OBJECTIVE To evaluate the cost-effectiveness of tafolecimab in patients with hypercholesterolemia， and provide support for optimizing management strategies for hypercholesterolemia and healthcare resource allocation. METHODS From the perspective of the Chinese healthcare system， an 11-state mutually exclusive Markov cohort model was developed to simulate disease progression and prognosis in the target population. The model cycle was set to one year， with a 30-year time horizon. Transition probabilities between health states were derived from the CREDIT series of clinical trials， while health utility values and medical cost parameters were sourced from the statistical yearbook and published literature. Quality-adjusted life years （QALYs） were used as the measure of health outcomes. Cost-effectiveness analysis was employed to calculate the incremental cost- effectiveness ratio （ICER） for three dosing regimens of tafolecimab [150 mg every 2 weeks （q2w）， 450 mg every 4 weeks （q4w）， and 600 mg every 6 weeks （q6w）] in combination with statins compared with control therapy （statins）. Using 1-3 times the per capita gross domestic product （GDP） of China in 2024 as willingness-to-pay threshold（WTP）， with a discount rate of 5%. Model robustness was assessed through one-way sensitivity analysis， probabilistic sensitivity analysis， and scenario analysis. RESULTS The 150 mg q2w regimen of tafolecimab yielded an ICER of 235 827.73 yuan/QALY， which was below the WTP （287 100 yuan/ QALY）， indicating that the regimen was cost-effective. In contrast， the ICERs for the 450 mg q4w and 600 mg q6w regimens were 329 498.24 and 318 630.51 yuan/QALY， respec-tively， both exceeding the WTP and thus not cost-effective.One-way sensitivity analysis identified the discount rate as a key influencing factor. Probabilistic sensitivity analysis showed that under the WTP set in this study， the probabilities of cost-effectiveness for the 450 mg q4w and 600 mg q6w regimens were 15.3% and 22.4%， respectively， while the 150 mg q2w regimen had an 85.2% probability of being cost-effective. The situational analysis revealed that， over a simulated time horizon of 5 to 30 years， the ICER of tafolecimab was progressively reduced compared with the control regimen. When the price of tafolecimab was lowered by more than 20%， all three dosing regimens were demonstrated to be cost-effective.CONCLUSIONS Under the current Chinese healthcare system， compared with statin monotherapy， tafolecimab （150 mg q2w） combination improves health outcomes in patients with hypercholesterolemia， and is cost-effective given the current WTP.

Autism Spectrum Disorders (ASDs) are reported as a group of neurodevelopmental disorders. The structural changes of brain regions including the hippocampus were widely reported in autistic patients and mouse models with dysfunction of ASD risk genes, but the underlying mechanisms are not fully understood. Here, we report that deletion of Trio, a high-susceptibility gene of ASDs, causes a postnatal dentate gyrus (DG) hypoplasia with a zigzagged suprapyramidal blade, and the Trio-deficient mice display autism-like behaviors. The impaired morphogenesis of DG is mainly caused by disturbing the postnatal distribution of postmitotic granule cells (GCs), which further results in a migration deficit of neural progenitors. Furthermore, we reveal that Trio plays different roles in various excitatory neural cells by spatial transcriptomic sequencing, especially the role of regulating the migration of postmitotic GCs. In summary, our findings provide evidence of cellular mechanisms that Trio is involved in postnatal DG morphogenesis.
Animals ; Dentate Gyrus/metabolism* ; Mice ; Morphogenesis/physiology* ; Neurons/pathology* ; Cell Movement ; Mice, Inbred C57BL ; Autism Spectrum Disorder/pathology* ; Mice, Knockout ; Neural Stem Cells ; Male ; Neurogenesis ; Autistic Disorder/genetics*

