Serum ASGR2 level: an efficacy biomarker for balloon pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension.

Background: This study aimed to employ plasma proteomics to investigate the molecular changes, pathway alterations, and potential novel biochemical markers associated with balloon pulmonary angioplasty (BPA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Methods: Pre- and post-BPA plasma samples from five CTEPH patients in the PRACTICE study were analyzed to identify differentially expressed proteins. Proteomic and bioinformatics analyses were conducted, and the identified proteins were further validated using ELISA assays in a separate cohort of the same study. Correlation and multivariate regression analyses were performed to investigate the associations between these differentially expressed proteins and clinical parameters. Results: Significantly higher serum levels of asialoglycoprotein receptor 2 (ASGR2) were detected in 5 CTEPH patients compared to those in healthy individuals but decreased significantly after successful BPA procedures. The decrease in serum levels of ASGR2 after the completion of BPA procedures was further validated in a separate cohort of 48 patients with CTEPH [0.70 (0.51, 1.11) ng/mL vs. 0.38 (0.27, 0.59) ng/mL, P < 0.001]. Significant associations were found between the pre-BPA ASGR2 level and clinical parameters, including neutrophil percentage (R = 0.285, P < 0.05), platelet (PLT) count (R = 0.386, P < 0.05), and high-density lipoprotein cholesterol (HDL-C) before BPA (R = -0.285, P < 0.05). Significant associations were detected between post-BPA serum ASGR2 levels and lymphocyte percentage (LYM%) (R = 0.306, P < 0.05), neutrophil-to-lymphocyte ratio (R = -0.294, P < 0.05), and pulmonary vascular resistance after BPA (R = -0.35, P < 0.05). Multivariate stepwise regression analysis revealed that pre-BPA ASGR2 levels were associated with HDL-C and PLT count (both P < 0.001), while post-BPA ASGR2 levels were associated with LYM% (P < 0.05). Conclusion: Serum levels of ASGR2 may be a biomarker for the effectiveness of BPA treatment in CTEPH patients. The pre-BPA serum level of ASGR2 in CTEPH patients was associated with HDL-C and the PLT count. The post-BPA serum level of ASGR2 was correlated with the LYM%, which may reflect aspects of immune and inflammatory status.

Targeted genetic analysis in a cohort of sporadic death from spontaneous rupture of thoracic aortic dissection in Han Chinese population.

PURPOSE: Thoracic aortic dissection (TAD) is a life-threatening cardiovascular disease that often results in sudden cardiac death (SCD). However, the genetic characteristics of individuals with TAD confirmed at autopsy have been rarely studied. Our objective was to determine the prevalence of pathogenic variants in TAD-associated genes in a cohort of sporadic deaths resulting from spontaneous rupture of TAD and identify relevant genotype-phenotype relationships in Han Chinese population. METHODS: We included sixty-one consecutive sporadic decedents whose primary cause of death was spontaneous rupture of TAD, and performed a whole exome sequencing based strategy comprising 26 known TAD-associated genes. RESULTS: We identified 7 pathogenic or likely pathogenic (P/LP) variants in 7 cases (11.48 %) and 22 variants of uncertain significance (VUS) in 22 cases (36.07 %). The FBN1 gene was found to be the major disease-causing gene. Notably, TAD decedents with P/LP variant exhibited significantly earlier mortality. Moreover, we reported for the first time that TAD decedents with P/LP variant had a shorter diagnosis and treatment time. CONCLUSION: Our study investigated the genetic characteristics of TAD individuals confirmed until autopsy in Han Chinese population. The findings enhanced the understanding of the genetic underpinnings of TAD and have significant implications for clinical management and forensic investigations.

Fly-scan high-throughput coded ptychographic microscopy via active micro-vibration and rolling-shutter distortion correction.

