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.

Hematologic malignancies, including leukemia, lymphoma, and multiple myeloma, are hazardous diseases characterized by the uncontrolled proliferation of cancer cells. Dysregulated cell cycle resulting from genetic and epigenetic abnormalities constitutes one of the central events. Importantly, cyclin-dependent kinases (CDKs), complexed with their functional partner cyclins, play dominating roles in cell cycle control. Yet, efforts in translating CDK inhibitors into clinical benefits have demonstrated disappointing outcomes. Recently, mounting evidence highlights the emerging significance of WEE1 G2 checkpoint kinase (WEE1) to modulate CDK activity, and correspondingly, a variety of therapeutic inhibitors have been developed to achieve clinical benefits. Thus, WEE1 may become a promising target to modulate the abnormal cell cycle. However, its function in hematologic diseases remains poorly elucidated. In this review, focusing on hematologic malignancies, we describe the biological structure of WEE1, emphasize the latest reported function of WEE1 in the carcinogenesis, progression, as well as prognosis, and finally summarize the therapeutic strategies by targeting WEE1.
Humans ; Protein-Tyrosine Kinases/physiology* ; Hematologic Neoplasms/drug therapy* ; Cell Cycle Proteins/antagonists & inhibitors* ; Nuclear Proteins/antagonists & inhibitors* ; Cyclin-Dependent Kinases ; Molecular Targeted Therapy ; Animals

BACKGROUND: It is inaccurate to reflect the level of dust exposure through working years. Furthermore, identifying a predictive indicator for lung function decline is significant for coal miners. The study aimed to explored whether club cell secretory protein (CC16) levels can reflect early lung function changes. METHODS: The cumulative respiratory dust exposure (CDE) levels of 1,461 coal miners were retrospectively assessed by constructed a job-exposure matrix to replace working years. Important factors affecting lung function and CC16 were selected by establishing random forest models. Subsequently, the potential of CC16 to reflect lung injury was explored from multiple perspectives. First, restricted cubic spline (RCS) models were used to compare the trends of changes in lung function indicators and plasma CC16 levels after dust exposure. Then mediating analysis was performed to investigate the role of CC16 in the association between dust exposure and lung function decline. Finally, the association between baseline CC16 levels and follow-up lung function was explored. RESULTS: The median CDE were 35.13 mg/m³-years. RCS models revealed a rapid decline in forced vital capacity (FVC), forced expiratory volume in the first second (FEV₁), and their percentages of predicted values when CDE exceeded 25 mg/m³-years. The dust exposure level (<5 mg/m³-years) causing significant changes in CC16 was much lower than the level (25 mg/m³-years) that caused changes in lung function indicators. CC16 mediated 11.1% to 26.0% of dust-related lung function decline. Additionally, workers with low baseline CC16 levels experienced greater reductions in lung function in the future. CONCLUSIONS CC16 levels are more sensitive than lung indicators in reflecting early lung function injury and plays mediating role in lung function decline induced by dust exposure. Low baseline CC16 levels predict poor future lung function.
Uteroglobin/blood* ; Humans ; Dust/analysis* ; Occupational Exposure/analysis* ; Male ; Middle Aged ; Adult ; Retrospective Studies ; Lung Injury/chemically induced* ; Coal Mining ; Biomarkers/blood* ; China/epidemiology* ; Air Pollutants, Occupational ; Female

Radiochemotherapy-induced oral mucositis (OM) is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy. Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment. To date, differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties, which has increased the uncertainty of treatment effects. On the basis of current research evidence, this expert consensus outlines risk factors, clinical manifestations, clinical grading, ancillary examinations, diagnostic basis, prevention and treatment strategies and efficacy indicators for OM. In addition to strategies such as basic oral care, anti-inflammatory and analgesic agents, anti-infective agents, pro-healing agents, and photobiotherapy recommended in previous guidelines, we also emphasize the role of traditional Chinese medicine in OM prevention and treatment. This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention, diagnosis, and treatment, standardizing clinical practice, reducing OM occurrence, promoting healing, and improving the quality of life of patients.
Humans ; Chemoradiotherapy/adverse effects* ; Consensus ; Risk Factors ; Stomatitis/etiology*

Sutureless scleral fixation of posterior chamber intraocular lens(SSF-PCIOL)is a technique mainly employed for the implantation and fixation of intraocular lens(IOL)when there is insufficient support from the crystalline lens capsule.In terms of clinical effects,SSF-PCIOL offers the advantages of improved visual quality and enhanced IOL stability in the patients.The surgical technique for SSF-PCIOL has evolved from the transvitreal scleral fixation approach,to the fibrin glue assisted approach,and then to the transconjunctival approach.The types of IOL available for clinical use have also shifted from traditional three-piece designs to specialized IOL designed for scleral fixation.SSF-PCIOL can be carried out in combination with other ophthalmic procedures and advanced auxiliary equipment to increase the precision of surgical procedures and the objectivity of outcome assessments while minimizing surgical trauma in the patients and ensuring surgical outcomes.This review discusses the evolution of SSF-PCIOL techniques,the characteristics of available IOL types,the synergistic application of combined procedures and auxiliary equipment,and the comprehensive evaluation of clinical outcomes,with the aim of providing clinical evidence for further refinement of the technique and offering references for surgical options for the patients with insufficient crystalline lens capsule support.

