innovative research team of high-level local universities in Shanghai (SHSMU-ZLCX20210201, SHSMU-ZLCX20210200, SSMU-ZLCX20180401), Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital Clinical Research Innovation Cultivation Fund Program (RJPY-DZX-003), Science and Technology Commission of Shanghai Municipality (23Y11901400), Shanghai Sailing Program (21YF1425000), Shanghai's Top Priority Research Center Construction Project (2023ZZ02002), Three-Year Action Plan for Strengthening the Construction of the Public Health System in Shanghai (GWVI-11.1-36), and Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (20161413). The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Activation of moderate autophagy promotes survival of fat graft.

Clinically unpredictable retention following fat grafting remains outstanding problems because of the unrevealed mechanism of grafted fat survival. The role of autophagy, a process to maintain cellular homeostasis through recycling cellular debris, has yet been to be reported in fat grafting. This study aims to improve the survival of fat grafting through the autophagy. First, the relationship between cell death and autophagy in the early stage of fat grafting was evaluated through immunostaining, RNA sequencing, and western blot. Next, rapamycin, an autophagic agonist, was used for the culturing of adipose-derived stem cells and adipocytes during ischemia. Cell death, autophagy, and reactive oxygen species (ROS) were assayed. Finally, rapamycin was used to assist fat grafting in nude mice. The results demonstrated that the peak of cell death at the early stage of fat grafting was accompanied by a decrease in autophagy. In vitro, during ischemia, 25 nM was confirmed as the optimal dose of rapamycin that reduces cell death with enhanced autophagy and mitophagy, improved mitochondrial quality as well as decreased ROS accumulation. In vivo, promoted mitophagy, alleviated oxidative stress, and decreased cell apoptosis of rapamycin-treated fat grafts were observed in the early stage. In addition, rapamycin increased the survival of fat grafts with increased neovascularization and reduced fibrosis. We suggested that moderate autophagy induced by rapamycin contribute to enhanced ischemic tolerance and long term survival of fat grafts through mitochondrial quality control.

Local glucose elevation activates pyroptosis via NLRP3 inflammasome in ovarian granulosa cells of overweight patients.

Overweight, with an increasing prevalence worldwide, significantly impairs the clinical outcomes following in vitro fertilization (IVF). Hyperglycemia, hyperlipidemia, and metabolic disorders are always accompanied by the majority of overweight patients. The association between granulosa cell function and metabolic alterations in follicular fluid including lipids, proteins, and growth factors has been extensively documented. However, the effects of higher glucose level on ovarian granulosa cells (GCs), remain largely unknown. In this study, we identified that overweight women had elevated follicular glucose level which profoundly activated NLRP3 inflammasome and pyroptosis. An in vitro correlation between follicular high glucose, NLRP3 inflammasome and pyroptosis was also established. More importantly, in granulosa cells of overweight patients, the activation of the NLRP3 inflammasome and pyroptosis induced by high glucose was involved in the dysregulation of estradiol synthesis. Our study may provide new options to interpretate and improve IVF outcomes in overweight women.

Successful treatment with oseltamivir phosphate in children with ITP who failed first-line therapy: a case series report.

Immune thrombocytopenia (ITP) is a common bleeding disorder in children. First-line medicines (glucocorticoids and immunoglobulin) may not be effective for some children, endangering their lives, posing challenges for healthcare facilities, and leading to an unfavorable prognosis. As a sialidase inhibitor, oseltamivir phosphate can reduce the destruction of platelets in liver macrophages by inhibiting the sialylation of platelets, and finally achieve the purpose of increasing platelet count. In this paper, three cases of children with ITP who failed first-line therapy and were cured by oral administration of oseltamivir phosphate granules were reported. The mechanism of action of oseltamivir phosphate granules was clarified.

Nonlinear relationship between vitamin D status on admission and bronchopulmonary dysplasia in preterm infants.

