In situ mapping identifies distinct vascular niches for myelopoiesis.

In contrast to nearly all other tissues, the anatomy of cell differentiation in the bone marrow remains unknown. This is owing to a lack of strategies for examining myelopoiesis-the differentiation of myeloid progenitors into a large variety of innate immune cells-in situ in the bone marrow. Such strategies are required to understand differentiation and lineage-commitment decisions, and to define how spatial organizing cues inform tissue function. Here we develop approaches for imaging myelopoiesis in mice, and generate atlases showing the differentiation of granulocytes, monocytes and dendritic cells. The generation of granulocytes and dendritic cells-monocytes localizes to different blood-vessel structures known as sinusoids, and displays lineage-specific spatial and clonal architectures. Acute systemic infection with Listeria monocytogenes induces lineage-specific progenitor clusters to undergo increased self-renewal of progenitors, but the different lineages remain spatially separated. Monocyte-dendritic cell progenitors (MDPs) map with nonclassical monocytes and conventional dendritic cells; these localize to a subset of blood vessels expressing a major regulator of myelopoiesis, colony-stimulating factor 1 (CSF1, also known as M-CSF)1. Specific deletion of Csf1 in endothelium disrupts the architecture around MDPs and their localization to sinusoids. Subsequently, there are fewer MDPs and their ability to differentiate is reduced, leading to a loss of nonclassical monocytes and dendritic cells during both homeostasis and infection. These data indicate that local cues produced by distinct blood vessels are responsible for the spatial organization of definitive blood cell differentiation.

Multi-omics to characterize the functional relationships of R-loops with epigenetic modifications, RNAPII transcription and gene expression.

Abnormal accumulation of R-loops results in replication stress, genome instability, chromatin alterations and gene silencing. Little research has been done to characterize functional relationships among R-loops, histone marks, RNA polymerase II (RNAPII) transcription and gene regulation. We built extremely randomized trees (ETs) models to predict the genome-wide R-loops using RNAPII and multiple histone modifications chromatin immunoprecipitation (ChIP)-seq, DNase-seq, Global Run-On sequencing (GRO-seq) and R-loop profiling data. We compared the performance of ET models to multiple machine learning approaches, and the proposed ET models achieved the best and extremely robust performances. Epigenetic profiles are highly predictive of R-loops genome-widely and they are strongly associated with R-loop formation. In addition, the presence of R-loops is significantly correlated with RNAPII transcription activity, H3K4me3 and open chromatin around the transcription start site, and H3K9me1 and H3K9me3 around the transcription termination site. RNAPII pausing defects were correlated with 5'R-loops accumulation, and transcriptional termination defects and read-throughs were correlated with 3'R-loops accumulation. Furthermore, we found driver genes with 5'R-loops and RNAPII pausing defects express significantly higher and genes with 3'R-loops and read-through transcription express significantly lower than genes without R-loops. These driver genes are enriched with chromosomal instability, Hippo-Merlin signaling Dysregulation, DNA damage response and TGF-ß pathways, indicating R-loops accumulating at the 5' end of genes play oncogenic roles, whereas at the 3' end of genes play tumor-suppressive roles in tumorigenesis.

Surfactant-like Additives Assisted the Lateral Growth of Pentacene Films.

Lateral growth of thin films is crucial for organic electronic devices, such as field-effect transistors. Here, we report a strategy to improve the lateral growth of pentacene films using rubrene as a surfactant-like additive. Atomic force microscopy (AFM) images confirm the enhanced lateral growth with the presence of rubrene, resulting in smooth and enlarged molecule domains in the films in comparison to those without rubrene. Molecular dynamics simulations are conducted to explore the interlayer diffusion of pentacene molecules during the growth. With the rubrene molecules as surfactant-like additives, mean square displacement (MSD) analysis shows that the pentacene molecules have a descending diffusion coefficient of 2.0 × 10-5 cm2 s-1, which is greater than the ascending diffusion coefficient of 1.6 × 10-5 cm2 s-1. The more descending molecules lead to an enhanced lateral growth of pentacene films, which is in good agreement with the experiments. As a result, the pentacene films grown with rubrene exhibit a rapid increase in carrier mobility over thickness due to the well-connected domains resulting from enhanced lateral growth. This finding will provide a new strategy to modulate the morphology of organic films for high-performance devices.

Resolvin D1 inhibits T follicular helper cell expansion in systemic lupus erythematosus.

