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.

[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 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.

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.

The mild-natured and bitter-flavored traditional Chinese medicines (MB-TCMs) are an important class of TCMs that have been widely used in clinical practice and recognized as safe long-term treatments for chronic diseases. However, as an important class of TCMs, the panorama of pharmacological effects and the mechanisms of MB-TCMs have not been systemically reviewed. Compelling studies have shown that gut microbiota can mediate the therapeutic activity of TCMs and help to elucidate the core principles of TCM medicinal theory. In this systematic review, we found that MB-TCMs commonly participated in the modulation of metabolic syndrome, intestinal inflammation, nervous system disease and cardiovascular system disease in association with promoting the growth of beneficial bacteria Bacteroides, Akkermansia, Lactobacillus, Bifidobacterium, Roseburia as well as inhibiting the proliferation of harmful bacteria Helicobacter, Enterococcus, Desulfovibrio and Escherichia-Shigella. These alterations, correspondingly, enhance the generation of protective metabolites, mainly including short-chain fatty acids (SCFAs), bile acid (BAs), 5-hydroxytryptamine (5-HT), indole and gamma-aminobutyric acid (GABA), and inhibit the generation of harmful metabolites, such as proinflammatory factors trimethylamine oxide (TAMO) and lipopolysaccharide (LPS), to further exert multiplicative effects for the maintenance of human health through several different signaling pathways. Altogether, this present review has attempted to comprehensively summarize the relationship between MB-TCMs and gut microbiota by establishing the TCMs-gut microbiota-metabolite-signaling pathway-diseases axis, which may provide new insight into the study of TCM medicinal theories and their clinical applications.

Objective:To analyze the disease characteristics of aspiration pneumonia and its risk factors.Methods:In this retrospective case-control study, analysis was conducted on data from 92 patients aged ≥ 60 years admitted to Beijing Jishuitan Hospital, Capital Medical University between June 1, 2018 and July 31, 2022, with aspiration pneumonia(AsP) as the primary diagnosis at the time of hospital discharge and from non-AsP patients admitted during the same period.The number of participants was matched at a 1∶1 ratio.Results:The average age of the AsP group was(80.88 ± 9.41) years and 57(62.0%) were men.The average age of the control group was(77.74 ± 10.98) years and 52(56.5%) were men.There was no statistically significant difference in age and sex ratio(age: t=1.973, P=0.060; sex ratio: χ2=0.661, P=0.416).Univariate analysis showed that, at admission, body mass index(BMI) and activities of daily living(ADL) scores of the AsP group were lower than those of the non-AsP group, the proportions of patients with gastroesophageal reflux disease, acute trauma, cerebrovascular disease, history of cerebral infarction/hemorrhage and sequelae of cerebrovascular disease were higher than those of the non-AsP group(all P<0.05), and the proportions of patients receiving feeding via indwelling nasogastric intubation and tracheal intubation were also higher in the AsP group(all P<0.05).The white blood cell count, the percentage of neutrophils and the procalcitonin level in the first round of tests were higher in the AsP group than those in the non-AsP group and the maximum values of the above parameters during hospitalization were also higher than those in non-AsP patients, while the levels of albumin and prealbumin were lower than those in the non-AsP group( P<0.05 for all).Chest CT showed that 83.7%(77/92) of patients with AsP had bilateral pneumonia, higher than 55.4%(51/92) in the non-AsP group( χ2=8.569, P=0.014).Multivariate Logistic regression analysis showed that male sex( OR=16.206, 95% CI: 1.268-207.191, P=0.032) was a risk factor for AsP, and BMI( OR=0.747, 95% CI: 0.582-0.959, P=0.022) and ADL score at admission( OR=0.945, 95% CI: 0.903-0.988, P=0.014) were protective factors against AsP.ADL score at admission( OR=0.951, 95% CI: 0.907-0.982, P=0.043), tumor history( OR=6.859, 95% CI: 1.484-31.700, P=0.014), history of cerebral infarction/intracerebral hemorrhage( OR=4.368, 95% CI: 1.087-17.511, P=0.038), history of chronic renal insufficiency( OR=5.820, 95% CI: 1.445-23.440, P=0.013), acute respiratory failure( OR=5.281, 95% CI: 1.237-22.545, P=0.013) and myocardial infarction( OR=9.466, 95% CI: 2.151-41.660, P=0.003) were independent factors affecting the prognosis of pneumonia in the elderly. Conclusions:Aspiration pneumonia in the elderly is more common in men and in individuals with low BMI and low ADL scores.There is no increased risk of mortality in people with AsP, compared with people without AsP, but some risk factors in AsP patients may lead to poor prognosis, calling for increased awareness and early intervention in clinical practice.

Objective To investigate the risk factors and independent risk factors associated with papillary thyroid carcinoma(PTC)cervical lymph node metastasis,and to assess the predictive efficacy of independent risk factors on metastatic lymph nodes.Methods Clinical and ultrasonographic data of 279 patients with PTC were collected,and the patients were divided into two groups according to the presence of cervical lymph node metastasis based on postoperative pathology,and the relevant characteristics of the two groups were ana-lyzed to explore the risk factors and independent risk factors associated with cervical lymph node metastasis in PTC,and the predictive ef-ficacy of independent risk factors on cervical metastatic lymph nodes was compared by receiver operating characteristic(ROC)curves.Results Age,gender and the maximum diameter,border,shape,microcalcifications,and distance from the thyroid capsule of cancer nodes were risk factors for cervical lymph node metastasis in both groups(P＜0.05);male,maximum diameter of cancer nodes 10mm,microcalcifications,and distance from the thyroid capsule ≤2mm were independent risk factors for cervical lymph node metastasis in PTC(P＜0.05);the AUC of the combination of four independent risk factors was 0.785(95％CI:0.721-0.849,P＜0.05),with the highest efficacy in predicting cervical lymph node metastasis.Conclusion Male,maximum diameter of cancer nodes ≥10mm,mi-crocalcifications,and distance from the thyroid capsule ≤2mm were independent risk factors for cervical lymph node metastasis of PTC,and the combination of four independent risk factors could assist in assessing the risk of cervical lymph node metastasis of PTC and improve patient prognosis.

Objective:To analyze the immune microenvironment characteristics of human dental follicle tissues from the third molars and to explore the mutual communication and the effects of innate immune cells and adaptive immune cells within the dental follicle.Methods:Sequencing data(GSA-Human:HRA008022)in the GSA database were analyzed.Bioinformatics tools were employed for gene identification and GO enrichment analysis was performed to define the biological function of innate and adaptive immune cells.CellChat analysis was used for explaining intercellular communication among immune cell populations.Results:Using t-SNE dimen-sionality reduction analysis for immune cell populations,innate immune cell populations were obtained,including innate lymphoid cells,dendritic cells,mast cells and macrophages,and adaptive immune cell populations including T cells and B cells.Pearson corre-lation analysis showed that innate immune cells,specifically innate lymphoid cells and macrophages,had a strong correlation with adap-tive immune cell populations.GO enrichment analysis revealed mutual coordination among innate immune cell populations and regulato-ry effects on adaptive immune cell populations.Further CellChat analysis indicated biological signal transmission between innate and a-daptive immune cell populations,with CLEC,MIF,ADGRE5,COLLAGEN and MIF signaling pathways is the most significant.Con-clusion:Dental follicle tissues are rich in immune cells and innate immune cell populations interact with adaptive immune cells to regulate immune responses and participate in maintaining the homeostasis of dental follicle.