The research and development of innovative drug have progressed remarkably, but the long development circle and high failure rate have become the bottleneck. Drug repurposing, discovering new indications of approved drugs, is a strategy to overcome these obstacles. By exploring new indications for approved drugs, rapid progress has been made in basic research and clinical translation in recent years. Rich resources of drugs, proven security, efficient development workflow and reduced cost are core advantages of this strategy, making the strategy a crucial direction of optimizing the pipeline of drug research and development. This review systematically summarizes drug repurposing cases that have received clinical approval over the past five years, and proposes core strategies for drug repurposing, including approaches based on targets, pathways, drug similarity, post-treatment phenotypes, and clinical side effects, aiming to provide some strategic guidance for drug repurposing efforts.

With the accelerating trend of population aging, the number of elderly patients with lung cancer continues to rise, and the disease burden is becoming increasingly heavy. The clinical management of these patients faces severe challenges due to their decreased physiological reserve, complex comorbidities, and significant individual heterogeneity. Consequently, under traditional diagnosis and treatment models, doctors often struggle to identify the individualized risks of elderly patients in a timely and comprehensive manner, which can easily lead to decision biases such as undertreatment or overtreatment. In view of this, this study advocates for the establishment of an umbrella decision-making model specifically tailored for elderly lung cancer patients. Grounded in a multidisciplinary team (MDT) platform, this model deeply integrates oncological indicators with the comprehensive geriatric assessment (CGA) system. By holistically considering multidimensional variables including tumor burden, organ function, frailty index, cognitive status, and social support, the model establishes an operational mechanism characterized by "single entry, precise stratification, and targeted selection". Accordingly, patients can be scientifically triaged into distinct intervention tiers, such as active surveillance, minimally invasive surgery, drug therapy, radiotherapy, and best supportive care, thereby achieving real-time alignment between treatment intensity and patient fitness. This article elaborates on the construction logic and key operational procedures of this novel decision-making framework, aiming to guide clinical practice beyond the limitations of a tumor-centric perspective toward a holistic, dynamic, whole-course management strategy. This transition seeks to ensure optimal quality of life and clinical net benefit for elderly patients alongside survival prolongation.

This article reports a rare case of autoinflammatory disease presenting initially with skin induration and swelling after trauma as the initial manifestation, followed by progressive limb weakness. The patient was a middle-aged female who developed skin induration and swelling after trauma, which gradually progressed to limb weakness, dysarthria and bilateral facial paralysis, accompanied by livedo reticularis of the lower extremities, diffuse skin induration of the limbs, and beaded subcutaneous nodules in the right upper limb. The patient had a susceptibility to infection since childhood and a history of chronic livedo reticularis. Skin pathological examination revealed panniculitis. A comprehensive etiological screening for special infections and autoimmune diseases was completed with an unremarkable results, and whole-exome sequencing showed no abnormal findings. Following a multidisciplinary discussion combined with RNA sequencing results, the patient was diagnosed with an autoinflammatory disease, with a suspected type Ⅰ interferonopathy. Treatment with tofacitinib resulted in gradual improvement of clinical symptoms. This case highlights the importance of detailed medical history collection, systematic physical examination and multidisciplinary collaborative diagnosis and treatment, and underscores the pivotal role of molecular diagnosis in the confirmation of rare diseases. It can provide a reference for the clinical diagnosis and management of similar rare cases.

Objective To analyze the epidemiological distribution,microbiological characteristics,drug-resistance status,and risk factors for mortality in adult intensive care unit(ICU)patients with Klebsiella pneumoniae infection.Methods This multi-center prospective cohort study included ICU patients with suspected infection from 67 hospitals across 16 Chinese provinces/municipalities between July 1,2021 and December 31,2022.Clinical data and microbiological results were collected,and patients were divided into survival and non-survival groups according to their survival status and drug-resistance situation.Risk factors for mortality and drug resistance in ICU patients with Klebsiella pneumonia infection were determined through univariate and multivariate logistic regression analyses.Results A total of 2964 ICU-infected patients were enrolled,with 12 175 microbial specimens submitted for testing.Among these,487 specimens tested positive for Klebsiella pneumoniae.Ultimately,314 patients with Klebsiella pneumoniae infection were identified,primarily from lung infections,with a drug-resistance rate of 78.3%.The in-hospital mortality rate of ICU patients infected with Klebsiella pneumoniae was 19.8%.Univariate and multivariate logistic regression analyses revealed that older age(P=0.027),high drug-resistance rate(P=0.028),and low clinical-effectiveness rate(P<0.001)were independent risk factors for mortality in ICU patients infected with Klebsiella pneumoniae.Drug-resistance analysis showed that,compared with non-resistant cases,ICU patients with drug-resistant Klebsiella pneumoniae infection had lower pathogen-clearance rates(P=0.003),clinical-effectiveness rates(P=0.004),and antibiotic-effectiveness rates(P<0.010),and higher mortality rates(P=0.006).Patients with Klebsiella pneumoniae abdominal infection(P=0.003)and urinary tract infection(P=0.007)had higher drug-resistance incidences.There were no statistically significant differences in clinical-effectiveness rate,Klebsiella pneumoniae clearance,drug-resistance incidence,mortality rate,or hospital-stay length between patients with lung infection and those with non-lung infection of Klebsiella pneumoniae(P>0.05).Compared with patients with non-bloodstream infection,patients with bloodstream infection of Klebsiella pneumoniae had lower clinical-effectiveness rates(P=0.027)and higher mortality rates(P=0.021).Conclusions Older age,high drug-resistance rate,and low clinical-effectiveness rate are independent risk factors for mortality in ICU patients infected with Klebsiella pneumoniae.ICU patients with bloodstream infection of Klebsiella pneumoniae may have lower clinical-effectiveness rates and higher mortality rates.ICU patients with abdominal and urinary tract infections caused by Klebsiella pneumoniae are more likely to develop drug resistance.

