Red cell alloimmunization represents the primary cause of hemolytic disease of the fetus and newborn (HDFN). With advancing clinical management of ABO and Rh alloimmunization, non-Rh alloimmunization has garnered increasing attention. Although MNS system alloimmunization remains rare, reported cases have gradually increased in recent years, particularly in East Asia. Current clinical practice still lacks standardized management protocols for MNS alloimmunization, especially HDFN caused by IgG anti-M antibodies. This review synthesizes recent global research advances in anti-M-mediated HDFN, particularly fetal hemolytic disease, summarizing the unique characteristics of anti-M alloimmunization to inform clinical management strategies for MNS system incompatibility.

AIM:To investigate the effects of total flavonoids of Pterocarya hupehensis Skan(PHSTF)on dex-tran sulfate sodium(DSS)-induced ulcerative colitis(UC)mouse model and lipopolysaccharide(LPS)-stimulated RAW264.7 macrophages.METHODS:Thirty-six male C57BL/6J mice(6 to 8 weeks old,SPF grade)were randomly di-vided into 6 groups:negative control(NC)group,3%DSS-induced model group,mesalazine(300 mg·kg-1·d-1)group,and low-dose(62.5 mg·kg-1·d-1),medium-dose(125 mg·kg-1·d-1)and high-dose(250 mg·kg-1·d-1)PHSTF treatment groups,with 6 mice in each group.The mice in NC group received distilled water,while those in other groups were treated with a 3%DSS solution for 7 d to induce the UC model.On the 1st day of DSS administration,the mice in treatment groups received the corresponding agents via oral gavage for 10 d,while those in NC and model groups were gavaged with distilled water.Throughout the study,the effects of PHSTF on body weight,fecal blood,and colon length were measured and recorded daily.Histopathological changes in colon tissues were assessed using hematoxylin-eosin staining.The levels of the pro-inflammatory cytokine interleukin-1β(IL-1β)and the anti-inflammatory cytokine IL-10 in colon tissues were quantified using ELISA.The LPS-induced RAW264.7 macrophage model was employed to evaluate the cellular effects of PHSTF.Cell viability was assessed by CCK-8 assay,and cell morphology was observed under a microscope.The mRNA expression of inflammatory markers[IL-1β,inducible nitric oxide synthase(iNOS),IL-10 and arginase-1(Arg-1)]was measured by RT-qPCR.Western blot and immunofluorescence double labeling were used to detect the protein expression of macrophage polarization markers(iNOS,CD206 and Arg-1).Finally,immunohistochemistry(IHC)was utilized to as-sess protein expression of iNOS in colon tissues.RESULTS:Compared to the DSS-induced UC model group,PHSTF sig-nificantly improved several parameters,including weight loss(P<0.05),rectal bleeding,and colon shortening in DSS-treated mice.PHSTF also reduced histopathological damage and inflammatory cell infiltration in the colon.It decreased IL-1β levels(P<0.05)and increased IL-10 levels(P<0.05)in colon tissues.In LPS-induced RAW264.7 cells,PHSTF reduced the mRNA expression of IL-1β and iNOS(P<0.01),while upregulating the mRNA expression of IL-10 and Arg-1(P<0.01).Additionally,PHSTF decreased iNOS protein expression(P<0.01)and elevated the expression of Arg-1 and CD206 proteins(P<0.01).IHC analysis further confirmed that PHSTF downregulated iNOS protein expression in colon tissues.CONCLUSION:Treatment with PHSTF promotes the polarization of macrophages from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype,thereby alleviating inflammation in colon tissue and ameliorating ulcer-ative colitis in mice.

