Objective:To compare the efficacy and safety of two induction regimens, homoharringtonine plus venetoclax and azacitidine (VHA) versus venetoclax and azacitidine (VA) , for newly diagnosed acute myeloid leukemia (AML) patients who are elderly or ineligible for intensive chemotherapy.Methods:We retrospectively analyzed the clinical data of 59 newly diagnosed AML patients treated with the VHA or VA regimen at Zhengzhou University Affiliated Cancer Hospital from September 2018 to July 2021. The cohort included 25 males and 34 females, with a median age of 63 years. The overall response rate (ORR) , composite complete remission (CRc) rate [CR+CR with incomplete hematologic recovery (CRi) ], minimal residual disease (MRD) negativity rate, overall survival (OS) , relapse-free survival (RFS) , and adverse events were compared between the two groups. Survival was estimated by the Kaplan-Meier method, and prognostic factors were evaluated using univariable and multivariable Cox regression.Results:At the end of the treatment, the ORR was 88.4% (23/26) in the VHA group [21 CR, 2 partial remissions (PR) ] and 90.9% (30/33) in the VA group (25 CR, 5 PR) , with no significant difference between the groups ( P=0.458) . The MRD negativity rates after one cycle of induction were 73.1% (19/26) in the VHA group and 60.6% (20/33) in the VA group, respectively ( P=0.315) . In the high-risk subgroup, the composite remission rates after one cycle were 78.6% (11/14) with VHA and 50.0% (5/10) with VA ( P=0.143) ; MRD negativity rates were 64.3% (9/14) and 20.0% (2/10) , respectively ( P=0.032) . The main adverse events were myelosuppression, gastrointestinal reactions, and infections during neutropenia. Rates of grade 3-4 neutropenia and decreased hemoglobin were similar between groups, whereas grade 3-4 thrombocytopenia was more frequent with VHA than with VA (76.9% vs 45.5%, P=0.015) . With a median follow-up of 13 months (range, 1-59) , 1 year RFS was 69.9% (95% CI: 53.1%-92.2%) with VHA and 55.6% (95% CI: 40.1%-77.1%) with VA ( P=0.305) . The 1 year OS rates were 91.7% (95% CI: 77.3%-100.0%) and 58.2% (95% CI: 41.7%-81.4%) , respectively ( P=0.024) . Among high risk patients, 1 year RFS and OS were higher with VHA than with VA (RFS: 66.2% vs 37.5%, P=0.046; OS: 85.7% vs 48.0%, P=0.011) . Undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) significantly improved RFS and OS ( P=0.027 and 0.047, respectively) . On multivariable analysis, ELN risk classification and MRD negativity after the first cycle were independent prognostic factors for RFS. Treatment regimen (VHA vs VA) , MRD negativity after the first cycle, and receipt of transplantation were independent prognostic factors for OS. Conclusion:VHA provides clinical benefit in newly diagnosed AML patients who are unfit for intensive chemotherapy and in older adults, with particularly favorable outcomes in high risk patients; sequential allo-HSCT confers additional benefit, and associated adverse events are manageable.

Objective:To investigate the application value of self-pulling latter transection(SPLT)in esophagojeju-nal anastomosis during total laparoscopic total gastrectomy.Methods:From January 2021 to December 2023,80 pa-tients who underwent total laparoscopic total gastrectomy at the Department of General Surgery,Yancheng Third People's Hospital,were selected.Patients were grouped based on the intraoperative esophagojejunal anastomosis method:the SPLT group(35 cases,using SPLT esophagojejunostomy)and the Overlap group(45 cases,using esoph-agojejunal overlapping side-to-side anastomosis).Surgical related indicators,complication incidence,nutritional status,and quality of life assessment were compared between the two groups.Results:The time to first postoperative anal exhaust,the number of lymph nodes dissected,and the postoperative hospital stay were compared between the two groups(P＞0.05).The SPLT group had shorter operation time and esophagojejunal anastomosis time,and less intraopera-tive blood loss compared to the control group(P＜0.05).The incidence of postoperative complications in the SPLT group was 8.57%,and in the Overlap group was 11.11%,with no significant difference between the two groups(P＞0.05).The nutritional status at 6 months postoperatively in the SPLT group[Hb(116.97±10.94)g/L、ALB(39.74±1.29)g/L、PA(0.30±0.45)g/L]and Overlap group[Hb(119.78±12.84)g/L、ALB(39.64±1.42)g/L、PA(0.30±0.36)g/L]were compared(P＞0.05).The quality of life assessment(overall health status,functional domains,symptom domains)at 6 months postoperatively between the SPLT group and the Overlap group was compared(P＞0.05).Conclusion:The use of SPLT esophagojeju-nal anastomosis in total laparoscopic total gastrectomy can improve the surgical efficiency,achieve high anastomosis,and its medium and short-term safety is comparable to that of esophagojejunal overlap side-to-side anastomosis.