BACKGROUND: This research will explore non-linear relationship between vitamin D status on admission and bronchopulmonary dysplasia (BPD) in preterm infants. METHODS: Data were retrospectively collected on preterm infants ≤32 weeks gestation and ≥28 weeks gestation hospitalized in our hospital between Jan. 2019 and Jul. 2022, which were classified into BPD and non-BPD groups according to BPD diagnostic criteria. Independent influences between the two groups were staged using comparison of differences between groups, univariate analysis, multivariate analysis, smoothed curve fitting, and threshold effect staging. RESULTS: 255 preterm infants were enrolled in this research, including 135 males and 120 females, with a mean gestational age of 30.59 ± 0.86 weeks. Vitamin D status on admission was an independent protective factor for BPD in preterm infants, with a 6% reduction in the probability of BPD for every 1 ng/ml increase in vitamin D status on admission (p = 0.036). There was also a non-linear relationship, with each 1 ng/ml increase in vitamin D status on admission being associated with an 87% reduction in the incidence of BPD when vitamin D status was <12.82 ng/ml (p = 0.010). CONCLUSION: Vitamin D status on admission and BPD are non-linearly in preterm infants at 28-32 weeks gestation. IMPACT STATEMENT: Analyzing the relationship between vitamin D status on admission and BPD. A nonlinear relationship and turning point between vitamin D status on admission and BPD was derived by curve fitting and threshold effect. We provide a new reference point for vitamin D supplementation for the prevention of neonatal BPD and to avoid ineffective overmedication.

Effect of azilsartan on myocardial remodeling after acute myocardial infarction.

PURPOSE: To investigate the effect of azilsartan on myocardial remodeling after acute myocardial infarction (AMI). METHODS: A total of 200 AMI patients under percutaneous coronary intervention (PCI) were selected from the Affiliated Huaian No.1 People's Hospital of Nanjing Medical University from Jan 2021 to Dec 2021. The subjects were randomly divided to take either azilsartan or benazepril. Serum C1q tumor necrosis factor-associated protein 1 (CTRP1) levels were detected in all subjects after admission, and the indices of left ventricular end-diastolic volume (LVEDV), left ventricular end-diastolic diameter (LVEDD), and left ventricular ejection fraction (LVEF) were measured by using echocardiography. At the follow-up of 6 months and 1 year after PCI, the differences in CTRP1 and echocardiogram indices between the two groups were compared, and the influencing factors of myocardial remodeling after acute myocardial infarction were analyzed. RESULTS: The levels of LVEDV and CTRP1 in all subjects at 6 months and 1 year after PCI were lower than those before discharge, and the LVEDV in the azilsartan group at 6 months and 1 year after PCI was lower than that in the benazepril group. An improvement in myocardial remodeling was obviously observed within 6 months after PCI, but the effect declined over time. CONCLUSIONS: Azilsartan can improve myocardial remodeling after acute myocardial infarction. CTRP1 may become an effective target for the prevention and treatment of myocardial remodeling after acute myocardial infarction.

Cardiac-specific deletion of BRG1 ameliorates ventricular arrhythmia in mice with myocardial infarction.

Malignant ventricular arrhythmia (VA) after myocardial infarction (MI) is mainly caused by myocardial electrophysiological remodeling. Brahma-related gene 1 (BRG1) is an ATPase catalytic subunit that belongs to a family of chromatin remodeling complexes called Switch/Sucrose Non-Fermentable Chromatin (SWI/SNF). BRG1 has been reported as a molecular chaperone, interacting with various transcription factors or proteins to regulate transcription in cardiac diseases. In this study, we investigated the potential role of BRG1 in ion channel remodeling and VA after ischemic infarction. Myocardial infarction (MI) mice were established by ligating the left anterior descending (LAD) coronary artery, and electrocardiogram (ECG) was monitored. Epicardial conduction of MI mouse heart was characterized in Langendorff-perfused hearts using epicardial optical voltage mapping. Patch-clamping analysis was conducted in single ventricular cardiomyocytes isolated from the mice. We showed that BRG1 expression in the border zone was progressively increased in the first week following MI. Cardiac-specific deletion of BRG1 by tail vein injection of AAV9-BRG1-shRNA significantly ameliorated susceptibility to electrical-induced VA and shortened QTc intervals in MI mice. BRG1 knockdown significantly enhanced conduction velocity (CV) and reversed the prolonged action potential duration in MI mouse heart. Moreover, BRG1 knockdown improved the decreased densities of Na+ current (INa) and transient outward potassium current (Ito), as well as the expression of Nav1.5 and Kv4.3 in the border zone of MI mouse hearts and in hypoxia-treated neonatal mouse ventricular cardiomyocytes. We revealed that MI increased the binding among BRG1, T-cell factor 4 (TCF4) and ß-catenin, forming a transcription complex, which suppressed the transcription activity of SCN5A and KCND3, thereby influencing the incidence of VA post-MI.

Characteristics of innate and adaptive immune disorder in IgA nephropathy based on integrated bioinformatics.

