Identification of an HLA-A*11:01-restricted neoepitope of mutant PIK3CA and its specific T cell receptors for cancer immunotherapy targeting hotspot driver mutations.

Hotspot driver mutations presented by human leukocyte antigens might be recognized by anti-tumor T cells. Based on their advantages of tumor-specificity and immunogenicity, neoantigens derived from hotspot mutations, such as PIK3CAH1047L, may serve as emerging targets for cancer immunotherapies. NetMHCpan V4.1 was utilized for predicting neoepitopes of PIK3CA hotspot mutation. Using in vitro stimulation, antigen-specific T cells targeting the HLA-A*11:01-restricted PIK3CA mutation were isolated from healthy donor-derived peripheral blood mononuclear cells. T cell receptors (TCRs) were cloned using single-cell PCR and sequencing. Their functionality was assessed through T cell activation markers, cytokine production and cytotoxic response to cancer cell lines pulsed with peptides or transduced genes of mutant PIK3CA. Immunogenic mutant antigens from PIK3CA and their corresponding CD8+ T cells were identified. These PIK3CA mutation-specific CD8+ T cells were subsequently enriched, and their TCRs were isolated. The TCR clones exhibited mutation-specific and HLA-restricted reactivity, demonstrating varying degrees of functional avidity. Identified TCR genes were transferred into CD8+ Jurkat cells and primary T cells deficient of endogenous TCRs. TCR-expressing cells demonstrated specific recognition and reactivity against the PIK3CAH1047L peptide presented by HLA-A*11:01-expressing K562 cells. Furthermore, mutation-specific TCR-T cells demonstrated an elevation in cytokine production and profound cytotoxic effects against HLA-A*11:01+ malignant cell lines harboring PIK3CAH1047L. Our data demonstrate the immunogenicity of an HLA-A*11:01-restricted PIK3CA hotspot mutation and its targeting therapeutic potential, together with promising candidates of TCR-T cell therapy.

High Pressure-Temperature Study of MgF2, CaF2, and BaF2 by Raman Spectroscopy: Phase Transitions and Vibrational Properties of AF2 Difluorides.

The phase transition of AF2 difluorides strongly depends on pressure, temperature, and cationic radius. Here, we have investigated the phase transition of three difluorides, including MgF2, CaF2, and BaF2, at simultaneously high pressures and temperatures using Raman spectroscopy and X-ray diffraction in externally heated diamond anvil cells up to 55 GPa at 300-700 K. Rutile-type difluoride MgF2 with a small cationic radius undergoes a transition to the CaCl2-type phase at 9.9(1) GPa and 300 K, to the HP-PdF2-type phase at 21.0(2) GPa, and to the cotunnite-type phase at 44.2(2) GPa. The phase transition pressure to the HP-PdF2 and cotunnite structure at 300 K for our single crystal was found to be higher than that in previous studies using polycrystalline samples. Elevating the temperature increases the transition pressure from rutile- to the CaCl2-type phase but has a negative influence on the transition pressure when MgF2 transforms from the HP-PdF2- to cotunnite-type phase. Meanwhile, the transition pressure from the CaCl2- to HP-PdF2-type phase for MgF2 was identified to be independent of the temperature. Raman peaks suspected to belong to the α-PbO2-type phase were observed at 14.6-21.0(1) GPa and 400-700 K. At 300 K, difluorides CaF2 and BaF2 in the fluorite structure with larger cationic radii transform to the cotunnite-type phase at 9.6(3) and 3.0(3) GPa at 300 K, respectively, and BaF2 further undergoes a transition to the Ni2In-type phase at 15.5(4) GPa. For both CaF2 and BaF2, elevating the temperature leads to a lower transition pressure from fluorite- to the cotunnite-type phase but has little influence on the transition to the Ni2In structure. Raman data provide valuable insights for mode Grüneisen parameters. We note that the mode Grüneisen parameters for both difluorides and dioxides vary linearly with the cation radius. Further calculations for the mode Grüneisen parameters at high pressures for MgF2, CaF2, and BaF2 yield a deeper understanding of the thermodynamic properties of the difluorides.

