Myeloid cell-expressed MNDA enhances M2 polarization to facilitate the metastasis of hepatocellular carcinoma.

Stable infiltration of myeloid cells, especially tumor-associated M2 macrophages, acts as one of the essential features of the tumor immune microenvironment by promoting the malignant progression of hepatocellular carcinoma (HCC). However, the factors affecting the infiltration of M2 macrophages are not fully understood. In this study, we found the molecular subtypes of HCC with the worst prognosis are characterized by immune disorders dominated by myeloid cell infiltration. Myeloid cell nuclear differentiation antigen (MNDA) was significantly elevated in the most aggressive subtype and exhibited a positively correlation with M2 infiltration and HCC metastasis. Moreover, MNDA functioned as an independent prognostic predictor and has a good synergistic effect with some existing prognostic clinical indicators. We further confirmed that MNDA was primarily expressed in tumor M2 macrophages and contributed to the enhancement of its polarization by upregulating the expression of the M2 polarization enhancers. Furthermore, MNDA could drive the secretion of M2 macrophage-derived pro-metastasis proteins to accelerate HCC cells metastasis both in vivo and in vitro. In summary, MNDA exerts a protumor role by promoting M2 macrophages polarization and HCC metastasis, and can serve as a potential biomarker and therapeutic target for HCC.

Proteomics Identifies LUC7L3 as a Prognostic Biomarker for Hepatocellular Carcinoma.

Alternative splicing has been shown to participate in tumor progression, including hepatocellular carcinoma. The poor prognosis of patients with HCC calls for molecular classification and biomarker identification to facilitate precision medicine. We performed ssGSEA analysis to quantify the pathway activity of RNA splicing in three HCC cohorts. Kaplan-Meier and Cox methods were used for survival analysis. GO and GSEA were performed to analyze pathway enrichment. We confirmed that RNA splicing is significantly correlated with prognosis, and identified an alternative splicing-associated protein LUC7L3 as a potential HCC prognostic biomarker. Further bioinformatics analysis revealed that high LUC7L3 expression indicated a more progressive HCC subtype and worse clinical features. Cell proliferation-related pathways were enriched in HCC patients with high LUC7L3 expression. Consistently, we proved that LUC7L3 knockdown could significantly inhibit cell proliferation and suppress the activation of associated signaling pathways in vitro. In this research, the relevance between RNA splicing and HCC patient prognosis was outlined. Our newly identified biomarker LUC7L3 could provide stratification for patient survival and recurrence risk, facilitating early medical intervention before recurrence or disease progression.

From PROTAC to TPD: Advances and Opportunities in Targeted Protein Degradation.

PROTAC is a rapidly developing engineering technology for targeted protein degradation using the ubiquitin-proteasome system, which has promising applications for inflammatory diseases, neurodegenerative diseases, and malignant tumors. This paper gives a brief overview of the development and design principles of PROTAC, with a special focus on PROTAC-based explorations in recent years aimed at achieving controlled protein degradation and improving the bioavailability of PROTAC, as well as TPD technologies that use other pathways such as autophagy and lysosomes to achieve targeted protein degradation.

Peptidoglycan biosynthesis-associated enzymatic kinetic characteristics and ß-lactam antibiotic inhibitory effects of different Streptococcus pneumoniae penicillin-binding proteins.