Recent advancements in ptychography have demonstrated the potential of coded ptychography (CP) for high-resolution optical imaging in a lensless configuration. However, CP suffers imaging throughput limitations due to scanning inefficiencies. To address this, we propose what we believe is a novel 'fly-scan' scanning strategy utilizing two eccentric rotating mass (ERM) vibration motors for high-throughput coded ptychographic microscopy. The intrinsic continuity of the 'fly-scan' technique effectively eliminates the scanning overhead typically encountered during data acquisition. Additionally, its randomized scanning trajectory considerably reduces periodic artifacts in image reconstruction. We also developed what we believe to be a novel rolling-shutter distortion correction algorithm to fix the rolling-shutter effects. We built up a low-cost, DIY-made prototype platform and validated our approach with various samples including a resolution target, a quantitative phase target, a thick potato sample and biospecimens. The reported platform may offer a cost-effective and turnkey solution for high-throughput bio-imaging.

Transcription factor Hoxb5 reveals the unidirectional hierarchy of hematopoietic stem cell pool.

Hoxb5 exhibits preferential expression in hematopoietic stem cells (HSCs) and uniquely marks the long-term HSCs (LT-HSCs). Previous studies have demonstrated the remarkable capability of Hoxb5 to alter cell fates when enforced expression in blood progenitors, such as B cell progenitors and multipotent progenitors. Additionally, Hoxb5 deficiency does not hinder the generation of LT-HSCs. However, the specific impact of Hoxb5 deletion on LT-HSCs has remained unexplored. To address this, we developed a conditional Hoxb5 knockout-reporter mouse model, wherein Hoxb5 was knock out by the Vav-cre recombinase, and the endogenous Hoxb5 promoter drove the expression of the blue fluorescent protein (BFP). Our findings revealed that the primary recipients, who transplanted with HSCs indicating Hoxb5 deficiency by the presence of BFP (BFP-positive HSCs), exhibited comparable levels of donor chimerism and lineage chimerism to recipients transplanted with HSCs that spontaneously did not express Hoxb5 and thus lacked BFP expression (BFP-negative HSCs). However, during the secondary transplantation, recipients receiving total bone marrow (BM) from the primary recipients with BFP-positive HSCs showed significantly higher levels of donor chimerism and more robust multi-lineage chimerism compared to those receiving total BM from the primary recipients with BFP-negative HSCs. Our results indicate that deleting Hoxb5 in LT-HSCs transiently influences their lineage differentiation bias without compromising their long-term self-renewal capacity. These findings highlight the primary role of Hoxb5 in regulating lineage commitment decisions in LT-HSCs, while emphasizing that its presence is not indispensable for the maintenance of long-term self-renewal capacity.

RAF1 mutation leading to hypertrophic cardiomyopathy in a Chinese family with a history of sudden cardiac death: A diagnostic insight into Noonan syndrome.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is predominantly caused by mutations in sarcomeric genes. However, a subset of cases is attributed to genetic disorders unrelated to sarcomeric genes, such as Noonan syndrome (NS) and other RASopathies. In this study, we present a family with a history of sudden cardiac death (SCD) and focus on two adults with syndromic left ventricular hypertrophy (LVH). METHODS: Clinical evaluations, including echocardiography, were conducted to assess cardiac manifestations. Whole-exome sequencing was performed to identify potential genetic variants underlying syndromic LVH in the study participants. RESULTS: Whole-exome sequencing revealed a missense variant in the RAF1 gene, c.782C>T (p.Pro261Leu). This variant confirmed the diagnosis of NS in the affected individuals. CONCLUSION: The findings of this study underscore the importance of family history investigation and genetic testing in diagnosing syndromic LVH. By identifying the underlying genetic cause, clinicians can better understand the etiology of RAS-HCM and its association with SCD in young adults.

Mutation in mitral valve prolapse susceptible gene DCHS1 causes familial mitral annular disjunction.