OBJECTIVE: Resolvin D1 (RvD1) is one of the specialized pro-resolving lipid mediators, which control inflammation resolution and regulate immune responses. Previous research showed that RvD1 could block the progression of systemic lupus erythematosus (SLE). However, the detailed mechanism remains to be fully understood. METHOD: Plasma RvD1 levels, and proportions of T follicular helper cells (Tfh cells) were measured in SLE patients and healthy controls. Plasma RvD1 levels and proportions of Tfh cells were quantitated in an MRL/lpr mouse model of lupus treated with RvD1. Naïve CD4+ T cells were purified from MRL/lpr mice to study the effect of RvD1 on Tfh cell differentiation in vitro. RESULTS: In patients, there were significant negative correlations between plasma RvD1 levels and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, as well as between plasma RvD1 and anti-double-stranded DNA antibody levels, and numbers of peripheral Tfh cells and plasma cells. In MRL/lpr mice, the expected amelioration of disease phenotype and inflammatory response with RvD1 treatment correlated with decreased percentages of Tfh cells and plasma cells. In addition, the differentiation and proliferation of Tfh cells were markedly suppressed by RvD1 in vitro. CONCLUSION: RvD1 may control SLE progression through the suppression of Tfh cell differentiation and subsequent inhibition of B-cell responses.

[Retrospective analysis of perioperative anaphylactic shock induced by cefuroxime].

This study investigated the characteristics and frequency of perioperative anaphylactic shock induced by cefuroxime, so as to provide a reference for the safe and rational use of cefuroxime in the perioperative period. Cases of perioperative anaphylactic shock caused by cefuroxime in our hospital from 2011 to 2021 were extracted from the Adverse Drug Reaction Monitoring System. Literature reporting adverse drug reactions (ADR) including cefuroxime-induced anaphylactic shock in perioperative settings was collected from the CNKI, VIP, Wanfang, PubMed, and Web of Science databases from their respective inception to May 2022. Statistical analysis was performed for all cases of cefuroxime-induced perioperative anaphylactic shock. A total of 31 patients were included [13 men (48.1%) and 14 women (51.9%)], most of whom were over 60 years old (n=16, 59.3%); 9 (29.0%) patients had a history of drug allergy; 5 (16.1%) patients had received skin tests, but with negative results; 28 (90.3%) patients received treatment intravenously; 22 (71.0%) patients were treated after anesthesia. For 20 (64.5%) patients the ADR occurred within 10 minutes after anesthesia. The main manifestations were hypotension, dyspnea, rash, and tachycardia. For all patients, symptoms resolved after withdrawal of the drug and active rescue, and there were no deaths. A history of allergy and skin test findings may have limitations in predicting perioperative anaphylactic shock caused by cefuroxime; greater vigilance should be exercised when using cefuroxime in the perioperative period. Close monitoring is recommended for patients undergoing treatment with cefuroxime. Rescue therapy should be administered for allergic shock, and suitable response measures must be taken in a timely manner to ensure the safety of patients.

[Expression of DARS2 in colorectal cancer and its clinical significance].

Objective: To investigate the expression of DARS2 and its clinical significance in colorectal cancer. Methods: In this study, bioinformatics tools, especially gene expression profile interactive analysis 2 (GEPIA2), were used to conduct an in-depth analysis of DARS2 expression in colorectal cancer tissues. Immunohistochemical staining was carried out in 108 colorectal cancer specimens and 30 normal colorectal tissues obtained from the First Affiliated Hospital of Nanchang University, Nanchang, China. Colorectal cancer cell lines (HCT116 and SW480) were transfected with small interfering RNA (siRNA) and DARS2 overexpression plasmid to examine the effects of DARS2 knockdown and overexpression on cell function. To assess the effects on cell function, CCK8 and transwell migration assays were used to assess proliferation and cell motility, respectively. Additionally, protein immunoblotting was employed to scrutinize the expression of proteins associated with the epithelial-mesenchymal transition of colorectal cancer cells. Results: DARS2 exhibited a pronounced upregulation in expression within colorectal cancer tissues compared to their normal epithelial counterparts. Furthermore, DARS2 expression was higher in colorectal cancer of stage Ⅲ-Ⅳ than those of stage Ⅰ-Ⅱ, exhibiting a significant correlation with N staging, M staging, and pathological staging (P<0.05). Kaplan-Meier analyses showed a decreased overall survival rate in colorectal cancer with DARS2 expression compared to those without DARS2 expression (P<0.05). In the siRNA transfection group, there was a significant reduction in cell proliferation and migration (P<0.01 and P<0.05, respectively). Conversely, the transfection of DARS2 overexpression plasmids substantially increased both cell proliferation and migration (P<0.05). Additionally, immunoblotting revealed that DARS2 knockdown led to an upregulation of E-cadherin expression and a downregulation of N-cadherin and vimentin expression. In contrast, DARS2 overexpression resulted in increased N-cadherin and vimentin expression, coupled with reduction in E-cadherin expression. Conclusions: There is a strong association between DARS2 expression and colorectal cancer progression. Silencing DARS2 inhibits cell proliferation and migration, exerting a discernible influence on the epithelial-mesenchymal transition process.

