Spatial metabolomics reveals key features of hippocampal lipid changes in rats with postoperative cognitive dysfunction.

Postoperative cognitive dysfunction (POCD) is a common complication after cardiac surgery. Numerous evidence suggest that dysregulation of lipid metabolism is associated with cognitive impairment; however, its precise role in the development of POCD is still obscure. In this study, we established a cardiopulmonary bypass (CPB) model in rats and employed the Barnes maze to assess cognitive function, selecting POCD rats for subsequent experimentation. Utilizing mass spectrometry imaging, we detected plenty of lipids accumulates within the hippocampal CA1in the POCD group. Immunofluorescence staining revealed a significant reduction in the fluorescence intensity of calcium-independent phospholipases A2 (iPLA2) in the POCD group compared to the control, while serine palmitoyl transferase (SPT) was markedly increased in the POCD group. Transmission electron microscopy revealed that the number of synapses in hippocampal CA1decreased significantly and postsynaptic density became thinner in POCD group. Furthermore, after reversing the metabolic disorders of iPLA2 and SPT in the rat brain with docosahexaenoic acid and myriocin, the incidence of POCD after CPB was significantly reduced and the disrupted lipid metabolism in the hippocampus was also normalized. These findings may offer a novel perspective for exploring the etiology and prevention strategies of POCD after CPB.

Composite Aerogel Scaffolds Containing Flexible Silica Nanofiber and Tricalcium Phosphate Enable Skin Regeneration.

Poor hemostatic ability and less vascularization at the injury site could hinder wound healing as well as adversely affect the quality of life (QOL). An ideal wound dressing should exhibit certain characteristics: (a) good hemostatic ability, (b) rapid wound healing, and (c) skin appendage formation. This necessitates the advent of innovative dressings to facilitate skin regeneration. Therapeutic ions, such as silicon ions (Si4+) and calcium ions (Ca2+), have been shown to assist in wound repair. The Si4+ released from silica (SiO2) can upregulate the expression of proteins, including the vascular endothelial growth factor (VEGF) and alpha smooth muscle actin (α-SMA), which is conducive to vascularization; Ca2+ released from tricalcium phosphate (TCP) can promote the coagulation alongside upregulating the expression of cell migration and cell differentiation related proteins, thereby facilitating the wound repair. The overarching objective of this study was to exploit short SiO2 nanofibers along with the TCP to prepare TCPx@SSF aerogels and assess their wound healing ability. Short SiO2 nanofibers were prepared by electrospinning and blended with varying proportions of TCP to afford TCPx@SSF aerogel scaffolds. The TCPx@SSF aerogels exhibited good cytocompatibility in a subcutaneous implantation model and manifested a rapid hemostatic effect (hemostatic time 75 s) in a liver trauma model in the rabbit. These aerogel scaffolds also promoted skin regeneration and exhibited rapid wound closure, epithelial tissue regeneration, and collagen deposition. Taken together, TCPx@SSF aerogels may be valuable for wound healing.

Selenium and Bacillus proteolyticus SES increased Cu-Cd-Cr uptake by ryegrass: highlighting the significance of key taxa and soil enzyme activity.

Many studies have focused their attention on strategies to improve soil phytoremediation efficiency. In this study, a pot experiment was carried out to investigate whether Se and Bacillus proteolyticus SES promote Cu-Cd-Cr uptake by ryegrass. To explore the effect mechanism of Se and Bacillus proteolyticus SES, rhizosphere soil physiochemical properties and rhizosphere soil bacterial properties were determined further. The findings showed that Se and Bacillus proteolyticus SES reduced 23.04% Cu, 36.85% Cd, and 9.85% Cr from the rhizosphere soil of ryegrass. Further analysis revealed that soil pH, organic matter, soil enzyme activities, and soil microbial properties were changed with Se and Bacillus proteolyticus SES application. Notably, rhizosphere key taxa (Bacteroidetes, Actinobacteria, Firmicutes, Patescibacteria, Verrucomicrobia, Chloroflexi, etc.) were significantly enriched in rhizosphere soil of ryegrass, and those taxa abundance were positively correlated with soil heavy metal contents (P < 0.01). Our study also demonstrated that in terms of explaining variations of soil Cu-Cd-Cr content under Se and Bacillus proteolyticus SES treatment, soil enzyme activities (catalase and acid phosphatase) and soil microbe properties showed 42.5% and 12.2% contributions value, respectively. Overall, our study provided solid evidence again that Se and Bacillus proteolyticus SES facilitated phytoextraction of soil Cu-Cd-Cr, and elucidated the effect of soil key microorganism and chemical factor.