Objective:To explore the gene mutation characteristics and the relationship between gene mutations and long-term prognosis in clinical stage ⅠA lung adenocarcinoma patients.Methods:A retrospective analysis was conducted on 63 clinical stage ⅠA lung adenocarcinoma patients who underwent surgical resection at the Cancer Hospital of the Chinese Academy of Medical Sciences from January 2007 to October 2012, with documented postoperative recurrence or metastasis, as well as those who had a follow-up duration of 10 years or more without recurrence or metastasis. Whole exome sequencing (WES) technology was used to analyze the gene mutation profiles in tumor tissues and univariate and multivariate Cox regression analysis were used to clarify the influencing factors for patient prognosis.Results:After long term follow-up, 13 out of the 63 patients (21%) experienced recurrence or metastasis. WES technology analysis revealed that the most common tumor related gene mutations occurred in epidermal growth factor receptor (EGFR), with a mutation rate of 65.1% (41/63), followed by tumor protein p53 (TP53), fatatypical cadherin 1 (FAT1), low density lipoprotein receptor-related protein 1B (LRP1B), mechanistic target of rapamycin (MTOR), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma (PIK3CG), and SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4 (SMARCA4), with mutation rates of 30.2% (19/63), 20.6% (13/63), 15.9% (10/63), 15.9% (10/63), 15.9% (10/63), and 15.9% (10/63), respectively. Multivariate Cox regression analysis showed that PIK3CG mutations ( HR=21.52, 95% CI: 3.19-145.01),smoothened (SMO) mutations ( HR=35.28, 95% CI: 3.12-398.39), catenin beta 1 (CTNNB1) mutations ( HR=332.86, 95% CI: 15.76-7 029.05), colony stimulating factor 1 receptor (CSF1R) mutations ( HR=8 109.60, 95% CI: 114.19-575 955.17), and v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutations ( HR=23.65, 95% CI: 1.86-300.43) were independent risk factors affecting the prognosis of clinical stage ⅠA lung adenocarcinoma patients. Conclusions:PIK3CG, SMO, CTNNB1, CSF1R, BRAF gene mutations are closely related to long-term recurrence or metastasis in clinical stage ⅠA lung adenocarcinoma. Patients with these gene mutations should be given closer clinical attention.

Objective To investigate the expression of essential meiotic endonuclease 1(EME1)in liver cancer tissue and its effect on the biological behavior of hepatoma cells.Methods The TCGA database was used to identify the differentially expressed genes between liver cancer tissue and paracancerous tissue.Immunohistochemistry and Western Blot were used to measure the expression abundance of EME1 in liver cancer tissue.A lentivirus was constructed by short hairpin RNA,and BEL-7404 cells were transfected with the lentivirus to interfere with the expression of the EME1 gene;the cells were divided into silencing group(shEME1 group)and control group(shCtrl group).Quantitative real-time PCR and Western Blot were used to measure the mRNA and protein expression levels of EME1;Celigo Image Cytometer and MTT assay were used to measure cell proliferation rate;flow cytometry was used to observe cell cycle;Caspase 3/7 activity was used to measure cell apoptosis.The independent-samples t-test was used for comparison between two groups.Results TCGA results showed that the mRNA expression level of EME1 in liver cancer tissue was 18.9 times that in paracancerous tissue(t=5.00,P<0.001),and the protein expression level of EME1 in liver cancer tissue was 7.0 times(based on immunohistochemistry:8.4±2.6 vs 1.2±0.4,t=7.55,P<0.001)or 2.5 times(based on Western Blot:249.0%±35.5%vs 100.0%±77.8%,t=3.02,P<0.05)that in paracancerous tissue.After lentivirus infection,compared with the shCtrl group,the shEME1 group had an mRNA expression level of EME1 reduced by 29.9%(29.9%±0.9%vs 100.0%±3.6%,t=32.82,P<0.001),a protein expression level of EME1 reduced by 35.7%(35.7%±14.9%vs 100.0%±28.9%,t=3.42,P<0.05),and a level of cell counting reduced by 45.1%(4 053±167 vs 8 988±477,t=16.91,P<0.001),as well as a level of cell activity reduced to 66.9%(0.518±0.046 vs 0.774±0.022,t=8.74,P<0.001)and a level of colony forming ability reduced to 29.0%(75±6 vs 260±9,t=28.92,P<0.001).Compared with the shCtrl group,the shEME1 group had a significant increase in the proportion of cells in G1 phase(49.9%vs 44.0%,t=8.96,P<0.001)and significant reductions in the proportion of cells in G2/M phase(15.9%vs 17.9%,t=9.13,P<0.001)and S phase(34.2%vs 38.1%,t=6.91,P<0.001),while Caspase 3/7 activity was enhanced by 1.5 times(145.8%±5.9%vs 100.0%±2.3%,t=12.50,P<0.001).Conclusion EME1 is highly expressed in liver cancer tissue,and silencing the EME1 gene can inhibit the proliferation of hepatoma cells and promote cell apoptosis.