OBJECTIVE To evaluate the current status of bacterial contamination control and prevention measures and construction of quality control laboratory in Chinese blood station,and find out the problems and put forward the improvement suggestions.METHODS A total of 41 questionnaires were sent out for performance comparison by secretariat of working group of Chinese blood collection and supply institutions from May 2024 to Jun.2024,and 40 questionnaires were received(14 blood centers and 26 central blood stations),39 of which were valid.The questionnaire survey covered four aspects,including disinfection and surveillance,construction of quality control laboratory,sterility test for blood component and monitoring of blood transfusion reactions.The data were pro-cessed through itemized statistics and descriptive analysis.RESULTS Totally 84.62％of the blood stations used io-dine-containing disinfectants for arm disinfection of the blood donors,and the monthly monitoring was the primary frequency.Among the quality control laboratories,43.59％were registered as biosafety level 2,while 35.90％lacked biosafety registration.As for the pressure settings of the laboratories,64.10％were under normal pres-sure,15.38％under negative pressure and 17.95％under positive pressure.In the sterility test,the utilization rate of ultra clean operating tables and biological safety cabinets was 48.72％,the blood stations that did not have the indoor quality control accounted for 79.49％,and only 35.90％participated the external quality assessment.Regarding the approaches to confirm the positive result,25.64％of the blood stations adopted the re-peated tests,and 15.38％adopted the combination with positive culture bottle.The shortage of fund was the ma-jor restricted factor for the sterility test,and the confirmation of positive result was the fundamental difficulty.The blood stations with the feedback of insufficient transfusion reactions reported from hospitals ac-counted for 53.85％,while the blood stations that encountered suspected bacterial transfusion reactions with nega-tive culture results accounted for 25.64％.CONCLUSIONS The infeciton control and prevention measures and the construction of quality control laboratory vary significantly in Chinese blood stations.The incomplete biosafety registration,non-standardized sterility test operation and weak surveillance of blood transfusion reactions are the major existing problems.It is suggested that the investment should be increased to push forward the standardi-zation and complete the laboratory biosafety system,and a hospital-blood station closed loop coordination mecha-nism should be established so as to raise the blood safety.

AIM:To investigate the effects of total flavonoids of Pterocarya hupehensis Skan(PHSTF)on dex-tran sulfate sodium(DSS)-induced ulcerative colitis(UC)mouse model and lipopolysaccharide(LPS)-stimulated RAW264.7 macrophages.METHODS:Thirty-six male C57BL/6J mice(6 to 8 weeks old,SPF grade)were randomly di-vided into 6 groups:negative control(NC)group,3%DSS-induced model group,mesalazine(300 mg·kg-1·d-1)group,and low-dose(62.5 mg·kg-1·d-1),medium-dose(125 mg·kg-1·d-1)and high-dose(250 mg·kg-1·d-1)PHSTF treatment groups,with 6 mice in each group.The mice in NC group received distilled water,while those in other groups were treated with a 3%DSS solution for 7 d to induce the UC model.On the 1st day of DSS administration,the mice in treatment groups received the corresponding agents via oral gavage for 10 d,while those in NC and model groups were gavaged with distilled water.Throughout the study,the effects of PHSTF on body weight,fecal blood,and colon length were measured and recorded daily.Histopathological changes in colon tissues were assessed using hematoxylin-eosin staining.The levels of the pro-inflammatory cytokine interleukin-1β(IL-1β)and the anti-inflammatory cytokine IL-10 in colon tissues were quantified using ELISA.The LPS-induced RAW264.7 macrophage model was employed to evaluate the cellular effects of PHSTF.Cell viability was assessed by CCK-8 assay,and cell morphology was observed under a microscope.The mRNA expression of inflammatory markers[IL-1β,inducible nitric oxide synthase(iNOS),IL-10 and arginase-1(Arg-1)]was measured by RT-qPCR.Western blot and immunofluorescence double labeling were used to detect the protein expression of macrophage polarization markers(iNOS,CD206 and Arg-1).Finally,immunohistochemistry(IHC)was utilized to as-sess protein expression of iNOS in colon tissues.RESULTS:Compared to the DSS-induced UC model group,PHSTF sig-nificantly improved several parameters,including weight loss(P<0.05),rectal bleeding,and colon shortening in DSS-treated mice.PHSTF also reduced histopathological damage and inflammatory cell infiltration in the colon.It decreased IL-1β levels(P<0.05)and increased IL-10 levels(P<0.05)in colon tissues.In LPS-induced RAW264.7 cells,PHSTF reduced the mRNA expression of IL-1β and iNOS(P<0.01),while upregulating the mRNA expression of IL-10 and Arg-1(P<0.01).Additionally,PHSTF decreased iNOS protein expression(P<0.01)and elevated the expression of Arg-1 and CD206 proteins(P<0.01).IHC analysis further confirmed that PHSTF downregulated iNOS protein expression in colon tissues.CONCLUSION:Treatment with PHSTF promotes the polarization of macrophages from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype,thereby alleviating inflammation in colon tissue and ameliorating ulcer-ative colitis in mice.

