Objective:To understand the latent categories of apathy in young and middle-aged patients with hemorrhagic stroke and analyze the relationship between these categories and disability acceptance, providing a theoretical basis for targeted interventions.Methods:A convenience sampling method was used to select young and middle-aged patients with hemorrhagic stroke hospitalized at Huai′an First Hospital Affiliated to Nanjing Medical University between September 2020 and September 2023. A general information questionnaire, the Apathy Evaluation Scale-Clinician Administered, and the Acceptance of Disability Scale Revised were used for a cross-sectional survey. Latent profile analysis was conducted using Mplus 8.7 software to categorize apathy in these patients, and differences in disability acceptance among the categories were compared.Results:A total of 210 questionnaires were distributed and 203 valid questionnaires were collected. Among 203 patients were included, with 112 males and 91 females, aged 30-59 (47.60 ± 8.51) years old. The apathy score was (46.66 ± 8.78) points, and three latent categories were identified: "high active ability-low apathy" (26.1%, 53/203), "high social ability-moderate apathy" (28.6%, 58/203), and "generally high apathy" (45.3%, 92/203). The total disability acceptance scores for the three categories were (78.19 ± 13.30), (69.50 ± 11.01), and (60.86 ± 14.00) points, respectively, with statistically significant differences ( F=30.39, P<0.01). Conclusions:Apathy in young and middle-aged patients with hemorrhagic stroke can be categorized into three latent profiles, with differences in disability acceptance among the categories. Targeted management and interventions should be developed based on these homogeneous groups to improve disability acceptance.

Objective:To understand the latent categories of apathy in young and middle-aged patients with hemorrhagic stroke and analyze the relationship between these categories and disability acceptance, providing a theoretical basis for targeted interventions.Methods:A convenience sampling method was used to select young and middle-aged patients with hemorrhagic stroke hospitalized at Huai′an First Hospital Affiliated to Nanjing Medical University between September 2020 and September 2023. A general information questionnaire, the Apathy Evaluation Scale-Clinician Administered, and the Acceptance of Disability Scale Revised were used for a cross-sectional survey. Latent profile analysis was conducted using Mplus 8.7 software to categorize apathy in these patients, and differences in disability acceptance among the categories were compared.Results:A total of 210 questionnaires were distributed and 203 valid questionnaires were collected. Among 203 patients were included, with 112 males and 91 females, aged 30-59 (47.60 ± 8.51) years old. The apathy score was (46.66 ± 8.78) points, and three latent categories were identified: "high active ability-low apathy" (26.1%, 53/203), "high social ability-moderate apathy" (28.6%, 58/203), and "generally high apathy" (45.3%, 92/203). The total disability acceptance scores for the three categories were (78.19 ± 13.30), (69.50 ± 11.01), and (60.86 ± 14.00) points, respectively, with statistically significant differences ( F=30.39, P<0.01). Conclusions:Apathy in young and middle-aged patients with hemorrhagic stroke can be categorized into three latent profiles, with differences in disability acceptance among the categories. Targeted management and interventions should be developed based on these homogeneous groups to improve disability acceptance.

Aim To study the diastolic effect and mechanism of farrerol on isolated pulmonary arteries of C57BL/6J mice.Methods After anesthesia,mouse lung tissue was quickly removed and placed into the 4 ℃ K-H buffer,pulmonary arteries were isolated under the microscope and cut into 2 mm long vascular rings for spare use.(1)The effect of farrerol on the resting tension of isolated mouse pulmonary arteries:in the resting state,the active mouse pul-monary artery rings were treated with different concentrations of farrerol(10-6,3×10-6,10-5,3×10-5 and 10-4 mol/L).(2)Farrerol relaxed mouse pulmonary artery experiment:pulmonary arteries were contracted using phenylephrine(PE,1 μmol/L)or KCl(60 mmol/L),and when the contraction reached the platform,different concentrations of farrerol(10-6,3×10-6,10-5,3×10-5 and 10-4 mol/L)was added.(3)Farrerol inhibited pulmonary artery contraction experi-ment:under conditions with or without the addition of farrerol,pulmonary arteries were contracted using different concen-trations of PE(10-9,3×10-9,10-8,3 × 10-8,10-7,3×10-7 and 10-6 mol/L)or KCl(20,30,40,60,80 and 120 mmol/L),and the pulmonary artery muscle tension was recorded.(4)Calcium free and recalcification experiments:under conditions with or without the addition of farrerol,the changes of isolated mouse pulmonary artery tension were meas-ured in the state of calcium free or recalcification { 2.5 mmol/L[Ca2+]ex }.(5)The relationship between farrerol in-duced relaxation of isolated mouse pulmonary arteries and potassium ion channels:firstly,60 mmol/L KCl solution was used to contract the mouse pulmonary arteries until the platform.Then,3 mmol/L aminopyridine(4-AP),2 mmol/L tet-raethylammonium(TEA),30 μmol/L BaCl2,and 10 μmol/L glibenclamide(Gli)were added and treated for 15 min.Subsequently,the pulmonary arteries were relaxed using a concentration gradient of farrerol.Results Farrerol had no significant effect on the mouse pulmonary arteries in the resting state,but had a concentration-dependent relaxing effect on the mouse pulmonary arteries pre-contracted with PE and KCl.While the pretreatment of 3×10-5 mol/L farrerol could sig-nificantly reduce the maximum contraction of mouse pulmonary arteries induced by PE and KCl(P＜0.01),as well as sig-nificantly reduce the contraction of mouse pulmonary arteries induced by KCl under calcium free or recalcification conditions(P＜0.01).Addition of the voltage-dependent potassium ion channel blocker 4-AP significantly reduced the maximum diastolic rate of mouse pulmonary arteries induced by farrerol(P＜0.01),while addition of the high conductivity calcium activated potassium ion channel blocker TEA,inward rectifying potassium ion channel blocker BaCl2,or ATP sensitive po-tassium ion channel blocker Gli had no significant effect on the vasodilation effect of farrerol(P＞0.05).Conclusion Farrerol has a relaxing effect on isolated mouse pulmonary arteries,and its mechanism may be related to open voltage-de-pendent potassium ion channels.