Objective:To explore the gene mutation characteristics and the relationship between gene mutations and long-term prognosis in clinical stage ⅠA lung adenocarcinoma patients.Methods:A retrospective analysis was conducted on 63 clinical stage ⅠA lung adenocarcinoma patients who underwent surgical resection at the Cancer Hospital of the Chinese Academy of Medical Sciences from January 2007 to October 2012, with documented postoperative recurrence or metastasis, as well as those who had a follow-up duration of 10 years or more without recurrence or metastasis. Whole exome sequencing (WES) technology was used to analyze the gene mutation profiles in tumor tissues and univariate and multivariate Cox regression analysis were used to clarify the influencing factors for patient prognosis.Results:After long term follow-up, 13 out of the 63 patients (21%) experienced recurrence or metastasis. WES technology analysis revealed that the most common tumor related gene mutations occurred in epidermal growth factor receptor (EGFR), with a mutation rate of 65.1% (41/63), followed by tumor protein p53 (TP53), fatatypical cadherin 1 (FAT1), low density lipoprotein receptor-related protein 1B (LRP1B), mechanistic target of rapamycin (MTOR), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma (PIK3CG), and SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4 (SMARCA4), with mutation rates of 30.2% (19/63), 20.6% (13/63), 15.9% (10/63), 15.9% (10/63), 15.9% (10/63), and 15.9% (10/63), respectively. Multivariate Cox regression analysis showed that PIK3CG mutations ( HR=21.52, 95% CI: 3.19-145.01),smoothened (SMO) mutations ( HR=35.28, 95% CI: 3.12-398.39), catenin beta 1 (CTNNB1) mutations ( HR=332.86, 95% CI: 15.76-7 029.05), colony stimulating factor 1 receptor (CSF1R) mutations ( HR=8 109.60, 95% CI: 114.19-575 955.17), and v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutations ( HR=23.65, 95% CI: 1.86-300.43) were independent risk factors affecting the prognosis of clinical stage ⅠA lung adenocarcinoma patients. Conclusions:PIK3CG, SMO, CTNNB1, CSF1R, BRAF gene mutations are closely related to long-term recurrence or metastasis in clinical stage ⅠA lung adenocarcinoma. Patients with these gene mutations should be given closer clinical attention.

BACKGROUND: Lifetime cancer risk is an index that indicates the cumulative probability of cancer at some age during a person's lifetime. Nevertheless, comparative evaluations regarding the probability of developing lung cancer and dying from the disease among diverse populations at the global, regional, and national levels are scarce. METHODS: Lung cancer data from 185 countries were obtained from GLOBOCAN 2022, and data on any other cause of death were acquired from the United Nations. The lifetime risks of lung cancer development and death were estimated using adjustment for multiple primary cancers (AMP) method. The lung cancer risks in countries or regions worldwide were compared by region and the Human Development Index (HDI). RESULTS: The global lifetime risk of developing and dying from lung cancer in 2022 was 3.49% and 2.69%, respectively. The lifetime probabilities of developing lung cancer in countries/areas with low, medium, high, and very high HDIs were 0.33%, 0.95%, 4.72%, and 5.29%, and dying from lung cancer in low, medium, high and very high HDI countries were 0.30%, 0.86%, 3.69% and 3.92%, respectively. After the age of 40 years, the remaining probability of lung cancer development and death decreased with age, leaving a residual risk of 2.00% and 1.71%, respectively, starting at 70 years. CONCLUSIONS The probability of developing lung cancer during one's lifetime is equivalent to 1 in 28 and 1 in 37 people suffering and dying from lung cancer. The age-related risk of developing and dying of lung cancer varies among geographic locations with different HDIs.
Humans ; Lung Neoplasms/epidemiology* ; Female ; Male ; Middle Aged ; Aged ; Adult ; Risk Factors

