Myelodysplastic syndrome (MDS), a myeloid tumor derived from the malignant clones of hematopoietic stem cells, has an annually increasing incidence. The contemporary research direction has shifted to analyzing the synergistic effect of immune surveillance collapse and abnormal bone marrow microenvironment in the pathological process of MDS. Against this backdrop, the immune checkpoint molecule TIM3 has emerged as a key target because of its persistently high expression on the surface of important immune cells such as T and NK cells. The abnormal activation of the TIM3 pathway is the mechanism by which solid tumors and hematological malignancies achieve immune escape and is a key hub in the formation of immune exhaustion phenotypes. This work integrates the original discoveries of our team with the latest international progress, systematically demonstrating the bidirectional regulatory network of TIM3 between the malignant clone proliferation of MDS and the immunosuppressive microenvironment. Integrating the evidence from emerging clinical trials allows us to consider the clinical significance of TIM3-targeted blocking for MDS, providing a transformative path to overcome the resistance of traditional treatments and marking a new chapter in the active immune reconstitution of MDS treatment.

Objective:To explore the predictive value of atherogenic index of plasma(AIP)combined with neutro-phil/HDL-C ratio(NHR),lymphocyte/HDL-C ratio(LHR)and monocyte/HDL-C ratio(MHR)for major adverse cardiovascular events(MACE)in patients with acute coronary syndrome(ACS).Methods:This retrospec-tive study enrolled 320 patients underwent coronary angiography in Department of Cardiovascular Medicine,Harri-son International Peace Hospital between January 2021 and December 2022,including 215 ACS patients and 105 pa-tients without ACS;according to Gensini score,ACS patients were divided into low risk group(n=50),medium risk group(n=70)and high risk group(n=95).According to the presence of MACE within 1 year,patients were divided into MACE group(n=55)and no MACE group(n=160).After admission,blood routine,blood lipids,C-reactive protein(CRP)and endothelin-1(ET-1)levels were measured,then NHR,LHR,MHR and AIP were calculated.Spearman method was used to analyze the association of above-mentioned indexes with Gensini score;stepwise Logistic regression was used to analyze the influencing factors of MACE within 1 year in ACS patients;and ROC curve was used to analyze the predictive value of single and combined detection of above indexes for MACE within 1 year in ACS patients.Results:Compared to patients in no ACS group,those in ACS group had significantly higher BMI[(23.59±0.85)kg/m2 vs.(21.57±1.16)kg/m2],proportions of hypertension(57.67％vs.13.33％),diabetes(23.26％vs.8.57％),NHR[(12.09±3.46)vs.(3.81±1.29)],MHR[(0.70±0.18)vs.(0.33±0.10)],LHR[(0.79±0.21)vs.(0.40±0.09)],AIP[(0.21±0.06)vs.(0.11±0.02)],CRP[(9.82±3.09)mg/L vs.(2.20±0.58)mg/L],ET-1[(31.25±10.34)μg/L vs.(10.60±1.96)μg/L](P＜0.001 all).Compared to those in no MACE group,patients in MACE group had significantly higher NHR[(17.33±3.87)vs.(10.12±2.68)],MHR[(0.93±0.24)vs.(0.61±0.13)],LHR[(1.05±0.27)vs.(0.71±0.16)],AIP[(0.28±0.04)vs.(0.17±0.02)],CRP[(15.52±3.83)mg/L vs.(7.69±2.40)mg/L],ET-1[(46.68±9.51)μg/L vs.(25.47±4.66)μg/L]levels(P＜0.001 all).Spearman correlation analysis showed that NHR,MHR,LHR and AIP were significant positively correlated with Gensini score(r=0.837～0.868,P＜0.001 all).Stepwise Logistic regression analysis showed that NHR(OR=1.225,95％CI 1.016～1.550,P=0.035),AIP(OR=2.632,95％CI 1.055～6.566,P=0.038)were independent risk factors for MACE within 1 year in ACS patients.ROC curve shows that AUC of AIP combined with NHR,MHR and LHR predicting MACE within 1 year in ACS patients was 0.786(95％CI 0.725～0.839),which was significantly higher than those of NHR(AUC 0.768,95％CI 0.706～0.823),LHR(AUC 0.749,95％CI 0.686～0.806)and AIP(AUC 0.764,95％CI 0.701～0.819)alone(Z=2.597,2.687,1.965,P＜0.05 or＜0.01).Conclusion:AIP combined with NHR,MHR and LHR have certain predictive value for MACE within 1 year in ACS patients.