[Pituitary Crooke cell neuroendocrine tumor of adrenocorticotropic hormone differentiation-specific transcription factor lineage: a clinicopathological analysis of six cases].

Objective: To investigate the clinicopathological features of Crooke cell tumor of adrenocorticotropic hormone differentiation specific transcription factor (TPIT, also known as transcription factor 19, TBX19) lineage neuroendocrine tumors. Methods: Six cases of Crooke cell tumor diagnosed at the First Affiliated Hospital of University of Science and Technology of China, Hefei, China from October 2019 to October 2023 were collected. The clinical and pathological features of these cases were analyzed. Results: Among the six cases, one was male and five were female, with ages ranging from 26 to 75 years, and an average age of 44 years. All tumors occurred within the sella turcica. Clinical presentations included visual impairment in two cases, menstrual disorders in one case, Cushing's syndrome in one case, headache in one case, and one asymptomatic case discovered during a physical examination. Preoperative serum analyses revealed elevated levels of cortisol and adrenocorticotropic hormones in two cases, elevated cortisol in two cases, elevated adrenocorticotropic hormone in one case, and one case with a mild increase in prolactin due to the pituitary stalk effect. Magnetic resonance imaging revealed uneven enhancement of masses with maximum diameters ranging from 1.7 to 3.2 cm, all identified as macroadenomas. Microscopically, tumor cells exhibited irregular polygonal shapes, solid sheets, or pseudo-papillary arrangements around blood vessels. The cell nuclei were eccentric or centrally located, varying in size, with abundant cytoplasm. Some tumor cells showed perinuclear halo. Immunohistochemistry demonstrated diffuse strong positivity for TPIT in five cases, focal weak positivity for TPIT in one case, diffuse strong positivity for adrenocorticotropic hormone in all cases, and faint staining around the nuclei in a few cells. CK8/18 showed a strong positive ring pattern in more than 50% of tumor cells, focal weak positive expression of p53, and the Ki-67 positive index ranged 1%-5%. Periodic acid-Schiff staining revealed positive cytoplasm and negative perinuclear areas. Conclusions: Crooke cell tumor is a rare type of pituitary neuroendocrine tumors. Its pathological characteristics include a distinctive perinuclear clear zone and immunohistochemical markers, such as CK8/18 exhibiting a ring or halo pattern. This entity represents a high-risk subtype among pituitary neuroendocrine tumors, displaying a high risk of invasion and a propensity for recurrence. Accurate diagnosis is crucial for the postoperative follow-up and multimodal treatment planning.

[COVID-19 in patients with Good syndrome: report of 4 cases and literature review].

Objective: To summarize the clinical characteristics of coronavirus disease 2019 (COVID-19) in patients with Good's syndrome. Methods: We included all cases of COVID-19 in patients with Good's syndrome in the Second Xiangya Hospital of Central South University from January 1, 2023 to August 31, 2023. In addition to our cases, we searched the published literature in Wanfang database and PubMed database using the keywords "Good's syndrome" and "COVID-19". The clinical characteristics, treatment and outcome of the patients were summarized and analyzed. Results: A total of four patients with Good's syndrome complicated by COVID-19 were identified in our hospital, all of them were male, and the days of hospitalization were 17, 23, 7, and 13 days, respectively. Databases were searched for a total of six patients with Good's syndrome complicated by COVID-19, including three females and three males, all foreign patients, with hospitalization days of 12, 22, 13, 25, 21, and 34 days respectively. All ten patients met the diagnostic criteria for severe or critical COVID-19, and three(all middle-aged males) of them died, two from sepsis and one from respiratory failure. They were. Conclusion: COVID-19 in patients with Good's syndrome are prone to develop severe or critical disease and are more likely to be infected with multiple pathogens. Timely immunoglobulin supplementation is the key to treatment.

[Prognostic performance of pulmonary effective arterial elastance in patients with heart failure].