Objective:To investigate the in vitro inhibitory effect of methylene blue mediated photodynamic therapy (PDT) combined with berberine on Porphyromonas gingivalis (P.g). Methods:P.g was cultured until the middle to late log phase, and methylene blue was added to P.g suspension at different mass concentrations for 5 min, and a laser (wavelength 660 nm, power 140 mW/cm 2) was irradiated for 2 min to find the optimal concentration of methylene blue combined with the laser for in vitro inhibition of P.g. The effect of methylene blue mediated PDT on the in vitro inhibition of P.g and the effect of berberine on the growth curve of P.g were observed. The inhibitory effect of methylene blue mediated PDT and berberine on P.g was investigated by successive combined applications. The effect of methylene blue mediated PDT on P.g morphology was observed by scanning electron microscopy. The absorption peaks of each component were measured by ultraviolet spectrophotometer. Results:The best inhibition was achieved at a methylene blue mass concentration of 24.414 1 μg/ml under 660 nm laser excitation. The differences were statistically significant in both the methylene blue and PDT groups compared with the control group (all P<0.001). 0.05 mg/ml berberine had an inhibitory effect on the planktonic bacteria of P.g. After P.g was treated with methylene blue mediated PDT, the bacterial cell walls were crumpled into clusters. Compared with the control group, the number of colonies was reduced in the 0.05 mg/ml berberine group, and the difference was statistically significant ( P<0.01). The difference between the 0.05 mg/ml berberine + light group and the control group was not statistically significant ( P>0.05). When PDT was combined with berberine, there was a synergistic inhibitory effect on P.g. PDT followed by berberine shows a better inhibitory effect on bacteria, and the differences were statistically significant (all P<0.01). After the berberine treatment, the bacterial surface became smooth, and the length of the bacterial body increased compared with the control group. Conclusions:Methylene blue mediated PDT has an inhibitory effect on P.g. When combined with berberine, it has a synergistic inhibitory effect on P.g., and the inhibition effect is better when PDT is applied first and then berberine is applied in combination.

Objective To investigate the independent influences on the occurrence of ICU Acquired Weakness(ICU-AW)in elderly patients undergoing third-and fourth-level surgeries,to construct a prediction model and draw a column-line diagram,and to internally validate the model.Methods A convenience sampling method was used to select 186 elderly patients undergoing tertiary and quaternary surgeries who were hospitalized in 3 tertiary A hospitals in Beijing from May to December 2022 as the study subjects.Single-factor and multifactor logistic regression were used to analyze the risk factors for ICU-AW in elderly patients undergoing third-and fourth-degree surgeries.A risk prediction model was established and the model was visualized by drawing a column-line diagram,and the receiver operator characteristic curve(ROC)and the Hosmer-Lemeshow tests were applied to verify the predictive effect of the model.Results ICU-AW occurred in 40 of 186 cases in the modeling group,with an incidence rate of 21.5％.The results of univariate analysis showed that the 2 groups of preoperative physiology score and surgical severity score included in the physiology and surgical severity scoring system,age,presence of cardiac disease,hemoglobin(within 24 h of admission to the ICU),blood urea nitrogen(within 24 h of admission to the ICU),blood creatinine(within 24 h of admission to the ICU),presence of braking,mode of establishment of mechanical ventilation,presence of nutritional therapy,number of sedative or analgesic drugs used,whether vasoactive drugs were used,whether diuretics were used,and the level of hemoglobin,blood urea nitrogen and blood creatinine within 24 h after admission to ICU the difference is statistically significant(P＜0.05).The results of multifactorial logistic regression analysis showed that preoperative physiology scores included in the physiology and surgical severity scoring system,the presence of cardiac disease,the presence of braking,the presence of nutritional therapy,and the number of sedative or analgesic medications used were the predictors of the occurrence of ICU-AW in elderly patients undergoing third-and fourth-degree surgeries(OR were 1.364,2.344,5.568,5.823,1.109,all P＜0.05).The above 5 factors were plotted as independent variables in a column-line graph,and the area under the ROC curve of the model was 0.859(95％CI 0.793～0.924),with an optimal critical value of 0.156,a sensitivity of 0.875,a specificity of 0.705,and a Hosmer-Lemeshow goodness-of-fit test of x2=3.906,P=0.865,Brier score of 0.109,and a decision analysis curve indicating that patients could benefit.Conclusion The predictive effect of the constructed model is good,and it can be used as a reference for early and rapid identification of the risk of ICU-AW in elderly patients undergoing third-and fourth-degree surgeries by clinical staff,and timely provision of preventive intervention programs.

