BackgroundChronic insomnia disorder has become a significant public health issue， and it may be associated with dyslipidemia. Previous studies on dyslipidemia in patients with chronic insomnia disorder have mainly focused on exploring the relationship between subjective short sleep duration and dyslipidemia， while there have been limited studies on the relationship between objective short sleep duration and dyslipidemia. ObjectiveTo explore the relationship between objective short sleep duration and dyslipidemia in patients with chronic insomnia disorder， in order to provide references for the prevention and intervention of dyslipidemia in this population. MethodsA total of 103 patients who were hospitalized at The Third Hospital of Mianyang from August 2022 to November 2023 and met the diagnostic criteria for chronic insomnia disorder as defined in the International Classification of Sleep Disorder， third edition （ICSD-3） were retrospectively collected. The objective sleep duration of the patients was obtained through polysomnography. The patients were divided into two groups based on their objective sleep duration： the group with objective sleep duration ≥ 7 hours （n=71） and the group with objective sleep duration < 7 hours （n=32）. Binary Logistic regression analysis was used to explore the impact of objective sleep duration < 7 hours on dyslipidemia. ResultsAmong 103 patients with chronic insomnia disorder， 59 cases （57.28%） were identified with dyslipidemia. The comparison of dyslipidemia conditions between the group with objective sleep duration ≥ 7 hours and the group with objective sleep duration < 7 hours showed a statistically significant difference （χ²=5.956， P<0.05）. Compared with the group with objective sleep duration ≥7 hours， the group with objective sleep duration < 7 hours exhibited significantly lower high-density lipoprotein cholesterol levels， and reduced sleep efficiency （t=-2.003， -5.482， P<0.05 or 0.01）. Binary Logistic regression analysis results showed that the risk of abnormal blood lipids in patients with chronic insomnia disorder with objective sleep duration < 7 hours was 3.128 times higher than that of patients with objective sleep duration ≥ 7 hours （OR=3.128， 95% CI： 1.139–8.588）. ConclusionObjective short sleep duration may be a risk factor for dyslipidemia in patients with chronic insomnia disorder.

BackgroundAnxiety symptoms have become a public health issue affecting the physical and mental health of the elderly population. Mental health literacy is a predictor of anxiety symptoms in the elderly. Currently， there are limited studies on the pathogenic mechanism between the two. Exploring the relationship and mechanism between mental health literacy and anxiety symptoms among the elderly is of great significance for improving the mental health level of the elderly. ObjectiveTo investigate the impact of mental health literacy on anxiety symptoms in the elderly， and to analyze the role of insomnia in this process， in order to provide references for the formulation of prevention and intervention strategies for anxiety symptoms in the elderly. MethodsFrom August 2021 to December 2022， a total of 10 650 older adults aged 60 years old and above were selected from a city in Sichuan Province using a multistage stratified sampling method. Participants completed the self-compiled demographic questionnaire， the Insomnia Severity Index （ISI）， the Generalized Anxiety Disorder Scale-7 item （GAD-7）， and the National Mental Health Literacy Questionnaire （NMHLQ）. Spearman correlation analysis was adopted to examine the correlation between the scores of the scales. Model 4 in SPSS 27.0 plugin Process 4.1 was employed to test the pathway of insomnia between mental health literacy （and its various dimensions） and anxiety symptoms. ResultsAmong the participants， 9 609 cases （90.23%） completed the valid questionnaire survey， and 1 680 cases （17.48%） were found to have anxiety symptoms. The total score of the NMHLQ for the elderly， as well as the scores of the knowledge， awareness， and skills dimensions， were negatively correlated with the GAD-7 score and the ISI score （r_s=-0.506–-0.054， P<0.01）， and the ISI score was positively correlated with the GAD-7 score （r_s=0.666， P<0.01）. Insomnia served as the mediating pathway between the mental health literacy and anxiety symptoms， with an indirect effect value of -0.210 （95% CI： -0.227–-0.193）， accounting for 54.97% of the total effect. Insomnia was the mediating pathway between the mental health literacy knowledge and anxiety symptoms of the elderly， with an indirect effect value of -0.161 （95% CI： -0.178–-0.144）， accounting for 52.61% of the total effect. Insomnia played a mediating role in the relationship between the awareness of mental health literacy and anxiety symptoms， with an indirect effect value of -0.323 （95% CI： -0.342–-0.302）， accounting for 76.36% of the total effect. Insomnia was the mediating pathway between the mental health literacy skills and anxiety symptoms of the elderly， with an indirect effect value of -0.172 （95% CI： -0.187–-0.159）， accounting for 53.75% of the total effect. ConclusionThe dimensions of mental health literacy， knowledge， awareness and skills of the elderly not only directly affect anxiety symptoms， but also indirectly influence anxiety symptoms through the pathway of insomnia.［Funded by Medical Research Project Plan of Sichuan Province （number， S23049）］