Single-cell RNA sequencing reveals recruitment of the M2-like CCL8high macrophages in Lewis lung carcinoma-bearing mice following hypofractionated radiotherapy.

BACKGROUND: Tumor-associated macrophages (TAMs) play a pivotal role in reshaping the tumor microenvironment following radiotherapy. The mechanisms underlying this reprogramming process remain to be elucidated. METHODS: Subcutaneous Lewis lung carcinoma (LLC) murine model was treated with hypofrationated radiotherapy (8 Gy × 3F). Single-cell RNA sequencing was utilized to identify subclusters and functions of TAMs. Multiplex assay and enzyme-linked immunosorbent assay (ELISA) were employed to measure serum chemokine levels. Bindarit was used to inhibit CCL8, CCL7, and CCL2. The infiltration of TAMs after combination treatment with hypofractionated radiotherapy and Bindarit was quantified with flow cytometry, while the influx of CD206 and CCL8 was assessed by immunostaining. RESULTS: Transcriptome analysis identified a distinct subset of M2-like macrophages characterized by elevated Ccl8 expression level following hypofractionated radiotherapy in LLC-bearing mice. Remarkbly, hypofractionated radiotherapy not only promoted CCL8high macrophages infiltration but also reprogrammed them by upregulating immunosuppressive genes, thereby fostering an immunosuppressive tumor microenvironment. Additioinally, hypofractionated radiotherapy enhanced the CCL signaling pathway, augmenting the pro-tumorigenic functions of CCL8high macrophages and boosting TAMs recruitment. The adjunctive treatment combining hypofractionated radiotherapy with Bindarit effectively reduced M2 macrophages infiltration and prolonged the duration of local tumor control. CONCLUSIONS: Hypofractionated radiotherapy enhances the infiltration of CCL8high macrophages and amplifies their roles in macrophage recruitment through the CCL signaling pathway, leading to an immunosuppressive tumor microenvironment. These findings highlight the potential of targeting TAMs and introduces a novel combination to improve the efficacy of hypofractionated radiotherapy.

Gastrointestinal manifestations of critical ill heatstroke patients and their associations with outcomes: A multicentre, retrospective, observational study.

BACKGROUND: Extreme heat exposure is a growing health problem, and the effects of heat on the gastrointestinal (GI) tract is unknown. This study aimed to assess the incidence of GI symptoms associated with heatstroke and its impact on outcomes. AIM: To assess the incidence of GI symptoms associated with heatstroke and its impact on outcomes. METHODS: Patients admitted to the intensive care unit (ICU) due to heatstroke were included from 83 centres. Patient history, laboratory results, and clinically relevant outcomes were recorded at ICU admission and daily until up to day 15, ICU discharge, or death. GI symptoms, including nausea/vomiting, diarrhoea, flatulence, and bloody stools, were recorded. The characteristics of patients with heatstroke concomitant with GI symptoms were described. Multivariable regression analyses were performed to determine significant predictors of GI symptoms. RESULTS: A total of 713 patients were included in the final analysis, of whom 132 (18.5%) patients had at least one GI symptom during their ICU stay, while 26 (3.6%) suffered from more than one symptom. Patients with GI symptoms had a significantly higher ICU stay compared with those without. The mortality of patients who had two or more GI symptoms simultaneously was significantly higher than that in those with one GI symptom. Multivariable logistic regression analysis revealed that older patients with a lower GCS score on admission were more likely to experience GI symptoms. CONCLUSION: The GI manifestations of heatstroke are common and appear to impact clinically relevant hospitalization outcomes.

Fisetin suppresses chondrocyte senescence and attenuates osteoarthritis progression by targeting sirtuin 6.