Objective:To carry out high-risk foot examination and grading combined with two examination methods for inpatients with type 2 diabetes, and explore the influencing factors of the occurrence and development of high-risk foot, and investigate their foot care behavior status.Methods:From July 2021 to January 2022, 409 patients with diabetes who were admitted to the Department of Endocrinology, Department of Geriatrics, Department of Cardiology, Urology Surgery and Department of Ophthalmology of Xuanwu Hospital of Capital Medical University were selected as research subjects by convenience sampling. The General Information Questionnaire, Standardized Process of At-risk Foot Screening and Stratification for Diabetic Patients, InIow's Screening for the High-Risk Diabetic Foot: A 60-Second Tool, and Foot Care Behavior Questionnaire for Diabetic Patients. Single factor analysis and Logistic regression analysis were used to explore the factors influencing the occurrence and development of high-risk foot in type 2 diabetes patients. A total of 409 questionnaires were distributed, and 392 valid questionnaires were collected, with an effective response rate of 95.8% (392/409) .Results:Among 392 patients, the detection rate of high-risk diabetic foot (HRDF) was 76.3% (299/392), and the proportion of high-risk foot grade 2 was the largest (193). Age ( OR=1.042, P<0.01) and years of hypertension ( OR=1.030, P<0.05) were independent influencing factors for the occurrence of HRDF, with statistically significant differences. Taking the high risk foot grade 3 as a reference, cerebrovascular disease [ OR=16.408, 95% CI (1.323, 203.417) ], diabetes course [ OR=1.066, 95% CI (1.008, 1.128) ], education level in middle school [ OR=0.180, 95% CI (0.056, 0.581) ], education level in primary school and below [ OR=0.126, 95% CI (0.019, 0.841) ] were independent influencing factors for the progress of high risk foot. The foot care behavior of high-risk foot patients with high risk levels was not superior to that of patients with low risk levels. Conclusions:The combination of the two screening methods can meet the examination needs of clinical and nursing medical staff for inpatients with type 2 diabetes. Emphasizing the influencing factors of HRDF occurrence and development can provide reference for early identification of high-risk foot.

Objective:To investigate risk factors for cognitive decline in elderly hospitalised hypertensive patients, develop a risk prediction model and validate it.Methods:By the convenient sampling method, a total of 379 elderly hypertensive patients admitted to Department of Cardiology, Department of Geriatrics (General) and Department of Endocrinology in Xuanwu Hospital of Capital Medical University from April to October 2022 were selected as the study objects. Binomial Logistic regression analysis was used to explore the risk factors of cognitive frailty in elderly hospitalized hypertensive patients and establish a prediction model. Receiver operating characteristic curve (ROC) and Hosmer-Lemeshow goodness of fit test were used to evaluate the prediction effect and calibration degree of the model, and Bootstrap method was used for internal verification.Results:Among 379 elderly hospitalized hypertensive patients, 145 (38.3%) had cognitive frailty. Binomial Logistic regression analysis showed that age, education level, drinking history, daily exercise, use of angiotensin receptor antagonists, Barthel index and nutritional status were the influential factors for cognitive frailty in elderly hospitalized hypertensive patients ( P< 0.05). The area under ROC curve of the prediction model was 0.770 (95% CI: 0.721-0.819, P< 0.001), the sensitivity was 0.607, the specificity was 0.838, and the maximum approximate entry index was 0.445. Hosmer Lemeshow goodness of fit test χ 2=3.581, P=0.893. Internal validation was conducted using the Bootstrap method to resample 1 000 times, and the results showed that the average area under the ROC curve of the prediction model was 0.737 (0.687-0.788) . Conclusions:The risk prediction model for cognitive decline in elderly hospitalized hypertensive patients can predict the risk of cognitive frailty in elderly hospitalized hypertensive patients, which can provide references for medical staff to develop corresponding intervention measures.