Objective To explore the relationship between serum Niemann-pick type C1 like protein1(NPC1L1)and propro-tein convertase subtilisin/kexin type 9(PCSK9)levels and the risk of type 2 diabetes mellitus(T2DM)in Mongolian residents.Methods A total of 72 Mongolian patients with T2DM treated in Peking University Cancer Hospital,Inner Mongolia Hospital and the Affiliated Hospital of Inner Mongolia Medical University from June 2022 to June 2024 were selected as the T2DM group,and 81 healthy people in the same period were selected as the control group.LASSO model and multivariate Logistic regression model were used to screen the risk factors of disease onset.Multiple linear regression was used to analyze the correlation between NPC1L1 and PCSK9 levels and insulin function.Restricted cubic spline(RCS)model was used to analyze the dose-response relationship between NPC1L1 and PCSK9 levels and the incidence of T2DM,and explored the interaction between NPC1L1 and PCSK9 levels on the incidence of T2DM.Results NPC1L1(3.11±0.80 ng/L)and PCSK9(10.63±0.79 ng/L)in T2DM group were significantly higher than those in the control group(0.52±0.22 ng/L,3.21±0.17 ng/L),and the differences were statisti-cally significant(t=27.982,82.443,all P<0.05).NPC1L1(OR=2.458,95%CI=2.364～2.594,P<0.05)and PCSK9(OR=2.905,95%CI=2.541～3.528)were risk factors for T2DM(all P<0.001).The results of multiple linear regression analysis showed that as NPC1L1 and PCSK9 levels increased,FINS,HbA1c,C-P and OGTT levels also increased accordingly.With the increase of NPC1L1 and PCSK9 levels,insulin function also decreased(all P<0.05).The results of RCS model showed that with the increase of NPC1L1 and PCSK9 levels,the probability of T2DM incidence also increased(χ2=22.334,25.537,all P<0.001).No significant interaction was found between NPC1L1,PCSK9 levels and islet function indexes(P>0.05).Conclusion The levels of NPC1L1 and PCSK9 are closely related to the risk of T2DM in Mongolian residents.With the increase of NPC1L1 and PCSK9 levels,the incidence probability of T2DM increases.

Objective To explore the relationship between serum Niemann-pick type C1 like protein1(NPC1L1)and propro-tein convertase subtilisin/kexin type 9(PCSK9)levels and the risk of type 2 diabetes mellitus(T2DM)in Mongolian residents.Methods A total of 72 Mongolian patients with T2DM treated in Peking University Cancer Hospital,Inner Mongolia Hospital and the Affiliated Hospital of Inner Mongolia Medical University from June 2022 to June 2024 were selected as the T2DM group,and 81 healthy people in the same period were selected as the control group.LASSO model and multivariate Logistic regression model were used to screen the risk factors of disease onset.Multiple linear regression was used to analyze the correlation between NPC1L1 and PCSK9 levels and insulin function.Restricted cubic spline(RCS)model was used to analyze the dose-response relationship between NPC1L1 and PCSK9 levels and the incidence of T2DM,and explored the interaction between NPC1L1 and PCSK9 levels on the incidence of T2DM.Results NPC1L1(3.11±0.80 ng/L)and PCSK9(10.63±0.79 ng/L)in T2DM group were significantly higher than those in the control group(0.52±0.22 ng/L,3.21±0.17 ng/L),and the differences were statisti-cally significant(t=27.982,82.443,all P<0.05).NPC1L1(OR=2.458,95%CI=2.364～2.594,P<0.05)and PCSK9(OR=2.905,95%CI=2.541～3.528)were risk factors for T2DM(all P<0.001).The results of multiple linear regression analysis showed that as NPC1L1 and PCSK9 levels increased,FINS,HbA1c,C-P and OGTT levels also increased accordingly.With the increase of NPC1L1 and PCSK9 levels,insulin function also decreased(all P<0.05).The results of RCS model showed that with the increase of NPC1L1 and PCSK9 levels,the probability of T2DM incidence also increased(χ2=22.334,25.537,all P<0.001).No significant interaction was found between NPC1L1,PCSK9 levels and islet function indexes(P>0.05).Conclusion The levels of NPC1L1 and PCSK9 are closely related to the risk of T2DM in Mongolian residents.With the increase of NPC1L1 and PCSK9 levels,the incidence probability of T2DM increases.

