CD59 gene: 143 haplotypes of 22,718 nucleotides length by computational phasing in 113 individuals from different ethnicities.

BACKGROUND: CD59 deficiency due to rare germline variants in the CD59 gene causes disabilities, ischemic strokes, neuropathy, and hemolysis. CD59 deficiency due to common somatic variants in the PIG-A gene in hematopoietic stem cells causes paroxysmal nocturnal hemoglobinuria. The ISBT database lists one nonsense and three missense germline variants that are associated with the CD59-null phenotype. To analyze the genetic diversity of the CD59 gene, we determined long-range CD59 haplotypes among individuals from different ethnicities. METHODS: We determined a 22.7 kb genomic fragment of the CD59 gene in 113 individuals using next-generation sequencing (NGS), which covered the whole NM_203330.2 mRNA transcript of 7796 base pairs. Samples came from an FDA reference repository and our Ethiopia study cohorts. The raw genotype data were computationally phased into individual haplotype sequences. RESULTS: Nucleotide sequencing of the CD59 gene of 226 chromosomes identified 216 positions with single nucleotide variants. Only three haplotypes were observed in homozygous form, which allowed us to assign them unambiguously as experimentally verified CD59 haplotypes. They were also the most frequent haplotypes among both cohorts. An additional 140 haplotypes were imputed computationally. DISCUSSION: We provided a large set of haplotypes and proposed three verified long-range CD59 reference sequences, based on a population approach, using a generalizable rationale for our choice. Correct long-range haplotypes are useful as template sequences for allele calling in high-throughput NGS and precision medicine approaches, thus enhancing the reliability of clinical diagnostics. Long-range haplotypes can also be used to evaluate the influence of genetic variation on the risk of transfusion reactions or diseases.

Epitranscriptomic orchestrations: Unveiling the regulatory paradigm of m6A, A-to-I editing, and m5C in breast cancer via long noncoding RNAs and microRNAs.

Breast cancer (BC) poses a persistent global health challenge, particularly in countries with elevated human development indices linked to factors such as increased life expectancy, education, and wealth. Despite therapeutic progress, challenges persist, and the role of epitranscriptomic RNA modifications in BC remains inadequately understood. The epitranscriptome, comprising diverse posttranscriptional modifications on RNA molecules, holds the potential to intricately modulate RNA function and regulation, implicating dysregulation in various diseases, including BC. Noncoding RNAs (ncRNAs), acting as posttranscriptional regulators, influence physiological and pathological processes, including cancer. RNA modifications in long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) add an extra layer to gene expression control. This review delves into recent insights into epitranscriptomic RNA modifications, such as N-6-methyladenosine (m6A), adenine-to-inosine (A-to-I) editing, and 5-methylcytosine (m5C), specifically in the context of lncRNA and miRNAs in BC, highlighting their potential implications in BC development and progression. Understanding this intricate regulatory landscape is vital for deciphering the molecular mechanisms underlying BC and identifying potential therapeutic targets.

Unlocking the potential of fondaparinux: guideline for optimal usage and clinical suggestions (2023).