OBJECTIVES: Whether vortioxetine has a utility as an adjuvant drug in the treatment of bipolar depression remains controversial. This study aimed to validate the efficacy and safety of vortioxetine in bipolar depression. METHODS: Patients with bipolar Ⅱ depression were enrolled in this prospective, two-center, randomized, 12-week pilot trial. The main indicator for assessing treatment effectiveness was a Montgomery-Asberg Depression Rating Scale (MADRS) of ≥50%. All eligible patients initially received four weeks of lurasidone monotherapy. Patients who responded well continued to receive this kind of monotherapy. However, no-response patients were randomly assigned to either valproate or vortioxetine treatment for eight weeks. By comprehensively comparing the results of MADRS over a period of 4‍‒‍12 weeks, a systematic analysis was conducted to determine whether vortioxetine could be used as an adjuvant drug for treating bipolar depression. RESULTS: Thirty-seven patients responded to lurasidone monotherapy, and 60 patients were randomly assigned to the valproate or vortioxetine group for eight weeks. After two weeks of combined valproate or vortioxetine treatment, the MADRS score in the vortioxetine group was significantly lower than that in the valproate group. There was no difference in the MADRS scores between the two groups at 8 and 12 weeks. The incidence of side effects did not significantly differ between the valproate and vortioxetine groups. Importantly, three patients in the vortioxetine group appeared to switch to mania or hypomania. CONCLUSIONS This study suggested that lurasidone combination with vortioxetine might have potential benefits to bipolar II depression in the early stage, while disease progression should be monitored closely for the risk of switching to mania.
Humans ; Bipolar Disorder/drug therapy* ; Vortioxetine/therapeutic use* ; Male ; Female ; Middle Aged ; Adult ; Valproic Acid/administration & dosage* ; Lurasidone Hydrochloride/administration & dosage* ; Prospective Studies ; Treatment Outcome ; Pilot Projects ; Drug Therapy, Combination ; Sulfides/therapeutic use* ; Antidepressive Agents/therapeutic use*

Traditional development of small protein scaffolds has relied on display technologies and mutation-based engineering, which limit sequence and functional diversity, thereby constraining their therapeutic and application potential. Protein design tools have significantly advanced the creation of novel protein sequences, structures, and functions. However, further improvements in design strategies are still needed to more efficiently optimize the functional performance of protein-based drugs and enhance their druggability. Here, we extended an evolution-based design protocol to create a novel minibinder, BindHer, against the human epidermal growth factor receptor 2 (HER2). It not only exhibits super stability and binding selectivity but also demonstrates remarkable properties in tissue specificity. Radiolabeling experiments with ^99mTc, ⁶⁸Ga, and ¹⁸F revealed that BindHer efficiently targets tumors in HER2-positive breast cancer mouse models, with minimal nonspecific liver absorption, outperforming scaffolds designed through traditional engineering. These findings highlight a new rational approach to automated protein design, offering significant potential for large-scale applications in therapeutic mini-protein development.

