Objective:To investigate the clinical efficacy and safety of venetoclax(VEN)in combination with hypomethylating agent(HMA)in the treatment of patients with high-risk myelodysplastic syndromes(MDS).Methods:A total of 30 patients with high-risk MDS who received the combination of VEN and HMA from March 2019 to November 2022 were included.The overall response rate(ORR),modified overall response rate(mORR),overall survival(OS),progression-free survival(PFS),and adverse events of all included patients were evaluated.Results:Among the 30 high-risk MDS patients treated with VEN combined with HMA regimen,24 cases achieved complete response(CR)/marrow complete response(mCR),2 cases achieved partial response(PR),the ORR was 24/30,the median OS was 28.1 months,and the median PFS was 28.1 months.In addition,patients who achieved complete remission/marrow complete remission after treatment had a significantly longer OS than those who did not.Moreover,12 patients were treated with allogeneic hematopoietic stem cell transplantation(allo-HSCT).There were grade 3 or higher hematologic adverse events including thrombocytopenia(14 cases),neutropenia(14 cases),febrile neutropenia(10 cases)and anemia(7 cases)as well as gastrointestinal adverse events of any grade,such as vomiting(7 cases),diarrhea(5 cases),and constipation(4 cases).Conclusion:VEN in combination with HMA is an effective and safe treatment option in patients with high-risk MDS.This regimen combined with allo-HSCT can improve the prognosis of these patients.Continuous attention to the monitoring and management of adverse events is essential for the patients'safety in this combination therapy.

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

Microphthalmos is a congenital ocular developmental anomaly that manifests as a significant reduction in the size of eyes,and is often combined with various ocular disorders such as cataract.Due to its special intraocular anatomical features,the risk of intraoperative and postoperative complications of cataract surgery in microphthalmos is usually high.Combined with subscleral sclerectomy,peripheral iridectomy,and anterior segment vitrectomy,the incidence of the pre-existing complications in cataract surgery has decreased,meanwhile,the additional procedures may also bring new complications.In-depth understanding of the research progress of cataract surgery in microphthalmos and the prevention of complications is of great guiding significance to improve surgical outcomes,and can reduce the incidence of postoperative complications such as uveal effusion syndrome,secondary glaucoma and corneal edema,and promote personalized treatments for microphthalmos patients who suffered from cataract.

This study was aimed at understanding the prevalence and drug resistance status of Salmonella of waterfowl ori-gin in the Guangdong region in the past decade,to guide prevention and control efforts.The drug-sensitive paper slide method was used to conduct drug susceptibility testing on 314 waterfowl-originating Salmonella strains isolated from 238 waterfowl farms in the Guangdong region from 2013 to 2023.The isolated Salmonella strains were most resistant to penicillin,amoxicil-lin,cefradine,and cefazolin in the β-lactam group;sulphadoxine dimethylpyrimidine in the sulphonamide group;and tetracy-cline in the tetracycline group.The resistance rates ranged from 73.57％to 89.49％.The highest sensitivity was observed to amikacin,gentamicin,and kanamycin in the aminoglycoside group,and norfloxacin in the quinolone group,with susceptibility rates all exceeding 50％.The 280 strains of Salmonella showed multi-drug resistance to six classes of antimicrobial drugs and high resistance(as much as 60.83％)to five drug classes.Correlation analysis revealed the highest correlations for florfenicol with gentamicin,and for amoxicillin with penicillin(r=0.650 for both),followed by gentamicin with kanamycin(r=0.620).Salmonella resistance in waterfowl in Guangdong Province was generally severe and showed a complex pattern of drug resist-ance.Detection of waterfowl pathogens should be strengthened to prevent the spread of drug-resistant bacteria and support ra-tional use of antibiotics.This work provides a reference for Salmonella prevention and control in waterfowl farms.

This study was aimed at understanding the prevalence and drug resistance status of Salmonella of waterfowl ori-gin in the Guangdong region in the past decade,to guide prevention and control efforts.The drug-sensitive paper slide method was used to conduct drug susceptibility testing on 314 waterfowl-originating Salmonella strains isolated from 238 waterfowl farms in the Guangdong region from 2013 to 2023.The isolated Salmonella strains were most resistant to penicillin,amoxicil-lin,cefradine,and cefazolin in the β-lactam group;sulphadoxine dimethylpyrimidine in the sulphonamide group;and tetracy-cline in the tetracycline group.The resistance rates ranged from 73.57％to 89.49％.The highest sensitivity was observed to amikacin,gentamicin,and kanamycin in the aminoglycoside group,and norfloxacin in the quinolone group,with susceptibility rates all exceeding 50％.The 280 strains of Salmonella showed multi-drug resistance to six classes of antimicrobial drugs and high resistance(as much as 60.83％)to five drug classes.Correlation analysis revealed the highest correlations for florfenicol with gentamicin,and for amoxicillin with penicillin(r=0.650 for both),followed by gentamicin with kanamycin(r=0.620).Salmonella resistance in waterfowl in Guangdong Province was generally severe and showed a complex pattern of drug resist-ance.Detection of waterfowl pathogens should be strengthened to prevent the spread of drug-resistant bacteria and support ra-tional use of antibiotics.This work provides a reference for Salmonella prevention and control in waterfowl farms.

