OBJECTIVE To evaluate the cost-effectiveness of cefiderocol versus best available therapy （BAT） or standard-of- care （SOC） for the treatment of confirmed or suspected carbapenem-resistant Gram-negative bacterial （CRGNB） serious infections from the perspective of the Chinese healthcare system， and to explore its reasonable pricing. METHODS A decision tree model was constructed based on data from two phase Ⅲ clinical trials （CREDIBLE-CR and GAME CHANGER） to simulate the cost- effectiveness of cefiderocol in two scenarios： salvage therapy for confirmed CRGNB infection （scenario 1） and empirical therapy for suspected CRGNB infection （scenario 2）. The primary outcome measure was the incremental cost-effectiveness ratio （ICER）. The willingness-to-pay （WTP） was set at 1 to 3 times China’s per capita GDP in 2024. To verify the robustness of the results， one- way and probabilistic sensitivity analyses were conducted， and based on these， a reasonable price range for cefiderocol in the Chinese market was explored. RESULTS The results for scenario 1 showed that the clinical cure rate in the cefiderocol group was higher than that in the BAT group （47.50% vs. 34.21%）， but its ICER was 415 065.03 yuan per cured case， exceeding three times China’s GDP per capita. Scenario 2 revealed that the ICER for cefiderocol relative to SOC was as high as 1 362 446.16 yuan per cured case， far exceeding the WTP. Sensitivity analysis indicated that the treatment duration and price of cefiderocol were key factors affecting its cost-effectiveness. In the two scenarios described above， the unit price of cefiderocol must fall below 683.47 and 242.00 yuan/g， respectively， to be considered cost-effective. CONCLUSIONS Based on the current market price， cefiderocol lacks sufficient cost-effectiveness for treating confirmed or suspected CRGNB serious infections within China’s healthcare system. To improve its accessibility， price negotiations or a tiered medical insurance payment strategy are required.

OBJECTIVE To evaluate the efficacy， safety and cost-effectiveness of serplulimab as a first-line treatment of small- cell lung cancer （SCLC）， and provide an evidence-based basis for drug selection in hospitals. METHODS Rapid health technology assessment was adopted； PubMed， Cochrane Library， Embase， CNKI， Wanfang， VIP and official websites of domestic and international health technology assessment agencies were systematically searched from the inception to Oct. 2024. Two reviewers independently screened the literature， assessed the quality of included studies and carried out the qualitative analysis according to the inclusion and exclusion criteria. RESULTS A total of 13 systematic reviews/meta-analyses and 9 economic studies were included， and the literature quality was generally good. In terms of effectiveness， compared with chemotherapy alone， serplulimab combined with chemotherapy significantly improved progression-free survival， overall survival， and objective response rate in patients with SCLC. In terms of safety， serplulimab combined with chemotherapy showed no significant difference in the incidence of ≥3 grade adverse events compared with chemotherapy alone in the treatment of SCLC， indicating a good safety profile； compared with combination therapies involving other immunosuppressive agents， the incidence rate of adverse events was also lower. In terms of cost-effectiveness， compared with chemotherapy alone， serplulimab combined with chemotherapy is not cost- effective， which may be related to the high price of serplulimab. CONCLUSIONS Serplulimab is effective and safe in the treatment of SCLC， but has no obvious advantage in terms of cost-effectiveness.