BACKGROUND: Our study aims to investigate the immunological pathogenesis underlying immunoglobulin A nephropathy (IgAN) and explore potential biomarkers for IgAN diagnosis. MATERIALS AND METHODS: Differentially expressed genes (DEGs) of formalin-fixed and paraffin-embedded (FFPE) samples were screened between IgAN patients and healthy people based on GSE115857. Gene oncology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) enrichment was performed to identify related biological processes and pathways. CIBERSORT was utilized to seek the relationship of immune cell infiltration with IgAN. Finally, the expression of paraoxonase 2 (PON2) related to innate immune response was verified in FFPE samples of minimal change disease and IgAN patients by immunohistochemistry and PAS staining. RESULTS: 25 down-regulated genes and 12 up-regulated genes were identified in IgAN patients, which mainly responded to endothelial cell proliferation, inflammatory response, and angiogenesis. Toll-like receptor signaling pathway and Epstein-Barr virus (EBV) infection might be involved in IgAN pathogenesis. In addition, the infiltration of macrophages M0, naïve B cells, and follicular helper T (Tfh) cells was positively correlated in IgAN patients. Macrophages M1 and M2 infiltration were up-regulated in IgAN patients, which indicated that innate immune response was closely associated with IgAN. Besides, the results of immunohistochemistry showed that PON2 was obviously positively expressed in acute and chronic lesions of IgAN patients. CONCLUSION: In addition to abnormalities in the adaptive immune response, macrophages M1/M2 and innate immune disorder may participate in IgAN pathogenesis. PON2 may become the feasible targets for further investigation of IgAN.

Convergent and divergent intra- and internetwork connectivity in Parkinson's disease with wearing-off.

OBJECTIVE: Our study aimed to explore the functional connectivity alterations between cortical nodes of resting-state networks in Parkinson's disease (PD) patients with wearing-off (WO) at different levels. METHODS: Resting-state functional magnetic resonance imaging was performed on 36 PD patients without wearing-off (PD-nWO), 30 PD patients with wearing-off (PD-WO), and 35 healthy controls (HCs) to extract functional networks. Integrity, network, and edge levels were calculated for comparison between groups. UPDRS-III, MMSE, MOCA, HAMA, and HAMD scores were collected for further regression analysis. RESULTS: We observed significantly reduced connectivity strength in the dorsal attention network and limbic network in the PD-WO group compared with the HC group. The PD-WO group showed a decreased degree of functional connectivity at 12 nodes, including the bilateral orbital part of the superior frontal gyrus, right olfactory cortex, left medial orbital part of the superior frontal gyrus, bilateral gyrus rectus, right parahippocampal gyrus, right thalamus, left Heschl's gyrus, right superior temporal gyrus part of the temporal pole, left middle temporal gyrus part of the temporal pole, and right inferior temporal gyrus. Furthermore, the PD-WO group showed a significantly lower degree of functional connectivity in the left orbital part of the superior frontal gyrus and right gyrus rectus than the PD-nWO group. Internetwork analysis indicated reduced functional connectivity in five pairs of resting-state networks. CONCLUSION: Our results demonstrated altered intra- and internetwork connections in PD patients with WO. These findings will facilitate a better understanding of the distinction between the network changes in PD pathophysiology.

Relationship between lymphocytes and idiopathic macular hole.

BACKGROUND: An idiopathic macular hole (IMH) is a full-thickness anatomic defect extending from the internal limiting membrane to the photoreceptor layer of the macula without any known cause. Recently, clinical laboratory markers of systemic inflammatory status derived from complete blood counts have been evaluated in ocular diseases. This study aimed to explore whether they could predict the development and progression of IMHs. METHODS: A retrospective review of 36 patients with IMH and 36 sex-and-age-matched patients with cataracts was conducted. We collected complete blood counts of all participating individuals and calculated systemic immunoinflammatory indicators. The maximum base diameter of the IMH (BD), minimum diameter of the IMH (MIN), height of the IMH (H), area of the intraretinal cyst (IRC), and curve lengths of the detached photoreceptor arms were measured on optical coherence tomography (OCT) images. We used these values to calculate the macular hole index (MHI), tractional hole index (THI), diameter hole index (DHI), hole form factor (HFF), and macular hole closure index (MHCI). We performed a receiver operating characteristic (ROC) curve analysis of 30 patients with IMH who were followed up 1 month after surgery. RESULTS: Lymphocyte counts were significantly higher in the IMH group. No other significant differences were observed between the IMH and control groups. Lymphocyte counts in the IMH group were significantly negatively correlated with MIN and BD and were significantly positively correlated with MHI, THI, and MHCI. However, lymphocyte counts were not significantly correlated with H, IRC, DHI, and HFF. In the ROC analysis, BD, MIN, MHI, THI, and MHCI were significant predictors of anatomical outcomes. According to the cut-off points of the ROC analysis, lymphocyte counts were compared between the above-cut-off and below-cut-off groups. Lymphocyte counts were significantly higher in the MIN ≤ 499.61 µm, MHI ≥ 0.47, THI ≥ 1.2, and MHCI ≥ 0.81 groups. There were no significant differences between the above-cut-off and below-cut-off BD groups. CONCLUSIONS: Although inflammation may not be an initiating factor, it may be involved in IMH formation. Lymphocytes may play a relatively important role in tissue repair during the developmental and postoperative recovery phases of IMH.