Matching actions to needs: shifting policy responses to the changing health needs of Chinese children and adolescents.

China is home to the second largest population of children and adolescents in the world. Yet demographic shifts mean that the government must manage the challenge of fewer children with the needs of an ageing population, while considering the delicate tension between economic growth and environmental sustainability. We mapped the health problems and risks of contemporary school-aged children and adolescents in China against current national health policies. We involved multidisciplinary experts, including young people, with the aim of identifying actionable strategies and specific recommendations to promote child and adolescent health and wellbeing. Notwithstanding major improvements in their health over the past few decades, contemporary Chinese children and adolescents face distinct social challenges, including high academic pressures and youth unemployment, and new health concerns including obesity, mental health issues, and sexually transmitted infections. Inequality by gender, geography, and ethnicity remains a feature of health risks and outcomes. We identified a mismatch between current health determinants, risks and outcomes, and government policies. To promote the health of children and adolescents in China, we recommend a set of strategies that target government-led initiatives across the health, education, and community sectors, which aim to build supportive and responsive families, safe communities, and engaging and respectful learning environments. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Machine learning in risk prediction of continuous renal replacement therapy after coronary artery bypass grafting surgery in patients.

OBJECTIVES: This study aimed to develop machine learning models for risk prediction of continuous renal replacement therapy (CRRT) following coronary artery bypass grafting (CABG) surgery in intensive care unit (ICU) patients. METHODS: We extracted CABG patients from the electronic medical record system of the hospital. The endpoint of this study was the requirement for CRRT after CABG surgery. The Boruta method was used for feature selection. Seven machine learning algorithms were developed to train models and validated using 10 fold cross-validation (CV). Model discrimination and calibration were estimated using the area under the receiver operating characteristic curve (AUC) and calibration plot, respectively. We used the SHapley Additive exPlanations (SHAP) method to illustrate the effects of the features attributed to the model and analyze the effects of individual features on the output of the mode. RESULTS: In this study, 72 (37.89%) patients underwent CRRT, with a higher mortality compared to those patients without CRRT. The Gaussian Naïve Bayes (GNB) model with the highest AUC were considered as the final predictive model and performed best in predicting postoperative CRRT. The analysis of importance revealed that cardiac troponin T, creatine kinase isoenzyme, albumin, low-density lipoprotein cholesterol, NYHA, serum creatinine, and age were the top seven features of the GNB model. The SHAP force analysis illustrated how created model visualized individualized prediction of CRRT. CONCLUSIONS: Machine learning models were developed to predict CRRT. This contributes to the identification of risk variables for CRRT following CABG surgery in ICU patients and enables the optimization of perioperative managements for patients.

Ni-catalysed assembly of axially chiral alkenes from alkynyl tetracoordinate borons via 1,3-metallate shift.

Asymmetric synthesis based on a metallate shift of tetracoordinate borons is an intriguing and challenging topic. Despite the construction of central chirality from tetracoordinate boron species via a 1,2-metallate shift, catalytic asymmetric synthesis of axially chiral compounds from such boron 'ate' complexes is an ongoing challenge. Axially chiral alkenes have received great attention due to their unique characteristics and intriguing molecular scaffolds. Here we report an enantioselective nickel-catalysed strategy for the construction of axially chiral alkenes via a 1,3-metallate shift of alkynyl tetracoordinate boron species. The chemoselectivity, regioselectivity and atroposelectivity can be regulated and well-controlled from readily accessible starting materials with a cheap transition-metal catalyst. Downstream transformations indicate the powerful conversion ability of such compounds in this protocol, and late-stage elaborations of bioactive compounds can also be achieved. Mechanistic experiments reveal that regioselective syn-addition of an aryl-Ni complex with a carbon-carbon triple bond and subsequent 1,3-phenyl migration are the two key steps for the synthesis of axially chiral alkenes.