Aim To study the diastolic effect and mechanism of farrerol on isolated pulmonary arteries of C57BL/6J mice.Methods After anesthesia,mouse lung tissue was quickly removed and placed into the 4 ℃ K-H buffer,pulmonary arteries were isolated under the microscope and cut into 2 mm long vascular rings for spare use.(1)The effect of farrerol on the resting tension of isolated mouse pulmonary arteries:in the resting state,the active mouse pul-monary artery rings were treated with different concentrations of farrerol(10-6,3×10-6,10-5,3×10-5 and 10-4 mol/L).(2)Farrerol relaxed mouse pulmonary artery experiment:pulmonary arteries were contracted using phenylephrine(PE,1 μmol/L)or KCl(60 mmol/L),and when the contraction reached the platform,different concentrations of farrerol(10-6,3×10-6,10-5,3×10-5 and 10-4 mol/L)was added.(3)Farrerol inhibited pulmonary artery contraction experi-ment:under conditions with or without the addition of farrerol,pulmonary arteries were contracted using different concen-trations of PE(10-9,3×10-9,10-8,3 × 10-8,10-7,3×10-7 and 10-6 mol/L)or KCl(20,30,40,60,80 and 120 mmol/L),and the pulmonary artery muscle tension was recorded.(4)Calcium free and recalcification experiments:under conditions with or without the addition of farrerol,the changes of isolated mouse pulmonary artery tension were meas-ured in the state of calcium free or recalcification { 2.5 mmol/L[Ca2+]ex }.(5)The relationship between farrerol in-duced relaxation of isolated mouse pulmonary arteries and potassium ion channels:firstly,60 mmol/L KCl solution was used to contract the mouse pulmonary arteries until the platform.Then,3 mmol/L aminopyridine(4-AP),2 mmol/L tet-raethylammonium(TEA),30 μmol/L BaCl2,and 10 μmol/L glibenclamide(Gli)were added and treated for 15 min.Subsequently,the pulmonary arteries were relaxed using a concentration gradient of farrerol.Results Farrerol had no significant effect on the mouse pulmonary arteries in the resting state,but had a concentration-dependent relaxing effect on the mouse pulmonary arteries pre-contracted with PE and KCl.While the pretreatment of 3×10-5 mol/L farrerol could sig-nificantly reduce the maximum contraction of mouse pulmonary arteries induced by PE and KCl(P＜0.01),as well as sig-nificantly reduce the contraction of mouse pulmonary arteries induced by KCl under calcium free or recalcification conditions(P＜0.01).Addition of the voltage-dependent potassium ion channel blocker 4-AP significantly reduced the maximum diastolic rate of mouse pulmonary arteries induced by farrerol(P＜0.01),while addition of the high conductivity calcium activated potassium ion channel blocker TEA,inward rectifying potassium ion channel blocker BaCl2,or ATP sensitive po-tassium ion channel blocker Gli had no significant effect on the vasodilation effect of farrerol(P＞0.05).Conclusion Farrerol has a relaxing effect on isolated mouse pulmonary arteries,and its mechanism may be related to open voltage-de-pendent potassium ion channels.