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective:To explore the predictive value of atherogenic index of plasma(AIP)combined with neutro-phil/HDL-C ratio(NHR),lymphocyte/HDL-C ratio(LHR)and monocyte/HDL-C ratio(MHR)for major adverse cardiovascular events(MACE)in patients with acute coronary syndrome(ACS).Methods:This retrospec-tive study enrolled 320 patients underwent coronary angiography in Department of Cardiovascular Medicine,Harri-son International Peace Hospital between January 2021 and December 2022,including 215 ACS patients and 105 pa-tients without ACS;according to Gensini score,ACS patients were divided into low risk group(n=50),medium risk group(n=70)and high risk group(n=95).According to the presence of MACE within 1 year,patients were divided into MACE group(n=55)and no MACE group(n=160).After admission,blood routine,blood lipids,C-reactive protein(CRP)and endothelin-1(ET-1)levels were measured,then NHR,LHR,MHR and AIP were calculated.Spearman method was used to analyze the association of above-mentioned indexes with Gensini score;stepwise Logistic regression was used to analyze the influencing factors of MACE within 1 year in ACS patients;and ROC curve was used to analyze the predictive value of single and combined detection of above indexes for MACE within 1 year in ACS patients.Results:Compared to patients in no ACS group,those in ACS group had significantly higher BMI[(23.59±0.85)kg/m2 vs.(21.57±1.16)kg/m2],proportions of hypertension(57.67％vs.13.33％),diabetes(23.26％vs.8.57％),NHR[(12.09±3.46)vs.(3.81±1.29)],MHR[(0.70±0.18)vs.(0.33±0.10)],LHR[(0.79±0.21)vs.(0.40±0.09)],AIP[(0.21±0.06)vs.(0.11±0.02)],CRP[(9.82±3.09)mg/L vs.(2.20±0.58)mg/L],ET-1[(31.25±10.34)μg/L vs.(10.60±1.96)μg/L](P＜0.001 all).Compared to those in no MACE group,patients in MACE group had significantly higher NHR[(17.33±3.87)vs.(10.12±2.68)],MHR[(0.93±0.24)vs.(0.61±0.13)],LHR[(1.05±0.27)vs.(0.71±0.16)],AIP[(0.28±0.04)vs.(0.17±0.02)],CRP[(15.52±3.83)mg/L vs.(7.69±2.40)mg/L],ET-1[(46.68±9.51)μg/L vs.(25.47±4.66)μg/L]levels(P＜0.001 all).Spearman correlation analysis showed that NHR,MHR,LHR and AIP were significant positively correlated with Gensini score(r=0.837～0.868,P＜0.001 all).Stepwise Logistic regression analysis showed that NHR(OR=1.225,95％CI 1.016～1.550,P=0.035),AIP(OR=2.632,95％CI 1.055～6.566,P=0.038)were independent risk factors for MACE within 1 year in ACS patients.ROC curve shows that AUC of AIP combined with NHR,MHR and LHR predicting MACE within 1 year in ACS patients was 0.786(95％CI 0.725～0.839),which was significantly higher than those of NHR(AUC 0.768,95％CI 0.706～0.823),LHR(AUC 0.749,95％CI 0.686～0.806)and AIP(AUC 0.764,95％CI 0.701～0.819)alone(Z=2.597,2.687,1.965,P＜0.05 or＜0.01).Conclusion:AIP combined with NHR,MHR and LHR have certain predictive value for MACE within 1 year in ACS patients.

To achieve rapid and visual detection of Plasmodium vivax,a detection method based on recombinase polymerase amplification(RPA)technology and lateral flow dipstick(LFD)was established and evaluated.Targeting the conserved sequence of the P.vivax 18S rRNA gene(GenBank:DQ660817.1)as the target sequence,primers and probes were designed with Primer Premier 5,and the P.vivax recombinant plasmid(pUCPv)was constructed as the standard.A sensitive and specific RPA-LFD-based rapid visual detection method for P.vivax nucleic acids was established.The plasmid standard was serially diluted 10-fold to concentrations of 1×103,1×102,1×101,1×10?,and 1×10?1 copies/μL for sensitivity testing.To evaluate specificity,whole blood DNA samples from patients infected with Plasmodium falciparum,Plasmodium malariae,Plasmodium ovale,or Leishmania donovani,as well as healthy participants,were tested by RPA-LFD.Additionally,The assay′s accuracy was evaluated by testing whole blood DNA samples from 24 confirmed P.vivax-infected patients.This study successfully established a sensitive,specific,and rapid visual RPA-LFD method for detecting P.vivax nucleic acids.The assay can complete P.vivax detection within 20 minutes under isothermal conditions at 39 ℃,achieving a sensitivity of 1 copy/μL.There is no significant cross reaction with parasites such as other Plasmodium species and L.donovani,and the specificity is 100%.All 24 DNA samples from confirmed P.vivax patients were detected,showing a 100%detection rate.The developed RPA-LFD assay exhibits excellent sensitivity and specificity,requires only simple heating equipment,and is user-friendly.This rapid visual detection method is particularly suitable for P.vivax screening in low-resource settings.