Objective: To explore the predictive value of pulmonary effective arterial elastance (Ea) in patients with heart failure (HF). Methods: This is a retrospective cohort study, which retrospectively included 284 patients with HF who underwent right heart catheterization at Heart Failure Center in Fuwai Hospital between September 2013 and February 2022. Data regarding baseline clinical characteristics, hemodynamic profiles, and prognosis were collected. Ea was calculated as mean pulmonary arterial pressure/stroke volume. Patients were divided into Ea<0.555 group and Ea≥0.555 group according to the median value of Ea (0.555 mmHg/ml, 1 mmHg=0.133 kPa). The primary outcome was the primary clinical event, set as the first occurrence of a series of composite events, including all-cause death, heart transplantation, left ventricular assist device implantation, and HF rehospitalization. Event-free survival was defined as the absence of primary clinical events. Spearman correlation analysis was used to calculate the correlation coefficient between Ea and parameters reflective of right heart function. The Kaplan-Meier analysis was used to compare the different groups for the estimation of outcomes with the log-rank test. We used Cox proportional-hazards regression models to estimate hazard ratios (HR) for primary clinical event. Subgroup analysis was performed based on the age, gender, New York Heart Association (NYHA) functional class, left ventricular ejection fraction, presence of pulmonary hypertension, and serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) values. We used receiver operating characteristic (ROC) curve to calculate the area under the curve (AUC) of Ea for predicting event-free survival in patients with HF. Results: The median age was 51 years, and 206 (72.5%) patients were male. Ea and pulmonary vascular resistance (PVR) were significantly correlated (r=0.698, P<0.001). The correlation between Ea and pulmonary arterial elastance (PAC) were even more significant (r=-0.888, P<0.001). Compared with Ea<0.555 group, Ea≥0.555 group presented with higher serum NT-proBNP values (4 443 (1 792, 8 554) ng/L vs. 1 721 (480, 4 528)ng/L,P<0.001), higher PVR (3.4 (2.5, 4.7) Wood vs. 1.4 (0.9, 2.2) Wood, P<0.001), lower cardiac output (3.0 (2.3, 3.9) L/min vs. 4.3 (3.8, 4.9) L/min, P<0.001), and lower PAC (1.6 (1.3, 2.0) ml/mmHg vs. 4.0 (3.0, 6.0) ml/mmHg, P<0.001). The median follow-up time was 392 (166, 811) days. The Kaplan-Meier survival curve demonstrated a lower event-free survival rate in the Ea≥0.555 group compared to the Ea<0.555 group (Plog-rank<0.001). After multivariate adjustment, Ea (HR=1.734, P<0.001) remained significantly associated with the primary outcome. Subgroup analysis indicated that Ea was associated with the primary outcome across all subgroups. The AUC was 0.724 (P<0.001) for Ea to predict event-free survival calculated from ROC analysis. Conclusions: Ea is closely related to parameters reflective of right ventricular afterload. Increased Ea is an independent predictor of adverse outcomes in patients with HF.

THE EFFECT OF CHILDHOOD SUBJECTIVE SOCIOECONOMIC STATUS ON MENTAL HEALTH: THE MEDIATING ROLES OF PERCEIVED DISCRIMINATION AND STATUS ANXIETY.

This study explored the effect of childhood subjective socioeconomic status on mental health and the chain-mediating mechanism of perceived discrimination and status anxiety. A random survey was conducted via an online survey platform with 999 college students in east China. Participants completed the Childhood Subjective Socioeconomic Status Scale, General Health Questionnaire, Status Anxiety Scale, and the Perceived Personal Discrimination Scale. The sample comprised 323 men and 676 women. The mean age was 20.49±2.70 years. Mediation analysis using Model 6 and 5,000 bootstrap samples was employed to explore the mediating role of perceived discrimination and status anxiety in the relationship between childhood subjective socioeconomic status and mental health. Mental health was significantly positively correlated with childhood socioeconomic status, and significantly negatively correlated with perceived discrimination and status anxiety. Perceived discrimination and status anxiety played a partial chain mediating role between childhood socioeconomic status and mental health. The mediation model accounted for 31% of the variance in mental health. Moreover, the results indicated that the significant mediating effect of perceived discrimination between childhood subjective SES and mental health had a value of 0.029 and a 95% confidence interval of [0.019, 0.041]. Furthermore, the significant mediating effect of status anxiety between childhood subjective SES and mental health had a value of 0.010 and a 95% confidence interval of [0.006, 0.014]. The results provide an explanation of how childhood subjective socioeconomic status influences their mental health. Interventions to address perceived discrimination and status anxiety can improve the mental health status of children who experience childhood adversity. The study's findings contribute to understanding mental health in childhood and inform potential interventions to improve the well-being of individuals who have experienced childhood adversity. The limitations of the study were self-report scales and potential biases in the sample population. Addressing these limitations will enhance the credibility of the research and pave the way for future studies.

Nanometer flat blazed x-ray gratings using ion beam figure correction.

With the development of nanometer accuracy stitching interferometry, ion beam figuring (IBF) of x-ray mirrors can now be achieved with unprecedented performance. However, the process of producing x-ray diffraction gratings on these surfaces may degrade the figure quality due to process errors introduced during the ruling of the grating grooves. To address this challenge, we have investigated the post-production correction of gratings using IBF, where stitching interferometry is used to provide in-process feedback. A concern with ion beam correction in this case is that ions will induce enough surface mobility of atoms to cause smoothing of the grating structure and degradation of diffraction efficiency. In this study we found however that it is possible to achieve a nanometer-level planarity of the global grating surface with IBF, while preserving the grating structure. The preservation was so good, that we could not detect a change in the diffraction efficiency after ion beam correction. This is of major importance in achieving ultra-high spectral resolution, and the preservation of brightness for coherent x-ray beams.