Assessing the price levels of medical service and influential factors: evidence from China.

BACKGROUND: Medical service prices play a crucial role in cost containment in China. This study aimed to assess the change in medical service price levels at the macro level and the relationship with relevant macroeconomic factors. METHODS: Data from the 2022 China Statistics Yearbook, the 2022 China Health Statistics Yearbook, and the 2020 China National Health Accounts Report were used. Time trends of health price levels, utilization, and health expenditure were examined. A time-series regression model was employed to measure the impact of service utilization and medical service prices on total medical service expenditure growth from 2000 to 2021. The Johansen cointegration test was conducted to test the cointegrating relationship between medical service price levels and total medical service expenditure, average wage of employees and CPI. The Granger causality test was performed to observe the direction of causality. RESULTS: Descriptive analyses showed consistent growth in utilization and medical service price levels from 2000 to 2021. The time-series model indicated that medical service expenditure was influenced by the rise in inpatient admissions and price levels of medical service and medicine. The Johansen cointegration test identified a long-term equilibrium relationship between medical service price levels and total medical service expenditure, average wage and CPI. The change in medical service price levels was the Granger cause of the change in medical service expenditure, but it had no impact on average wage and CPI. However, the change in medical service price levels was influenced by these three macroeconomic factors. CONCLUSIONS: The growth of medical service expenditure in China was driven by inpatient use and price level. There was a long-term equilibrium relationship between medical service price levels and relevant macroeconomic factors. However, medical service price levels only affected medical service expenditure and have no impact on average wage and CPI. It is necessary to improve the value transmission mechanism of medical service prices.

Glycine recalibrates iron homeostasis of lens epithelial cells by blocking lysosome-dependent ferritin degradation.

One of the major pathological processes in cataracts has been identified as ferroptosis. However, studies on the iron metabolism mechanism in lens epithelial cells (LECs) and the methods of effectively alleviating ferroptosis in LECs are scarce. Along these lines, we found that in the ultraviolet radiation b (UVB) induced cataract model in vitro and in vivo, the ferritin of LECs is over-degraded by lysosomes, resulting in the occurrence of iron homeostasis disorder. Glycine can affect the ferritin degradation through the proton-coupled amino acid transporter (PAT1) on the lysosome membrane, further upregulating the content of nuclear factor erythrocyte 2 related factor 2 (Nrf2) to reduce the damage of LECs from two aspects of regulating iron homeostasis and alleviating oxidative stress. By co-staining, we further demonstrate that there is a more sensitive poly-(rC)-binding protein 2 (PCBP2) transportation of iron ions in LECs after UVB irradiation. Additionally, this study illustrated the increased expression of nuclear receptor coactivator 4 (NCOA4) in NRF2-KO mice, indicating that Nrf2 may affect ferritin degradation by decreasing the expression of NCOA4. Collectively, glycine can effectively regulate cellular iron homeostasis by synergistically affecting the lysosome-dependent ferritin degradation and PCBP2-mediated ferrous ion transportation, ultimately delaying the development of cataracts.

Nuclear factor-KB signaling pathway and gender differences in alcoholic liver fibrosis / 解剖学报

Objective To investigate the relationship between nuclear factor(NF)-κB signaling pathway and gender differences in alcoholic liver fibrosis. Methods C57BL/6 N mice at 7-8 weeks of age were randomly divided into: male normal group, male model group, female normal group and female model group of 20 mice each. The normal group was fed with control liquid diet for 8 weeks, and the model group was fed with alcoholic liquid diet for 8 weeks combined with 31.5% ethanol gavage (5g/kg twice a week) to establish an alcoholic liver fibrosis model. The mice were executed at the end of 8 weekends, and the alanine aminotransferase (ALT), aspartate aminotransferase (AST) activity, estradiol (E

Alterations in nasal microbiota of patients with amyotrophic lateral sclerosis / 中华医学杂志(英文版)