Penicillin-binding proteins (PBPs) include transpeptidases, carboxypeptidases, and endopeptidases for biosynthesis of peptidoglycans in the cell wall to maintain bacterial morphology and survival in the environment. Streptococcus pneumoniae expresses six PBPs, but their enzymatic kinetic characteristics and inhibitory effects on different ß-lactam antibiotics remain poorly understood. In this study, all the six recombinant PBPs of S. pneumoniae displayed transpeptidase activity with different substrate affinities (Km = 1.56-9.11 mM) in a concentration-dependent manner, and rPBP3 showed a greater catalytic efficiency (Kcat = 2.38 s-1) than the other rPBPs (Kcat = 3.20-7.49 × 10-2 s-1). However, only rPBP3 was identified as a carboxypeptidase (Km = 8.57 mM and Kcat = 2.57 s-1). None of the rPBPs exhibited endopeptidase activity. Penicillin and cefotaxime inhibited the transpeptidase and carboxypeptidase activity of all the rPBPs but imipenem did not inhibited the enzymatic activities of rPBP3. Except for the lack of binding of imipenem to rPBP3, penicillin, cefotaxime, and imipenem bound to all the other rPBPs (KD = 3.71-9.35 × 10-4 M). Sublethal concentrations of penicillin, cefotaxime, and imipenem induced a decrease of pneumococcal pbps-mRNA levels (p < 0.05). These results indicated that all six PBPs of S. pneumoniae are transpeptidases, while only PBP3 is a carboxypeptidase. Imipenem has no inhibitory effect on pneumococcal PBP3. The pneumococcal genes for encoding endopeptidases remain to be determined.

RNF149 Promotes HCC Progression through Its E3 Ubiquitin Ligase Activity.

Hepatocellular carcinoma (HCC) accounts for over 80% of cases among liver cancer, with high incidence and poor prognosis. Thus, it is of valuable clinical significance for discovery of potential biomarkers and drug targets for HCC. In this study, based on the proteomic profiling data of paired early-stage HCC samples, we found that RNF149 was strikingly upregulated in tumor tissues and correlated with poor prognosis in HCC patients, which was further validated by IHC staining experiments of an independent HCC cohort. Consistently, overexpression of RNF149 significantly promoted cell proliferation, migration, and invasion of HCC cells. We further proved that RNF149 stimulated HCC progression via its E3 ubiquitin ligase activity, and identified DNAJC25 as its new substrate. In addition, bioinformatics analysis showed that high expression of RNF149 was correlated with immunosuppressive tumor microenvironment (TME), indicating its potential role in immune regulation of HCC. These results suggest that RNF149 could exert protumor functions in HCC in dependence of its E3 ubiquitin ligase activity, and might be a potential prognostic marker and therapeutic target for HCC treatment.

Rapid diagnosis of Mycobacterium marinum infection using targeted nanopore sequencing: a case report.

Mycobacterium marinum (M. marinum) is a non-tuberculous mycobacterium (NTM) that can cause infectious diseases in aquatic animals and humans. Culture-based pathogen detection is the gold standard for diagnosing NTM infection. However, this method is time-consuming and has low positivity rates for fastidious organisms. Oxford Nanopore MinION sequencing is an emerging third-generation sequencing technology that can sequence DNA or RNA directly in a culture-independent manner and offers rapid microbial identification. Further benefits include low cost, short turnaround time, long read lengths, and small equipment size. Nanopore sequencing plays a crucial role in assessing drug resistance, clinical identification of microbes, and monitoring infectious diseases. Some reports on Mycobacterium tuberculosis (MTB) using nanopore sequencing have been published, however, there are few reports on NTM, such as M. marinum. Here, we report the use of nanopore sequencing for the diagnosis of M. marinum.

Advanced Design and Fabrication of Dual-Material Honeycombs for Improved Stiffness and Resilience.

Auxetic re-entrant honeycomb (AREH) structures, consisting of a single soft or tough material, have long faced the challenge of balancing stiffness and rebound resilience. To achieve this balance, dual-material printing technology is employed to enhance shock absorption by combining layers of soft and tough materials. Additionally, a novel structure called the curved re-entrant honeycomb (CREH) structure has been introduced to improve stiffness. The selected materials for processing the composite structures of AREH and CREH are the rigid thermoplastic polymer polylactic acid (PLA) and the soft rubber material thermoplastic polyurethane (TPU), created utilizing fused deposition modeling (FDM) 3D printing technology. The influence of the material system and structure type on stress distribution and mechanical response was subsequently investigated. The results revealed that the dual-material printed structures demonstrated later entry into the densification phase compared to the single-material printed structures. Moreover, the soft material in the interlayer offered exceptional protection, thereby ensuring the overall integrity of the structure. These findings effectively serve as a reference for the design of dual-material re-entrant honeycombs.