Background: Thromboembolic disease is associated with a high rate of disability or death and gravely jeopardizes people's health and places considerable financial pressure on society. The primary treatment for thromboembolic illness is anticoagulant medication. Fondaparinux, a parenteral anticoagulant medicine, is still used but is confusing due to its disparate domestic and international indications and lack of knowledge about its usage. Its off-label drug usage in therapeutic settings and irrational drug use are also common. Objective: The aim of this guideline is to enhance the judicious clinical application of fondaparinux by consolidating the findings of evidence-based research on the drug and offering superior clinical suggestions. Methods: Seventeen clinical questions were developed by 37 clinical pharmacy experts, and recommendations were formulated under the supervision of three methodologists. Through methodical literature searches and the use of recommendation, assessment, development and evaluation grading techniques, we gathered evidence. Results: This guideline culminated in 17 recommendations, including the use of fondaparinux for venous thromboembolism (VTE) prevention and treatment, perioperative surgical prophylaxis, specific diseases, special populations, bleeding and overdose management. For different types of VTE, we recommend first assessing thrombotic risk in hospitalized patients and then administering the drug according to the patient's body mass. In surgical patients in the perioperative period, fondaparinux may be used for VTE prophylaxis, but postoperative use usually requires confirmation that adequate hemostasis has been achieved. Fondaparinux may be used for anticoagulation prophylaxis in patients hospitalized for oncological purposes, in patients with atrial fibrillation (AF) after resuscitation, in patients with cirrhosis combined with portal vein thrombosis (PVT), in patients with antiphospholipid syndrome (APS), and in patients with inflammatory bowel disease (IBD). Fondaparinux should be used with caution in special populations, such as pregnant female patients with a history of heparin-induced thrombocytopenia (HIT) or platelet counts less than 50 × 109/L, pregnant patients with a prethrombotic state (PTS) combined with recurrent spontaneous abortion (RSA), and children. For bleeding caused by fondaparinux, dialysis may partially remove the drug. Conclusion: The purpose of this guideline is to provide all healthcare providers with high-quality recommendations for the clinical use of fondaparinux and to improve the rational use of the drug in clinical practice. Currently, there is a lack of a dedicated antidote for the management of fondaparinux. The clinical investigation of activated prothrombin complex concentrate (APCC) or recombinant activated factor VII (rFⅦa) as potential reversal agents is still pending. This critical gap necessitates heightened scrutiny and research emphasis, potentially constituting a novel avenue for future inquiries into fondaparinux sodium. A meticulous examination of adverse events and safety profiles associated with the utilization of fondaparinux sodium will contribute significantly to a more comprehensive understanding of its inherent risks and benefits within the clinical milieu.

A promising therapy for fatty liver disease: PCSK9 inhibitors.

BACKGROUND: Fatty liver disease (FLD) poses a significant global health concern worldwide, with its classification into nonalcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) contingent upon the presence or absence of chronic and excessive alcohol consumption. The absence of specific therapeutic interventions tailored to FLD at various stages of the disease renders its treatment exceptionally arduous. Despite the fact that FLD and hyperlipidemia are intimately associated, there is still debate over how lipid-lowering medications affect FLD. Proprotein Convertase Subtilisin/ Kexin type 9 (PCSK9) is a serine protease predominantly synthesized in the liver, which has a crucial impact on cholesterol homeostasis. Research has confirmed that PCSK9 inhibitors have prominent lipid-lowering properties and substantial clinical effectiveness, thereby justifying the need for additional exploration of their potential role in FLD. PURPOSE: Through a comprehensive literature search, this review is to identify the relationship and related mechanisms between PCSK9, lipid metabolism and FLD. Additionally, it will assess the pharmacological mechanism and applicability of PCSK9 inhibitors (including naturally occurring PCSK9 inhibitors, such as conventional herbal medicines) for the treatment of FLD and serve as a guide for updating the treatment protocol for such conditions. METHODS: A comprehensive literature search was conducted using several electronic databases, including Pubmed, Medline, Embase, CNKI, Wanfang database and ClinicalTrials.gov, from the inception of the database to 30 Jan 2024. Key words used in the literature search were "fatty liver", "hepatic steatosis", "PCSK9", "traditional Chinese medicine", "herb medicine", "botanical medicine", "clinical trial", "vivo", "vitro", linked with AND/OR. Most of the included studies were within five years. RESULTS: PCSK9 participates in the regulation of circulating lipids via both LDLR dependent and independent pathways, and there is a potential association with de novo lipogenesis. Major clinical studies have demonstrated a positive correlation between circulating PCSK9 levels and the severity of NAFLD, with elevated levels of circulating PCSK9 observed in individuals exposed to chronic alcohol. Numerous studies have demonstrated the potential of PCSK9 inhibitors to ameliorate non-alcoholic steatohepatitis (NASH), potentially completely alleviate liver steatosis, and diminish liver impairment. In animal experiments, PCSK9 inhibitors have exhibited efficacy in alleviating alcoholic induced liver lipid accumulation and hepatitis. Traditional Chinese medicine such as berberine, curcumin, resveratrol, piceatannol, sauchinone, lupin, quercetin, salidroside, ginkgolide, tanshinone, lunasin, Capsella bursa-pastoris, gypenosides, and Morus alba leaves are the main natural PCS9 inhibitors. Excitingly, by inhibiting transcription, reducing secretion, direct targeting and other pathways, traditional Chinese medicine exert inhibitory effects on PCSK9, thereby exerting potential FLD therapeutic effects. CONCLUSION: PCSK9 plays an important role in the development of FLD, and PCSK9 inhibitors have demonstrated beneficial effects on lipid regulation and FLD in both preclinical and clinical studies. In addition, some traditional Chinese medicines have improved the disease progression of FLD by inhibiting PCSK9 and anti-inflammatory and antioxidant effects. Consequently, the inhibition of PCSK9 appears to be a promising therapeutic strategy for FLD.