BACKGROUND@#Links between alterations in gut microbiota composition and amyotrophic lateral sclerosis (ALS) have previously been reported. This study aimed to examine the microbiota in the nasal cavity of ALS.@*METHODS@#Sixty-six ALS patients and 40 healthy caregivers who live in close proximity with patients were enrolled. High throughput metagenomic sequencing of the 16S ribosomal deoxyribonucleic acid (rDNA) gene V3-V4 region of nasal microbiota was used to characterize the alpha and beta diversity and relative abundance of bacterial taxa, predict function, and conduct correlation analysis between specific taxa and clinical features.@*RESULTS@#The nasal microbiome of ALS patients showed lower alpha diversity than that of corresponding healthy family members. Genera Gaiella , Sphingomonas , Polaribacter _1, Lachnospiraceae _NK4A136_group, Klebsiella , and Alistipes were differentially enriched in ALS patients compared to controls. Nasal microbiota composition in ALS patients significantly differed from that in healthy subjects (unweighted UniFrac P = 0.001), while Linear discriminant analysis Effect Size (LEfSe) analysis indicated that Bacteroidetes and Firmicutes dominated healthy nasal communities at the phylum level, whereas Actinobacteria was the predominant phylum and Thermoleophilia was the predominant class in ALS patients. Genus Faecalibacterium and Alistipes were positively correlated with ALS functional rating scale revised (ALSFRS-R; rs = 0.349, P = 0.020 and rs = 0.393, P = 0.008), while Prevotella -9 and Bacteroides operational taxonomic units (OTUs) were positively associated with lung function (FVC) in ALS patients ( rs = 0.304, P = 0.045, and rs = 0.300, P = 0.048, respectively). Prevotella -1 was positively correlated with white blood cell counts (WBC, rs = 0.347, P = 0.021), neutrophil percentage (Neu%, rs = 0.428, P = 0.004), and neutrophil-to-lymphocyte ratio (NLR, rs = 0.411, P = 0.006), but negatively correlated with lymphocyte percentage (Lym%, rs = -0.408, P = 0.006). In contrast, Streptococcus was negatively associated with Neu% ( rs = -0.445, P = 0.003) and NLR ( rs = -0.436, P = 0.003), while positively associated with Lym% ( rs = 0.437, P = 0.003). No significant differences in nasal microbiota richness and evenness were detected among the severe and mild ALS patients.@*CONCLUSIONS@#ALS is accompanied by altered nasal microbial community composition and diversity. The findings presented here highlight the need to understand how dysbiosis of nasal microbiota may contribute to the development of ALS.

Specific PCR for Identification of Astragalus membranaceus var. mongholicus Seeds， A. membranaceus Seeds， and Adulterants / 中国实验方剂学杂志

ObjectiveTo establish a method based on specific polymerase chain reaction （PCR） that can accurately and rapidly identify Astragalus membranaceus var. mongholicus （AMM） seeds and A. membranaceus （AM） seeds. MethodThe Chloroplast Genome Information Resource （CGIR） and IdenDSS were used to obtain the characteristic DNA fragments of AMM and AM， and the specific single nucleotide polymorphism （SNP） sites of AMM and AM were screened out， on the basis of which the specific primers MG-F/MG-R of AMM and MJ-F/MJ-R of AM were designed. The specific PCR method for identifying AMM and AM was established and optimized， and the specificity and applicability of the method were investigated. ResultThe specific PCR conditions for the identification of AMM were primers MG-F/MG-R， annealing at 62 ℃， and 28 cycles. After PCR amplification and gel electrophoresis， the specific band appeared at about 220 bp， with no band for the seeds of AM or adulterants. The specific PCR conditions for identifying the AM were primers MJ-F/MJ-R， annealing at 58 ℃， and 28 cycles. After PCR amplification and gel electrophoresis， the band appeared at about 150 bp， with no band of AMM or adulterants. ConclusionThe specific PCR method established in this study can accurately and quickly identify the seeds of AMM and AM， which provides a basis for the classification and accurate identification of Astragalus seeds and adulterants.