Correction: Mononuclear-macrophages but not neutrophils act as major infiltrating anti-leptospiral phagocytes during leptospirosis.

[This corrects the article DOI: 10.1371/journal.pone.0181014.].

From materials to clinical use: advances in 3D-printed scaffolds for cartilage tissue engineering.

Osteoarthritis caused by articular cartilage defects is a particularly common orthopedic disease that can involve the entire joint, causing great pain to its sufferers. A global patient population of approximately 250 million people has an increasing demand for new therapies with excellent results, and tissue engineering scaffolds have been proposed as a potential strategy for the repair and reconstruction of cartilage defects. The precise control and high flexibility of 3D printing provide a platform for subversive innovation. In this perspective, cartilage tissue engineering (CTE) scaffolds manufactured using different biomaterials are summarized from the perspective of 3D printing strategies, the bionic structure strategies and special functional designs are classified and discussed, and the advantages and limitations of these CTE scaffold preparation strategies are analyzed in detail. Finally, the application prospect and challenges of 3D printed CTE scaffolds are discussed, providing enlightening insights for their current research.

Identification of Talaromyces marneffei Infection in an HIV-Negative Patient by ITS Sequencing.

Disseminated ankle mycosis is a life-threatening systemic infection caused by the emerging opportunistic and lethal fungal pathogen Talaromyces marneffei which is more common in HIV-positive patients. However, an increasing number of infections are occurring in HIV-negative patients. Here, we report a case of Talaromyces marneffei infection in HIV-negative patient. A 50s HIV-negative male patient with fever, cough, bloody sputum expectoration, pulmonary sarcoidosis and body rashes was hospitalized at Zhejiang Provincial People's Hospital. CT scanning showed pulmonary multiple nodules with apical bronchial occlusion, patchy infiltration and pathological biopsy demonstrated bronchiolitis obliterans with organized pneumonia and chronic active inflammation of lung tissue with infiltration of numerous lymphocytes, plasma cells, phagocytes and neutrophils. Laboratory tests revealed significantly increased white blood cells count 18.3 ×109/L, neutrophil count 15.34 ×109/L, monocyte count 0.66 ×109/L, platelet count 517 ×109/L, C-reactive protein 116 mg/L, erythrocyte sedimentation rate 112mm/h. The ß-D-glucan test was negative (33.06 pg/mL) while fungal culture of broncho alveolar lavage fluid revealed colonies with temperature-dependent dimorphic growth character and Talaromyces marneffei was confirmed by ITS sequencing of the colonies. The patient exhibited radiological improvement and clinical recuperation after intravenously guttae of voriconazole. Talaromycosis in immunocompetent and HIV-negative individuals is relatively rare and is characterized by an insidious onset, various clinical manifestations, and is clinically challenging. Fungal culture and ITS sequencing are warranted for diagnosis Talaromyces marneffei infection. This is the first report on identification of Talaromyces marneffei infection in an HIV-negative patient with skin involvement by ITS sequencing in Zhejiang.

OTTM: an automated classification tool for translational drug discovery from omics data.