Objective:To explore the efficacy and safety of orelabrutinib combined with R-CHOP in patients with high-risk nongerminal center B-cell (non-GCB) diffuse large B-cell lymphoma (DLBCL) with extranodal involvement.Methods:This retrospective study was conducted on 35 patients who were seen at Guangxi Medical University Cancer Hospital and were immunohistochemically confirmed to have non-GCB DLBCL, had an International Prognostic Index score of 3 - 5, and confirmed to have ≥2 extranodal involvement on PET/CT. The treatment comprised the standard R-CHOP regimen combined with oral orelabrutinib (150 mg/day) for six cycles. In patients who developed neutropenia or grade 3 neutropenia with fever during treatment, administration of prophylactic pegylated granulocyte colony-stimulating factor 48 h after the end of chemotherapy was started on the next cycle. The endpoints included overall response rate (ORR), complete response (CR) rate, progression-free survival (PFS) time, overall survival (OS) time, and safety assessment.Results:The 35 eligible patients enrolled had a median age of 53 years (21 - 72 years) and a median follow-up time of 28 months (12 - 36 months) ; 19 patients had double-expressor (DE) status. The ORR was 88.6%, and the CR rate was 68.6%. The 2-year PFS and OS rates were 68.6% (95% CI 54.0% - 7.2%) and 87.5% (95% CI 76.7% - 100%), respectively. The 2-year PFS rate was significantly lower in patients with DE status than in those without DE status [54.4% (95% CI 35.4% - 84.2%) vs. 85.2% (95% CI 68.3% - 100%), P=0.048]. Serious adverse events included febrile neutropenia, pneumonia, and atrial flutter, but no treatment-related deaths. Conclusion:In patients with high-risk non-GCB DLBCL and extranodal involvement, the combination of orelabrutinib with R-CHOP regimen had good efficacy and manageable toxicity.

Objective:To investigate the effect of Lulongzaisheng decoction on ferroptosis in aplastic anemia (AA) model mice and its potential mechanism of action on AA.Methods:Using female BALB/c mice as controls (control group), a mouse model of AA was established by intraperitoneal injection of interferon-γ (IFN-γ) combined with oral gavage of busulfan. The AA group was treated with continuous oral gavage of Lulongzaisheng decoction for 10 days. The effects on the Jak2/Stat3/Acsl4 signaling pathway were assessed. Bone marrow biopsy and histopathological examination were performed to observe the degree of AA in each group of mice. Flow cytometry was used to detect the production of lipid reactive oxygen species (ROS) in the bone marrow cells. Immunohistochemical staining was performed to observe the expression of 4-HNE in the sternum. Western blot analysis was conducted to determine the protein expression levels of Jak2, p-Jak2, Stat3, p-Stat3, and Acsl4. ELISA was used to measure the levels of interleukin-6 (IL-6) in the peripheral blood plasma.Results:Compared with the control group, mice in the AA group exhibited a reduction in hematopoietic tissues within the bone marrow cavity and significant fatty infiltration. In contrast, mice in the AA+Lulongzaisheng decoction group showed partial recovery of the bone marrow and a decrease in fatty infiltration. The lipid ROS proportions in the control, AA, and AA+Lulongzaisheng decoction groups were (47.01±3.07) %, (53.81±1.99) %, and (49.50±3.98) %, respectively ( P<0.05), indicating that the AA + Lulongzaisheng decoction group had a slightly lower accumulation of lipid ROS than the AA group. The expression areas of 4-HNE in the bone marrow cavity for the control, AA, and AA+Lulongzaisheng decoction groups were (6.34±1.07) %, (35.26±3.68) %, and (16.97±1.30) %, respectively ( P<0.05), demonstrating a significant reduction in 4-HNE accumulation in the bone marrow in the AA + Lulongzaisheng decoction group compared with that in the AA group. Compared with the control group, the AA group exhibited upregulated expression of the ferroptosis-related protein Acsl4, along with increased expression of p-Stat3 and p-Jak2. In the AA+ Lulongzaisheng decoction group, the expression of Acsl4 was downregulated, whereas those of p-Stat3 and p-Jak2 were inhibited ( P<0.05). The levels of IL-6 in the peripheral blood plasma were (65.60±6.01), (166.50±3.32), and (119.37±4.29) pg/ml in the control, AA, and AA+Lulongzaisheng decoction groups, respectively ( P<0.05). Compared with the AA group, the AA + Lulongzaisheng decoction group exhibited a significant decrease in IL-6 levels. Conclusion:This study shows that Lulongzaisheng decoction has a significant therapeutic effect on AA model mice by regulating the Jak2/Stat3/Acsl4 pathway. The mechanism of action of this traditional Chinese medicine involves inhibiting the Jak2/Stat3 signaling pathway and regulating the expression of Acsl4, thereby improving hematopoietic function in AA model mice. These findings provide new drug targets and treatment strategies for the treatment of AA.

