Post-stroke depression is a common complication after a stroke. Based on the theory of ＂deficiency of heart qi leading to sadness＂recorded in Huangdi Neijing, our team proposes that deficiency of heart qi is the basic pathogenesis of post-stroke depression, with sadness being its main manifestation. Therefore, we advocate treating post-stroke depression from the perspective of the heart, and clinically, it can be divided into four stages: heart-liver stage, heart-lung stage, heart-spleen stage, and heart-kidney stage. Treating post-stroke depression with the principle of regulating qi and nourishing the heart, patients in the heart-liver and heart-lung stages are mainly middle-aged and young adults, with a pathological nature of qi stagnation and mild deficiency of heart qi, and therefore, the method of promoting the flow of meridians and regulating qi should be adopted. In contrast, patients in the heart-spleen and heart-kidney stages are mainly middle-aged and elderly, with a pathological nature of qi deficiency and severe deficiency of heart qi, and therefore, nourishment and tonification should be prioritized. In response to the above four stages, our team has achieved good clinical efficacy by administering Xiaoyao Powder, Baihe Dihuang Decoction, Ganmai Dazao Decoction and Jingui Shenqi Pill respectively. This study discusses the approach to treating post-stroke depression from the perspective of a "deficiency of heart qi leading to sadness" by examining three aspects: the theoretical basis of Chinese and Western medicine to treat post-stroke depression from the heart, the basic pathogenesis and staging of post-stroke depression, and the treatment principle of regulating qi and nourishing the heart. The study also briefly analyzes the clinical experience of the medications used for this condition to provide a reference for the treatment of post-stroke depression.

Objective:To investigate the causal association between immune cell and different types of sepsis by using Mendelian randomization (MR) method, and to find the immune cell phenotypes causally associated with sepsis.Methods:Summary data for various circulating immune cell phenotypes were obtained from the GWAS catalog (GCST90001391-GCST90002121). Sepsis data were sourced from the UK Biobank database. Single nucleotide polymorphisms (SNP) were used as instrumental variables. The correlation threshold of P < 5×10 -6 was used to identify the strongly correlated instrumental variables, and the code was used to remove the linkage disequilibrium and the instrumental variables with F-value < 10. Inverse variance weighting (IVW) was used as the main research method to evaluate the stability and reliability of the results, including Cochran's Q test, MR-Egger regression and Leave one out. Reverse MR analysis was performed based on the immunophenotypic results of the removal of horizontal pleiotropy, and the immune cell phenotype with one-way causal association was obtained. Odds ratio ( OR) and 95% confidence interval (95% CI) were used to represent the effect value of the results. Results:CD16 on CD14 -CD16 + monocyte had horizontal pleiotropy in sepsis ( OR = 0.965?4, 95% CI was 0.933?5-0.998?3, P = 0.039?6). There were five immunophenotypes that had reverse causal associations with the types associated with sepsis. After excluding immune cell phenotypes with horizontal pleiotropy and reverse causation, a total of 42 immune cell phenotypes with sepsis, 36 immune cell phenotypes with sepsis (28-day death in critical care), 32 immune cell phenotypes with sepsis (critical care), 44 immune cell phenotypes with sepsis (28-day death), and 30 immune cell phenotypes had potential causal associations with sepsis (under 75 years old). After false discovery rate (FDR) correction, the correlations between BAFF-R on IgD - CD38br and sepsis (28-day death) were negative and strong ( OR = 0.737?8, 95% CI was 0.635?9-0.856?0, P = 6.05×10 -5, PFDR = 0.044?2). Conclusion:A variety of immune cell phenotypes may have a protective effect on sepsis, especially BAFF-R on IgD - CD38br expression is negatively correlated with sepsis (28-day death), which provides a new idea for immune modulation therapy in sepsis.