Omics data from clinical samples are the predominant source of target discovery and drug development. Typically, hundreds or thousands of differentially expressed genes or proteins can be identified from omics data. This scale of possibilities is overwhelming for target discovery and validation using biochemical or cellular experiments. Most of these proteins and genes have no corresponding drugs or even active compounds. Moreover, a proportion of them may have been previously reported as being relevant to the disease of interest. To facilitate translational drug discovery from omics data, we have developed a new classification tool named Omics and Text driven Translational Medicine (OTTM). This tool can markedly narrow the range of proteins or genes that merit further validation via drug availability assessment and literature mining. For the 4489 candidate proteins identified in our previous proteomics study, OTTM recommended 40 FDA-approved or clinical trial drugs. Of these, 15 are available commercially and were tested on hepatocellular carcinoma Hep-G2 cells. Two drugs-tafenoquine succinate (an FDA-approved antimalarial drug targeting CYC1) and branaplam (a Phase 3 clinical drug targeting SMN1 for the treatment of spinal muscular atrophy)-showed potent inhibitory activity against Hep-G2 cell viability, suggesting that CYC1 and SMN1 may be potential therapeutic target proteins for hepatocellular carcinoma. In summary, OTTM is an efficient classification tool that can accelerate the discovery of effective drugs and targets using thousands of candidate proteins identified from omics data. The online and local versions of OTTM are available at http://otter-simm.com/ottm.html.

MWCNTs-GNPs Reinforced TPU Composites with Thermal and Electrical Conductivity: Low-Temperature Controlled DIW Forming.

As an effective technique for fabricating conductive and thermally conductive polymer composites, a multi-filler system incorporates different types and sizes of multiple fillers to form interconnected networks with improved electrical, thermal, and processing properties. In this study, DIW forming of bifunctional composites was achieved by controlling the temperature of the printing platform. The study was based on enhancing the thermal and electrical transport properties of hybrid ternary polymer nanocomposites with multi-walled carbon nanotubes (MWCNTs) and graphene nanoplates (GNPs). With thermoplastic polyurethane (TPU) used as the matrix, the addition of MWCNTs, GNPs and both mixtures further improved the thermal conductivity of the elastomers. By adjusting the weight fraction of the functional fillers (MWCNTs and GNPs), the thermal and electrical properties were gradually explored. Here, the thermal conductivity of the polymer composites increased nearly sevenfold (from 0.36 W·m-1·k-1 to 2.87 W·m-1·k-1) and the electrical conductivity increased up to 5.49 × 10-2 S·m-1. It is expected to be used in the field of electronic packaging and environmental thermal dissipation, especially for modern electronic industrial equipment.

Aberrant LYZ expression in tumor cells serves as the potential biomarker and target for HCC and promotes tumor progression via csGRP78.

Hepatocellular carcinoma (HCC) takes the predominant malignancy of hepatocytes with bleak outcomes owing to high heterogeneity among patients. Personalized treatments based on molecular profiles will better improve patients' prognosis. Lysozyme (LYZ), a secretory protein with antibacterial function generally expressed in monocytes/macrophages, has been observed for the prognostic implications in different types of tumors. However, studies about the explicit applicative scenarios and mechanisms for tumor progression are still quite limited, especially for HCC. Here, based on the proteomic molecular classification data of early-stage HCC, we revealed that the LYZ level was elevated significantly in the most malignant HCC subtype and could serve as an independent prognostic predictor for HCC patients. Molecular profiles of LYZ-high HCCs were typical of those for the most malignant HCC subtype, with impaired metabolism, along with promoted proliferation and metastasis characteristics. Further studies demonstrated that LYZ tended to be aberrantly expressed in poorly differentiated HCC cells, which was regulated by STAT3 activation. LYZ promoted HCC proliferation and migration in both autocrine and paracrine manners independent of the muramidase activity through the activation of downstream protumoral signaling pathways via cell surface GRP78. Subcutaneous and orthotopic xenograft tumor models indicated that targeting LYZ inhibited HCC growth markedly in NOD/SCID mice. These results propose LYZ as a prognostic biomarker and therapeutic target for the subclass of HCC with an aggressive phenotype.

Application of medical-nurse integration health education in aged patients undergoing percutaneous vertebroplasty.