Critical body fat percentage required for puberty onset: the Taiwan Pubertal Longitudinal Study.

PURPOSE: Prepubescent body fat percentage (BFP) is associated with puberty onset; however, the association between the timing of puberty onset and BFP remains unclear. This study aimed to determine whether and how the timing of puberty onset is associated with various anthropometric measures, and to investigate the critical time period of the BFP transition before and after puberty. METHODS: The Taiwan Pubertal Longitudinal Study (TPLS) has a multicenter, population-based prospective cohort and was established in July 2018 at 4 pediatric departments. We included girls aged 6-14 years and boys aged 9-17 years evaluated as having puberty onset and excluded those with precocious puberty diagnosis. The anthropometric measures were collected every 3 months. The main outcome was age at puberty onset. Data were analyzed between July 2018 and September 2020. RESULTS: For 153 girls and 83 boys, BFP was significantly related to puberty onset for girls. Longitudinal analysis revealed that BFP in the girls was reduced to less than 18% 6 months before puberty and rapidly increased by 2.85% over 3 months, then exceeding 20% before puberty onset. After puberty onset, BFP was no longer lower than 22%. CONCLUSIONS: BFP is an essential predictor of age at puberty onset. BFP first decreases and then begins to increase 3-6 months before puberty in girls. Parents and schools could monitor the BFP of prepubescent girls every 6 months to predict puberty onset.

[Clinical features and prognosis of patients hospitalized with heart failure and low T3 syndrome].

Objective: To investigate the association between triiodothyronine (T3) and inflammatory factors, and its potential effect on long-term outcomes in hospitalized patients with heart failure (HF). Methods: A total of 2 475 patients with HF admitted in Heart Failure Care Unit were consecutively enrolled in this retrospective cohort study from December 2006 to June 2018. Patients were divided into low T3 syndrome group (n=610, 24.6%) and normal thyroid function group (n=1 865, 75.4%). The median follow-up time was 2.9 (1.0, 5.0) years. A total of 1 048 all-cause deaths were recorded at the final follow-up. The effects of free T3 (FT3) and high-sensitivity C-reactive protein (hsCRP) on the risk of all-cause death were evaluated by Cox regression analysis and Kaplan-Meier analysis. Results: The age of the total population was 19-95 (57±16) years, 1 823 cases (73.7%) were male. Compared to those with normal thyroid function, albumin [(36.5±5.4) vs. (40.7±4.7) g/L], hemoglobin [(129.4±25.1) vs. (140.6±20.6) g/L], total cholesterol [3.6 (3.0, 4.4) vs. 4.2 (3.5, 4.9) mmol/L] (all P<0.001) were lower, Whereas age [(60.5±16.0) vs. (55.2±15.4) years], creatinine [105.0 (83.6, 137.0) vs. 87.8 (75.6, 106.3) mmol/L], log N-terminal B-type natriuretic peptide [(8.2±1.3) vs. (7.2±1.4) ng/L] were higher in LT3S patients (all P<0.001). In Kaplan-Meier survival analysis, patients with lower FT3 and higher hsCRP had significantly lower cumulative survival (P<0.001), lower FT3 combined with higher hsCRP subgroup had the highest risk of all-cause death (Ptrend<0.001). In multivariate Cox regression analysis, LT3S was an independent predictor of all-cause mortality (HR=1.40, 95%CI 1.16-1.69, P<0.001). Conclusion: LT3S is an independent predictor of poor prognosis in patients with heart failure. FT3 combined with hsCRP improve the predictive value of all-cause death in hospitalized patients with heart failure.

[Clinical characteristics of patients referred to cardio-oncology clinic].

To explore characteristics of outpatients in a single cardio-oncology clinic, patients visiting cardio-oncology clinic of Fuwai Hospital CAMS&PUMC (Beijing, China) from January 2020 to December 2021 were analyzed retrospectively. In total, 330 patients were included, the median age (Q1, Q3) was 58(46, 66) years, and there were 192 females (58.2%). The purposes for visit included an evaluation and treatment of cardiovascular adverse reactions (n=247, 74.8%), pre-antitumor therapy assessment (n=51, 15.5%), and management of primary or metastatic cardiac tumors (n=32, 9.7%). For patients with cardiovascular adverse reactions, the most common tumor type was breast cancer (n=88, 29.5%), followed by gastrointestinal cancer (n=70, 23.5%), and hematological cancers (n=62, 20.8%). Among them, 236 cases (95.5%) had received antitumor drugs in the past; 38 cases (15.4%) had a history of chest radiotherapy; some cases were complicated with hypertension (n=69, 23.2%) and/or hyperlipidemia (n=69, 23.2%); 42 cases (14.1%) had a history of coronary heart disease; and 16 cases (5.4%) were complicated with atrial fibrillation or flutter. Among 32 patients with cardiac tumors, 11 cases (34.4%) had primary malignant tumors; 6 cases (18.8%) had benign tumors; 2 cases (6.3%) had metastatic tumors; and 13 (40.6%) had unknown pathological types. This study explores the epidemiology of cardio-oncology in China and provides clinical insights for the future development of cardio-oncology. In the future, it is still necessary to study the benefits of cardio-oncology clinics and develop standardized indicators to evaluate their benefits.