Central nervous system(CNS)degenerative disorders refer to a spectrum of pathological alterations triggered by struc-tural damage to cerebral neural tissues,clinically manifested as diverse neurological dysfunction syndromes,including multiple sclerosis(MS),neurodegenerative diseases(NDs),and ische-mic stroke.The hallmark pathological features of these disorders involve irreversible neuronal damage and decompensation of functional neural networks,ultimately leading to progressive neurological deficits.Notably,with the accelerating global popu-lation aging,the incidence of these diseases has surged signifi-cantly.According to WHO statistics,they now rank among the top three global causes of disability and mortality.Current re-search has confirmed that the pathogenesis of CNS degenerative disorders exhibits high heterogeneity,encompassing multifaceted pathophysiological processes such as genetic predisposition,oxi-dative stress,protein misfolding,and metabolic dysregulation.This intricate pathogenic network not only complicates clinical differential diagnosis but also poses substantial challenges to the development of precision therapeutic strategies.Importantly,re-cent studies have revealed that mitochondrial homeostasis disrup-tion-induced inflammatory cascades(termed mitochondrial in-flammation)play a pivotal regulatory role in neurodegenerative progression.Key molecular mechanisms include impaired mito-phagy,aberrant mitochondrial DNA(mtDNA)release and NL-RP3 inflammasome activation.This review systematically deci-phers the molecular regulatory network of mitochondrial inflam-mation,with a focus on its biological effects in critical pathologi-cal events such as blood-brain barrier disruption,microglial hy-peractivation and neuronal apoptosis.The overarching aim is to provide a theoretical foundation for developing innovative thera-peutic strategies targeting mitochondrial homeostasis restoration.

OBJECTIVE T o compare the biological characteristics,drug resistance and pathogenicity between two strains of mucoid Pseudomonas aeruginosa and the standard strain PAO1.METHODS The strains were identified,and biofilms were detected by 96-well plates method.The bacterial drug resistance was detected by fully automatic drug susceptibility analysis system,the expression levels of RNA of virulence factors were detected by real-time fluorescent quantitative polymerase chain reaction(RT-PCR);the models of rats with pneumonia infection were established through liquid aerosol lung delivery method,the survival status of the rats was observed,and the lev-els of cytokines in bronchoalveolar lavage fluid(BALF)were detected.RESULTS NY4593,NY4605 and PAO1 strains were successfully isolated and identified.NY4593 and NY4605 showed high-yield biofilms,while PAO1 showed low-yield biofilms.The drug resistance rates of NY4593 and NY4605 were remarkably higher than those of the PAO1.The expression levels of exoT and exoY gene RNA of the NY4593 and NY4605 strains were higher than those of the PAO1 strains(P＜0.05);the expression level of exoS gene RNA of the NY4605 was lower than that of the PAO1(P＜0.05).Under the same infection dose,the PAO1 showed more powerful pathogenicity,and the secretion volumes of inflammatory factors interleukin-6(IL-6),interleuki-1β(IL-1β)and interleukin-17A(IL-17A)of the PAO1 were(2858.00±150.30)pg/ml,(7821.00±761.20)pg/ml and(1079.00±225.40)pg/ml respectively,remarkably higher than those of the NY4593 and NY4605(P＜0.05).CONCLUSION The clini-cal mucoid NY4593 and NY4605 remarkably differ from PAO1 in biology and pathogenicity.The study may facilitate deep understanding of the mechanisms of PA infection and provide guidance for clinical treatment,prevention and control.