Objective:To study the role of a novel brain-derived peptide hypoxic-ischemic brain damage associated peptide (HIBDAP) in regulating pyroptosis of oxygen-glucose deprived (OGD) microglia.Methods:The sequence of HIBDAP was coupled with the sequence of cell-penetrating peptide transactivator of transcription (TAT) to form TAT-HIBDAP. Fluorescein isothiocyanate (FITC) labeled TAT-HIBDAP was added to microglia cells and observed under fluorescence microscope. Microglia cells were treated with different concentrations of TAT-HIBDAP (1, 5, 10, 20 μmol/L) and then OGD process. Cell pyroptosis was analyzed using lactate dehydrogenase (LDH) assay. The concentration of TAT-HIBDAP with the most prominent inhibiting effects was determined and selected for subsequent experiments. The pyroptosis morphology of the control group, the OGD group and the HIBDAP group (5 μmol/L TAT-HIBDAP+OGD) was observed using transmission electron microscope. The mRNA and protein expression of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasomes were examined using real-time quantitative PCR and Western Blot analysis.Results:Fluorescence microscope showed FITC-labeled TAT-HIBDAP could successfully enter microglia cells. Compared with the OGD group, low concentrations of TAT-HIBDAP (1, 5, 10 μmol/L) could significantly reduce microglia pyroptosis and the concentration of 5 μmol/L showed the most prominent effects. Compared with the control group, OGD group showed typical pyroptosis morphology and HIBDAP group showed significantly improved morphology. The mRNA and protein expression of NLRP3 inflammasomes in the OGD group were significantly higher than the control group and also the HIBDAP group.Conclusions:The novel brain-derived peptide HIBDAP may reduce the expression of NLRP3 inflammasomes and inhibit the pyroptosis of OGD microglia.

Early distinction of bipolar disorder (BD) from major depressive disorder (MDD) is difficult since no tools are available to estimate the risk of BD. In this study, we aimed to develop and validate a model of oxidative stress injury for predicting BD. Data were collected from 1252 BD and 1359 MDD patients, including 64 MDD patients identified as converting to BD from 2009 through 2018. 30 variables from a randomly-selected subsample of 1827 (70%) patients were used to develop the model, including age, sex, oxidative stress markers (uric acid, bilirubin, albumin, and prealbumin), sex hormones, cytokines, thyroid and liver function, and glycolipid metabolism. Univariate analyses and the Least Absolute Shrinkage and Selection Operator were applied for data dimension reduction and variable selection. Multivariable logistic regression was used to construct a model for predicting bipolar disorder by oxidative stress biomarkers (BIOS) on a nomogram. Internal validation was assessed in the remaining 784 patients (30%), and independent external validation was done with data from 3797 matched patients from five other hospitals in China. 10 predictors, mainly oxidative stress markers, were shown on the nomogram. The BIOS model showed good discrimination in the training sample, with an AUC of 75.1% (95% CI: 72.9%-77.3%), sensitivity of 0.66, and specificity of 0.73. The discrimination was good both in internal validation (AUC 72.1%, 68.6%-75.6%) and external validation (AUC 65.7%, 63.9%-67.5%). In this study, we developed a nomogram centered on oxidative stress injury, which could help in the individualized prediction of BD. For better real-world practice, a set of measurements, especially on oxidative stress markers, should be emphasized using big data in psychiatry.
Biomarkers/metabolism* ; Bipolar Disorder/metabolism* ; Depressive Disorder, Major/diagnosis* ; Early Diagnosis ; Humans ; Oxidative Stress

To investigate the distribution and clinical significance of nuclear dense fine speckled (DFS) pattern in various diseases. A total of 95 289 patients who received DFS tests at Peking Union Medical College Hospital from January 2019 to December 2020 were included in this study. The results of indirect immunofluorescence assay (IIF) for detection of antinuclear antibody (ANA) were evaluated. The positive rates of ANA and DFS were 39.60% (37 733/95 289) and 1.19% (1 139/95 289) respectively. The positive rate of DFS in ANA-positive patients was 3.02% (1 139/37 733). DFS and ANA positivity were significantly different among different age groups rather than gender. The positivity rate of DFS reached the peak (55.57%, 633/1 139) in young patients between 21-40 years, while positive ANA with negative DFS was mainly observed in patients between 41-60 years (37.26%, 13 636/36 594). Additionally, single ANA-positivity were mainly detected in rheumatology department (59.23%, 18 402/31 066), whereas positive DFS was more common in obstetrics and gynecology department (3.08%, 49/1 593). There were 82.88% (944/1 139) patients with positive DFS diagnosed with non-autoimmune disease (non-AID), and 19.49%(222/1 139) with dermatosis. Positive DFS with higher titer (≥1∶320) was detected more frequently in autoimmune disease (AID) patients (5.13%, 10/195) than in non-AID patients (1.69%, 16/944) ( P<0.05). The DFS pattern is rare in ANA positive patients, which is mainly observed in women between 21-49 years. High titer of DFS is prevalent in AID patients, but positive DFS is detected more in non-AID patients, especially those with dermatosis.