[The prognostic value of free triiodothyronine/free thyroxine ratio in patients hospitalized with heart failure].

Objective: To investigate the effect of free triiodothyronine/free thyroxine (FT3/FT4) ratio on the prognosis of patients with heart failure (HF). Methods: A total of 3 527 patients hospitalized in the Heart Failure Center of Fuwai Hospital from March 2009 to June 2018 were analyzed in our study. Patients were divided into two groups according to median of FT3/FT4 ratio: low FT3/FT4 group (n=1 764, FT3/FT4<2.15) and high FT3/FT4 group (n=1 763, FT3/FT4≥2.15). The primary endpoint was defined as a composite endpoint of all-cause death or heart transplantation or implantation of a left ventricular assist device. The baseline characteristics of patients with different FT3/FT4 ratio groups were compared, and a multivariate Cox proportional hazard regression model was used to analyze the relationship between FT3/FT4 ratio and the prognosis of hospitalized patients with HF. Results: The age of the total population was (56.8±16.0) years, and 2 544 cases (72.1%) were males. The median follow-up time was 2.79 (1.00, 5.03) years, and a total of 1 542 end-point events were recorded at the final follow-up. The mean ages of patients in the low FT3/FT4 group and high FT3/FT4 group were (58.8±16.5) and (54.8±15.2) years (P<0.001), respectively; and the cumulative survival rates were 38.4% and 61.9%, respectively (P<0.001). FT3 (HR=0.72, 95%CI: 0.63-0.84, P<0.001), FT3/FT4 (HR=0.76, 95%CI: 0.65-0.87, P<0.001) was associated with all-cause death, heart transplantation, or LVAD implantation in patients with heart failure. HR values (95%CI) of FT3/FT4 ratio predicting the risk of composite endpoint in the subgroup of left ventricular ejection fraction (LVEF)<40%, 40% to 49%, and≥50% were 0.91 (0.77-1.08), 0.83 (0.50-1.39), and 0.65 (0.50-0.85), respectively (P interaction=0.045). Conclusions: Low FT3 and low FT3/FT4 are important correlative factors for poor prognosis in hospitalized HF patients, especially in patients with LVEF≥50%.

[Association between serum potassium levels and all-cause mortality in patients with acute heart failure].

Objective: To investigate the relationship between different serum potassium levels at admission and discharge and all-cause mortality in patients with acute heart failure (HF). Methods: A total of 2 621 patients with acute HF who were hospitalized in the Heart Failure Center of Fuwai Hospital from October 2008 to October 2017 were analyzed. Patients were divided into three groups according to the different serum potassium levels at admission: hypokalemia with serum potassium<3.5 mmol/L (n=329), normokalemia with 3.5-5.5 mmol/L (n=2 270), and hyperkalemia with serum potassium>5.5 mmol/L (n=22). Clinical data such as patient history, comorbidities, clinical examination and drug use were collected, and systematic outpatient review or telephone follow-up was performed after patients were discharged from the hospital until January 2020. The primary outcome was all-cause death at 90 days, 2 years, and 5 years of follow-up. We compared the clinical characteristics of patients with different serum potassium levels at admission and discharge, and used a multivariate Cox proportional hazards regression model to analyze the association between serum potassium levels at admission and discharge and all-cause mortality. Results: The age of all patients was (58.0±15.3) years old, and 1 877 patients (71.6%) were male. There were 329 (12.6%) and 22 (0.8%) patients with hypokalemia and hyperkalemia at admission, and 38 (1.4%) and 18 (0.7%) at discharge, respectively. The serum potassium levels of all patients were (4.01±0.50) and (4.25±0.44) mmol/L at admission and discharge, respectively. The follow-up time[M(Q1,Q3)] of this study was 2.63(1.00,4.42)years, and a total of 1 076 all-cause deaths were recorded at the last follow-up. Compared with patients with normokalemia at discharge, discharged patients with hypokalemia and hyperkalemia were followed up for 90 days (90.3% vs 76.3% vs 38.9%), 2 years (73.8% vs 60.5% vs 33.3%) and 5 years (63.4% vs 44.7% vs 22.2%), respectively, and the difference of which in cumulative survival rates were statistically significant (all P values<0.001). The multivariate-adjusted Cox regression analysis showed that hypokalemia (HR=0.979, 95%CI: 0.812-1.179, P=0.820) and hyperkalemia (HR=1.368, 95%CI: 0.805-2.325, P=0.247) at admission were not associated with all-cause mortality risk, however, hypokalemia (HR=1.668, 95%CI: 1.081-2.574, P=0.021) and hyperkalemia (HR=3.787, 95%CI: 2.264-6.336, P<0.001) at discharge were associated with increased all-cause mortality risk. Conclusions: Both hypokalemia and hyperkalemia at discharge in hospitalized patients with acute HF were associated with increased short-and long-term all-cause mortality, and serum potassium levels should be closely monitored.