Diabetic cardiomyopathy(DCM)is a serious complication of diabetes mellitus(DM).Recent studies have reported that the NOD-like receptor protein 3(NLRP3)inflammasome activation-mediated pyroptosis aggravates the formation and development of DCM.This review summarizes the mechanism of action of NLRP3 inflammasome in the development of DCM,and focus on the potential effects of targeted inhibition of NLRP3 inflammasome activation in the treatment of DCM.

Objective:To compare the efficacy and safety of two induction regimens, homoharringtonine plus venetoclax and azacitidine (VHA) versus venetoclax and azacitidine (VA) , for newly diagnosed acute myeloid leukemia (AML) patients who are elderly or ineligible for intensive chemotherapy.Methods:We retrospectively analyzed the clinical data of 59 newly diagnosed AML patients treated with the VHA or VA regimen at Zhengzhou University Affiliated Cancer Hospital from September 2018 to July 2021. The cohort included 25 males and 34 females, with a median age of 63 years. The overall response rate (ORR) , composite complete remission (CRc) rate [CR+CR with incomplete hematologic recovery (CRi) ], minimal residual disease (MRD) negativity rate, overall survival (OS) , relapse-free survival (RFS) , and adverse events were compared between the two groups. Survival was estimated by the Kaplan-Meier method, and prognostic factors were evaluated using univariable and multivariable Cox regression.Results:At the end of the treatment, the ORR was 88.4% (23/26) in the VHA group [21 CR, 2 partial remissions (PR) ] and 90.9% (30/33) in the VA group (25 CR, 5 PR) , with no significant difference between the groups ( P=0.458) . The MRD negativity rates after one cycle of induction were 73.1% (19/26) in the VHA group and 60.6% (20/33) in the VA group, respectively ( P=0.315) . In the high-risk subgroup, the composite remission rates after one cycle were 78.6% (11/14) with VHA and 50.0% (5/10) with VA ( P=0.143) ; MRD negativity rates were 64.3% (9/14) and 20.0% (2/10) , respectively ( P=0.032) . The main adverse events were myelosuppression, gastrointestinal reactions, and infections during neutropenia. Rates of grade 3-4 neutropenia and decreased hemoglobin were similar between groups, whereas grade 3-4 thrombocytopenia was more frequent with VHA than with VA (76.9% vs 45.5%, P=0.015) . With a median follow-up of 13 months (range, 1-59) , 1 year RFS was 69.9% (95% CI: 53.1%-92.2%) with VHA and 55.6% (95% CI: 40.1%-77.1%) with VA ( P=0.305) . The 1 year OS rates were 91.7% (95% CI: 77.3%-100.0%) and 58.2% (95% CI: 41.7%-81.4%) , respectively ( P=0.024) . Among high risk patients, 1 year RFS and OS were higher with VHA than with VA (RFS: 66.2% vs 37.5%, P=0.046; OS: 85.7% vs 48.0%, P=0.011) . Undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) significantly improved RFS and OS ( P=0.027 and 0.047, respectively) . On multivariable analysis, ELN risk classification and MRD negativity after the first cycle were independent prognostic factors for RFS. Treatment regimen (VHA vs VA) , MRD negativity after the first cycle, and receipt of transplantation were independent prognostic factors for OS. Conclusion:VHA provides clinical benefit in newly diagnosed AML patients who are unfit for intensive chemotherapy and in older adults, with particularly favorable outcomes in high risk patients; sequential allo-HSCT confers additional benefit, and associated adverse events are manageable.