OBJECTIVE To evaluate the current status of bacterial contamination control and prevention measures and construction of quality control laboratory in Chinese blood station,and find out the problems and put forward the improvement suggestions.METHODS A total of 41 questionnaires were sent out for performance comparison by secretariat of working group of Chinese blood collection and supply institutions from May 2024 to Jun.2024,and 40 questionnaires were received(14 blood centers and 26 central blood stations),39 of which were valid.The questionnaire survey covered four aspects,including disinfection and surveillance,construction of quality control laboratory,sterility test for blood component and monitoring of blood transfusion reactions.The data were pro-cessed through itemized statistics and descriptive analysis.RESULTS Totally 84.62％of the blood stations used io-dine-containing disinfectants for arm disinfection of the blood donors,and the monthly monitoring was the primary frequency.Among the quality control laboratories,43.59％were registered as biosafety level 2,while 35.90％lacked biosafety registration.As for the pressure settings of the laboratories,64.10％were under normal pres-sure,15.38％under negative pressure and 17.95％under positive pressure.In the sterility test,the utilization rate of ultra clean operating tables and biological safety cabinets was 48.72％,the blood stations that did not have the indoor quality control accounted for 79.49％,and only 35.90％participated the external quality assessment.Regarding the approaches to confirm the positive result,25.64％of the blood stations adopted the re-peated tests,and 15.38％adopted the combination with positive culture bottle.The shortage of fund was the ma-jor restricted factor for the sterility test,and the confirmation of positive result was the fundamental difficulty.The blood stations with the feedback of insufficient transfusion reactions reported from hospitals ac-counted for 53.85％,while the blood stations that encountered suspected bacterial transfusion reactions with nega-tive culture results accounted for 25.64％.CONCLUSIONS The infeciton control and prevention measures and the construction of quality control laboratory vary significantly in Chinese blood stations.The incomplete biosafety registration,non-standardized sterility test operation and weak surveillance of blood transfusion reactions are the major existing problems.It is suggested that the investment should be increased to push forward the standardi-zation and complete the laboratory biosafety system,and a hospital-blood station closed loop coordination mecha-nism should be established so as to raise the blood safety.

Red cell alloimmunization represents the primary cause of hemolytic disease of the fetus and newborn (HDFN). With advancing clinical management of ABO and Rh alloimmunization, non-Rh alloimmunization has garnered increasing attention. Although MNS system alloimmunization remains rare, reported cases have gradually increased in recent years, particularly in East Asia. Current clinical practice still lacks standardized management protocols for MNS alloimmunization, especially HDFN caused by IgG anti-M antibodies. This review synthesizes recent global research advances in anti-M-mediated HDFN, particularly fetal hemolytic disease, summarizing the unique characteristics of anti-M alloimmunization to inform clinical management strategies for MNS system incompatibility.