Osteoarthritis (OA) is the most common type of arthritis and is an age-related joint disease that is particularly prevalent in subjects over 65 years old. The chronic rise of senescent cells has a close correlation with age-related diseases such as OA, and the senescence-associated secretory phenotype (SASP) is implicated in OA cartilage degeneration pathogenesis. Sirtuin 6 (SIRT6) is likely to be a key senescence-related regulator. Fisetin (FST) is a natural flavonol of the flavonoid family that is recommended as a senolytic drug to extend health and lifespan. However, the potential chondroprotective effects of FST on OA rats are largely unclarified. The aim of this study is to investigate the ameliorative effects of FST on OA joint cartilage and the relationship with SIRT6 and the detailed mechanisms from anti-inflammatory and anti-senescent perspectives. Rats were subjected to destabilization of the medial meniscus (DMM) surgery as a means of inducing the experimental OA model in vivo. Chondrocytes treated with IL-1ß were utilized for mimicking the OA cell model in vitro. Intra-articular injection of FST, OSS_128,167 (OSS, SIRT6 inhibitor), and MDL800 (MDL, SIRT6 agonist) in vivo or administering them in IL-1ß-induced rat chondrocytes in vitro were performed in order to determine the effects FST has on OA and the link with SIRT6. This study found SIRT6 level to be negatively correlated with OA severity. SIRT6 downregulation was validated in the joint cartilages of DMM rats and IL-1ß-treated chondrocytes. It was also notably demonstrated that FST can activate SIRT6. Both the administration of FST and activation of SIRT6 using MDL were found to rescue cartilage erosion, decrease extracellular matrix (ECM) degradation, prevent cartilage from apoptosis, and improve detrimental senescence-related phenotype. The alleviative effects of FST against inflammation, ECM degradation, apoptosis, and senescence in IL-1ß-stimulated chondrocytes were also confirmed. SIRT6 loss occurs in articular cartilage in OA pathogenesis, which is linked to aging. FST attenuates injury-induced aging-related phenotype changes in chondrocytes through the targeting of SIRT6.

Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023 edition) / 中草药·英文版

To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization, led by the National Expert Committee on Research and Application of Chinese Herbal Vesicles, research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on Research and Application of Chinese Herbal Vesicles, Professional Committee on Extracellular Vesicle Research and Application, Chinese Society of Research Hospitals and the Guangdong Engineering Research Center of Chinese Herbal Vesicles. Based on the collation of relevant literature, we have adopted the Delphi method, the consensus meeting method combined with the nominal group method to form a discussion draft of "Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023)". The first draft was discussed in online and offline meetings on October 12, 14, November 2, 2022 and April and May 2023 on the current status of research, nomenclature, isolation methods, quality standards and research applications of extracellular vesicles of Chinese herbal medicines, and 13 consensus opinions were finally formed. At the Third Academic Conference on Research and Application of Chinese Herbal Vesicles, held on May 26, 2023, Kewei Zhao, convenor of the consensus, presented and read the consensus to the experts of the Expert Committee on Research and Application of Chinese Herbal Vesicles. The consensus highlights the characteristics and advantages of Chinese medicine, inherits the essence, and keeps the righteousness and innovation, aiming to provide a reference for colleagues engaged in research and application of Chinese herbal vesicles at home and abroad, decode the mystery behind Chinese herbal vesicles together, establish a safe, effective and controllable accurate Chinese herbal vesicle prevention and treatment system, and build a bridge for Chinese medicine to the world.

Disease spectrum and pathogenic genes of inherited metabolic disorder in Gansu Province of China / 中国当代儿科杂志

OBJECTIVES@#To investigate the disease spectrum and pathogenic genes of inherited metabolic disorder (IMD) among neonates in Gansu Province of China.@*METHODS@#A retrospective analysis was conducted on the tandem mass spectrometry data of 286 682 neonates who received IMD screening in Gansu Provincial Maternal and Child Health Hospital from January 2018 to December 2021. A genetic analysis was conducted on the neonates with positive results in tandem mass spectrometry during primary screening and reexamination.@*RESULTS@#A total of 23 types of IMD caused by 28 pathogenic genes were found in the 286 682 neonates, and the overall prevalence rate of IMD was 0.63 (1/1 593), among which phenylketonuria showed the highest prevalence rate of 0.32 (1/3 083), followed by methylmalonic acidemia (0.11, 1/8 959) and tetrahydrobiopterin deficiency (0.06, 1/15 927). In this study, 166 variants were identified in the 28 pathogenic genes, with 13 novel variants found in 9 genes. According to American College of Medical Genetics and Genomics guidelines, 5 novel variants were classified as pathogenic variants, 7 were classified as likely pathogenic variants, and 1 was classified as the variant of uncertain significance.@*CONCLUSIONS@#This study enriches the database of pathogenic gene variants for IMD and provides basic data for establishing an accurate screening and diagnosis system for IMD in this region.

Selenium-induced rhizosphere microorganisms endow salt-sensitive soybeans with salt tolerance.