This study was designed to explore the effect of medical-nurse integration health education in aged patients undergoing percutaneous vertebroplasty. A total of 72 aged patients with osteoporotic vertebral compression fractures, who obtained percutaneous vertebroplasty from June 2019 to May 2022 were selected in this study. Patients were divided into control group (n = 36) and experimental group (n = 36) according to the time of hospitalization. The patients in control group received routine health education, while the patients in the experimental group received medical-nurse integration health education. We evaluated participants on 4 key aspects, their understanding of relevant knowledge, compliance with functional exercise, residual lower back pain rate, and satisfaction with the health education received. Our study found that patients in the experimental group had a significantly higher mastery rate of health education knowledge compared to those in the control group (88.89% vs 50.00%, P < .001). Additionally, compliance with the functional exercise program was higher in the experimental group, with over 80% of patients fully compliant, compared to only about 44.4% in the control group (P = .001). The average Japanese Orthopaedic Association score of the observation group 1 week after operation was higher than that of the control group (P < .05). Moreover, most patients in the experimental group were very satisfied with the medical-nurse integration health education, while most patients in the control group were only satisfied (P < .001). For aged patients with osteoporotic vertebral compression fractures treated by percutaneous vertebroplasty, medical-nurse integration health education could be an effective method to improve the ability of patients to obtain relevant education, enhance the compliance of patients for functional exercise and increase patient satisfaction to the education, and reduce residual low back pain in patients.

Azithromycin Exposure Induces Transient Microbial Composition Shifts and Decreases the Airway Microbiota Resilience from Outdoor PM2.5 Stress in Healthy Adults: a Randomized, Double-Blind, Placebo-Controlled Trial.

Inappropriate antibiotic prescriptions are common for patients with upper respiratory tract infections (URTIs). Few data exist regarding the effects of antibiotic administration on airway microbiota among healthy adults. We conducted a randomized, double-blind, placebo-controlled trial to characterize the airway microbiota longitudinally in healthy adults using 16S rRNA gene sequencing and quantification. Both the induced sputum and oral wash samples were collected over a 60-day period following a 3-day intervention with 500 mg azithromycin or placebo. Environmental information, including air quality data (particulate matter [PM2.5] and PM10, air quality index [AQI] values), were also collected during the study. A total of 48 healthy volunteers were enrolled and randomly assigned into two groups. Azithromycin did not alter bacterial load but significantly reduced species richness and Shannon index. Azithromycin exposure resulted in a decrease in the detection rate and relative abundance of different genera belonging to Veillonellaceae, Leptotrichia, Fusobacterium, Neisseria, and Haemophilus. In contrast, the relative abundance of taxa belonging to Streptococcus increased immediately after azithromycin intervention. The shifts in the diversity of the microbiology composition took between 14 and 60 days to recover, depending on the measure used: either UniFrac phylogenetic distance or α-diversity. Outdoor environmental perturbations, especially the high concentration of PM2.5, contributed to novel variability in microbial community composition of the azithromycin group at D30 (30 days after baseline). The network analysis found that azithromycin altered the microbial interactions within airway microbiota. The influence was still obvious at D14 when the relative abundance of most taxa had returned to the baseline level. Compared to the sputum microbiota, oral cavity microbiota had a different pattern of change over time. The induced sputum microbial data can represent the airway microbiota composition in healthy adults. Azithromycin may have transient effects in the airway microbiota of healthy adults and decrease the airway microbiota resilience against outdoor environmental stress. The influence of azithromycin on microbial interactions is noteworthy, although the airway microbiota has returned to a near-baseline level. IMPORTANCE The influence of antibiotic administration on the airway microbiota of healthy adults remains unknown. This study is a randomized, double-blind, placebo-controlled trial aiming to investigate the microbial shifts in airways after exposure to azithromycin among heathy adults. We find that azithromycin changes the airway microbial community composition of healthy adults and decreases the airway microbiota resilience against outdoor environmental stress. This study depicts the longitudinal recovery trajectory of airway microbiota after the antibiotic perturbation and may provide reference for appropriate antibiotic prescription.