Objective To explore the effects of CDP-diacylglycerol synthase 1(CDS1)on autophagy and amyloid deposition in hippocampal neurons of mice and the related mechanism.Methods Congo red and immunohistochemical staining were used to observe the amyloid deposition in hippocampus of amyloid precursor protein(APP)/presenilin 1(PS1)double-transgenic mice.Lentivirus-mediated overexpression of APP was induced in HT22 cells,and Congo red staining was used to observe the amyloid deposition in HT22 cells.The protein expression levels of microtubule-associated protein 1 light chain 3(LC3)-Ⅱ and P62 in the hippocampus of APP/PS1 double-transgenic mice and APP-overexpressed HT22 cells were detected by Western blotting.The differential protein CDS1 was screened based on the hippocampal proteomics results of APP/PS1 double-transgenic mice.The expression of CDS1 protein in hippocampal tissue of APP/PS1 transgenic mice and APP-overexpressed HT22 cells was detected by Western blotting.After lentivirus-mediated APP overexpression in HT22 cells,CDS1 was overexpressed,and the protein expression levels of LC3-Ⅱ and P62 were detected by Western blotting.Results β-amyloid protein(Aβ)was deposited in the hippocampus of APP/PS1 mice and in HT22 cells overexpressing APP.The levels of LC3-Ⅱ and P62 protein in the hippocampus of APP/PS1 double-transgenic mice and APP-overexpressed HT22 cells were significantly increased.A differential metabolic pathway,glycerophospholipid metabolic pathway,was screened by Kyoto Encyclopedia of Genes and Genomes pathway analysis in the proteomic results of APP/PS1 double-transgenic mice,and the differential protein CDS1 was obtained.Compared with wild-type C57BL/6 mice,APP/PS1 double-transgenic mice exhibited a significantly decrease in CDS1 protein expression in the hippocampus(0.46±0.07 vs 1.00±0.25,P＜0.01).Similarly,lentivirus-mediated overexpression of APP in HT22 cells resulted in decreased CDS1 protein levels compared to cells infected with empty viral vector controls(0.68±0.18 vs 1.00±0.13,P＜0.01).The autophagy flow of nerve cells was significantly restored after the CDS1 overexpression in APP-overexpressed HT22 cells(LC3-Ⅱ:1.00±0.15 vs 0.21±0.05,P＜0.01;P62:1.00±0.16 vs 0.67±0.10,P＜0.01),and Aβ deposition was significantly decreased.Conclusion Downregulation of CDS1 expression can induce dysfusion of autophagosome and lysosome,promoting amyloid deposition in hippocampus of mice with Alzheimer's disease.

Periodontal bone defects, primarily caused by periodontitis, are highly prevalent in clinical settings and manifest as bone fenestration, dehiscence, or attachment loss, presenting a significant challenge to oral health. In regenerative medicine, harnessing developmental principles for tissue repair offers promising therapeutic potential. Of particular interest is the condensation of progenitor cells, an essential event in organogenesis that has inspired clinically effective cell aggregation approaches in dental regeneration. However, the precise cellular coordination mechanisms during condensation and regeneration remain elusive. Here, taking the tooth as a model organ, we employed single-cell RNA sequencing to dissect the cellular composition and heterogeneity of human dental follicle and dental papilla, revealing a distinct Platelet-derived growth factor receptor alpha (PDGFRA) mesenchymal stem/stromal cell (MSC) population with remarkable odontogenic potential. Interestingly, a reciprocal paracrine interaction between PDGFRA⁺ dental follicle stem cells (DFSCs) and CD31⁺ Endomucin⁺ endothelial cells (ECs) was mediated by Vascular endothelial growth factor A (VEGFA) and Platelet-derived growth factor subunit BB (PDGFBB). This crosstalk not only maintains the functionality of PDGFRA⁺ DFSCs but also drives specialized angiogenesis. In vivo periodontal bone regeneration experiments further reveal that communication between PDGFRA⁺ DFSC aggregates and recipient ECs is essential for effective angiogenic-osteogenic coupling and rapid tissue repair. Collectively, our results unravel the importance of MSC-EC crosstalk mediated by the VEGFA and PDGFBB-PDGFRA reciprocal signaling in orchestrating angiogenesis and osteogenesis. These findings not only establish a framework for deciphering and promoting periodontal bone regeneration in potential clinical applications but also offer insights for future therapeutic strategies in dental or broader regenerative medicine.
Receptor, Platelet-Derived Growth Factor alpha/metabolism* ; Humans ; Neovascularization, Physiologic/physiology* ; Dental Sac/cytology* ; Single-Cell Analysis ; Transcriptome ; Mesenchymal Stem Cells/metabolism* ; Bone Regeneration ; Animals ; Dental Papilla/cytology* ; Periodontium/physiology* ; Stem Cells/metabolism* ; Regeneration ; Angiogenesis