Chronic visceral pain is a persistent and debilitating condition arising from dysfunction or sensitization of the visceral organs and their associated nervous pathways. Increasing evidence suggests that imbalances in central nervous system function play an essential role in the progression of visceral pain, but the exact mechanisms underlying the neural circuitry and molecular targets remain largely unexplored. In the present study, the ventral tegmental area (VTA) was shown to mediate visceral pain in mice. Visceral pain stimulation increased c-Fos expression and Ca²⁺ activity of glutamatergic VTA neurons, and optogenetic modulation of glutamatergic VTA neurons altered visceral pain. In particular, the upregulation of NMDA receptor 2A (NR2A) subunits within the VTA resulted in visceral pain in mice. Administration of a selective NR2A inhibitor decreased the number of visceral pain-induced c-Fos positive neurons and attenuated visceral pain. Pharmacology combined with chemogenetics further demonstrated that glutamatergic VTA neurons regulated visceral pain behaviors based on NR2A. In summary, our findings demonstrated that the upregulation of NR2A in glutamatergic VTA neurons plays a critical role in visceral pain. These insights provide a foundation for further comprehension of the neural circuits and molecular targets involved in chronic visceral pain and may pave the way for targeted therapies in chronic visceral pain.
Animals ; Male ; Visceral Pain/metabolism* ; Up-Regulation/physiology* ; Ventral Tegmental Area/metabolism* ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors* ; Neurons/drug effects* ; Mice, Inbred C57BL ; Mice ; Proto-Oncogene Proteins c-fos/metabolism* ; Chronic Pain/metabolism* ; Glutamic Acid/metabolism*

Aim To explore the mechanism of Epimedii folium-Astmgali radix activating the SCF/c-kit signa-ling pathway to activate the PI3K/Akt signaling path-way and its effect on sperm production and vitality in oligoasthenospermia.Methods Sixty male SD rats were used to establish a model of oligoasthenospermia with cyclophosphamide.They were randomly divided into six groups:experimental group(further divided into high,medium,and low dose group),model group,control group and blank group.The oligoasthenosper-mia model was established by using cyclophosphamide in experimental group,levocarnitine group and model group.The rats in the high,medium,and low dose group of the experimental group were orally adminis-tered Epimedii folium-Astmgali radix extract at doses of 800,400,and 200 mg·kg-1,respectively,Once daily for 35 days.Rats of the control group were orally ad-ministered 250 mg·kg-1·d-1 of levocarnitine,Once daily for 35 days.ELISA was used to detect serum of T,E2,FSH,and LH.Western blot and IHC staining were used to detect the expression of SCF,c-kit,Bcl-2,Bax,PI3K,and Akt proteins in rat testicular tissues.Sperm activity is examined by microscopy.The testicu-lar tissue structure and cell morphology of rats in each group were observed.Results Compared with the model group,Epimedii folium-Astmgali radix increased the sperm density,total viability rate,and vitality(P＜0.05,P＜0.01),decreased sperm apoptosis rate and LH,T,and E2 levels(P＜0.05,P＜0.01),decreased Bax protein expression in testicular tissue(P＜0.01),and increased Bcl-2,SCF,c-Kit,PI3K,and Akt protein expression(P＜0.05,P＜0.01);it increased the number of germ cells,thickened basement membrane,and significantly improved seminiferous tubule mor-phology,even showing germ cells at different develop-mental stages and mature sperm.Conclusions Epi-medii folium-Astmgali radix has a significant therapeu-tic effect on oligoasthenospermia in rats.Its mechanism may be related to the activation of the SCF/c-kit signa-ling pathway to activate the PI3K/Akt signaling path-way promoting the proliferation and differentiation of germ cells,and promoting sperm production,maturation and motility.