Identifying the critical areas and primary sources for agricultural non-point source pollution management of an emigrant town within the Three Gorges reservoir area.

Agricultural non-point source pollution is threatening water environmental health of the Three Gorges reservoir. However, current studies for precision management of the agricultural non-point source pollution within this area are still limited. The objective of this study was identifying the critical areas and primary sources of agricultural non-point source pollution for precision management. Firstly, the inventory analysis approach was used to estimate the discharge amount of total nitrogen (TN), total phosphorus (TP), and chemical oxygen demand (COD) from farmland fertilizer, crop residues, livestock breeding, and daily activities. Afterwards, the deviation standardization method was applied to evaluate the emission intensity of TN, TP, and COD, as well as calculating the comprehensive pollution index (CPI) of each village, based on which the critical areas for agricultural non-point source pollution management could be distinguished. Moreover, the equivalence pollution load method was conducted to identify the primary pollution sources within each critical zone. The above methods were implemented to an emigrant town within the Three Gorges reservoir area named Gufu. Results showed that agricultural non-point source pollution in Gufu town has been alleviated to a certain extent since 2016. Nevertheless, in four areas of the town (i.e., Longzhu, Fuzi, Shendu, and Maicang), the agricultural non-point source pollution still deserved attention and improvement. For the mentioned critical areas, farmland fertilizer and livestock breeding were the primary sources causing agricultural non-point source pollution. The emission amount of TN and TP from farmland fertilizer accounted for 60% and 48% of the total, respectively. And those from livestock breeding were 29% and 46%. Our research could provide definite targets to relieve agricultural non-point source pollution, which had great significance to protect water environment while coordinating regional economic growth after emigrant resettlement.

Molecular features and predictive models identify the most lethal subtype and a therapeutic target for osteosarcoma.

Background: Osteosarcoma is the most common primary malignant bone tumor. The existing treatment regimens remained essentially unchanged over the past 30 years; hence the prognosis has plateaued at a poor level. Precise and personalized therapy is yet to be exploited. Methods: One discovery cohort (n=98) and two validation cohorts (n=53 & n=48) were collected from public data sources. We performed a non-negative matrix factorization (NMF) method on the discovery cohort to stratify osteosarcoma. Survival analysis and transcriptomic profiling characterized each subtype. Then, a drug target was screened based on subtypes' features and hazard ratios. We also used specific siRNAs and added a cholesterol pathway inhibitor to osteosarcoma cell lines (U2OS and Saos-2) to verify the target. Moreover, PermFIT and ProMS, two support vector machine (SVM) tools, and the least absolute shrinkage and selection operator (LASSO) method, were employed to establish predictive models. Results: We herein divided osteosarcoma patients into four subtypes (S-I ~ S-IV). Patients of S- I were found probable to live longer. S-II was characterized by the highest immune infiltration. Cancer cells proliferated most in S-III. Notably, S-IV held the most unfavorable outcome and active cholesterol metabolism. SQLE, a rate-limiting enzyme for cholesterol biosynthesis, was identified as a potential drug target for S-IV patients. This finding was further validated in two external independent osteosarcoma cohorts. The function of SQLE to promote proliferation and migration was confirmed by cell phenotypic assays after the specific gene knockdown or addition of terbinafine, an inhibitor of SQLE. We further employed two machine learning tools based on SVM algorithms to develop a subtype diagnostic model and used the LASSO method to establish a 4-gene model for predicting prognosis. These two models were also verified in a validation cohort. Conclusion: The molecular classification enhanced our understanding of osteosarcoma; the novel predicting models served as robust prognostic biomarkers; the therapeutic target SQLE opened a new way for treatment. Our results served as valuable hints for future biological studies and clinical trials of osteosarcoma.

