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.

[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。

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

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.

Objective:To explore the effect of multidisciplinary comprehensive nursing intervention on skin itching among maintenance hemodialysis (MHD) patients with malignant tumors.Methods:From July 2021 to December 2023, 69 patients with malignant tumors undergoing MHD admitted to the Fourth Affiliated Hospital of Nanjing Medical University were selected as study subjects using convenience sampling. The study subjects were divided into the control group ( n=34) and the observation group ( n=35) using a random number table method. Patients in the control group received routine nursing, while those in the observation group received multidisciplinary comprehensive nursing, and the intervention period was three months for both groups. Visual Analogue Scale (VAS) scores, Pittsburgh Sleep Quality Index (PSQI) scores before and after intervention, and the incidence of skin adverse events after intervention were compared between the two groups. Results:After the intervention, the VAS, PSQI scores, and incidence of skin adverse events in the observation group were lower than those in the control group, and the difference was statistically significant ( P<0.05) . Conclusions:Multidisciplinary comprehensive nursing intervention has a positive effect on alleviating skin itching severity, reducing the incidence of adverse skin events, and improving sleep quality in MHD patients with malignant tumors.

Objective:To analyze whether there are differences in reproductive outcomes between preimplantation genetic testing for aneuploidies (PGT-A) and conventional in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) in patients with recurrent spontaneous abortion (RSA). Methods:A retrospective cohort study was conducted at the Reproductive Center of Sun Yat-sen Memorial Hospital, Sun Yat-sen University, including RSA patients who underwent assisted reproductive technology (ART) between January 2018 and June 2023. Patients were categorized into two groups based on the type of ART, the PGT-A group (78 patients, 100 embryo transfer cycles) and the IVF/ICSI group (95 patients, 105 embryo transfer cycles). Multivariate logistic regression analysis was performed to compare the impact of these two techniques on reproductive outcomes. Further analysis was conducted to evaluate the effects of maternal age, number of miscarriages, and previous chromosomal abnormalities in miscarried embryos on pregnancy outcomes. The primary outcome measure was the live birth rate, while secondary outcomes included the pregnancy rate and the miscarriage rate.Results:The live birth rate in the PGT-A group [50.0% (50/100)] was higher than that in the IVF/ICSI group [37.1% (39/105)], while the miscarriage rate [20.6% (13/63)] was lower than that in the IVF/ICSI group [39.1% (25/64)], with both differences being statistically significant ( P=0.043, P=0.023). Among RSA patients aged 37-45 years with ≥3 miscarriages, the miscarriage rate in the PGT-A group (0%) was significantly lower than that in the IVF/ICSI group [46.2%(6/13), P=0.017], whereas the differences in live birth rate and pregnancy rate between the two groups were not statistically significant (all P>0.05). For RSA patients with previous chromosomal abnormalities in miscarried embryos, the miscarriage rate in the PGT-A group [21.1% (12/57)] was significantly lower than that in the IVF/ICSI group [71.4% (5/7), P=0.012]. Additionally, the pregnancy rate [66.3% (57/86)] and the live birth rate [52.3% (45/86)] in the PGT-A group were significantly higher than those in the IVF/ICSI group [33.3% (7/21), P=0.006; 9.5% (2/21), P<0.001]. Among 37-45 years patients, the miscarriage rate in the PGT-A group [5.9% (1/17)] was significantly lower than that in the IVF/ICSI group [38.7% (12/31), P=0.035], and the live birth rate [57.1% (16/28)] was significantly higher than that in the IVF/ICSI group [31.7% (19/60), P=0.023]. These differences were statistically significant. Conclusion:Compared with conventional IVF/ICSI-assisted reproduction, the use of PGT-A in RSA patients younger than 37 years, with or without a history of chromosomally normal miscarried embryos, did not significantly improve reproductive outcomes, regardless of whether they had experienced more than three miscarriages. However, for RSA patients with chromosomal abnormalities in miscarried embryos, PGT-A significantly reduced the miscarriage rate across the age range of 26-45 years. In RSA patients aged 37-45 years, PGT-A significantly improved reproductive outcomes. However, for patients with two miscarriages and a history of chromosomally normal miscarried embryos, the therapeutic benefit of PGT-A was limited.

Objective To evaluate the efficacy,safety,and economic efficiency of toripalimab therapy for advanced esophageal cancer by rapid health technology assessment(rHTA),so as to provide clinical reference for drug use.Methods PubMed,Embase,Cochrane Library,CNKI,WanFang Data,VIP databases and official websites of health technology assessment institutions were electronically searched to collect high-quality clinical evidence and economic evaluation literature of toripalimab therapy for advanced esophageal cancer from inception to September 30,2025.Two reviewers independently identified studies,extracted data,assessed the quality of included studies,then the results were summarised and analysed using qualitative descriptive methods.Results A total of 18 articles were included,including 9 systematic reviews/Meta-analysis and 9 economic studies.In terms of efficacy,compared with the simple chemotherapy regimen,the combination chemotherapy regimen of toripalimab could significantly prolong the overall survival(OS)and progression free survival(PFS)of patients with advanced esophageal cancer,while improving the objective response rate(ORR)of patients.In terms of safety,there was no significant difference in the incidence of serious adverse events and overall adverse events between combination chemotherapy with toripalimab and chemotherapy alone.Moreover,compared with other immunotherapy combination therapies,the incidence of adverse events in combination chemotherapy with toripalimab was lower.In terms of economy,the combination of toripalimab and chemotherapy not only improves the clinical symptoms of advanced esophageal cancer patients,but also offers economic advantages.Conclusion Toripalimab is effective,safe and economical in the treatment of advanced esophageal cancer.

Objective:To explore the effect of multidisciplinary comprehensive nursing intervention on skin itching among maintenance hemodialysis (MHD) patients with malignant tumors.Methods:From July 2021 to December 2023, 69 patients with malignant tumors undergoing MHD admitted to the Fourth Affiliated Hospital of Nanjing Medical University were selected as study subjects using convenience sampling. The study subjects were divided into the control group ( n=34) and the observation group ( n=35) using a random number table method. Patients in the control group received routine nursing, while those in the observation group received multidisciplinary comprehensive nursing, and the intervention period was three months for both groups. Visual Analogue Scale (VAS) scores, Pittsburgh Sleep Quality Index (PSQI) scores before and after intervention, and the incidence of skin adverse events after intervention were compared between the two groups. Results:After the intervention, the VAS, PSQI scores, and incidence of skin adverse events in the observation group were lower than those in the control group, and the difference was statistically significant ( P<0.05) . Conclusions:Multidisciplinary comprehensive nursing intervention has a positive effect on alleviating skin itching severity, reducing the incidence of adverse skin events, and improving sleep quality in MHD patients with malignant tumors.

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.