Methods for Identifying Seeds of Chinese Medicinal Materials： A Review / 中国实验方剂学杂志

Seeds are the source for the production of Chinese medicinal materials. The seed authenticity and quality of directly affect the effectiveness and safety of Chinese medicinal materials. The seed quality is faced with the problems such as mixed sources， existence of adulterants and seeds stocked for years， low maturity， and low purity. To ensure the high-quality and sustainable development of the Chinese medicinal material industry， it is urgent to standardize the seed market and identify and evaluate the quality of the seeds circulating in the market. Seed identification methods include visual inspection， microscopic observation， micro-character identification， chemical fingerprinting， molecular identification， electronic nose， X-ray diffraction， electrochemical fingerprinting， spectral imaging， and artificial intelligence. These methods have different application scopes and unique advantages and disadvantages. According to the different species of Chinese herbal medicines and different requirements of testing sites， suitable methods can be selected to achieve rapid and accurate identification with low costs. In the future， the seed identification methods should be developed based on emerging technologies with interdisciplinary knowledge， and intelligent， nondestructive， and single-grain detection methods are needed for the modern Chinese medicinal material industry. This paper introduces the seed identification technologies currently applied in research and production， compares the principles， applicability， advantages， and disadvantages of different technologies， and provides an outlook on the future development of seed identification technologies， aiming to provide a reference for the identification and quality evaluation of seeds of Chinese medicinal material.

Towards responsive policy and actions to address non-communicable disease risks amongst adolescents in Indonesia: insights from key stakeholders.

Background: Non-communicable diseases (NCDs) such as cancer, diabetes, heart disease, mental disorder and chronic lung conditions are the leading cause of death and disability in Indonesia. Adolescence is when risks for NCDs emerge and it is also an important life stage for intervention, yet young people are often at the margins of NCD policy and actions. This study aimed to understand how policies and actions should address NCD risks (tobacco smoking, inadequate physical activity, and diet) for adolescents in Indonesia, and how young people can be meaningfully involved. Methods: Qualitative in-depth interviews over videoconference (n = 21) were conducted in English or Bahasa with stakeholders in Indonesia. Participants included policymakers, implementation partners, and advocates who were focused on adolescent health or NCDs. Interviews were recorded, transcribed, translated, and thematically analysed using NVivo12. Findings were disseminated to participants for validation and feedback. Youth participants (n = 7) attended an additional workshop and considered recommendations and actions arising from this research. Findings: Participants identified that government and non-government organisations are acting on NCDs in Indonesia, but few of the existing initiatives target adolescents, and adolescent services rarely addressed NCD risks. Participants also felt that policies to protect adolescents from NCD risks (i.e., smoke-free areas in public) were not always enforced. For programs or initiatives focused on adolescent health, those that had engaged adolescents as co-creators and leaders were perceived to be more successful. As such, participants recommended more meaningful engagement of young people, including young people's leadership of initiatives. Additional recommendations included the need for intersectoral engagement and a 'whole-of-government' approach to prevention given the complex determinants of NCD risks, and the need for evidence-based actions that are underpinned by quality data to enable monitoring of progress. Interpretation: There is a recognised need to strengthen policies and actions to address NCD risks amongst adolescents in Indonesia. Meaningful youth engagement that allows young people to take the lead, intersectoral actions, and evidence-based data driven responses were key strategies identified. Funding: UNICEF East Asia and Pacific Regional Office.

Spatial price differences of medical services: evidence from the Yangtze River Delta in China.

BACKGROUND: Price differences of medical services across regions may affect equity in health financing. This study aimed to estimate the spatial price index of medical services to measure price levels across regions in the Yangtze River Delta, China. METHODS: Gini-Éltetö-Köves-Szulc method and minimum spanning tree method based on the purchasing power parities were used in this study. RESULTS: According to the Gini-Éltetö-Köves-Szulc method, Shanghai and Anhui province had price levels that are 127.55% and 103.45% respectively of the price level in Zhejiang province, whereas in Jiangsu medical services were priced at 92.71% of that in Zhejiang province. The spatial price index of medical services in the Yangtze River Delta based on the minimum spanning tree method provided similar results. CONCLUSIONS: Regions in the Yangtze River Delta had significant gaps in medical services price levels. And the price levels tended to not correlate with socioeconomic levels. It is necessary to promote the regional coordination of medical services price and better achieve equity in health.