Microphthalmos is a congenital ocular developmental anomaly that manifests as a significant reduction in the size of eyes,and is often combined with various ocular disorders such as cataract.Due to its special intraocular anatomical features,the risk of intraoperative and postoperative complications of cataract surgery in microphthalmos is usually high.Combined with subscleral sclerectomy,peripheral iridectomy,and anterior segment vitrectomy,the incidence of the pre-existing complications in cataract surgery has decreased,meanwhile,the additional procedures may also bring new complications.In-depth understanding of the research progress of cataract surgery in microphthalmos and the prevention of complications is of great guiding significance to improve surgical outcomes,and can reduce the incidence of postoperative complications such as uveal effusion syndrome,secondary glaucoma and corneal edema,and promote personalized treatments for microphthalmos patients who suffered from cataract.

Home-based palliative care (HBPC) has emerged as a critical model to address the complex needs of individuals with life-limiting illnesses, particularly in super-aged societies. This review explored the key components of HBPC and elaborated on its benefits, challenges, opportunities, and future directions, drawing on international evidence and practical frameworks. HBPC is reported to enhance the quality of life, reduce unnecessary hospitalizations, and increase the likelihood of patients dying in their preferred settings. Successful care delivery requires integrated multidisciplinary teams, effective symptom management, holistic care, and timely support from caregivers. However, barriers such as resource constraints, caregiver burden, and a lack of psychosocial support remain significant. Future directions and opportunities include integrating hospital-at-home models into routine HBPC services, strengthening the education of healthcare professionals and the public, and fostering compassionate communities to promote social engagement in end-of-life care. Advancing HBPC within diverse sociocultural contexts can bridge the gap between patient preferences and actual care delivery, offering a sustainable pathway to improve continuous palliative care provision for older adults globally.

Vaccination is the most effective measure for reducing and preventing influenza and related complications. In this study, we analyzed the mutation trend and the antigen dominant site changes of the amino acid sequence of hemagglutinin subunit 1 (HA1) of human influenza A virus (IAV) in the northern hemisphere from 2012 to 2022. According to the HA1 sequences of A/Darwin/6/2021 (H3N2) and A/Wisconsin/588/2019 (H1N1) recommended by the World Health Organization in the 2022 influenza season in northern hemisphere, we employed the mosaic algorithm to design three Mosaic-HA1 antigens through stepwise substitution. Mosaic-HA1 was expressed and purified in 293F cells and then mixed with the alum adjuvant at a volume ratio of 1:1. The mixture was used to immunize BALB/c mice, and the immunogenicity was evaluated. Enzyme-linked immunosorbent assay showed that Mosaic-HA1 induced the production of IgG targeting two types of HA1, the specific IgG titers for binding to H3 protein and H1 protein reached 10⁵ and 10³ respectively. The challenge test showed that Mosaic-HA1 protected mice from H3N2 or H1N1. This study designs the vaccines by recombination of major antigenic sites in different subtypes of IAV, giving new insights into the development of multivalent subunit vaccines against influenza.
Animals ; Influenza A Virus, H1N1 Subtype/genetics* ; Influenza A Virus, H3N2 Subtype/genetics* ; Mice, Inbred BALB C ; Mice ; Influenza Vaccines/genetics* ; Hemagglutinin Glycoproteins, Influenza Virus/genetics* ; Humans ; Antibodies, Viral/blood* ; Antigens, Viral/genetics* ; Immunoglobulin G/immunology* ; Female ; Orthomyxoviridae Infections/prevention & control* ; HEK293 Cells