Background and Objectives: Induced pluripotent stem cells (iPSCs) are usually generated by reprogramming differentiated cells through the introduction of specific transcription factors, but this is a difficult and inefficient process.Valproic acid (VPA) is a histone deacetylase inhibitor that significantly improves the efficiency of iPSC generation.But its role and mechanism are still unclear. Methods: and Results: We transduced Bactrian camel fetal fibroblasts (BCFFs) with retroviruses carrying defined factors (OCT4, SOX2, KLF4, c-MYC and EGFP; OSKMG) in the presence of VPA. Cells were collected (Day 7) and analyzed using RNA-seq technology. Afterwards, different groups of cells and transcriptomics results were detected by PCR and qRT-PCR technology. The results showed that VPA promoted the expression of the endogenous gene c-Myc and inhibited cell proliferation; at the same time, it promoted the expression of VEGF and other genes related to angiogenesis. Conclusions When VPA is added to the culture medium, only the cells that have begun to reprogram can break the G2/M repression through the expression of the endogenous gene c-Myc, and use the nutrients and space in the culture dish to proliferate normally, which can achieve the purpose of directly improving the efficiency of reprogramming.Another new discovery for Bactrian camels, VPA significantly increased the expression of VEGFC and other genes, promoting the transformation of fibroblasts to endothelial cells (different from the mesenchymal-to-epithelial transition process of other species) to accelerate the early induction of Bactrian camels iPSc process. Overall, this study proved the new mechanism of VPA in enhancing the induction of pluripotency from the transcriptome level.

Background and Objectives: Induced pluripotent stem cells (iPSCs) are usually generated by reprogramming differentiated cells through the introduction of specific transcription factors, but this is a difficult and inefficient process.Valproic acid (VPA) is a histone deacetylase inhibitor that significantly improves the efficiency of iPSC generation.But its role and mechanism are still unclear. Methods: and Results: We transduced Bactrian camel fetal fibroblasts (BCFFs) with retroviruses carrying defined factors (OCT4, SOX2, KLF4, c-MYC and EGFP; OSKMG) in the presence of VPA. Cells were collected (Day 7) and analyzed using RNA-seq technology. Afterwards, different groups of cells and transcriptomics results were detected by PCR and qRT-PCR technology. The results showed that VPA promoted the expression of the endogenous gene c-Myc and inhibited cell proliferation; at the same time, it promoted the expression of VEGF and other genes related to angiogenesis. Conclusions When VPA is added to the culture medium, only the cells that have begun to reprogram can break the G2/M repression through the expression of the endogenous gene c-Myc, and use the nutrients and space in the culture dish to proliferate normally, which can achieve the purpose of directly improving the efficiency of reprogramming.Another new discovery for Bactrian camels, VPA significantly increased the expression of VEGFC and other genes, promoting the transformation of fibroblasts to endothelial cells (different from the mesenchymal-to-epithelial transition process of other species) to accelerate the early induction of Bactrian camels iPSc process. Overall, this study proved the new mechanism of VPA in enhancing the induction of pluripotency from the transcriptome level.

Objective:To explore the will of the aged to participate in long-term care insurance in Qinhuangdao and its influencing factors under the background of aging of population.Methods:From April to May 2019, we selected 450 elderly people as subjects by stratified cluster random sampling in Qinhuangdao. All elderly people were investigated with the self-designed Long-term Care Insurance Need Questionnaire for the Aged. The individual characteristics, economic state and consciousness were analyzed with the methods of descriptive analysis, chi-square test and Logistic regression analysis.Results:A total of 445 valid questionnaires were collected. There were 60.7% (270/445) of aged with the wills to participate in long-term care insurance and 57.8% (156/270) of them hope the insurance mostly in cash or nursing service. Single factor analysis showed that there were statistical differences in the wills to participate in long-term care insurance among the aged with different ages, education levels, with or without a spouse, living situation, number of children, number of sons, primary caregivers, conscious health status, number of chronic diseases, number of hospitalizations in the past year, main source of income, monthly income, type of medical security, preference for care places (χ 2=50.228, 19.662, 26.504, 36.934, 16.456, 23.963, 44.482, 27.684, 24.783, 29.278, 22.313, 14.836, 10.446, 9.087; P<0.05) . Logistic regression analysis showed that the influencing factors of the will of the aged to participate in long-term care insurance included the ages, spouses and caregivers with statistical differences ( P<0.05) . Conclusions:Elderly people in Qinhuangdao are not willing to participate in long-term care insurance, and the elderly who are low age, have no spouse and have no caregivers are more willing to participate in long-term care insurance.