Nanoreactor based on Cu nanoparticles confined in B, N co-doped porous carbon nanotubes for glutathione biosensing.

A cost-effective approach has been developed to synthesize Cu nanoparticles encapsulated into B and N double-doped carbon nanotubes (Cu@BCNNTs) by one-step pyrolysis. According to the specific binding of Cu-Cl and Cu-glutathione (GSH), we employed Cu@BCNNTs to build an electrochemical sensing platform to detect GSH. The unique space-confined structure can prevent Cu nanoparticles from agglomeration. In addition, B and N co-doped porous hollow tubes can improve the electrochemical conductivity, expand the number of active sites, enhance surface adsorption, and shorten the transport path. These favorable characteristics of Cu@BCNNTs make them have excellent electrocatalytic properties. These results display that the prepared sensor can detect GSH from 0.5 to 120 µM with a detection limit of 0.024 µM. The obtained sensors can be successfully applied in the human serum with recovery of GSH ranging from 100.2 to 103.9%. This work provides a new vision to synthesize nanoparticles confined in a hollow tube for the applications in biosensing and medical diagnostics.

Seasonal variations, source apportionment and dry deposition of chemical species of total suspended particulate in Pengjia Yu Island, East China Sea.

Total of 172 total suspended particulate (TSP) samples and its chemical compositions were collected and analyzed from January to December 2010 in Pengjia Yu Island, an open region in East China Sea (ECS). Despite the predominance of sea-salt major ions (Na+, Cl-), the presence of non-sea-salt SO42- (nss-SO42-) and NO3- as well as combustion-derived trace metals clearly establishes the impact of anthropogenic sources over ECS. The annual contributions of coal, heavy-fuel oil and traffic to the measured chemical species were 21.0 %, 15.0 % and 15.5 %, respectively. Especially in spring, the contributions of crustal minerals to measured chemical species during dust period (33.6 %) were higher than that (13.2 %) during non-dust period. The calculated annual average dry deposition fluxes for trace metals and total inorganic nitrogen were 246.1 ± 345.8 µg/m2/d and 2950.4 ± 2245.0 µg/m2/d, suggesting that atmospheric deposition is an important source of nutrient elements for the south of ECS.

Atorvastatin ameliorates lipid overload-induced mitochondrial dysfunction and myocardial hypertrophy by decreasing fatty acid oxidation through inactivation of the p-STAT3/CPT1 pathway.

Although statins are shown to have cardiac pleiotropic effects independent of lowering cholesterol, the underlying mechanism remains unclear. Mitochondrial dysfunction induced by increased fatty acid oxidation (FAO) is the culprit in the development of cardiac hypertrophy and dysfunction. This study was to explore whether the cardiac pleiotropic effects of atorvastatin were associated with FAO regulation, with a specific focus on carnitine palmitoyltransferase 1 (CPT1). High-fat diet (HFD)-fed mice and palmitic acid (PA)-stimulated neonatal rat primary cardiomyocytes (NRCMs) were treated with atorvastatin, with or without FAO modulators, signal transducer and activator of transcription 3 (STAT3) agonist, and inhibitor. Atorvastatin (3 mg/kg) did not reduce serum cholesterol levels in HFD-fed mice but ameliorated mitochondrial dysfunction and cardiac hypertrophy. In vitro, atorvastatin and the FAO inhibitor alleviated PA-induced mitochondrial dysfunction and cardiomyocyte hypertrophy. However, the FAO enhancer eliminated atorvastatin's protective effects. Furthermore, atorvastatin decreased CPT1 and FAO levels and prevented STAT3 phosphorylation and nuclear translocation. STAT3 inhibitor had the same inhibitory effects as atorvastatin on CPT1, FAO levels, and cardiomyocyte hypertrophy, whereas STAT3 agonist disrupted these effects of atorvastatin. Our results demonstrate that atorvastatin decreases myocardial FAO by inactivating the p-STAT3/CPT1 signaling pathway, which improves lipid overload-induced mitochondrial dysfunction and cardiac hypertrophy in a cholesterol-independent manner. This is the first study to explore the cardiac pleiotropic effects of atorvastatin with respect to FAO. However, whether atorvastatin regulates FAO in the cardiac hypertrophy model induced by other variables has not been investigated in this work, and this is expected to be performed in the future.