PLAU and GREM1 are prognostic biomarkers for predicting immune response in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is a common malignant tumor. Identification of biomarkers and understanding their potential functions will facilitate the treatment and diagnosis in LUAD patients. The yellow module (cor = 0.31, P = 2e-6) was selected as the core module based on weighted gene co-expression network analysis (WGCNA) by integrating RNA-seq data and tumor stage. Two upregulated genes (PLAU and GREM1) in yellow module were identified to be biomarkers. Kaplan-Meier curve analysis displayed that high expression levels of them had a poor overall survival (OS). And, their high expression levels revealed higher tumor stage and relapse possibility in LUAD patients, and could be a prognostic parameter. Both biomarkers showed similar immune cell expression profiles in low- and high-expression groups. Strongly positive correlation between both biomarkers and biomarkers of tumor-infiltrating lymphocytes were also clarified in TCGA-LUAD cohort. Importantly, single gene GSEA showed that transcriptional mis-regulation in cancer and microRNAs in cancer were enriched in LUAD patients. Therefore, a miRNA-mRNA-transcription factors (TFs) co-expression regulatory networks was constructed for each biomarker, various miRNAs and TFs were related to PLAU and GREM1. Among which, 6 downstream TFs were overlapped genes for both biomarkers. Notably, 2 of these TFs (FOXF1 and TFAP2A) exhibited significantly abnormal expression levels. Among which, FOXF1 was downregulated and TFAP2A was upregulated in TCGA-LUAD cohort. Both TFs showed a significantly positive correlation with the expression level of PLAU. In conclusion, we identified 2 biomarkers related to immune response and achieved a good accuracy in predicting OS in patients with LUAD.

The integration of multidisciplinary approaches revealed PTGES3 as a novel drug target for breast cancer treatment.

BACKGROUND: The main challenge in personalized treatment of breast cancer (BC) is how to integrate massive amounts of computing resources and data. This study aimed to identify a novel molecular target that might be effective for BC prognosis and for targeted therapy by using network-based multidisciplinary approaches. METHODS: Differentially expressed genes (DEGs) were first identified based on ESTIMATE analysis. A risk model in the TCGA-BRCA cohort was constructed using the risk score of six DEGs and validated in external and clinical in-house cohorts. Subsequently, independent prognostic factors in the internal and external cohorts were evaluated. Cell viability CCK-8 and wound healing assays were performed after PTGES3 siRNA was transiently transfected into the BC cell lines. Drug prediction and molecular docking between PTGES3 and drugs were further analyzed. Cell viability and PTGES3 expression in two BC cell lines after drug treatment were also investigated. RESULTS: A novel six-gene signature (including APOOL, BNIP3, F2RL2, HINT3, PTGES3 and RTN3) was used to establish a prognostic risk stratification model. The risk score was an independent prognostic factor that was more accurate than clinicopathological risk factors alone in predicting overall survival (OS) in BC patients. A high risk score favored tumor stage/grade but not OS. PTGES3 had the highest hazard ratio among the six genes in the signature, and its mRNA and protein levels significantly increased in BC cell lines. PTGES3 knockdown significantly inhibited BC cell proliferation and migration. Three drugs (gedunin, genistein and diethylstilbestrol) were confirmed to target PTGES3, and genistein and diethylstilbestrol demonstrated stronger binding affinities than did gedunin. Genistein and diethylstilbestrol significantly inhibited BC cell proliferation and reduced the protein and mRNA levels of PTGES3. CONCLUSIONS: PTGES3 was found to be a novel drug target in a robust six-gene prognostic signature that may serve as a potential therapeutic strategy for BC.

Establishing a trigger tool based on global trigger tools to identify adverse drug events in obstetric inpatients in China.