Objective This study aimed to assess the diagnostic value of anti-mutated citrullinated vimentin (MCV) antibodies in rheumatoid arthritis (RA) and its correlation with disease progression, extra-articular manifestations and overlap syndrome. Methods Retrospective Studies. Clinical data of 837 patients in PekingUnionMedicalCollegeHospitalfrom June to August 2017 were collected, including the result of anti-MCV, anti-cyclic citrullinated peptide (anti-CCP) antibodies, rheumatoid factor (RF), erythrocyte sedimentation rate (ESR) and High-sensitivity-C-reactive protein (CRP). According to the 1987 American College of Rheumatology classification criteria for rheumatoid arthritis, there were 323 patients diagnosed with RA, including 59 males and 264 females with the average age of 51 years. According to whether the RA patients have overlap syndrome with other autoimmune disease (AID) or have extra-articular manifestations, 258 cases were categorized into RA group, including 47 males and 211 females with the average age of 50 years; 14 cases were categorized into the group of overlap syndrome, including 1 male and 13 females with the average age of 36 years;51 cases were categorized into the group of extra-articular manifestations, including 11 males and 40 females with the average age of 59 years.According to 2010 rheumatoid arthritis classification criteria for destruction in joints, the radiographic changes were divided into 4 stages. There were 203 casesenrolled in our study, 88 caseswere fitted into early stage group (stage I)including 21 males and 67 females with the average age of 48 years; 115 caseswere fitted into progressive stage group, which compromisedstageⅡ (interim stage), stage Ⅲ (severe stage) and stage Ⅳ(final stage) cases, including 19 males and 96 females with the average age of 53 years. Mann-Whitney U test, x2 test, Receiver operating characteristic (ROC) curves and Spearmancorrelation coefficientwere used in Statistical analysis. Results Ⅰ Amongdiagnosed RA patients, 199 (61.6％) cases were positive for anti-MCV, anti-CCP and RFsimultaneously, 42 (13％) cases were positive for anti-MCV, which was higher than anti-CCP positive (1 cases, 0.3％) or RF positive (7cases, 2.2％). The difference was statistically significant(P<0.001, P<0.001). ⅡROC was calculated and MCV=35.95 U/ml was used as best-fit cut-off value. The AUC for anti-MCV was 0.867, while the sensitivity was 80.5％and specificity was 80.9％.ⅢThe detection levels of anti-MCV (682.8 (106.4-1000.0)), anti-CCP (407 (4.0-1536.0)) and RF (82.8 (21.1-244.9)) in the group of progressive stage were higher than those in the group of early stage (114.5 (28.5-1000.0), 62.5 (5.0-1020.7), 50.1 (6.7-127.1)), which showed a significant difference(P<0.05, P<0.05, P<0.05). The anti-MCV, anti-CCP and RF were positively related to the degree of joint destruction (r=0.229, P<0.05;r=0.187, P<0.05;r=0.167, P<0.05);anti-MCV and anti-CCP were positively related to extra-articular manifestation (r=0.152, P<0.05;r=0.136, P<0.05). Conclusion Anti-MCV antibodies are more sensitive in patients with RA, and have complementary diagnostic value for anti-CCP and RF-negative patients; high levels of anti-MCV and anti-CCP in RA patients are associated with RA progression and extra-articular involvement.

? Frailty is a multidimensional syndrome, reflecting the decline of the body's physiological reserve. The patients are often accompanied by a variety of diseases. The postoperative complications and mortality were significantly increased on frail patients due to improper anesthesia and perioperative management. Enhanced recovery after surgery optimizes perioperative treatment and achieves rapid recovery compared with traditional measures. However, perioperative management of patients with frailty is still in the exploratory stage. Common assessment methods for weakness are the debilitating phenotype and the debilitating index. This article focuses on the perioperative related problems of debilitated patients (low nutritional status, poor mental condition, complicated condition and many complications, multi-disciplinary collaboration, prone to fall and fall), and provide the basis for the frailty management of elderly medical workers.