BACKGROUND: Mitral annular disjunction (MAD) is an under-recognised phenotype associated with severe ventricular arrhythmias. Limited knowledge has been gained on its molecular genesis. METHODS: A total of 150 unrelated deceased Chinese were collected for whole-exome sequencing, with analysis focusing on a panel of 118 genes associated with 'abnormal mitral valve morphology'. Cases were prespecified as 'longitudinally extensive MAD (LE-MAD)' or 'longitudinally less-extensive MAD (LLE-MAD)' according to the gross disjunctional length with a cut-off of 4.0 mm. The pedigree investigation was conducted on a case carrying an ultra-rare (minor allele frequency <0.1%) deleterious variant in DCHS1. RESULTS: Seventy-seven ultra-rare deleterious variants were finally identified. Exclusively, 12 ultra-rare deleterious variants distributed in nine genes occurred in LE-MAD, which were ANK1, COL3A1, DCHS1, FBN2, GNPTAB, LZTR1, PLD1, RYR1 and VPS13B. Ultra-rare deleterious variants in those nine genes were predominantly distributed in LE-MAD compared with LLE-MAD (28% vs 5%, OR 7.30, 95% CI 2.33 to 23.38; p<0.001), and the only gene related to LE-MAD with borderline significance was DCHS1. LE-MAD was consistently observed in a sizeable Chinese family, in which LE-MAD independently co-segregated with an ultra-rare deleterious variant in DCHS1, rs145429962. CONCLUSION: This study initially proposed that isolated LE-MAD might be a particular phenotype of MAD with a complex genetic predisposition. Deleterious variants in DCHS1 might be associated with the morphogenesis of LE-MAD.

The characteristics of thoracic aortic dissection in autopsy-diagnosed individuals: An autopsy study.

Thoracic aortic dissection (TAD) is the most common cause of sudden cardiac death associated with aortic diseases. The age of TAD victims in forensic studies is significantly younger than hospitalized patients with TAD, while only a few studies have been conducted on autopsy-diagnosed TAD deceased. A retrospective study was conducted at the Medicolegal Center of Sun Yat-sen University from 1999 to 2019 to address the characteristics of TAD victims. A total of 200 deceased from spontaneous rupture of TAD were assessed, with 165 (82.5%) males and 175 (87.5%) Stanford type A deceased. Our main results showed that compared with patients with TAD diagnosed during their lifetime, individuals diagnosed with TAD until an autopsy showed an earlier onset (43.80 years old) and less accompanied hypertension (<50%). Sudden death was the initial symptom of 32 decedents. Instead of chest/back pain (40 decedents), abdominal pain (59 decedents) was the most common initial symptom, and 42 decedents presented with no accompanying pain. A higher proportion of abdominal pain and the painless symptom was associated with a higher risk of misdiagnosis. Women showed a more atypical clinical presentation and rapid progression than men. Younger decedents showed more pronounced left heart changes. The present study implicated the TAD individuals diagnosed until an autopsy as a particular entity, indicating the urgent need for further investigation on early diagnosis and pathogenesis of patients with TAD with atypical pain and painless or with younger age to reduce the burden of TAD-related sudden death.

Deep learning for denoising in a Mueller matrix microscope.

The Mueller matrix microscope is a powerful tool for characterizing the microstructural features of a complex biological sample. Performance of a Mueller matrix microscope usually relies on two major specifications: measurement accuracy and acquisition time, which may conflict with each other but both contribute to the complexity and expenses of the apparatus. In this paper, we report a learning-based method to improve both specifications of a Mueller matrix microscope using a rotating polarizer and a rotating waveplate polarization state generator. Low noise data from long acquisition time are used as the ground truth. A modified U-Net structured network incorporating channel attention effectively reduces the noise in lower quality Mueller matrix images obtained with much shorter acquisition time. The experimental results show that using high quality Mueller matrix data as ground truth, such a learning-based method can achieve both high measurement accuracy and short acquisition time in polarization imaging.

Epidemiology of Sports-Related Sudden Death in Guangdong Province.

OBJECTIVES: By retrospective study of the epidemiological characteristics of sports-related sudden death (SrSD), the risk factors associated with SrSD were analyzed and explored to provide a scientific basis for comprehensive prevention and treatment of SrSD. METHODS: The personal information (sex, age, occupation, etc.), case information (time, place, type of sports, relative time between SrSD occurrence and exercise, etc.), death related information (sign or prodrome, medical history and surgical history, etc.), rescue situation (witnesses, on-site assistance, the availability of paramedics, etc.) of 374 SrSD cases in Guangdong Province from 2017 to 2021 were collected. Statistical analysis was conducted aiming at the key factors. RESULTS: In the 374 cases, there were significantly more males than females (19.78:1); the number of people aged between >39 and 59 was the largest (151, 40.37%); non-manual workers (68.98%) were more than manual workers; the top three sports with the highest number cases were basketball (34.49%), running (19.52%) and badminton (12.03%); from 3 pm to 9 pm (63.10%) was the time period with the highest incidence of events; sudden death mainly occurred during exercise (75.27%) and within 1 h after exercise (20.05%); the on-site rescue rate was very low (6.15%); the rate of autopsies was extremely low (1.07%); sudden cardiac death was the most common cause (67.11%). CONCLUSIONS: SrSD is most common in males aged >39 to 59 years old, mostly in non-manual workers, and usually occurs in basketball and running. Sudden death is more likely to occur during exercise and within 1 h after exercise. Therefore, the above potential risk factors should be focused on and studied in daily comprehensive prevention and treatment to provide scientific basis for accurate prevention and first aid of such sudden death.