Objective To explore the biological functions of pyroptosis-related genes in pneumonic plague using bioinformatics methods,and to evaluate their potential applicability as diagnostic markers.Methods The pneumonic plague-related dataset GSE220123 was retrieved from the Gene Expression Omnibus(GEO)database and screened for differentially expressed pyroptosis-related genes(DE-PRGs).The functions of DE-PRGs were studied via Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,and immune infiltration analysis.The hub genes were identified via protein-protein interaction(PPI)network analysis,and further screened for key genes with sustained high expression characteristics based on differential expression analysis.The relative expression levels of the key genes were verified using the reverse transcription real-time quantitative PCR(qPCR)method.Results A total of 17 DE-PRGs were screened,and PPI network analysis revealed 7 Hub genes.Among them,Casp4 continued to be up-regulated during the course of pneumonic plague.The results of reverse transcription qPCR were consistent with the those of bioinformatic analyses.Conclusion DE-PRGs play a crucial role in the immune response of pneumonic plague,especially Casp4,which has significant applications as a diagnostic biomarker and potential therapeutic target for pneumonic plague.

Facing the requirements of promoting the healthy China initiative and improving people's health, the "bone health program" was proposed in 2024. In-depth development of a traditional Chinese medicine(TCM) prevention and control system is of strategic significance to the implementation of the "bone health program". Focusing on osteoporosis(OP), a representative disease affecting people's bone health, this paper concludes that accelerating the research on the prevention and control of OP by TCM is conducive to enhancing the knowledge and awareness of OP among the public, and it is beneficial to revealing the evolutionary pattern of OP and improving the understanding and management of this disease. Additionally, it can provide an overall framework for and strengthen the systematicity and completeness of the research on the prevention and treatment of OP by TCM. Meanwhile, it can help to explore new research paradigms and optimize the existing research model, so as to promote innovative breakthroughs in the prevention and treatment of bone health-related diseases by TCM. Under the overall layout of the "bone health program", importance should be attached to the early prevention and the innovation of very early diagnosis and intervention of OP. Emphasis should be put on the discovery of the target network of disease and treatment mechanism for revealing the core pathogenesis of OP and the therapeutic mechanism of TCM. In addition to local lesions of the bone and its clinical outcomes, attention should be paid to the development of multiple metabolic complications. The fusion of advanced interdisciplinary technologies should be promoted for OP and its complications, and thus a research and development system based on clinical application scenarios and driven by big data can be built. The measures above will facilitate the progress in the prevention and treatment of OP and other bone diseases by TCM and provide new momentum for enriching and deepening the research connotation of the "bone health program".
Osteoporosis/therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal/therapeutic use* ; China ; Bone and Bones/drug effects*

INTRODUCTION: Obstructive sleep apnoea (OSA) is common in Singapore, with moderate to severe OSA affecting around 30% of residents. These consensus statements aim to provide scientifically grounded recommendations for the management of OSA, standar-dise the management of OSA in Singapore and promote multidisciplinary collaboration. METHOD: An expert panel, which was convened in 2024, identified several areas of OSA management that require guidance. The expert panel reviewed the current literature and developed consensus statements, which were later independently voted on using a 3-point Likert scale (agree, neutral or disagree). Consensus (total ratings of agree and neutral) was set a priori at ≥80% agreement. Any statement not reaching consensus was excluded. RESULTS: The final consensus included 49 statements that provide guidance on the screening, diagnosis and management of adults with OSA. Additionally, 23 statements on the screening, diagnosis and management of paediatric OSA achieved consensus. These 72 consensus statements considered not only the latest clinical evidence but also the benefits and harms, resource implications, feasibility, acceptability and equity impact of the recommendations. CONCLUSION The statements presented in this paper aim to guide clinicians based on the most updated evidence and collective expert opinion from sleep specialists in Singapore. These recommendations should augment clinical judgement rather than replace it. Management decisions should be individualised, taking into account the patient's clinical characteristics, as well as patient and caregiver concerns and preferences.
Humans ; Sleep Apnea, Obstructive/diagnosis* ; Singapore ; Consensus ; Adult