BACKGROUND: Pregnant women belong to the special population of drug therapy, and their physiological state, pharmacokinetics and pharmacodynamics are significantly different from the general population. Drug safety during pregnancy involves two generations, which is a hot issue widely concerned in the whole society. Global Trigger Tool (GTT) of the Institute for Healthcare Improvement (IHI) has been wildly used as a patient safety measurement strategy by several institutions and national programs, and the effectiveness had been demonstrated. But only one study reports the use of GTT in obstetric delivery until now. The aim of the study is to establish triggers detecting adverse drug events (ADEs) suitable for obstetric inpatients on the basis of the GTT, to examine the performance of the obstetric triggers in detecting ADEs experienced by obstetric units compared with the spontaneous reporting system and GTT, and to assess the utility and value of the obstetric trigger tool in identifying ADEs of obstetric inpatients. METHODS: Based on a literature review searched in PubMed and CNKI from January of 1997 to October of 2023, retrospective local obstetric ADEs investigations, relevant obstetric guidelines and the common adverse reactions of obstetric therapeutic drugs were involved to establish the initial obstetric triggers. According to the Delphi method, two rounds of expert questionnaire survey were conducted among 16 obstetric and neonatological physicians and pharmacists until an agreement was reached. A retrospective study was conducted to identity ADEs in 300 obstetric inpatient records at the Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital from June 1 to September 30, 2018. Two trained junior pharmacists analyzed the first eligible records independently, and the included records reviewed by trained pharmacist and physician to identify ADEs. Sensitivity and specificity of the established obstetric triggers were assessed by the number of ADEs/100 patients and positive predictive value with the spontaneous reporting system (SRS) and GTT. Excel 2010 and SPSS22 were used for data analysis. RESULTS: Through two rounds of expert investigation, 39 preliminary triggers were established that comprised four modules (12 laboratory tests, 9 medications, 14 symptoms, and 4 outcomes). A total of 300 medical records were reviewed through the obstetric triggers, of which 48 cases of ADEs were detected, with an incidence of ADEs of 16%. Among the 39 obstetric triggers, 22 (56.41%) were positive and 11 of them detected ADEs. The positive predictive value (PPV) was 36.36%, and the number of ADEs/100 patients was 16.33 (95% CI, 4.19-17.81). The ADE detection rate, positive trigger rate, and PPV for the obstetric triggers were significantly augmented, confirming that the obstetric triggers were more specific and sensitive than SRS and GTT. CONCLUSION: The obstetric triggers were proven to be sensitive and specific in the active monitoring of ADE for obstetric inpatients, which might serve as a reference for ADE detection of obstetric inpatients at medical institutions.

DEL variants: review of molecular mechanisms, clinical consequences and molecular testing strategy.

Patients with DEL phenotype, a D variant with a low number of D antigens per red blood cell, are routinely typed as RhD-negative in serology testing and are detectable only by adsorption and elution techniques or molecular methods. DEL is of clinical importance worldwide, as indicated by its genotype-phenotype discrepancies among different populations and its potential to cause anti-D alloimmunization when DEL phenotype individuals are inadvertently managed as RhD-negative. This narrative review summarized the DEL alleles causing DEL phenotype and the underlying mechanisms. The clinical consequences and current molecular testing approach were discussed to manage the transfusion needs of patients and donors with DEL phenotype.

Adverse drug events in Chinese elder inpatients: a retrospective review for evaluating the efficiency of the Global Trigger Tool.

Background: Elderly patients frequently experience a high incidence of adverse drug events (ADEs) due to the coexistence of multiple diseases, the combination of various medications, poor medication compliance, and other factors. Global Trigger Tool (GTT) is a new method for identifying ADEs, introducing the concept of a trigger, that is, clues including abnormal laboratory values, reversal drugs, and clinical symptoms that may suggest ADEs, and specifically locating information related to ADEs in the medical record to identify ADEs. The aim of this study was to establish a GTT-based trigger tool for adverse medication events in elderly patients and to investigate the risk variables associated with such events. Methods: The triggers were identified by reviewing the frequency of ADEs in elderly patients in Sichuan, China, retrieving relevant literature, and consulting experts. A retrospective analysis was carried out to identify adverse medication occurrences among 480 elderly inpatients in Sichuan People's Hospital. Results: A total of 56 ADEs were detected in 51 patients (10.62%), 13.04 per 1,000 patient days, and 11.67 per 100 admissions. The overall positive predictive value (PPV) of the triggers was 23.84, and 94.64% of ADEs caused temporary injury. Gastrointestinal system injury (27.87%) and metabolic and nutritional disorders (24.53%) were the primary organ-systems affected by ADEs. The majority of ADEs were caused by drugs used to treat cardiovascular diseases. 71.43% of ADE occurred within 2 days of administration and the risk factor analysis of ADE revealed that the number of medicines had a significant correlation. Conclusion: This study demonstrated GTT's value as a tool for ADEs detection in elderly inpatients in China. It enhances the level of medication management and comprehensively reflects the situation of ADE of the elderly.