[摘 要] 目的：探讨白蛋白结合型紫杉醇联合PD-1抑制剂用于治疗一线化疗失败的骨与软组织肉瘤的疗效及安全性。方法：回顾性分析北京积水潭医院骨肿瘤科2017年8月至2020年8月收治的一线化疗失败的晚期骨与软组织肉瘤患者。患者接受白蛋白结合型紫杉醇（125~140 mg/m2，第1天和第8天）与PD-1抑制剂（信迪利单抗或特瑞普利单抗，每21 d一次）联合治疗。每2个治疗周期评估1次疗效，按RECIST 1.1标准评估肿瘤疗效，按NCI-CTCAE5.0标准评估不良反应。结果：共20名患者纳入研究，完成1至8个治疗周期，中位治疗周期数为3个。所有患者均可评估疗效，完全缓解4例（20%），部分缓解0例，稳定9例（45%），疾病进展7例（35%）。客观缓解率（ORR）为20%，疾病控制率（DCR）为65%。中位无进展生存期（PFS）为3.0个月。治疗期间主要不良反应包括2级白细胞减少（40%）、1-2级神经毒性反应（20%），以及2级甲状腺功能减退（10%）。结论：白蛋白结合型紫杉醇联合PD-1抑制剂治疗为一线化疗失败的晚期骨与软组织肉瘤患者提供了一种潜在的治疗选择，其不良反应可控，值得开展更大样本的前瞻性研究进一步验证其疗效。

Objective:To investigate the clinical efficacy of liquid nitrogen cryopreservation and reimplantation versus allograft reconstruction in patients underwent resection of primary malignant bone tumors of the long bones of the extremities.Methods:A retrospective analysis was conducted on 144 patients who underwent resection of primary malignant bone tumors of the long bones of the extremities followed by either liquid nitrogen cryopreservation and reimplantation or massive allografts reconstruction at the Beijing Jishuitan Hospital affiliated with Capital Medical University from January 2012 to July 2023. The study included 82 males and 62 females, with an average age of 23.8±12.3 years (range, 6-64 years). Patients were divided into two groups based on the reconstruction method: the cryopreservation and reimplantation group (72 cases) and the allograft group (72 cases). The following outcomes were recorded during follow-up: local tumor recurrence, bone union, union time, graft survival, and reasons for graft removal. Graft-related complications were recorded using the modified Henderson classification system of the International Limb Salvage Association. Limb function was assessed at the last follow-up using the Musculoskeletal Tumor Society score (MSTS-93).Results:All patients completed surgery and were followed up for a mean of 60.2±32.1 months (range, 12-149 months). At the last follow-up, 24 patients were dead from the tumor, 16 patients survived with the tumor (2 cases of local recurrence and 14 cases of distant metastasis), and 104 patients survived without the tumor. The bone union rate and union time in cryopreservation and reimplantation group were 90% (65/72) and 9.6±4.8 months, respectively, which was significantly superior to those in allograft group [68% (49/72) and 15.9±6.7 months, P<0.05]. The 5-year overall graft survival rate was 86.8% [95% CI (80.1%, 95.7%)] in cryopreservation and reimplantation group, higher than 73.2% [95% CI(68.4%, 84.5%)] in allograft group significantly (χ 2=7.122, P=0.017). The rates of graft removal due to non-union and infection in the cryopreservation and reimplantation group were 0% (0/72) and 1.4% (1/72), respectively, which were significantly lower than those in the allograft group [5.6% (4/72) and 9.7% (7/72), P<0.05]. Overall, 48.6% (70/144) of patients experienced at least one graft-related complication, with a complication rate of 33.3% in cryopreservation and reimplantation group, lower than the 61.1% in allograft group significantly (χ 2=11.146, P<0.001). The complications with the highest incidence rate were nonunion (20.8%, 30/144), followed by structural failure (17.4%, 25/144), tumor progression (10.4%, 15/144), infection (10.4%, 15/144), and soft tissue failure (5.6%, 8/144). The incidence rates of the atrophic non-union and the structural failure of grafts were 9.7% (7/72) and 1.4% (1/72) respectively in the cryopreservation and reimplantation group, which were significantly lower compared to the allograft group [29.2% (21/72) and 13.9% (10/72), P<0.05]. At the last follow-up, the MSTS-93 score was 89.7%±8.3% in the cryopreservation and reimplantation group, and 87.6%±7.5% in the allograft group, with no statistically significant difference ( t=0.326, P=0.542). Conclusion:Compared with allograft reconstruction, autologous inactivated bone grafting demonstrated superior bone union efficiency and fewer complications, it may be considered for reconstruction in cases whose tumor bone is not severely osteolytic or pathologically fractured.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Liver diseases have a high prevalence rate worldwide with relatively poor long-term clinical outcomes and have become one of the leading causes of disease burden and death around the world,which poses significant challenges to public health.Eosinophils(Eos)are a class of highly conserved multifunctional immune cells that play critical effector roles in allergic diseases.In recent years,an increasing amount of evidence has shown that Eos plays an important role in the pathogenesis of liver diseases,exerting a protective or harmful effect in different liver diseases,which has become a research hotspot in this field.This article elaborates on the role and potential mechanism of action of Eos in liver diseases,in order to provide a new perspective for in-depth research on the pathogenesis of liver diseases and lay the foundation for developing therapeutic strategies targeting Eos.