Endothelial-mesenchymal transition as a novel mechanism for generating myofibroblasts during wound healing and scarring.

BACKGROUND: The endothelial-mesenchymal transition (EndMT) is an important mechanism in tissue regeneration and the development of organ fibrosis. Whether EndMT occurs in wound healing and scarring remains unknown. MATERIALS AND METHODS: The isolated cells from the normal dermal tissue and the wound tissue of mouse with full-thickness skin wound, and human scar tissue sections were performed with CD31/factorVII and α-SMA immunohistochemical staining and H and E staining. The ratio of factor VII or CD31/α-SMA double-positive cells in factor VII-positive cells was assessed in the isolated cells and in scar tissues. RESULTS: In this study, we found that approximately 27-60% of ECs coexpressed VII factor and α-SMA in the isolated cells from the wound tissues of mice, which was significantly higher than that of normal dermal tissue cells. Accordingly, the number of CD31/α-SMA double-positive cells in mouse wound tissue sections was also significantly more than that in normal dermal tissue sections. In scar tissues, in addition to high-density microvessels, a large number of proliferative ECs in scar strama and CD31/α-SMA double-positive cells were also found. Approximately 46.82 to 84.11% of ECs and 68.77 to 95.25% of myofibroblasts coexpressed VII factor and α-SMA, and these two values in hypertrophic scars were significantly higher than those in keloids. CONCLUSION: These results confirmed that ECs might contribute to the emergence of myofibroblasts in the wound and scar tissue via the process of EndMT.

Four-corners traction combined with continuous everting suture technique as a modification in bicaval anastomosis for orthotopic heart transplantation.

BACKGROUND: Although standard bicaval techniques has become popular in orthotopic heart transplantation, distortion, bleeding, thrombosis and arrhythmia were still causes for concern. This study was designed to compare the standard bicaval techniques and modified bicaval techniques in our institution. MATERIALS AND METHODS: A total of 70 recipients underwent orthotopic heart transplantation at our center from June 2015 to April 2019 (standard group = 24 cases, modified group = 46 cases). The average follow-up period was 46.4 ± 17.4 months. Atrioventricular cavity diameter was measured by ultrasonography and left atrial morphology was evaluated by CT-angiography and three-dimensional reconstruction. RESULTS: Recipients in both groups were similar with pre-operative characteristics. Total ischemic, cardiopulmonary bypass and cross-clamp times were similar. The modified bicaval techniques group has a significantly fewer blood transfusion, lower post-transplant tricuspid regurgitation grade and the incidence of post-operative atrial arrhythmia than standard bicaval techniques group. CT-angiography and three-dimensional reconstruction illustrated ideal and physiologic left atrial morphological structure. Short-term survival differed significantly and the cumulative proportion of survival was significantly higher in the modified bicaval techniques group than that in the standard bicaval techniques group. CONCLUSIONS: This study showed that modified bicaval techniques offers a better early outcome than standard bicaval techniques. The significant reduction of intraoperative blood transfusion and post-transplant tricuspid regurgitation grade in the modified bicaval techniques group may has a major impact on the short-term survival.