Soil salinization is a prevalent abiotic stress that adversely affects soybean production. Rhizosphere microorganisms have been shown to modulate the rhizosphere microenvironment of plants, leading to improved stress resistance. Selenium is known to optimize the rhizosphere microbial community, however, it remains uncertain whether selenium-induced rhizosphere microorganisms can enhance plant salt tolerance. In this study, we selected two soybean varieties, including salt-tolerant and salt-sensitive, and conducted pot experiments to explore the impact of selenium application on the structure and composition of the rhizosphere microbial community of soybean plants under salt stress. Four salt-tolerant bacteria from salt-tolerant soybean rhizosphere soil fertilized with selenium under salt stress were isolated, and their effects on improving salt tolerance in salt-sensitive soybean were also investigated. Our results showed that selenium application enhanced soybean salt tolerance by optimizing the structure of the plant rhizosphere microbial community and improving soil enzyme activities in both salt-tolerant and salt-sensitive varieties. Moreover, compared with salt-only treatment, inoculation of the four bacteria led to a significant increase in the plant height (7.2%-19.8%), aboveground fresh weight (57.3%-73.5%), SPAD value (8.4%-30.3%), and K+ content (4.5%-12.1%) of salt-sensitive soybean, while reducing the content of proline (84.5%-94%), MDA (26.5%-49.3%), and Na+ (7.1%-21.3%). High-throughput sequencing of the 16 S ribosomal RNA gene indicated that the four bacteria played a crucial role in changing the community structure of salt-sensitive soybean and mitigating the effects of salt stress. This study highlighted the importance of selenium combined with beneficial microorganisms in the plant rhizosphere in alleviating salinity stress.

Dietary resveratrol supplementation on growth performance, immune function and intestinal barrier function in broilers challenged with lipopolysaccharide.

This study discusses the effects of resveratrol (RES) on the productive performance, immune function and intestinal barrier function of broiler chickens challenged with lipopolysaccharide (LPS). Two hundred and forty 1-day-old male Arbor Acres broilers were randomly divided into 4 groups of 6 replicates each, with 10 broilers per replicate. This experiment used a 2 × 2 factorial design with dietary factors (basal diets or basal diets supplemented with 400 mg/kg RES were administered from d 1 to 21) and stress factors (intraperitoneal injection of 0.5 mg/kg BW of saline or LPS at 16, 18 and 20 d of age). The results showed that LPS challenge had a significant adverse effect on average daily gain (ADG) in broilers at 16 to 21 d of age (P < 0.05), whereas the addition of RES to the diet inhibited the LPS-induced decrease in ADG (P < 0.05). RES also alleviated LPS-induced immune function damage in broilers, which was manifested by the decrease of spleen index (P < 0.05) and the recovery of serum immunoglobulin M and ileal secretory immunoglobulin A content (P < 0.05). The LPS challenge also disrupts intestinal barrier function and inflammation, and RES mitigates these adverse effects in different ways. RES attenuated LPS-induced reduction of villus height in the jejunum and ileum of broilers (P < 0.05). LPS also caused an abnormal increase in plasma D-lactic acid levels in broilers (P < 0.05), which was effectively mitigated by RES (P < 0.05). LPS challenge resulted in a significant decrease in mRNA expression of occludin in the intestinal mucosa (P < 0.05), which was mitigated by the addition of RES (P < 0.05). RES significantly decreased the mRNA expression of toll-like receptor 4, nuclear factor kappa-B and tumor necrosis factor alpha in the ileum tissue stimulated by LPS (P < 0.05). Taken together, this study shows that RES exerts its beneficial effect on broilers challenged with LPS by alleviating immune function damage, relieving intestinal inflammation and barrier damage, and thus improving growth performance.

Phagocyte extracellular traps formation contributes to host defense against Clostridium perfringens infection.

Clostridium perfringens (C. perfringens) is an important Gram-positive anaerobic spore-forming pathogen that provokes life-threatening gas gangrene and acute enterotoxaemia, although it colonizes as a component of the symbiotic bacteria in humans and animals. However, the mechanisms by which C. perfringens is cleared from the host remains poorly understood, thereby impeding the development of novel strategies for control this infection. Here, we uncover a beneficial effect of extracellular traps (ETs) formation on bacterial killing and clearance by phagocytes. C. perfringens strain ATCC13124, and wild-type isolates CP1 and CP3 markedly trigger ETs formation in macrophages and neutrophils. As expected, visualization of DNA decorated with histone, myeloperoxidase (MPO) and neutrophils elastase (NE) in C. perfringens-triggered classical ETs structures. Notably, the bacteria-induced ETs formation is an ERK1/2-, P38 MAPK-, store-operated calcium entry (SOCE)-, NADPH oxidase-, histone-, NE-, and MPO-dependent process, and is independent of LDH activity. Meanwhile, the defect of bactericidal activity is mediated by impairing ETs formation in phagocytes. Moreover, In vivo studies indicated that degradation of ETs by DNase I administration leads to a defect in the protection against experimental gas gangrene, with higher mortality rates, exacerbated tissue damage, and more bacterial colonization. Together, these results suggest that phagocyte ETs formation is essential for the host defense against C. perfringens infection.