The co-occurrence of sarcoidosis and anti-PLA2R-associated membranous nephropathy in a patient with underlying genetic susceptibility.

BACKGROUND: Sarcoidosis is a multisystemic inflammatory disease, characterized by the presence of non-caseating, epithelioid granulomas. Glomerular disease in patients with sarcoidosis is rare and membranous nephropathy (MN) is cited as the most common. The association between the two diseases remained unclear. This article reported a case of co-occurrence of sarcoidosis and anti-PLA2R-associated MN, to provide a possible relationship between these two entities. CASE PRESENTATION: A 61-year-old Chinese Han woman with a history of sarcoidosis was admitted to our hospital for nephrotic syndrome. Her sarcoidosis was diagnosed according to the adenopathy observed on the computed tomography scan and the biopsy of lymph nodes. The MN presented with nephrotic syndrome with a PLA2R antibody titer of 357RU/ml, and the final diagnosis was based on a renal biopsy. The patient's sarcoidosis was remitted after treatment with prednisone. One year later MN was diagnosed, and she was treated with prednisone combined with calcineurin inhibitors, based on a full dose of renin-angiotensin system (RAS) inhibitor. The patient's sarcoidosis had been in remission while the MN was recurrent, and her renal function deteriorated to end-stage renal disease 6 years later due to discontinuation of immunosuppression. A genetic test led to the identification of the HLA-DRB1*0301 and HLA-DRB1*150 genes associated with both sarcoidosis and MN, which provides a new possible explanation of the co-occurrence of these two diseases. CONCLUSION: This case suggested for the first time a potential genetic connection between idiopathic MN and sarcoidosis which needs further studies in the future.

The association between sex and neonatal respiratory distress syndrome.

BACKGROUND: To investigate the association between sex and neonatal respiratory distress syndrome (NRDS). METHODS: Neonates born at our hospital and transferred to the neonatal department within 1 h were retrospectively analyzed. Depending on whether they developed NRDS during their hospital stay, the neonates was divided into NRDS and non-NRDS groups. There were 142 neonates in the NRDS group (95 males and 47 females) and 310 neonates in the non-NRDS group (180 males and 140 females). The neonates' data on gestational age (GA), sex, birth weight, white blood cell count (WBC), platelet count (PLT), C-reactive protein (CRP), total immunoglobulin M (total IgM), gestational diabetes mellitus(GDM), antenatal steroids use, meconium-stained amniotic fluid, and preterm premature rupture of membranes(PPROM) were gathered. RESULTS: 452 neonates (265 males and 187 females) were involved for the purpose of collecting basic characteristic. Multivariate analysis, males had a 1.87 times higher risk of NRDS than females (P < 0.05) after controlling for the confounding effects of GA, birth weight, WBC, PLT, CRP, total IgM, GDM, antenatal steroids use, meconium-stained amniotic fluid, and PPROM. CONCLUSIONS: Sex was associated with NRDS; males had a considerably higher risk of NRDS than females.

Factors influencing C-reactive protein status on admission in neonates after birth.