[Safety and immunogenicity of freeze-dried rabies vaccine (Vero-cells) for human use in healthy people aged 9-65 years].

Objective: To assess the safety and immunogenicity of freeze-dried rabies vaccine (Vero-cells) for human use on different immunization procedures in healthy people aged 9-65 years. Methods: A randomized, blind, positive-controlled clinical study was conducted in March 2015. The eligible residents aged 9-65 were recruited in Dengfeng city and Biyang County, Henan Province. A total of 1 956 subjects were enrolled. The subjects were randomly (1∶1∶1) assigned to 5-dose control group, 4-dose trial group and 5-dose trial group, with 652 subjects in each group. The subjects of 5-dose control group were immunized with control vaccine on days 0, 3, 7, 14 and 28. The subjects of 4-dose trial group were immunized with trial vaccine on days 0, 7 and 21 (2-1-1 phases) and the subjects of 5-dose trial group were immunized with trial vaccine on days 0, 3, 7, 14 and 28. A combination of regular follow-up and active reporting was used to observe local and systemic adverse reactions till 30 days after the first and full immunization, and the incidence rate of adverse reactions in three groups was analyzed and compared. The venous blood was collected before the first immunization, 7 days after the first immunization, 14 days after the first immunization and 14 days after the full immunization. The neutralizing antibody of rabies virus was detected by rapid fluorescent focus inhibition test (RFFIT), and the seropositive conversion rate and geometric mean concentration (GMC) of antibody were calculated. Results: The adverse reaction rates in 5-dose control group, 4-dose trial group and 5-dose trial group were 41.87% (273/652), 35.43% (231/652) and 34.97% (228/652), respectively. The adverse reaction rates of 4-dose trial group and 5-dose trial group were lower than those of the 5-dose control group (P<0.05). The local reactions were mainly pain, itching, swelling and redness in injection site, while the systemic reactions were mainly fever, fatigue, headache and muscle pain. The severity of adverse reactions was mainly mild (level 1), accounting for 85.33% (518/607), 89.02% (373/419) and 88.96% (427/480) of the total number of adverse reactions in each group. At 14 days after the first immunization and 14 days after the full immunization, the antibody positive conversion rates of three groups were all 100%. At 7 days, 14 days after the first immunization and 14 days after the full immunization, the GMCs of three groups were 0.60, 0.72, 0.59 IU/ml, 20.42, 23.99, 24.38 IU/ml and 22.95, 23.52, 24.72 IU/ml, respectively, with no significant difference (P>0.05). Conclusion: The freeze-dried rabies vaccine (Vero-cells) for human use has good safety and immunogenicity when inoculated according to 5-dose and 4-dose immunization procedures.

The Mechanism of the Anti-Cardiac Hypertrophy Effect of Glycyrrhizic Acid Is Related to Reducing STIM1-Dependent Store-Operated Calcium Entry.

We explored the anti-cardiac hypertrophy mechanism of glycyrrhizic acid from the perspective of calcium regulation under pathological conditions. For this purpose, we used a rat model of myocardial hypertrophy induced by pressure overload. The effect of glycyrrhizic acid on BP was measured non-invasively with a sphygmomanometer and recorded in PC. In rats with modeled cardiac hypertrophy, the effect of GA on expression of type 1 matrix interaction molecules was determined in horizontal tissues and cultured cardiomyocytes of the left ventricle. The laser confocal microscopy and calcium ion probe Fluo-4 AM were used to assess the effect of glycyrrhizic acid on stromal interaction molecule 1 (STIM1)-dependent store-operated calcium entry in cultured cardiomyocytes derived from the hypertrophic myocardium. Glycyrrhizic acid exerted the anti-hypertrophic effect in rats with hypertrophic myocardium by down-regulating STIM1 protein expression and reducing the intensity of STIM1-dependent store-operated calcium entry.

B-Cell-Activating Factor Contributes to Elevation of the Content of Regulatory B Cells in Neonatal Sepsis.