Objective:To investigate the application of time series models in forecasting pre-hospital emergency ambulance trips in Handan City and develop the LPro ensemble model for improved prediction accuracy to support emergency resource allocation.Methods:Pre-hospital emergency data from Handan Emergency Medical Command Center (2019-2023) were retrospectively analyzed. From 324 799 original records, 289 949 valid records were included after cleaning. The training set (2019-2022: 215 918 records) included 35 527 records in 2019, 52 015 in 2020, 61 836 in 2021, and 66 540 in 2022. The validation set (2023) contained 74 031 records. ARIMA, linear trend seasonal, exponential smoothing, and Prophet models were fitted to the training set. The LPro ensemble model was constructed using MAPE-based weighting (linear trend seasonal model: 0.38, Prophet: 0.62). Performance metrics included MAPE, RMSE, MAE, and R 2. Results:Data showed annual growth (compound annual growth rate 23.27%) and seasonal patterns (October peaks, February troughs). Ambulance dispatches increased annually with monthly cyclical patterns. For 2023 validation predictions: ARIMA (MAPE 8.76%, RMSE 619, MAE 491, R 2 0.4563), linear trend seasonal (MAPE 9.83%, RMSE 671, MAE 545, R 2 0.3608), Prophet (MAPE 8.43%, RMSE 562, MAE 503, R 2 0.5513), exponential smoothing (MAPE 8.08%, RMSE 643, MAE 410, R 2 0.4124). LPro model showed superior performance (MAPE 7.05%, RMSE 491, MAE 393, R 2 0.6570), with 16.37% lower MAPE, 12.63% lower RMSE, 21.87% lower MAE, and 19.17% higher R 2 versus Prophet. Conclusion:The LPro ensemble model substantially enhances prediction accuracy and reliability, offering scientific support for emergency resource optimization and dispatch scheduling in Handan City.