Assisting Role of Pulmonary Hypostasis Phenomenon in Diagnosis of Drowning.

OBJECTIVES: To study the phenomenon of pulmonary hypostasis in corpses of various causes of death, and to explore the potential value of this phenomenon in assisting forensic pathological diagnosis of drowning. METHODS: A total of 235 cases with clear cause of death through systematic autopsy were collected from January 2011 to June 2021 in Guangzhou. According to the location of body discovery, the cases were divided into the water body group (97 cases) and the non-water body group (138 cases), and the water body group was further divided into the water drowning group (90 cases) and the water non-drowning group (7 cases). Non-water body group was further divided into the non-water drowning group (1 case) and the non-water non-drowning group (137 cases). Three senior forensic pathologists independently reviewed autopsy photos to determine whether there was hypostasis in the lungs. The detection rate of pulmonary hypostasis was calculated. RESULTS: The detection rate of pulmonary hypostasis in the water drowning group (90 cases) was 0, and the negative rate was 100%. The detection rate of pulmonary hypostasis in the water non-drowning group (7 cases) was 100% and the negative rate was 0. The detection rate of pulmonary hypostasis in the water body group and in the non-water body group (after excluding 2 cases, 136 cases were calculated) was 7.22% and 87.50%, respectively. There were statistically significant differences in the detection rate of pulmonary hypostasis between water body group and non-water body group, and between water drowning group and water non-drowning group (P<0.05). CONCLUSIONS: The disappearance of pulmonary hypostasis can be used as a specific cadaveric sign to assist in the forensic pathological diagnosis of drowning.

Hoxb5 reprogrammes murine multipotent blood progenitors into haematopoietic stem cell-like cells.

OBJECTIVES: The expression of transcription factor Hoxb5 specifically marks the functional haematopoietic stem cells (HSC) in mice. However, our recent work demonstrated that ectopic expression of Hoxb5 exerted little effect on HSC but could convert B-cell progenitors into functional T cells in vivo. Thus, cell type- and development stage-specific roles of Hoxb5 in haematopoietic hierarchy await more extensive exploration. In this study, we aim to investigate the effect of Hoxb5 expression in multipotent blood progenitor cells. MATERIALS AND METHODS: A Mx1cre/RosaLSL-Hoxb5-EGFP/+ mouse model was used to evaluate the effect of Hoxb5 expression in blood multipotent progenitor cells (MPP). Golden standard serial transplantation experiments were used to test the long-term haematopoiesis potential of Hoxb5-expressing MPP. Single-cell RNA-seq analysis was used to characterize the gained molecular features of Hoxb5-expressing MPP and to compare with the global transcriptome features of natural adult HSC and fetal liver HSC (FL HSC). RESULTS: Here, with a mouse strain engineered with conditional expression of Hoxb5, we unveiled that induced expression of Hoxb5 in MPP led to the generation of a de novo Sca1+ c-kit+ CD11b+ CD48+ (CD11b+ CD48+ SK) cell type, which can repopulate long-term multilineage haematopoiesis in serial transplantations. RNA-seq analysis showed that CD11b+ CD48+ SK cells exhibited acquired features of DNA replication and cell division. CONCLUSIONS: Our current study uncovers that Hoxb5 can empower MPP with self-renewal ability and indicates an alternative approach for generating HSC-like cells in vivo from blood lineage cells.

Case Report: A report on the countermeasures after the rupture of the scalp venous indwelling needle catheter in 12 cases.