Objective To investigate the status quo of indwelling needles use in the hospitals at all lev-els in Chongqing city,and to evaluate the normalization and safety of indwelling needles use by referring to Nursing Practice Standards for Intravenous Therapy.Methods A self-designed questionnaire was used in July 2023 to conduct a cross-sectional survey on the use of indwelling needles in the hospitals at all levels in Chongqing city.Results A total of 30 807 patients in 77 hospitals were included,among them 62.67%used indwelling needles.The closed type indwelling needles accounted for 88.87%and the safety type indwelling needles accounted for 41.74%.Non-needle infusion connectors accounted for 37.78%,and steel needle con-nected with heparin caps accounted for 51.69%.95.66%of puncture site was in the upper limb,the non-cor-rosive drug infusion accounted for 87.57%,and the complications occurrence rate was 2.46%.Among the 6 419 surveyed nurses,75.51%removed indwelling needles based on clinical indications.There were statistically significant differences in the usage rates of closed type indwelling needles and non-needle infusion connectors among hospitals at different levels(P<0.05).There were also statistically significant differences in the inci-dence rates of complication and phlebitis(P<0.05).Conclusion The overall application of indwelling needles in the hospitals at all levels in Chongqing city is generally standardized,but the use of safety type indwelling needles and needle-free infusion connectors still needs to be improved.

Lipopolysaccharides (LPS) are major outer membrane components of Gram-negative bacteria. Unlike most Gram-negative bacteria, Acinetobacter baumannii can still survive and acquire polymyxin resistance after complete loss of LPS. Previous studies of LPS-deficient Acinetobacter baumannii mostly focused on LPS-deficient strains induced by polymyxin, whose background was complex and unstable. To investigate LPS loss-mediated polymyxin resistant-Acinetobacter baumannii, this study constructed a stable and clear background LPS-deficient strain by knocking out lpxC gene in Acinetobacter baumannii ATCC 19606 with CIRSPR/Cas9, and then studied the phenotypic changes of the lpxC-deficient strain including morphology, growth rate, antibiotic susceptibility, virulence, membrane permeability, and membrane potential. Animal experiments were approved by the Animal Care and Welfare Committee Institute of Medicinal Biotechnology, CAMS and PUMC (approval number: IMB-20240119D₉). The results indicated that the lpxC gene of Acinetobacter baumannii ATCC 19606 was successfully knocked out. After losing the lpxC, the strain underwent the morphological change from rod-shaped to spherical. Furthermore, it leads to reduced growth rate, enhanced membrane permeability, decreased membrane potential, lower virulence, and increased antibiotic susceptibility to β-lactams, quinolones, aminoglycosides, macrolides, glycopeptides. The lpxC deletion results in significant changes in membrane homeostasis and adaptability of Acinetobacter baumannii. Understanding the phenotypic changes of colistin-resistant Acinetobacter baumannii mediated by LPS loss is useful for exploring the resistance mechanism of Acinetobacter baumannii and developing new therapeutic strategies.

Objective:To evaluate the effects of pulmonary embolism response team (PERT) on the quality of care and clinical outcomes in patients with acute pulmonary embolism.Methods:This was a single-center retrospective cohort study. Patients with acute pulmonary embolism treated in Beijing Anzhen Hospital Affiliated to Capital Medical University from July 5, 2016 to July 4, 2018 were enrolled. Patients with acute pulmonary embolism who had traditional care from July 5, 2016 to July 4, 2017 (before the implementation of PERT) were classified as PERT pre-intervention group. Patients with acute pulmonary embolism who started PERT care from July 5, 2017 to July 4, 2018 were divided into the PERT intervention group. The diagnosis and treatment information of patients was collected through the electronic medical record system, and the quality of care (time from visit to hospitalization, time from hospitalization to anticoagulation initiation, time from visit to definitive diagnosis, total hospital stay, time in intensive care unit (ICU), hospitalization cost) and clinical outcomes (in-hospital mortality and incidence of bleeding) were compared between the two groups.Results:A total of 210 patients with acute pulmonary embolism, aged (63.3±13.7) years old, with 102 (48.6%) female patients were included. There were 108 cases in PERT pre-intervention group and 102 cases in PERT intervention group. (1) Quality of diagnosis and treatment: there was a statistical significance between the two groups in the distribution of time from diagnosis to definitive diagnosis ( P=0.002). Among them, the rate of completion of diagnosis within 24 hours after PERT intervention was higher than that before PERT intervention (80.4% (45/56) vs. 50.0% (34/68), P<0.001). The time from treatment to hospitalization was shorter than that before PERT intervention (180.0 (60.0, 645.0) min vs. 900.0 (298.0, 1 806.5) min, P<0.001). The total length of hospital stay was less than that before PERT intervention (12 (10, 14) d vs. 14 (11, 16) d, P=0.001). There was no statistical significance in the time from hospitalization to anticoagulant therapy, the length of ICU stay and hospitalization cost between the two groups (all P>0.05). (2) Clinical outcomes during hospitalization: There was no statistical significance in the incidence of hemorrhage and mortality between the two groups during hospitalization (both P>0.05). Conclusion:PERT has improved the efficiency of diagnosis and treatment of patients with acute pulmonary embolism and significantly shortened the total hospital stay, but its impact on clinical outcomes still needs further study.