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is the main pathogen that causes COVID-19,which is fast-mutating and highly transmissible.The infection has led to a global epidemic.As the main preventive and control measure,vaccination plays a critical role in fighting a-gainst COVID-19.Although a large number of epitope-based and mucosal vaccines have been stud-ied,few peptide epitope vaccines targeting the mucosa and their functional evaluation have been re-ported.In this study,we used SARS-CoV-2 structural protein M peptide epitope predicted by the IEDB database as an antigenic target to design the MS-3S gene containing 3 050 and 1 229 signal peptides and DCpep optimized for insertion into MS2 phage coat proteins.The expression plasmid pSIP:MS-3S was constructed by cloning the PCR fragments seamlessly and was transformed into Lactiplantibacillus plantarum 18 to obtain the recombinant bacterium LP18:MS-3S.Expression conditions such as induction time,inducer concentration,rotational speed and initial pH were opti-mized.The intranasal immunization experiments were performed to examine the vaccine efficacy.The results showed that the 916 bp-long target gene MS-3S modified and optimized was amplified and used to successfully construct the recombinant bacterial strain LP18:MS-3S.The optimal con-ditions for recombinant protein expression were obtained and verified by Western blot,flow cy-tometry,immunofluorescence and other detection methods.The optimal expression conditions were determined as follows:induction time was 4 h with 100 pg/L of SppIP as the optimal induction concentration.Antibody-specific for the epitope was verified by ELISA experiments in serum,alve-olar lavage fluid and fecal dilutions of mice.In summary,a recombinant bacterial strain expressing the epitope antigen of the SARS-CoV-2 M protein peptide was constructed.The obtained protein can induce the body to produce humoral and mucosal immunity,which lays the foundation for the development of a vaccine candidate for the mucosal immunity of COVID-19.

This paper discussed how to set the limit of impurities in the quality standard when the impurities in small-molecular innovative drugs were metabolites.Firstly,through the analysis and interpretation of each relevant guideline,in combination with the review cases of FDA and EMA,found out the conditions for qualification of im-purity,and then establ ish the acceptable limit of impurities based on the test results of multiple batches,the incre-ments of production process and storage process.

Objective:To observe the diagnostic value of six classification intelligent auxiliary diagnosis lightweight model for common fundus diseases based on fundus color photography.Methods:A applied research. A dataset of 2 400 color fundus images from Nanjing Medical University Eye Hospital and Zhejiang Mathematical Medical Society Smart Eye Database was collected, which was desensitized and labeled by a fundus specialist. Of these, 400 each were for diabetic retinopathy, glaucoma, retinal vein occlusion, high myopia, age-related macular degeneration, and normal fundus. The parameters obtained from the classical classification models VGGNet16, ResNet50, DenseNet121 and lightweight classification models MobileNet3, ShuffleNet2, GhostNet trained on the ImageNet dataset were migrated to the six-classified common fundus disease intelligent aid diagnostic model using a migration learning approach during training as initialization parameters for training to obtain the latest model. 1 315 color fundus images of clinical patients were used as the test set. Evaluation metrics included sensitivity, specificity, accuracy, F1-Score and agreement of diagnostic tests (Kappa value); comparison of subject working characteristic curves as well as area under the curve values for different models.Result:Compared with the classical classification model, the storage size and number of parameters of the three lightweight classification models were significantly reduced, with ShuffleNetV2 having an average recognition time per sheet 438.08 ms faster than the classical classification model VGGNet16. All 3 lightweight classification models had Accuracy > 80.0%; Kappa values > 70.0% with significant agreement; sensitivity, specificity, and F1-Score for the diagnosis of normal fundus images were ≥ 98.0%; Macro-F1 was 78.2%, 79.4%, and 81.5%, respectively.Conclusion:The intelligent assisted diagnosis of common fundus diseases based on fundus color photography is a lightweight model with high recognition accuracy and speed; the storage size and number of parameters are significantly reduced compared with the classical classification model.

Lung cancer is one of the most common malignancies with the highest incidence rate and mortality rate worldwide, and non-small cell lung cancer (NSCLC) accounts for about 85%. Only 5% NSCLC patients are anaplastic lymphoma kinase (ALK) rearrangement positive NSCLC, but the prognosis of these patients is poor, and treatment is urgent. Ensartinib (X-396), a next-generation ALK tyrosine kinase inhibitor (ALK-TKI), has shown greater potency on inhibiting ALK activity and controlling brain metastases than crizotinib, which is indicated for the treatment of crizotinib-resistant, ALK-positive NSCLC patients. Several phase I to III clinical trials included both healthy volunteers and NSCLC patients have been conducted both in China and abroad. In this review, we briefly summarized the results of these trials, and preliminary efficacy, safety, pharmacology and pharmacokinetics/pharmacodynamics of ensartinib were discussed.