Preoperative frailty assessment could be a predictive factor for the prognosis of elderly patients undergoing coronary artery bypass grafting: a retrospective case-control study.

BACKGROUND: Frailty has been considered to be associated with major mortality and increased length of stay after cardiac surgery. This study aimed to explore the predictive potential of frailty assessment in the prognosis of elderly patients undergoing bypass surgery. METHODS: This study assessed the preoperative frailty according to the Fried's frailty phenotype, and included 150 frail and 150 non-frail elderly patients (≥ 65 y) who underwent bypass surgery. The present study evaluated the prognosis of elderly patients based on sequential organ failure assessment (SOFA) score, and collected clinical indicators to construct logistic regression models with the prognosis as the dependent variable, to explore the potential predictive ability of preoperative frailty. Moreover, this study focused on the complications and analyzed the relationship between preoperative frailty and postoperative complications. RESULTS: In the present study, 244 patients were divided into the favorable prognosis group and 56 patients were divided into the unfavorable prognosis group. Logistic regression analysis showed that increased myoglobin and high cardiac function classification were independent risk factors for unfavorable prognosis in elderly patients undergoing bypass surgery. The discrimination of the clinical prediction model was determined by the receiver operating characteristic (ROC) curve, and the area under curve (AUC) was 0.928. After adding preoperative frailty assessment, the AUC was improved to 0.939. This study found a significant correlation between preoperative frailty and postoperative complications, mainly in the circulatory system. CONCLUSION: Preoperative frailty assessment could be a predictive factor for the prognosis of elderly patients undergoing coronary artery bypass grafting. According to our study, frailty assessment and appropriate intervention before bypass surgery may be beneficial to the enhanced recovery after cardiac surgery. TRIAL REGISTRATION: The clinical study was approved by the Medical Ethics Committee of The First Affiliated Hospital of Nanjing Medical University (2021-SR-393). All patients signed an informed consent form.

Express delivery logistics with high-speed railway: a perspective of payment scheme and forecast information sharing.

This paper investigates the payment scheme and forecast information sharing issues in the express delivery logistics with the high-speed railway. The HSR carriers need to coordinate the transportation capacity between passenger and freight. It is widely recognized that the advance payment scheme (APS) using as deposit is a beneficial way for the HSR carriers to make decisions on the transportation capacity preserved for express delivery. However, the express service providers, who possess private forecast information of express delivery demand, may share inaccurate information with the HSR carriers to acquire sufficient preserved transportation capacity. This paper discusses what payment scheme is preferred by the HSR carrier, the express service provider through discussing the deposit decisions with or without forecast information sharing. We show that sharing demand forecast information can reduce the prereserved capacity and increase the profits of the HSR carrier. With the delayed payment scheme (DPS), the express service provider has no motivation to share the information; while with the APS, the HSR carrier can reasonably choose the deposit to encourage the express service provider to share the demand information. Our analysis also shows that the HSR carrier's profits with the APS is restricted by the investment returns and the express service provider's information sharing decisions. We also analyze the value range of the deposit, which is a proportion of the overall payment, that allows both the HSR carrier and the express service provider to prefer the APS, as well as to encourage the express service provider to share the demand information.

Association Between the Early Serum Lipid Metabolism Profile and Delayed Neurocognitive Recovery After Cardiopulmonary Bypass in Cardiac Surgical Patients: a Pilot Study.

Cardiac surgery with extracorporeal circulation is considered to be one of the surgical types with the highest incidence of delayed neurocognitive recovery (DNR), but the mechanism is unclear. Metabolomics technology can be used to understand the early postoperative metabolic profile and find the relationship between serum metabolites and disease. We performed untargeted analyses of postoperative serum metabolites in all surgical groups, as well as serum metabolites in healthy nonsurgical adults, by using liquid chromatography‒mass spectrometry (LC‒MS). DNR after cardiopulmonary bypass surgery occurred in 35% of surgical patients. Sixty-nine metabolites were found to be associated with DNR. Lipids and lipid-like molecules occupy a total of 55 positions. Lipid metabolism occupies an important position in the serum metabolic profile of DNR patients in the early postoperative period. Phosphatidylinositol (PI), sphingomyelin (SM), and phosphatidylglycerol (PG) appear at the highest frequency. Correlation analysis and receiver operator characteristic curve analysis confirmed PI and SM as potential biomarkers for an increased risk of DNR.