OBJECTIVE: To explore the factors influencing C-reactive protein (CRP) status in neonates on admission after birth. METHODS: 820 newborns born and hospitalized at Xiangya Hospital of Central South University from Jan. 2020 to Dec. 2020 were retrospectively analyzed. Maternal medical history and medication use during pregnancy, neonatal demographic information and status at birth were collected through the electronic medical record system. Statistical software was used to analyze the possible relationship between perinatal factors and CRP on admission after birth. RESULTS: A total of 820 neonates were analyzed, including 463 males and 357 females with a mean gestational age (GA) of 36.07 ± 3.30 weeks. (1) Multifactor Logistic regression analysis: larger GA (OR: 1.13, 95%CI: 1.00-1.28, P = 0.042), premature rupture of membranes (PROM) ≥ 18 h (OR: 2.39, 95%CI: 1.35-4.23, P = 0.003) and maternal autoimmune diseases (OR: 5.30, 95%CI: 2.15-13.07, P < 0.001) were independent risk factors for CRP ≥ 8 mg/L. Cesarean delivery (OR 0.40, 95%CI: 0.26-0.60, P < 0.001) was independent protective factor for CRP ≥ 8 mg/L. (2) Threshold effect analysis: A non-linear relationship was found between GA and CRP. When GA is less than 33.9 weeks, the risk of CRP ≥ 8 mg/L was reduced by 28% with one week increased (P < 0.001), and when GA is more than 33.9 weeks, the risk of CRP ≥ 8 mg/L was increased by 61% with one week increased (P < 0.001). CONCLUSIONS: GA, PROM, maternal autoimmune diseases and cesarean delivery were all independent influences neonatal CRP ≥ 8 mg/L on admission, and there was a nonlinear relationship between GA and neonatal CRP ≥ 8 mg/L on admission.

Application of Kirschner wire placement guided technology in paediatric supracondylar humerus fractures.

BACKGROUND: To analyze the clinical efficacy of K-wire placement guided technology in paediatric supracondylar humerus fractures. METHODS: A retrospective study was conducted in 105 patients who underwent closed reduction and percutaneous pinning surgeries in our hospital from June 2019 to August 2022. 54 patients treated with a assisted reduction fixation device to assist in closed reduction and percutaneous K-wire cross-fixation were allocated into the Non-guided group, and 51 patients with K-wire placement guided technology to guide K-wire placement were assigned into the Guided group. The operation duration, number of disposable K-wire placement, intraoperative fluoroscopy frequency, Baumann angle, carrying angle, fracture healing time and Flynn score of elbow joint function at the final follow-up were compared between two groups. The postoperative complications of two groups were recorded. RESULTS: There were significant differences between two groups in terms of operation duration, intraoperative fluoroscopy frequency, and disposable K-wire placement rate (p < 0. 05), while no significant differences of Baumann angle, carrying angle and the fracture healing time between two groups were observed (p > 0. 05). In the control group, ulnar nerve injury in 2 case, pin site infection in 4 cases, mild cubitus varus in 2 cases and loss of reduction in 4 cases were detected. In the study group, ulnar nerve injury in 1 case, pin site infection in 2 cases and loss of reduction in 1 case was observed. There was no significant difference in Flynn scores between two groups. CONCLUSION: K-wire placement guided technology is simple and convenient. The application of K-wire placement guided technology could relatively improved disposable K-wire placement rate, shorten the intraoperative fluoroscopy frequencies and reduce complication rates.

A Kalirin missense mutation enhances dendritic RhoA signaling and leads to regression of cortical dendritic arbors across development.

Normally, dendritic size is established prior to adolescence and then remains relatively constant into adulthood due to a homeostatic balance between growth and retraction pathways. However, schizophrenia is characterized by accelerated reductions of cerebral cortex gray matter volume and onset of clinical symptoms during adolescence, with reductions in layer 3 pyramidal neuron dendritic length, complexity, and spine density identified in multiple cortical regions postmortem. Nogo receptor 1 (NGR1) activation of the GTPase RhoA is a major pathway restricting dendritic growth in the cerebral cortex. We show that the NGR1 pathway is stimulated by OMGp and requires the Rho guanine nucleotide exchange factor Kalirin-9 (KAL9). Using a genetically encoded RhoA sensor, we demonstrate that a naturally occurring missense mutation in Kalrn, KAL-PT, that was identified in a schizophrenia cohort, confers enhanced RhoA activitation in neuronal dendrites compared to wild-type KAL. In mice containing this missense mutation at the endogenous locus, there is an adolescent-onset reduction in dendritic length and complexity of layer 3 pyramidal neurons in the primary auditory cortex. Spine density per unit length of dendrite is unaffected. Early adult mice with these structural deficits exhibited impaired detection of short gap durations. These findings provide a neuropsychiatric model of disease capturing how a mild genetic vulnerability may interact with normal developmental processes such that pathology only emerges around adolescence. This interplay between genetic susceptibility and normal adolescent development, both of which possess inherent individual variability, may contribute to heterogeneity seen in phenotypes in human neuropsychiatric disease.