As a substitute for a scalp needle, the intravenous indwelling needle is easy to operate and easy to use. it is not only conducive to the rescue of critically ill children, improves nursing efficiency, but also avoids pain caused by repeated venipuncture. However, cases of indwelling needle catheter breaking and remaining in scalp vessels are rarely reported. This study collected 12 cases of scalp vein indwelling needle rupture and retention in scalp vessels in our center from January 2012 to January 2022. It was found that there were 7 males and 5 females, with an average age of 19.17 ± 8.96 months. The average length of the severed end was 15.00 ± 1.54 mm. In 8 cases, the catheter was broken during the haircut, and in 2 cases, the wall structure was damaged and broken after repeated folding of the catheter. In 2 cases, the children did not cooperate during extubation, the head twisted violently and the catheter was broken.5 cases tried to extract it by manipulation and hemostatic forceps, of which 4 cases were successful, and 1 case was successfully removed after the completion of three-dimensional computerized tomography (3D-CT) imaging positioning. The remaining 7 cases were removed by operation, and the success rate of the first operation was 100% in 4 cases who chose 3D-CT. The other 3 cases chose ordinary CT plain scan positioning, the success rate of the first operation was 66.6%, and one child was successfully removed after the second operation after the failure of the operation plus 3D-CT scan positioning. All the children were in stable condition after the operation and were discharged smoothly. When the broken catheter is relatively shallow and the scalp is not completely closed, we could choose the preliminary positioning of B-ultrasound or ordinary CT, and then try to remove it by manual squeezing combined with hemostatic forceps. However B-ultrasound and ordinary CT could not meet the requirements of accurate location, 3D-CT has a very important localization value for surgery, which can improve the success rate and help successfully remove the ruptured catheter.

Research Progress on Sport-Related Sudden Cardiac Death.

Physical exercise can reduce the overall risk of cardiovascular disease, prolong lifespan and improve the quality of life, but some studies have shown that there is a certain correlation between vigorous physical exercise and sudden cardiac death. A number of retrospective or prospective studies on sports-related sudden cardiac death (SrSCD) have been conducted at home and abroad. This article reviews the related studies on the definition, epidemiological characteristics, common causes of SrSCD and effects of excercise on cardiovascular function, pre-exercise screening and evaluation of SrSCD, in order to understand the latest research progress on SrSCD and provide clues and references for SrSCD research.

Exosomes: A new option for osteoporosis treatment.

Osteoporosis is a systemic bone disease characterized by reduced bone mass and destruction of bone microarchitecture, leading to increased bone fragility and susceptibility to fracture. However, the pathogenesis and molecular mechanisms of this disease remain unclear. Extracellular vesicles, structures originating from the plasma membrane and ranging from 30 nm to 5 µm in diameter, play an important role in intercellular communication in the bone microenvironment. Exosomes are extracellular vesicles that deliver cargo molecules, including endogenous proteins, lipids and nucleic acids. These cargo molecules are encapsulated in a lipid bilayer and internalized by target cells through receptor-ligand interactions or lipid membrane fusion. With the advancement of exosome research, exosome therapy for osteoporosis is fast becoming a research hotspot for researchers. This review aims to discuss the role of exosomes in the pathogenesis of osteoporosis. In addition, emerging diagnostic and therapeutic properties of exosomes are described to highlight the potential role of exosomes in osteoporosis.

Does Anatomic Phenotype of Mitral Annular Disjunction Impact Survival? An Autopsy-Based Retrospective Study.

Controversies have been raised regarding the prevalence and potential clinical significance of mitral annular disjunction (MAD). We aim to address the anatomic characteristics of MAD and their association, if any, on survival. We retrospectively reviewed 1373 consecutive dissected hearts (1017 men, mean age at death 44.9 ± 0.4 y) and frequently detected MAD (median disjunctional length: 2.0 mm, range: 1.5 mm~8.5 mm), with the prevalence of 92.1% over the entire mitral annulus and 74.9% within the posterior annulus (pMAD). The presence of pMAD was associated with increased all-cause mortality (45 y vs. 49 y, hazard ratio [HR]: 1.28, 95% confidence interval [CI]: 1.11~1.47, p < 0.001), which persisted in the context of cardiovascular diseases (CVDs; 46 y vs. 51 y, HR: 1.33, 95% CI: 1.14~1.56, p < 0.001) but was insignificant in those without CVDs. Compared to those without pMAD, individuals with pMAD affecting the entire posterior annulus or having a mean standardized length of ≥1.78 showed other clinically significant cardiovascular phenotypes, including the enlargement of aortic annular circumferences and a higher occurrence of thoracic aortic aneurysm/dissection. This largest series of autopsies show that MAD is a common phenotype that may exert additive influence on the survival of individuals. It is necessary to establish a precise classification and stratification of MAD.