Effects of EW-7197 on the proliferation and migration of TGF-β1 induced human Tenon fibroblasts and its mechanism / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the effect of ALK5 inhibitor EW-7197 on the proliferation and migration of human Tenon fibroblasts(HTFs)induced by transforming growth factor-β1(TGF-β1)and its mechanism.METHODS: The cell proliferation rate was detected by MTS assay, and the optimal concentration and time of EW-7197 were explored. Then HTFs were divided into three groups: normal control group, TGF-β1 induced group and TGF-β1+EW-7197 group. Cell migration was observed by Transwell assay. The protein expression levels of Fibronectin, α-SMA, as well as the phosphorylated Smad2, Smad3(p-Smad2, p-Smad3)were measured by Western blot.RESULTS: MTS assay showed that the proliferation rate of cells treated with 6.0 μmol/L EW-7197 for 24h was the lowest(all P&#x003C;0.01). Transwell assay showed that the migrated number of HTFs in TGF-β1 induced group was 228.0±17.0/field, which was significantly more than that in normal control group(149.0±15.0/field)and TGF-β1+EW-7197 group(46.0±8.0/field; all P&#x003C;0.01). Western blot showed that the protein relative expression levels of Fibronectin, α-SMA and p-Smad2, p-Smad3 of HTFs in TGF-β1 induced group were significantly higher than that in normal control group and TGF-β1+EW-7197 group(all P&#x003C;0.001).CONCLUSION:EW-7197 can suppress the proliferation and migration of TGF-β1-induced HTFs through TGF-β/Smad signaling pathways.

A multi-center study on evaluation of leukocyte differential performance by an artificial intelligence-based Digital Cell Morphology Analyzer / 中华检验医学杂志

Objective:To evaluate the performance of an artificial intelligent (AI)-based automated digital cell morphology analyzer (hereinafter referred as AI morphology analyzer) in detecting peripheral white blood cells (WBCs).Methods:A multi-center study. 1. A total of 3010 venous blood samples were collected from 11 tertiary hospitals nationwide, and 14 types of WBCs were analyzed with the AI morphology analyzers. The pre-classification results were compared with the post-classification results reviewed by senior morphological experts in evaluate the accuracy, sensitivity, specificity, and agreement of the AI morphology analyzers on the WBC pre-classification. 2. 400 blood samples (no less than 50% of the samples with abnormal WBCs after pre-classification and manual review) were selected from 3 010 samples, and the morphologists conducted manual microscopic examinations to differentiate different types of WBCs. The correlation between the post-classification and the manual microscopic examination results was analyzed. 3. Blood samples of patients diagnosed with lymphoma, acute lymphoblastic leukemia, acute myeloid leukemia, myelodysplastic syndrome, or myeloproliferative neoplasms were selected from the 3 010 blood samples. The performance of the AI morphology analyzers in these five hematological malignancies was evaluated by comparing the pre-classification and post-classification results. Cohen′s kappa test was used to analyze the consistency of WBC pre-classification and expert audit results, and Passing-Bablock regression analysis was used for comparison test, and accuracy, sensitivity, specificity, and agreement were calculated according to the formula.Results:1. AI morphology analyzers can pre-classify 14 types of WBCs and nucleated red blood cells. Compared with the post-classification results reviewed by senior morphological experts, the pre-classification accuracy of total WBCs reached 97.97%, of which the pre-classification accuracies of normal WBCs and abnormal WBCs were more than 96% and 87%, respectively. 2. The post-classification results reviewed by senior morphological experts correlated well with the manual differential results for all types of WBCs and nucleated red blood cells (neutrophils, lymphocytes, monocytes, eosinophils, basophils, immature granulocytes, blast cells, nucleated erythrocytes and malignant cells r>0.90 respectively, reactive lymphocytes r=0.85). With reference, the positive smear of abnormal cell types defined by The International Consensus Group for Hematology, the AI morphology analyzer has the similar screening ability for abnormal WBC samples as the manual microscopic examination. 3. For the blood samples with malignant hematologic diseases, the AI morphology analyzers showed accuracies higher than 84% on blast cells pre-classification, and the sensitivities were higher than 94%. In acute myeloid leukemia, the sensitivity of abnormal promyelocytes pre-classification exceeded 95%. Conclusion:The AI morphology analyzer showed high pre-classification accuracies and sensitivities on all types of leukocytes in peripheral blood when comparing with the post-classification results reviewed by experts. The post-classification results also showed a good correlation with the manual differential results. The AI morphology analyzer provides an efficient adjunctive white blood cell detection method for screening malignant hematological diseases.