Corrigendum: Magnesium application improves the morphology, nutrients uptake, photosynthetic traits, and quality of tobacco (Nicotiana tabacum L.) under cold stress.

[This corrects the article DOI: 10.3389/fpls.2023.1078128.].

Magnesium application improves the morphology, nutrients uptake, photosynthetic traits, and quality of tobacco (Nicotiana tabacum L.) under cold stress.

Cold stress is one of the major constraints limiting the productivity of many important crops, including tobacco (Nicotiana tabacum L.) production and quality worldwide. However, the role of magnesium (Mg) nutrition in plants has been frequently overlooked, especially under cold stress, and Mg deficiency adversely affects plant growth and development. Here, we evaluated the influence of Mg under cold stress on tobacco morphology, nutrient uptake, photosynthetic and quality attributes. The tobacco plants were grown under different levels of cold stress, i.e., 8°C, 12°C, 16°C, including with a controlled temperature of 25°C, and evaluated their effects with Mg (+Mg) and without Mg (-Mg) application. Cold stress resulted in reduced plant growth. However, the +Mg alleviated the cold stress and significantly increased the plant biomass on an average of 17.8% for shoot fresh weight, 20.9% for root fresh weight, 15.7% for shoot dry weight, and 15.5% for root dry weight. Similarly, the nutrients uptake also increased on average for shoot-N (28.7%), root-N (22.4%), shoot-P (46.9%), root-P (7.2%), shoot-K (5.4%), root-K (28.9%), shoot-Mg (191.4%), root-Mg (187.2%) under cold stress with +Mg compared to -Mg. Mg application significantly boosted the photosynthetic activity (Pn 24.6%) and increased the chlorophyll contents (Chl-a (18.8%), Chl-b (25%), carotenoids (22.2%)) in the leaves under cold stress in comparison with -Mg treatment. Meanwhile, Mg application also improved the quality of tobacco, including starch and sucrose contents, on an average of 18.3% and 20.8%, respectively, compared to -Mg. The principal component analysis revealed that tobacco performance was optimum under +Mg treatment at 16°C. This study confirms that Mg application alleviates cold stress and substantially improves tobacco morphological indices, nutrient absorption, photosynthetic traits, and quality attributes. In short, the current findings suggest that Mg application may alleviate cold stress and improve tobacco growth and quality.

Red blood cell alloimmunizations in thalassaemia patients with regular transfusion in China: A systematic review and meta-analysis.

OBJECTIVE: The development of red blood cell alloimmunization intensifies transfusion complication in thalassaemia patients. The purpose of this paper is to evaluate the existing evidence on the prevalence of erythrocyte alloimmunization in China by meta-analysis. We systematically searched cross-sectional studies regarding the alloimmunization of thalassaemia patients with regular blood transfusion in China from year 2000 to May 2021 in the Cochrane library, PubMed, EMBASE, Web of Science, and Chinese databases including CNKI, Wanfang Data, Vip and CBM. Data extraction and quality evaluation of the included studies were performed. Meta-analysis was performed using the DerSimonian and Laird random-effects models with inverse variance weighting. The presence of publication bias was tested by Egger's test, and the methodological quality of each included article was evaluated by the criteria specific to prevalence studies. RESULTS: A total of 1874 patients and 263 alloantibodies from 11 studies were identified and included in the meta-analysis. The proportion of alloantibodies against antigens belonging to the Rh, MNSs and Kidd systems were as high as 70.3%, 17.9%, and 6.5%, respectively. Meta-analysis showed that the overall prevalence of alloimmunization among transfusion-dependent thalassaemia patients in China is 11.4% (95%CI: 7.2%∼16.3%). CONCLUSIONS: The characteristics of red blood cell alloimmunization among thalassaemia patients with regular transfusion in China differ greatly from those in other countries. Therefore, transfusion strategies shall be actively adapted in line with thalassaemia patients in China to minimize the risk of alloimmunization.