BackgroundInternet addiction poses serious harm to the physical and mental health of college students. Insecure attachment is one of the key factors of internet addiction， while self-compassion and psychological resilience serve as crucial psychological factors closely related to it. However， the chain mediating role of self-compassion and psychological resilience between insecure attachment and college students' internet addiction remains unclear. ObjectiveTo explore the mediating role of self-compassion and psychological resilience in the relationship between insecure attachment and internet addiction in college students， so as to provide references for the prevention and intervention of internet addiction in this population. MethodsFrom November 2023 to February 2024， a total of 1 380 college students were recruited using a cluster sampling method from two universities in Sichuan Province. The assessment was conducted using the Chinese Internet Addiction Scale （CIAS）， the Self-Compassion Scale （SCS）， the Experiences in Close Relationships Scale （ECR）， and the Resilience Scale for Chinese Adolescents （RSCA）. Pearson correlation analysis was conducted to examine the correlations of the scores of each scale. Model 6 in Process 4.2 was used to test the mediating roles of self-compassion and psychological resilience in the relationship between insecure attachment and internet addiction among college students. ResultsA total of 1 232 （89.28%） college students completed the valid questionnaire survey. The ECR score was positively correlated with the CIAS score （r=0.299， P<0.01）， and SCS score was positively correlated with the RSCA score （r=0.299， P<0.01）. The ECR score was negatively correlated with both SCS score and RSCA score （r=-0.122、-0.147，P<0.01）； the SCS score was negatively correlated with both RSCA score and CIAS score （r=-0.238、-0.263， P<0.01）. Self-compassion and psychological resilience were the pathways between insecure attachment and internet addiction， with effect sizes of 0.015 （95% CI： 0.007–0.023） and 0.010 （95% CI： 0.004–0.017）， respectively. Self-compassion and psychological resilience played chain mediating role between insecure attachment and internet addiction， with effect sizes of 0.003 （95% CI： 0.001–0.006）. ConclusionInsecure attachment can directly affect internet addiction in college students， and it can also influence internet addiction through independent pathway of self-compassion and psychological resilience， as well as the chain mediating pathways involving both self-compassion and psychological resilience.

Objective:To analyze the evolution of ceftazidime/avibactam (CZA) resistance phenotyes and clinical features of 11 ST11-KL64 carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates carrying bla KPC. Methods:Eleven CRKP isolates, designated K01 to K11, obtained from infected liver transplant patients from June to September 2024 were retrospectively studied. Broth microdilution method, whole genome sequencing (WGS) and plasmid conjugation assays were employed to investigate the antimicrobial susceptibility, resistance mechanisms, and genetic structural characteristics of these CRKP isolates. Clinical data were simultaneously collected and organized to analyze the correlation between bla KPC gene mutations and the clinical efficacy of antimicrobial therapy. Results:All eleven isolates of CRKP exhibited multidrug resistance phenotypes. Among them, K01-K09 and K11 were sensitive to CZA and resistant to carbapenems, while K10 was resistant to CZA and displayed sensitivity or intermediate resistance to carbapenems. WGS analysis showed that all 11 CRKP isolates belonged to the ST11-KL64 clonal type. Among these isolates, the K01-K09 and K11 isolates carry the bla KPC-2 gene, whereas the K10 isolate carries the bla KPC-33 gene. A single nucleotide mutation in bla KPC-2 (G532T) resulted in a substitution of tyrosine (Y) for aspartic acid (D) at Ambler position 179 (D179Y), causing resistance of CRKP to CZA and reduced sensitivity to Imipenem and Meropenem. The conjugative plasmid was successfully constructed, and compared to the parental strain, its minimum inhibitory concentration (MIC) to CZA increased 32 folds. Clinical data revealed that the patient developed the bla KPC-33 mutation after 51 days of CZA treatment. Conclusions:The bla KPC-33 mutation following CZA treatment for CRKP infection exhibits a considerable delay. It is essential to dynamically monitor the evolution of CRKP resistance to ensure timely adjustment of therapeutic strategies in case of the occurrence of mutations such as bla KPC-33.

Objective To investigate the predictive value of the geriatric nutritional risk index(GNRI)for short-term mortality and the presence of concomitant heart failure in intensive care unit(ICU)patients with sepsis.Methods Based on the medical information mart for intensive care(MIMIC)-Ⅳ database,we analyzed the relationship between GNRI and 30-day and 90-day mortality in sepsis patients,and further evaluated its potential value in predicting sepsis complicated by heart failure.Results Patients with low GNRI had significantly higher 30-day and 90-day mortality and were effective in predicting the presence of combined heart failure in sepsis patients.Conclusion GNRI is a reliable predictor of short-term mortality in elderly sepsis patients and can also assist in assessing the risk of heart failure in these patients,which is valuable for clinical prognosis assessment and treatment decisions.