Current status of surgery for portal hypertension in China: a national multi-center survey analysis / 中华器官移植杂志

Objective:To explore the current status of surgery for portal hypertension to grasp current status and future development of surgery in China.Methods:This study is jointly sponsored by China Hepatobiliary & Pancreatic Specialist Alliance & Portal Hypertension Alliance in China (CHESS).Comprehensive surveying is conducted for basic domestic situations of surgery for portal hypertension, including case load, surgical approaches, management of postoperative complications, primary effects, existing confusion and obstacles, liver transplantation(LT), laparoscopic procedures and transjugular intrahepatic portosystemic shunt(TIPS), etc.Results:A total of 8 512 cases of portal hypertension surgery are performed at 378 hospitals nationwide in 2021.Splenectomy plus devascularization predominated(53.0%)and laparoscopy accounted for 76.1%.Primary goal is preventing rebleeding(67.0%) and 72.8% of hospitals used preventive anticoagulants after conventional surgery.And 80.7% of teams believe that the formation of postoperative portal vein thrombosis is a surgical dilemma and 65.3% of hospitals practiced both laparoscopy and TIPS.The major reasons for patients with portal hypertension not receiving LT are due to a lack of qualifications for LT(69.3%)and economic factors(69.0%).Conclusions:Surgery is an integral part of management of portal hypertension in China.However, it is imperative to further standardize the grasp of surgical indications, the handling of surgical operation and the management of postoperative complications.Moreover, prospective, multi-center randomized controlled clinical studies should be performed.

Clinical value of ultrasound-guided fine-needle aspiration biopsy in the diagnosis of thyroid cancer and assessment of cervical lymph node metastasis / 中国基层医药

Objective:To explore the clinical value of ultrasound-guided fine-needle aspiration biopsy in the diagnosis of thyroid cancer and assessment of cervical lymph node metastasis.Methods:The clinical data of 90 patients with thyroid cancer who received treatment in Zhoushan Hospital from October 2018 to April 2021 were retrospectively analyzed. All patients underwent a two-dimensional ultrasound examination and ultrasound-guided fine-needle aspiration biopsy before surgery. Taking surgical and pathological diagnosis as the gold standard, the efficiency of two-dimensional ultrasound examination versus ultrasound-guided fine-needle aspiration biopsy in the diagnosis of thyroid cancer and cervical lymph node metastasis and in the identification of benign and maligant lymph nodes were investigated. Multivariate Logistic regression analysis was performed to analyze the correlation between different ultrasound signs and the detection rate of lymph nodes. Results:Pathological results showed that among the 90 patients, 73 patients had thyroid cancer, and 17 patients had benign lesions. Ultrasound-guided fine-needle aspiration biopsy results showed that 70 patients had thyroid cancer, and 20 patients had benign lesions, including 4 cases of missed diagnosis and 2 cases of misdiagnosis. The diagnostic sensitivity, specificity, accuracy rate, and Kappa value were 94.52%, 88.24%, 93.33%, and 0.79, respectively. These were highly consistent with the surgical and pathological diagnosis (Kappa value > 0.75). Two-dimensional ultrasound revealed 69 patients with thyroid cancer and 21 patients with benign lesions, including 7 cases of missed diagnosis and 4 cases of misdiagnosis. The diagnostic sensitivity, specificity, accuracy rate, and Kappa value were 90.41%, 76.47%, 87.78%, and 0.63, respectively. Pathological results revealed that cervical lymph node metastasis occurred in 12 patients, and it did not occur in 78 patients. The diagnostic sensitivity, specificity, accuracy rate, and Kappa value of ultrasound-guided fine-needle aspiration biopsy were 83.33%, 97.50%, 95.65%, and 0.81 respectively. These were highly consistent with surgical and pathological results (Kappa value > 0.75). The diagnostic sensitivity, specificity, accuracy rate, and Kappa value of two-dimensional ultrasound examination were 75.00%, 94.87%, 92.22%, and 0.67, respectively. A total of 156 lymph nodes were detected by ultrasound-guided fine-needle aspiration biopsy, including 103 benign lymph nodes and 53 malignant lymph nodes, with a diagnostic accuracy rate of 94.17% and 96.22%, respectively. A total of 173 lymph nodes were detected by two-dimensional ultrasound, including 111 benign lymph nodes and 62 malignant lymph nodes, with a diagnostic accuracy rate of 91.89% and 91.93%, respectively. There were no significant differences in the diagnostic accuracy of benign and malignant lymph nodes between the two examination methods ( χ2 = 0.42, 0.92, both P > 0.05). Multivariate logistic regression analysis showed that hyperechoic masses, cystic lesions, and internal calcification were significantly correlated with the detection rate of lymph nodes diagnosed by two-dimensional ultrasound and ultrasound-guided fine-needle aspiration biopsy ( OR = 6.64, 5.32, 4.12, 7.07, 5.60, 5.06, all P < 0.05). Conclusion:Ultrasound-guided fine-needle aspiration biopsy has high diagnostic efficiency for thyroid cancer and cervical lymph node metastasis. Ultrasound signs of hyperechoic mass, cystic lesions, and internal calcification are significantly correlated with the detection rate of lymph nodes.