Objective:To develop a treatment-related quality of life scale for Chinese patients with multiple myeloma (MM) and to test its reliability and validity.Methods:The initial scale was constructed through a literature search, Delphi expert correspondence, and cognitive testing. This study conducted a preliminary survey of 379 patients with MM and a formal survey of 865 patients from the hematology departments of 155 hospitals nationwide from February 2024 to March 2024. The final scale was obtained after conducting item analysis and reliability and validity tests on the initial scale.Results:The constructed scale contains 36 items covering six domains: physiological, psychological, social, treatment side effects, general health, and others. In the preliminary survey, the Cronbach’s alpha coefficient of each item ranged from 0.597 to 0.939, and the test-retest reliability was 0.747 ( P<0.001). Exploratory factor analysis extracted eight common factors with a cumulative variance contribution of 60.058%. In the formal survey, the Cronbach’s alpha coefficient of each item ranged from 0.484 to 0.930, and the test-retest reliability was 0.835 ( P<0.001). Confirmatory factor analysis revealed a comparative fit index of 0.750, a root-mean-square error of approximation of 0.090, and a root-mean-square residual of 0.067. Conclusion:The treatment-related quality of life scale for Chinese patients with MM designed in this study exhibited good reliability and validity, reflecting the impact of treatment on the quality of life of patients. This scale can provide a reference to clinicians for assessing the disease status of patients.

Objective:To develop a treatment-related quality of life scale for Chinese patients with multiple myeloma (MM) and to test its reliability and validity.Methods:The initial scale was constructed through a literature search, Delphi expert correspondence, and cognitive testing. This study conducted a preliminary survey of 379 patients with MM and a formal survey of 865 patients from the hematology departments of 155 hospitals nationwide from February 2024 to March 2024. The final scale was obtained after conducting item analysis and reliability and validity tests on the initial scale.Results:The constructed scale contains 36 items covering six domains: physiological, psychological, social, treatment side effects, general health, and others. In the preliminary survey, the Cronbach’s alpha coefficient of each item ranged from 0.597 to 0.939, and the test-retest reliability was 0.747 ( P<0.001). Exploratory factor analysis extracted eight common factors with a cumulative variance contribution of 60.058%. In the formal survey, the Cronbach’s alpha coefficient of each item ranged from 0.484 to 0.930, and the test-retest reliability was 0.835 ( P<0.001). Confirmatory factor analysis revealed a comparative fit index of 0.750, a root-mean-square error of approximation of 0.090, and a root-mean-square residual of 0.067. Conclusion:The treatment-related quality of life scale for Chinese patients with MM designed in this study exhibited good reliability and validity, reflecting the impact of treatment on the quality of life of patients. This scale can provide a reference to clinicians for assessing the disease status of patients.

OBJECTIVE: This study aimed to investigate the impact of glycemic control and diabetes duration on subsequent myocardial infarction (MI) in patients with both coronary heart disease (CHD) and type 2 diabetes (T2D). METHODS: We conducted a retrospective cohort study of 33,238 patients with both CHD and T2D in Shenzhen, China. Patients were categorized into 6 groups based on baseline fasting plasma glucose (FPG) levels and diabetes duration (from the date of diabetes diagnosis to the baseline date) to examine their combined effects on subsequent MI. Cox proportional hazards regression models were used, with further stratification by age, sex, and comorbidities to assess potential interactions. RESULTS: Over a median follow-up of 2.4 years, 2,110 patients experienced MI. Compared to those with optimal glycemic control (FPG < 6.1 mmol/L) and shorter diabetes duration (< 10 years), the fully-adjusted hazard ratio ( HR) (95% Confidence Interval [95% CI]) for those with a diabetes duration of ≥ 10 years and FPG > 8.0 mmol/L was 1.93 (95% CI: 1.59, 2.36). The combined effects of FPG and diabetes duration on MI were largely similar across different age, sex, and comorbidity groups, although the excess risk of MI associated with long-term diabetes appeared to be more pronounced among those with atrial fibrillation. CONCLUSION Our study indicates that glycemic control and diabetes duration significant influence the subsequent occurrence of MI in patients with both CHD and T2D. Tailored management strategies emphasizing strict glycemic control may be particularly beneficial for patients with longer diabetes duration and atrial fibrillation.
Humans ; Diabetes Mellitus, Type 2/blood* ; Male ; Female ; Middle Aged ; Aged ; Coronary Disease/complications* ; Myocardial Infarction/etiology* ; Retrospective Studies ; China/epidemiology* ; Glycemic Control ; Blood Glucose ; Adult ; Risk Factors ; Time Factors