INTRODUCTION: Although influenza vaccination reduces rates of pneumonia, hospitalisation and mortality, influenza vaccination uptake remains low in older patients. The primary aim was to compare individualised counselling with educational pamphlets alone in improving influenza vaccination uptake. The secondary aims were to evaluate knowledge and attitudes towards influenza vaccination and factors influencing uptake. METHODS: A randomised controlled study was conducted in two government polyclinics with 160 participants per arm. Patients aged 65 years and above attending for doctor consultation were recruited. All participants received an educational pamphlet on influenza vaccination. The intervention group received additional face-to-face counselling. Participants filled a pre- and postintervention questionnaire assessing knowledge of influenza and attitudes towards the vaccine. Follow-up calls and verification of electronic records was done at three months to determine actual vaccine uptake. RESULTS: At three months, 16 (10%) patients in the intervention group and 20 (12.5%) patients in the control group had completed influenza vaccination (P = 0.48). Factors positively associated with vaccine uptake were willingness to receive vaccination immediately after intervention (adjusted odds ratio [OR] 12.15, 95% confidence interval [CI] 4.42-33.38), and male gender (adjusted OR 2.96, 95% CI 1.23-7.12). Individualised counselling was more effective in improving knowledge (P < 0.01). Overall knowledge scores did not influence actual vaccine uptake rates. (adjusted OR 1.10 [0.90-1.3]). CONCLUSION Both arms of patient education increased uptake of influenza vaccination. Individualised counselling was not superior to pamphlets alone in improving uptake. Performing vaccination at the initial point of contact improves actual uptake rates.
Humans ; Male ; Aged ; Influenza Vaccines ; Influenza, Human/prevention & control* ; Vaccination ; Research Design ; Surveys and Questionnaires ; Health Knowledge, Attitudes, Practice

Objective: To investigate the clinical value of plasma scaffold protein SEC16A level and related models in the diagnosis of hepatitis B virus-related liver cirrhosis (HBV-LC) and hepatocellular carcinoma (HBV-HCC). Methods: Patients with HBV-LC and HBV-HCC and a healthy control group diagnosed by clinical, laboratory examination, imaging, and liver histopathology at the Third Hospital of Hebei Medical University between June 2017 and October 2021 were selected. Plasma SEC16A level was detected using an enzyme-linked immunosorbent assay (ELISA). Serum alpha-fetoprotein (AFP) was detected using an electrochemiluminescence instrument. SPSS 26.0 and MedCalc 15.0 statistical software were used to analyze the relationship between plasma SEC16A levels and the occurrence and development of liver cirrhosis and liver cancer. A sequential logistic regression model was used to analyze relevant factors. SEC16A was established through a joint diagnostic model. Receiver operating characteristic curve was used to evaluate the clinical efficacy of the model for liver cirrhosis and hepatocellular carcinoma diagnosis. Pearson correlation analysis was used to identify the influencing factors of novel diagnostic biomarkers. Results: A total of 60 cases of healthy controls, 60 cases of HBV-LC, and 52 cases of HBV-HCC were included. The average levels of plasma SEC16A were (7.41 ± 1.66) ng/ml, (10.26 ± 1.86) ng/ml, (12.79 ± 1.49) ng /ml, respectively, with P < 0.001. The sensitivity and specificity of SEC16A in the diagnosis of liver cirrhosis and hepatocellular carcinoma were 69.44% and 71.05%, and 89.36% and 88.89%, respectively. SEC16A, age, and AFP were independent risk factors for the occurrence of HBV-LC and HCC. SAA diagnostic cut-off values, sensitivity, and specificity were 26.21 and 31.46, 77.78% and 81.58%, and 87.23% and 97.22%, respectively. The sensitivity and specificity for HBV-HCC early diagnosis were 80.95% and 97.22%, respectively. Pearson correlation analysis showed that AFP level was positively correlated with alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), and γ-glutamyltransferase (GGT) with P < 0.01, while the serum SEC16A level was only slightly positively correlated with ALT and AST in the liver cirrhosis group (r = 0.268 and 0.260, respectively, P < 0.05). Conclusion: Plasma SEC16A can be used as a diagnostic marker for hepatitis B-related liver cirrhosis and hepatocellular carcinoma. SEC16A, combined with age and the AFP diagnostic model with SAA, can significantly improve the rate of HBV-LC and HBV-HCC early diagnosis. Additionally, its application is helpful for the diagnosis and differential diagnosis of the progression of HBV-related diseases.
Humans ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/pathology* ; alpha-Fetoproteins/metabolism* ; Endoplasmic Reticulum/metabolism* ; Golgi Apparatus/metabolism* ; Vesicular Transport Proteins ; Liver Cirrhosis/complications* ; Hepatitis B/complications* ; ROC Curve ; Hepatitis B virus/metabolism* ; Biomarkers, Tumor