Potential anticoagulant of traditional chinese medicine and novel targets for anticoagulant drugs.

BACKGROUND: Anticoagulants are the main drugs used for the prevention and treatment of thrombosis. Currently, anticoagulant drugs are primarily multitarget heparin drugs, single-target FXa inhibitors and FIIa inhibitors. In addition, some traditional Chinese drugs also have anticoagulant effects, but they are not the main direction of treatment at present. But the anticoagulant drugs mentioned above, all have a common side effect is bleeding. Many other anticoagulation targets are under investigation. With further exploration of coagulation mechanism, how to further determine new anticoagulant targets and how to make traditional Chinese medicine play anticoagulant role have become a new field of exploration. PURPOSE: The purpose of the study was to summarize the recent research progress on coagulation mechanisms, new anticoagulant targets and traditional Chinese medicine. METHODS: A comprehensive literature search was conducted using four electronic databases, including PubMed, Embase, CNKI, Wanfang database and ClinicalTrials.gov, from the inception of the study to 28 Feb 2023. Key words used in the literature search were "anticoagulation", "anticoagulant targets", "new targets", "coagulation mechanisms", "potential anticoagulant", "herb medicine", "botanical medicine", "Chinese medicine", "traditional Chinese medicine", "blood coagulation factor", keywords are linked with AND/OR. Recent findings on coagulation mechanisms, potential anticoagulant targets and traditional Chinese medicine were studied. RESULTS: The active components extracted from the Chinese medicinal herbs, Salvia miltiorrhiza, Chuanxiong rhizoma, safflower and Panax notoginseng have obvious anticoagulant effects and can be used as potential anticoagulant drugs, but the risk of bleeding is unclear. TF/FVIIa, FVIII, FIX, FXI, FXII, and FXIII have all been evaluated as targets in animal studies or clinical trials. FIX and FXI are the most studied anticoagulant targets, but FXI inhibitors have shown stronger advantages. CONCLUSION: This review of potential anticoagulants provides a comprehensive resource. Literature analysis suggests that FXI inhibitors can be used as potential anticoagulant candidates. In addition, we should not ignore the anticoagulant effect of traditional Chinese medicine, and look forward to more research and the emergence of new drugs.

Immune-related biomarkers predict the prognosis and immune response of breast cancer based on bioinformatic analysis and machine learning.

Breast cancer (BC) is the malignancy with the highest mortality rate among women, identification of immune-related biomarkers facilitates precise diagnosis and improvement of the survival rate in early-stage BC patients. 38 hub genes significantly positively correlated with tumor grade were identified based on weighted gene coexpression network analysis (WGCNA) by integrating the clinical traits and transcriptome analysis. Six candidate genes were screened from 38 hub genes basing on least absolute shrinkage and selection operator (LASSO)-Cox and random forest. Four upregulated genes (CDC20, CDCA5, TTK and UBE2C) were identified as biomarkers with the log-rank p < 0.05, in which high expression levels of them showed a poor overall survival (OS) and recurrence-free survival (RFS). A risk model was finally constructed using LASSO-Cox regression coefficients and it possessed superior capability to identify high risk patients and predict OS (p < 0.0001, AUC at 1-, 3- and 5-years are 0.81, 0.73 and 0.79, respectively). Decision curve analysis demonstrated risk score was the best prognostic predictor, and low risk represented a longer survival time and lower tumor grade. Importantly, multiple immune cell types and immunotherapy targets were observed increase in expression levels in high-risk group, most of which were significantly correlated with four genes. In summary, the immune-related biomarkers could accurately predict the prognosis and character the immune responses in BC patients. In addition, the risk model is conducive to the tiered diagnosis and treatment of BC patients.

Immune-related adverse events of immune checkpoint inhibitors: a review.