Antagonistic effect of SC79 on high glucose-induced apoptosis of RPE cells and its regulatory mechanism on AKT-XIAP signaling pathway / 中华实验眼科杂志

Objective:To investigate the antagonistic effect and potential mechanism of specific AKT activator SC79 on the apoptosis of human retinal pigment epithelial (ARPE)-19 cells induced by high glucose in vitro. Methods:The ARPE-19 cells were cultured in high glucose medium (containing 30 mmol/L glucose) plus 5, 10 or 20 μg/ml SC79, respectively.After 6-, 12- and 24-hour culture, the optimal experimental concentration and timing were determined according to cell proliferation rate.Then ARPE-19 cells were divided into four groups, normal control group cultured in normal medium containing 5.6 mmol/L glucose for 48 hours, mannitol group cultured in medium containing 5.6 mmol/L glucose and 24.4 mmol/L mannitol for 48 hours, high glucose group cultured in high glucose medium for 48 hours, and high glucose+ SC79 group cultured in normal medium containing 10 μg/ml SC79 for 12 hours plus in high glucose medium for 36 hours.The proliferation rate of APRE-19 cells was detected by MTS assay.The apoptosis rate was measured by flow cytometry.The relative expression levels of phosphorylated protein kinase B (p-Akt), X-linked inhibitor of apoptosis protein (XIAP), caspase-9, caspase-3 and its active fragments (active-caspase-3) were assayed by Western blot.The ARPE-19 cells were divided into Neg-shRNA group, AKT shRNA group and blank control group and were treated with the corresponding transfection complex and serum-free medium.The AKT mRNA expression was detected by real-time PCR.The transfected ARPE-19 cells were divided into Neg-shRNA+ SC79 group and AKT shRNA+ SC79 group and were cultured according to the culturing method of high-glucose+ SC79 group.The apoptosis rate of the two groups was tested by flow cytometry.Results:Among different concentrations of SC79 and treatment times, the proliferation rate of cells treated with 10 μg/ml SC79 for 12 hours was the highest.The proliferation rate of ARPE-19 cells in high-glucose group was significantly lower than that in normal control group, mannitol group and high-glucose+ SC79 group, and the differences were statistically significant (all at P<0.01). The apoptosis rate of cells in the high-glucose group was (52.27±3.21)%, which was significantly higher than (3.90±0.71)% in normal control group and (20.70±3.62)% in high-glucose+ SC79 group (both at P<0.01). The relative expression levels of p-Akt, XIAP, caspase-9 and caspase-3 were significantly lower and the relative expression level of active-caspase-3 was significantly higher in high glucose group than those in normal control group and high-glucose+ SC79 group (all at P<0.05). The relative expression level of AKT mRNA in normal control group, Neg-shRNA group and AKT shRNA group was 0.60±0.07, 0.59±0.03 and 0.11±0.10, respectively, showing a statistically significant difference among the groups ( F=30.44, P<0.01). The apoptosis rate of cells in the AKT shRNA+ SC79 group was significantly higher than that in high-glucose+ SC79 group and Neg-shRNA+ SC79 group (both at P<0.001). Conclusions:SC79 can partially antagonize the apoptosis of ARPE-19 cells induced by high glucose, which is related to the activation of AKT/XIAP pathway and the inhibition of the caspase family.