Objective To evaluate the efficacy,safety and economy of sugemalimab in the first-line treatment of non-small cell lung cancer(NSCLC)by rapid health technology assessment.Methods PubMed,Cochrane Library,Embase,CNKI,WanFang Data,VIP and official websites of health technology assessment(HTA)institutions were systematically searched to collect HTA reports,systematic reviews/Meta-analysis and pharmacoeconomic studies of sugemalimab in first-line treatment of NSCLC from inception to October 31,2024.Two reviewers independently screened the literature,extracted information and performed quality assessment of the included studies,and then performed descriptive analysis on the results.Results A total of 15 articles were selected,including 4 systematic reviews/Meta-analysis and 11 pharmacoeconomic studies.In terms of effectiveness,compared with chemotherapy alone,sugemalimab combined with chemotherapy significantly improved progression-free survival(PFS),overall survival(OS),and objective response rate(ORR)in patients with NSCLC.In terms of safety,compared with chemotherapy alone,sugemalimab combined chemotherapy had higher incidence of overall adverse events,but it had a better safety profile compared to other immune combination therapies.In terms of economy,most studies suggested that compared with chemotherapy alone,sugemalimab combined with chemotherapy was not cost-effective,which may be related to the high price of sugemalimab.However,a few studies indicated that sugemalimab combined with chemotherapy could be cost-effective in specific scenarios.Conclusion Sugemalimab has good efficacy in the first-line treatment of NSCLC,but its safety and economy need to be further studied.

Objective To investigate the mediating role of anxiety and depression in social sup-port and burnout among primary caregivers of stroke patients.Methods A convenience sampling method was employed to select 506 primary caregivers of stroke patients as research subjects.The Gen-eral Information Questionnaire,Caregiver Burnout Inventory for Stroke Patients,Multidimensional Scale of Perceived Social Support,and Hospital Anxiety and Depression Scale were used for data col-lection.Results The total scores for caregiver burnout,social support,anxiety,and depression a-mong primarycaregivers of stroke patients were(72.83±14.32),(47.79±7.74),(10.49±3.00),and(10.45±3.06),respectively.Correlation analysis revealed a negative correlation between caregiver burnout and social support(r=-0.245,P＜0.001),and positive correlations with anxiety and depression(r=0.178,0.216,P＜0.001).Anxiety and depression partially media-ted the relationship between social support and caregiver burnout,accounting for 7.9％and 10.7％of the total effect,respectively.Conclusion Social support,anxiety,depression,and burnout are closely interrelated.Social support can directly or indirectly influence the occurrence of burnoutthrough anxiety and depression.Medical staff should pay attention to the anxiety and depression status of primary caregivers of stroke patients and enhance social support levels to reduce the incidence of burnout by alleviating anxiety and depression.