Since the first Immune Checkpoint Inhibitor was developed, tumor immunotherapy has entered a new era, and the response rate and survival rate of many cancers have also been improved. Despite the success of immune checkpoint inhibitors, resistance limits the number of patients who can achieve a lasting response, and immune-related adverse events complicate treatment. The mechanism of immune-related adverse events (irAEs) is unclear. We summarize and discuss the mechanisms of action of immune checkpoint inhibitors, the different types of immune-related adverse events and their possible mechanisms, and describe possible strategies and targets for prevention and therapeutic interventions to mitigate them.

Long Non-Coding RNAs, Cell Cycle, and Human Breast Cancer.

The long non-coding RNAs (lncRNAs) constitute an important class of the human transcriptome. The discovery of lncRNAs provided one of many unexpected results of the post-genomic era and uncovered a huge number of previously ignored transcriptional events. In recent years, lncRNAs are known to be linked with human diseases, with particular focus on cancer. Growing evidence has indicated that dysregulation of lncRNAs in breast cancer (BC) is strongly associated with the occurrence, development, and progress. Increasing numbers of lncRNAs have been found to interact with cell cycle progression and tumorigenesis in BC. The lncRNAs can exert their effect as a tumor suppressor or oncogene and regulate tumor development through direct or indirect regulation of cancer-related modulators and signaling pathways. What is more, lncRNAs are excellent candidates for promising therapeutic targets in BC due to the features of high tissue and cell-type specific expression. However, the underlying mechanisms of lncRNAs in BC still remain largely undefined. Here, we concisely summarize and sort out the current understanding of research progress in relationships of the roles for lncRNA in regulating the cell cycle. We also summarize the evidence for aberrant lncRNA expression in BC, and the potential for lncRNA to improve BC therapy is also discussed. Together, lncRNAs can be considered as exciting therapeutic candidates whose expression can be altered to impede BC progression.

Converting Nafion into Li+ -Conductive Nanoporous Materials.

Sulfonated polymers have long been used as proton-conducting materials in fuel cells, and their ionic transport features are highly attractive for electrolytes in lithium-ion/metal batteries (LIBs/LMBs). However, most studies are still based on a preconceived notion of using them directly as polymeric ionic carriers, which precludes exploring them as nanoporous media to construct efficient lithium ions (Li+ ) transport network. Here, effective Li+ -conducting channels realized by swelling nanofibrous Nafion is demonstrated, which is a classical sulfonated polymer in fuel cells. The sulfonic acid groups, interact with LIBs liquid electrolytes to form porous ionic matrix of Nafion and assist partial desolvation of Li+ -solvates to further enhance Li+ transport. Li-symmetric cells and Li-metal full cells (Li4 Ti5 O12 or high-voltage LiNi0.6 Co0.2 Mn0.2 O2 as a cathode) with such membrane show excellent cycling performance and stabilized Li-metal anode. The finding provides a strategy to convert the vast sulfonated polymer family into efficient Li+ electrolyte, promoting the development of high-energy-density LMBs.

ABO Blood Group and the Risk and Prognosis of Lymphoma.

ABO blood group antigens exhibit alternative phenotypes and genetically derived structures that are located on the red cell surface. The role of ABO blood group in cancer biology has been intensely reported by several studies, and it is now widely recognized that ABO antigens are associated with the risk and prognosis of several types of tumors, namely gastric cancer and pancreatic cancer. However, there have been contentious limited issues with the association between the ABO blood group and lymphoma. In this narrative review, based on literature data, we discuss the role of ABO blood group in the risk and prognosis of lymphoma and summarize the current knowledge of the underlying pathogenic mechanisms of the association. The possible association of ABO blood group with racial disparities and pathological classification in lymphoma patients is also discussed.

Transfusion management of Africans with RHD variants in China.

The presence of D variant among minorities could produce a higher rate of alloimmunization observed in patients from this group. This is partly due to the ethnic and racial specificity of RHD variants and the limited availability of Rh-matched blood donors. Approximately half a million African migrants in China carrying distinct Rh blood type composition have presented to the health care system with an imperative safety requirement of blood transfusion among 1.3 billion Chinese individuals. We depict the clinically significant RHD alleles among African migrants living in China and identify the genetic similarities and disparities to Chinese. We discussed practical strategies to manage the unique transfusion needs of African migrants in China.

Comparison of efficacy and safety between aspirin and oral anticoagulants for venous thromboembolism prophylaxis after major orthopaedic surgery: a meta-analysis of randomized clinical trials.