We studied the role of B cell-activating factor (BAFF) in PI3K/AKT/mTOR signaling pathway in promoting proliferation and maintaining survival of regulatory B lymphocytes (Breg) in newborns with sepsis. The peripheral blood samples were collected from preterm neonates (n=40) diagnosed with sepsis on the day of diagnosis and on days 7, 14, and 21 after diagnosis, as well as from the matched preterm neonates without sepsis (n=40; control group). The peripheral blood mononuclear cells and B cells were isolated, cultured, and stimulated with LPS and immunostimulant CpG-oligodeoxynucleotide (CpG-ODN). Proliferation and differentiation of B-cells into CD19+CD24hiCD38hi Breg cells and the role of the PI3K/AKT/mTOR signaling pathway in these processes were studied by flow cytometry, real-time quantitative reverse transcription PCR (qRT-PCR), and Western blotting. BAFF levels in the peripheral blood of neonates with sepsis were significantly increased at one week after diagnosis in parallel with increasing trend of expression of BAFF receptor. When applied with LPS and CpG-ODN, BAFF promoted differentiation of B cells into CD19+CD24hiCD38hi Breg cells. Phosphorylation of 4E-BP1 factor and 70S6K kinase located downstream in PI3K/AKT/mTOR signaling pathway was significantly up-regulated when stimulated with BAFF in combination with LPS and CpG-ODN. Thus, increased level of BAFF activates PI3K/AKT/mTOR signaling pathway and induces in vitro differentiation of peripheral blood B cells into CD19+CD24hiCD38hi Breg cells.

[Psychological effect of physical function dependence on maintenance hemodialysis patients and their primary family caregivers].

Objective: To investigate the psychological effect of physical function dependence on maintenance hemodialysis (MHD) patients and their primary family caregivers. Methods: The study was a cross-sectional survey. The MHD patients in the hemodialysis centre, the Third Affiliated Hospital of Guangzhou Medical University from March 2022 to June 2022 were enrolled. The patients' demographics and laboratory data were collected. Katz and Lawton-Brody questionnaires were used to assess patients' physical function, and Five Item Mental Health Inventory (MHI-5) was used to evaluate the psychological conditions of the patients and their primary family caregivers. Multiple linear regression analysis was used to analyze the influencing factors of MHI-5 scores of the patients and their primary family caregivers. Results: A total of 116 patients were included, with 61 males and 55 females. There were 47 patients (40.5%) with physical function dependence. In the physical function dependence group, serum albumin (t=-2.512, P=0.013), MHI-5 scores of patients and their primary family caregivers (t=-8.461, P < 0.001; t=-8.533, P < 0.001) and male ratio (χ2=8.467, P=0.002) were significantly lower, and the age (t=9.754, P < 0.001) and the proportions of hypertension (χ2=20.421, P < 0.001), diabetes (χ2=10.470, P=0.002), cardiovascular and cerebrovascular diseases (χ2=9.898, P=0.003) were significantly higher than those in the normal physical function group. The incidence of mental disorders in MHD patients was 39.7%(46/116), and the incidence of mental disorders in the physical function dependence group was significantly higher than that in the normal physical function group [72.3%(34/47) vs. 17.4%(12/69), χ2=35.275, P < 0.001]. The incidence of mental disorders in the primary family caregivers was 32.8%(38/116), and the incidence of mental disorders in the primary family caregivers of physical function dependence group was significantly higher than that in the normal physical function group [66.0%(31/47) vs. 10.1%(7/69), χ2=39.536, P < 0.001]. The incidence of mental disorders in the primary family caregivers of MHD patients who were not spouses was significantly higher than that of spouses [46.0%(29/63) vs. 17.0%(9/53), χ2=11.028, P=0.001], and in physical function dependence group, the incidence of mental disorders in non-spouses was significantly higher than that in spouses [80.6%(25/31) vs. 37.5%(6/16), χ2=8.749, P=0.003]. Multiple linear analysis showed that bathing (ß=-5.182, P=0.015), doing laundry (ß=-7.053, P < 0.001), taking medication (ß=-8.680, P=0.003), and female patients (ß=-2.982, P=0.030) were the influencing factors of MHI-5 scores decline in MHD patients. Bathing (ß=-4.404, P=0.032), preparing meals (ß=-3.954, P=0.041), managing money (ß=-5.067, P=0.021), and female patients (ß=-2.466, P=0.042) were the influencing factors of MHI-5 scores decline in primary family caregivers. Conclusions: The incidence of physical function dependence in MHD patients is high, and its manifestations and influencing factors are diverse. The incidence of mental disorders in MHD patients and their primary family caregivers is also high, especially in patients with physical function dependence and non- spouse family caregivers. Clinicians should pay attention to and assess the physical function dependence of MHD patients as early as possible, and intervene in time. At the same time, they should also pay attention to the mental health of MHD patients and their primary family caregivers.