Bioinformatics analysis and identification to immune-related markers of osteoporosis / 细胞与分子免疫学杂志

Objective To identify immune-related dysregulation mechanisms and potential diagnostic predictive biomarkers in osteoporosis. Methods Gene expression data for both osteoporosis and control populations were retrieved from the GSE35958 and GSE56815 datasets. Immune-related differentially expressed genes (DEGs) were obtained by screening DEGs and were compared with the immunology database and analysis portal (ImmPort) database. Enrichment analysis of these immune-related DEGs was conducted using the Clusterprofiler software package. A protein-protein interaction network was built with the STRING database, which is a search tool for finding interacting genes/proteins, and the top 10 genes with the highest network connectivity were identified as candidate genes. Subsequently, the diagnostic predictive effect of candidate genes was evaluated using receiver operating characteristic (ROC) curves, logistic regression, and column plots. Finally, PCR and Western blot analysis were applied to detect the differential expression of these genes in bone marrow tissue of patients with osteoporosis. Results A total of 138 immune-related DEGs were obtained through intersection analysis. The results of the enrichment analysis indicated that these genes were involved in biological functions such as immune inflammation and signaling pathways including T cell receptors, mitogen activated protein kinase (MAPK), rat sarcoma virus oncogene homologs (Ras), osteoclast differentiation, and B cell receptors. In addition, among the candidate genes, upregulated vascular endothelial growth factor A (VEGFA) and epidermal growth factor receptor (EGFR) and downregulated AKT1, SRC, and JUN in osteoporosis showed the highest connectivity. Among them, VEGFA, EGFR, JUN, and AKT1 demonstrated the best diagnostic predictive value. Conclusion The screening of immune-related DEGs will enhance the understanding of osteoporosis and facilitate the development of immunotherapy targets.

Observation on the clinical outcomes of continued pregnancy following cesarean scar pregnancy in 55 women / 中华妇产科杂志

Objective:To observe the clinical outcomes of continued pregnancy in pregnant women with cesarean scar pregnancy (CSP).Methods:A retrospective analysis was performed on the pregnancy outcomes of 55 pregnant women who were diagnosed with CSP at the Second Affiliated Hospital of Army Medical University during the first trimester of pregnancy from August 1st, 2018 to October 31st, 2021 and strongly requested to continue the pregnancy.Results:Of the 55 pregnant women, 15 terminated the pregnancy in the first trimester, 1 underwent hysterotomy at 23 weeks of gestation due to cervical dilation, and 39 (71%, 39/55) continued pregnancy to the third trimester achieving live births via cesarean section. The gestational age of the 39 pregnant women delivered by cesarean section was 35 +6 weeks (range: 28 +5-39 +2 weeks), of whom 7 cases at 28 +5-33 +6 weeks, 20 cases at 34-36 +6 weeks, and 12 cases at 37-39 +2 weeks. The results of pathological examination were normal placenta in 3 cases (8%, 3/39), placenta creta in 4 cases (10%, 4/39), placenta increta in 9 cases (23%, 9/39) and placenta percreta in 23 cases (59%, 23/39). Among the 36 pregnant women who were pathologically confirmed as placenta accreta spectrum disorders (PAS) after surgery, the last prenatal ultrasonography showed placenta previa in 27 cases (75%, 27/36) and not observed placenta previa in 9 cases. The median intraoperative blood loss, autologous blood transfusion, and allogeneic suspended red blood cell infusion of 39 pregnant women during cesarean section were 1 000 ml (300-3 500 ml), 300 ml (0-2 000 ml) and 400 ml (0-2 400 ml), respectively. The uterine preservation rate was 100% (39/39), and only 1 case received cystostomy due to intracystic hemorrhage. The birth weight of the newborn was 2 580 g (1 350-3 800 g), and 1 case of mild asphyxia. Conclusions:Pregnant women with CSP who continue pregnancy under close monitoring after adequate ultrasound evaluation and doctor-patient communication could achieve better maternal and infant outcomes, but pregnant women with CSP are highly likely to continue pregnancy and develop into PAS. Effective hemostasis means and multidisciplinary team cooperation are needed in perinatal period for ensuring maternal and fetal safety.