Geometric optimization method for a polarization state generator of a Mueller matrix microscope.

We propose a geometric optimization method combined with the Coulombic energy indicator that can uniformly distribute N polarization states on the Poincaré sphere. Based on this method, we investigate the optimal frames of a rotating polarizer and rotating quarter-wave plate (RPRQ)-based polarization state generator (PSG) at different numbers of modulations. We use the PSG on a dual DoFP polarimeter-based Mueller matrix microscope to measure standard samples and pathological sections for testing the performance of an optimized RPRQ. The experimental results show that this method can effectively restrain noise and improve measurement accuracy.

Review and Thinking on Forensic Pathological Changes of Coronavirus-Infected Diseases.

Since the beginning of this century, three types of coronavirus have widely transmitted and caused severe diseases and deaths, which strongly indicates that severe infectious diseases caused by coronavirus infection are not accidental events. Coronavirus-infected diseases are mainly manifested by respiratory symptoms, with multiple organ dysfunctions. Precisely investigating the pathological process, characteristics and pathogenesis of coronavirus-infected diseases will be beneficial for us to understand clinical manifestations and provide targeted suggestions on prophylaxis and treatment. This paper briefly reviews the pathological findings of three known coronavirus-infected diseases, and attempts to construct the pathological spectrum of coronavirus-infected diseases, aiming to provide reference and thinking for autopsy, histopathological examination and animal infection model study of coronavirus-infected diseases.

Guide to forensic pathology practice for death cases related to coronavirus disease 2019 (COVID-19) (Trial draft).

Autopsy is of great significance for elucidating the pathological changes, pathogenesis and cause of death of Coronavirus Disease 2019 (COVID-19) and can provide a theoretical basis for scientific and accurate prevention and control of its outbreak. Based on related laws and regulations, such as the Law of the People's Republic of China on Prevention and Control of Infectious Diseases, clinical manifestations and epidemiological characteristics of COVID-19 and guidelines on the prevention and control of this epidemic, combined with the practical work of forensic pathology examinations, we developed the Guide to Forensic Pathology Practice for Death Cases Related to Coronavirus Disease 2019 (COVID-19) (Trial Draft). This guide describes the background investigation of the death cases, autopsy room requirements, personal prevention and protections, external examinations, autopsy practices and auxiliary examinations, and thus offers a reference for forensic and pathological examination institutions and staff.

Generation of hematopoietic cells from mouse pluripotent stem cells in a 3D culture system of self-assembling peptide hydrogel.

In vitro generation of hematopoietic stem cells from pluripotent stem cells (PSCs) can be regarded as novel therapeutic approaches for replacing bone marrow transplantation without immune rejection or graft versus host disease. To date, many different approaches have been evaluated in terms of directing PSCs toward different hematopoietic cell types, yet, low efficiency and no function restrict the further hematopoietic differentiation study, our research aims to develop a three dimension (3D) hematopoietic differentiation approach that serves as recapitulation of embryonic development in vitro to a degree of complexity not achievable in a two dimension culture system. We first found that mouse PSCs could be efficiently induced to hematopoietic differentiation with an expression of hematopoietic makers, such as c-kit, CD41, and CD45 within self-assembling peptide hydrogel. Colony-forming cells assay results suggested mouse PSCs (mPSCs) could be differentiated into multipotential progenitor cells and 3D induction system derived hematopoietic colonies owned potential of differentiating into lymphocyte cells. In addition, in vivo animal transplantation experiment showed that mPSCs (CD45.2) could be embedded into nonobese diabetic/severe combined immunodeficiency mice (CD45.1) with about 3% engraftment efficiency after 3 weeks transplantation. This study demonstrated that we developed the 3D induction approach that could efficiently promote the hematopoietic differentiation of mPSCs in vitro and obtained the multipotential progenitors that possessed the short-term engraftment potential.