Objective:To explore the predictive value of myocardial work echocardiography on short-term mortality of patients with sepsis and septic shock(SSS).Methods:Patients who hospitalized in the ICU department of the Affiliated Lianyungang Hospital of Xuzhou Medical University from September 2022 to December 2023 were selected through prospective research.These patients,who need use vasopressor drugs,appeared clinical symptoms of sepsis and occurred septic shock.A total of 33 adult patients were continuously enrolled.According to whether patients with SSS died or survived within 28 days,they were divided into a survival group(23 cases)and a non-survival group(10 cases).The changes of myocardial function,serum lactic acid level,white blood cell(WBC)count,c-reactive protein(CRP)and other indexes were compared and assessed between the two groups after admission,and the predictive value of these parameters on short-term mortality in patients with sepsis and septic shock was investigated.Results:On the 3rd day after admission of patients with sepsis and septic shock,the heart rate,serum lactic acid level,white blood cell(WBC)count,global wasted work(GWW),and high-sensitivity cardiac troponin Ⅰ(hs-cTnⅠ)of non-survival group significantly higher than those of survival group(Z=-2.668,-2.550,-2.338,-2.175,-2.998,P＜0.05),and the global work efficiency(GWE)of non-survival group significantly decreased(Z=-2.311,P＜0.05).On the 5th day after admission,the heart rate,serum lactic acid level,WBC count,c-reactive protein(CRP)level of non-survival group significantly increased(Z=-3.073,-2.494,-3.408,-2.999,P＜0.05),and the pH value and global work index(GWI)of that significantly decreased(Z=-1.997,-2.546,P＜0.05).Serum lactic acid on the 3rd day and global work index on the 5th day were respectively independent risk factors for 28-day mortality in SSS patients after admission(OR=5.120,0.997,P＜0.05).On the 5rd GwI and serum lactic acid on the 3rd have similar values in predicting 28-day mortality in SSS patients[area under curve(AUC)value of receiver operating characteristics(ROC)curve of them were respectively 0.784 and 0.801,P＞0.05].Conclusion:Myocardial work echocardiography is helpful to identify the high risk of short-term death of SSS patients.Serum lactic acid of the 3rd day and global work index of the 5th day after admission are respectively independent risk factors for 28-day death in SSS patients.

Objective:To explore the mediating effect of attentional bias of negative information between fatalism and death anxiety in lung neoplasms patients.Methods:This study was a cross-sectional study. It was convenient to select 312 lung neoplasms patients treated in the Department of Oncology, First Affiliated Hospital and Second Affiliated Hospital of Air Force Military Medical University the Chinese People′s Liberation Army, from April 2021 to April 2022 as the research subjects. Questionnaires were conducted with Fatalism Scale, Attention to Negative Information Scale, and Templer′s Death Anxiety Scale. Structural equation model were constructed based on self-regulatory executive function models.Results:The total score of fatalism, attentional bias of negative information, and death anxiety of 312 lung neoplasms patients were (61.68 ± 11.92) points, (39.57 ± 5.19) points, and (61.23 ± 9.30) points, respectively. Attentional bias of negative information was significantly positively correlated with fatalism ( r = 0.594, P<0.01). Death anxiety was significantly positively correlated with fatalism and attentional bias of negative information ( r = 0.494, 0.558, both P<0.01). Attentional bias of negative information played a partial mediating role between fatalism and death anxiety, and the mediating effect accounted for 37.7% of the total effect. The value of each fitness index of the mediation effect model was within the acceptable range. Conclusions:Attentional bias of negative information is an intermediary variable between fatalism and death anxiety of lung neoplasms patients. Nursing staff should pay attention to the level of attentional bias of negative information of lung neoplasms patients and carry out targeted nursing interventions from the emotional processing process to reduce the level of death anxiety in patients with lung neoplasms.

OX40 is a costimulatory receptor that is expressed primarily on activated CD4⁺, CD8⁺, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.
Mice ; Animals ; Receptors, Tumor Necrosis Factor/physiology* ; Receptors, OX40 ; Membrane Glycoproteins ; Ligands ; Antibodies, Monoclonal/pharmacology* ; Antineoplastic Agents/pharmacology*

The vagina contains at least a billion microbial cells,dominated by lactobacilli.Here we perform metagenomic shotgun sequencing on cervical and fecal samples from a cohort of 516 Chinese women of reproductive age,as well as cervical,fecal,and salivary samples from a second cohort of 632 women.Factors such as pregnancy history,delivery history,cesarean section,and breastfeeding were all more important than menstrual cycle in shaping the microbiome,and such information would be necessary before trying to interpret differences between vagino-cervical micro-biome data.Greater proportion of Bifidobacterium breve was seen with older age at sexual debut.The relative abundance of lactobacilli especially Lactobacillus crispatus was negatively associated with pregnancy history.Potential markers for lack of menstrual regularity,heavy flow,dysmenor-rhea,and contraceptives were also identified.Lactobacilli were rare during breastfeeding or post-menopause.Other features such as mood fluctuations and facial speckles could potentially be predicted from the vagino-cervical microbiome.Gut and salivary microbiomes,plasma vitamins,metals,amino acids,and hormones showed associations with the vagino-cervical microbiome.Our results offer an unprecedented glimpse into the microbiota of the female reproductive tract and call for international collaborations to better understand its long-term health impact other than in the settings of infection or pre-term birth.