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 value of MRI subtraction technique(ST)for evaluating the efficacy of systemic therapy for advanced hepatocellular carcinoma(HCC)and predicting prognosis after combining with surgery.Methods Totally 35 patients with 39 HCC lesions who received systemic therapy+radical resection were retrospectively collected.Based on preoperative MRI,tumor activity ratio(recorded as tumor activityST)was obtained with ST,while tumor activity value(recorded as tumor activitypathology)was obtained through postoperative pathology,and their correlation was analyzed.The patients were regularly followed up after surgery,and the survival data were recorded.Receiver operating characteristic(ROC)curve was drawn to evaluate the efficacy of tumor activityST for predicting patients'survival status.Then the patients were divided into survival benefit group and no survival benefit group according to the cut-off value,and survival analysis was conducted.Results Tumor activityST was positively correlated with tumor activitypathology(r=0.900,P＜0.001).The median follow-up time was 32.93 months,during which 8 patients died,and the median survival time was 29.9 months.The area under the curve(AUC)of tumor activityST for predicting patients'survival status was 0.67,and the cut-off value was 0.36.Thirty patients with tumor activityST＜0.36 were enrolled in survival benefit group,while 5 patients≥0.36 were collected in no survival benefit group.The overall survival in survival benefit group was longer than that in no survival benefit group(P＜0.001).Conclusion MRI ST could be used to non-invasively evaluate the efficacy of systemic therapy for advanced HCC and predict prognosis after combining with surgery.

S100a8 and S100a9 protein are important members of the S100 protein family.It can induce inflammation by acti-vating intracellular signal cascade,and its strong calcium binding ability makes it play an important role in regulating cell contraction.It has been reported that S100a8 and S100a9 could not only regulate asthmatic airway inflammation,but also have a protective effect on asthmatic airway hyperresponsiveness.This article intends to review the role of S100a8 and S100a9 proteins in airway inflammation and airway hyperresponsiveness in asthma,so as to provide new ideas for the research and prevention of asthma.

To formulate an expert consensus on the principles of preoperative hair removal and provide scientific guidance for standardized removal of hair before surgical procedures so as to reduce the incidence of surgical site infections.METHODS Led by the Hospital Management Institute of National Health Commission of the People's Republic of China,this consensus was reached with the joint efforts from the expects of relevant fields such as surgeries,interventional therapies,nursing,and infection prevention and control.The consensus facilitates the classification and evaluation of literatures by following the evidence grade formulated by Oxford Evidence-based Medicine Center and focuses on the association of preoperative hair removal with surgical site infection,it reaches the evidence grade of expert consensus and recommendation intensity by integrating with discussions on meetings and clinical experience of the expects from relevant fields.RESULTS A total of 6 items of consensus were reached by summarizing the latest evidence on the aspects including the indications for preoperative hair removal,tools,range,timing and places.CONCLUSION The consensus,to some extent,make supplements to and complete the exiting regulations and standards.It provides guidance for the medical institutions to carry out the preoperative hair removal.

Objective:To explore the influencing factors of self-management of first-treatment pulmonary tuberculosis patients based on the random forest model, and to provide a theoretical basis for clinical staff to improve the self-management of pulmonary tuberculosis patients by providing efficient, high-quality, and individualized interventions.Methods:A cross-sectional study was used to select pulmonary tuberculosis patients who were hospitalized in the Department of Respiratory Medicine of the Fourth People′s Hospital of the Ningxia Hui Autonomous Region and who met the inclusion and exclusion criteria from December 2023 to February 2024 by using the convenience sampling method as the study subjects. General information questionnaire, Chronic Disease Patients′ Self-health Management Ability Assessment Scale, Perceived Social Support Scale, Hospital Anxiety and Depression Scale, and a tuberculosis prevention and treatment knowledge questionnaire were used to conduct the survey, and Spearman′s correlation was used to analyze the correlation between variables, and multivariate linear regression and a random forest model were used to analyze the influencing factors of self-management.Results:A total of 204 first-treatment pulmonary tuberculosis patients, 111 males and 93 females, 64 patients aged 18-44 years, 59 patients aged 45-59 years, and 81 patients ≥60 years were finally investigated. The total self-management score of tuberculosis patients was 162.00 (148.00, 176.75), and the total self-management score was positively correlated with the total perceived social support score, family support, friend support, and other support, respectively ( r values were 0.307-0.400, all P<0.01), negatively correlated with the anxiety and depression scores, respectively ( r=-0.195, -0.313, both P<0.01), and positively correlated with the total score of knowledge of tuberculosis control ( r=0.257, P<0.01); the results of multiple linear stepwise regression analysis showed that literacy, family support, other support, anxiety, and knowledge of tuberculosis control were the influencing factors of self-management ability ( t values were -2.89-2.98, all P<0.05), which explained a total of 23.1% of the total variance; and the random forest model ranked the importance of the influencing factors in the order of high to low were other support, family support, knowledge of tuberculosis control, literacy, and anxiety. Conclusions:The self-management of first-treatment pulmonary tuberculosis patients is at an intermediate level, In order to improve the self-management ability of first-treatment pulmonary tuberculosis patients, clinical personnel should establish a "patient-centered" self-management education concept, pay attention to the construction of their social support system, provide adequate, continuous, individualized knowledge education and information support, promote their psychological health, and reduce their negative emotions.

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.