Background: venous thromboembolism (VTE) is one of the most common complications after major orthopaedic surgery. Recent studies have suggested that aspirin may also be effective in preventing VTE, but it is still controversial whether it can be routinely used. Objectives: To compare the efficacy and safety of aspirin against oral anticoagulants in the prevention of VTE following total hip arthroplasty (THA), total knee arthroplasty (TKA) or hip fracture surgery (HFS). Methods: Relevant publications have been obtained using electronic search databases such as PubMed, Embase, Web of Science, Cochrane Library, and Clinical Trials. gov. from inception to 20 July 2023. Only RCTs evaluating the efficacy and safety of aspirin compared with oral anticoagulants undergoing major orthopaedic surgery were included in the meta-analysis. The primary outcome reported was any VTE event (including deep vein thrombosis (DVT) and pulmonary embolism (PE)). Secondary outcomes included mortality, major bleeding (including gastrointestinal bleed, cerebrovascular hemorrhage, or any bleeding requiring a return to the theater), minor bleeding (ecchymosis, epistaxis, hematuria), and wound complications. The risk of bias for all included studies was assessed according to the Cochrane Collaboration's tool. Results: After screening 974 studies, 12 randomized clinical trials (RCTs) were included, involving 5,088 participants, including 2,540 participants in aspirin, 2,205 participants in rivaroxaban, and 323 participants in warfarin. Aspirin was found to be less effective than oral anticoagulants in thromboprophylaxis after major orthopedic surgery (RR = 1.206, 95% CI 1.053-1.383). After subgroup analysis according to the type of oral anticoagulant, the results showed that aspirin was similar to rivaroxaban and inferior to warfarin. Considering that the studies in the warfarin group were all conducted before 2000, our results need to be further confirmed. In addition, the aspirin group had a higher risk of VTE than the control group in other subgroups, including a follow-up time of ≤3 months, type of procedure as TKA, high-dose aspirin (≥650 mg qd), and no combined use of mechanical prophylaxis. In terms of safety events, aspirin did not show significant differences in major bleeding (RR = 0.952, 95% CI 0.499-1.815), all-cause mortality (RR = 1.208, 95% CI 0.459-3.177), and wound-related events (RR = 0.618, 95% CI 0.333-1.145) compared with oral anticoagulants, and aspirin was associated with a reduction in the risk of minor bleeding (RR = 0.685, 95% CI 0.552-0.850) events and total bleeding (RR = 0.726, 95% CI 0.590-0.892). Conclusion: Aspirin reduces bleeding risk after major orthopedic surgery compared with oral anticoagulants, but may sacrifice VTE prevention to some extent. Updated evidence is needed to analyze the thromboprophylaxis effects of aspirin in patients undergoing major orthopedic surgery. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=463481, identifier CRD42023463481.

Decoding signaling mechanisms: unraveling the targets of guanylate cyclase agonists in cardiovascular and digestive diseases.

Soluble guanylate cyclase agonists and guanylate cyclase C agonists are two popular drugs for diseases of the cardiovascular system and digestive systems. The common denominator in these conditions is the potential therapeutic target of guanylate cyclase. Thanks to in-depth explorations of their underlying signaling mechanisms, the targets of these drugs are becoming clearer. This review explains the recent research progress regarding potential drugs in this class by introducing representative drugs and current findings on them.

Outcome of antithrombotic therapy in cancer patients with catheter-related thrombosis: a systematic review.

Introduction: The guidelines' recommendations for anticoagulation in cancer patients with catheter-related thrombosis are unclear. The aim of this systematic review was to assess anticoagulation management in cancer patients with catheter-related thrombosis (CRT) based on previously published studies. Methods: As of June 10, 2023,we searched databases including PubMed, Embase, and Cochrane and included 11 observational studies that met the criteria. We evaluated 770 adults with active cancer and objectively confirmed patients with CRT who were using drugs including warfarin, LMWH, and new oral anticoagulants as antithrombotic therapy. Results: We extracted outcome data, including thrombosis recurrence, catheter dysfunction, major bleeding, and death, and performed a meta-analysis. Discussion: In this study we found that the risk of VTE recurrence was higher with rivaroxaban, the risk of bleeding and death appeared to be greater with warfarin, and although the risk of catheter dysfunction due to LMWH is a concern, it is still a more reasonable option for cancer patients with catheter-related thrombosis. Systematic Review Registration: http://www.clinicaltrials.gov, identifier (CRD42022367979).