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

Objective To investigate the effect of Huangqi Shengmai Yin(HSY)on myocardial fibrosis in rats with acute myocardial infarction(AMI)by adjusting P2X purinoceptor 7(P2X7R)/NOD-like receptor protein 3(NLRP3)pathway.Methods Sixty rats were divied into a sham operation group and model group(5 groups),with 10 rats in each group.The AMI rat model was constructed by ligating the left anterior descending branch and randomly grouped into AMI group,the HSY-low group(intragastric administration of 1.6 ml/kg HSY),the HSY group(intragastric administration of 6.2 ml/kg HSY),the compound miltiorhiza group(intragastric administration of 300 mg/kg),and the HSY-high+P2X7R agonist-ATP group(intragastric administration of 6.2 ml/kg HSY,and tail vein administration of 10 mmol/L ATP).After the intervention,cardiac function,myocardial injury and inflammatory factor markers were detected.The tissue sections were prepared to examine pathological changes,myocardial fibrosis,type Ⅰ and type Ⅲ collagen(COL1A1,COL3A1).Western blotting was performed to detecte the protein expression of P2X7R,NLRP3,tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and the expression of activated Caspase-1.Results Compared with the sham surgery group,the AMI group showed an increase in the left ventricular end diastolic diameter(LVEDD),the coatent of brain natriuretic peptide(BNP)and cardiac troponin I(cTn I),fibrosis volume fraction,the positive expression of COL1A1,COL3A1,TNF-α,IL-1β,P2X7R,NLRP3,and activated Caspase-1 proteins(P＜0.05),and a decrease in left ventricular ejection fraction(LVEF)(P＜0.05).The HSY-low group,HSY-high groups,and compound miltiorhiza group showed a decrease in LVEDD,the content of BNP and cTn I,fibrosis volume fraction,the positive expression of COL1A1 and COL3A1,TNF-α,IL-1β,P2X7R,NLRP3,and activated Caspase-1 proteins(P＜0.05),and an increase in LVEF than these in the AMI group(P＜0.05).The HSY-high+ATP group showed an increase in LVEDD,the content of BNP,cTn I,fibrosis volume fraction,the positive expression of COL1A1 and COL3A1,TNF-α,IL-1β,P2X7R,NLRP3,and activated Caspase-1 proteins(P＜0.05),and a decrease in LVEF than those in the HSY-high group(P＜0.05).Conclusion HSY inhibits P2X7R/NLRP3 pathway to alleviate myocardial fibrosis in AMI rats.

Objective To use imaging features of pulmonary nodules to predict the risk of lymph node metastasis in patients with cT1-stage non-small cell lung cancer (NSCLC), providing a reference for clinical decision-making. Methods A retrospective analysis was conducted on the imaging features and postoperative pathological results of cT1 NSCLC patients who underwent surgical treatment at Linyi People’s Hospital from July 2019 to July 2022. Patients were grouped and analyzed according to lymph node metastasis status. Results A total of 1 123 patients were included, comprising 471 males and 652 females, with a median age of 59 (52, 66) years. Comparative analysis revealed that sex, age, nodule location, nodule size on imaging, solid component size, consolidation tumor ratio (CTR), average CT value, and tumor proximity to the pleura all influenced lymph node metastasis. A nomogram was constructed, indicating that the probability of lymph node metastasis in cT1 NSCLC was positively correlated with solid component size, CTR, and average CT value of the pulmonary nodule, and negatively correlated with patient age. The area under the receiver operating characteristic curve was 0.929. Conclusion For cT1 NSCLC patients, the probability of lymph node metastasis can be predicted by measuring the solid component size, CTR, and average CT value of the pulmonary nodule, in conjunction with patient age. However, relying solely on pulmonary nodule imaging characteristics is insufficient to determine a specific lymph node dissection strategy.

The focus of green analytical chemistry(GAC)is to minimize the negative impacts of analytical pro-cedures on human safety,human health,and the environment.Several factors,such as the reagents used,sample collection,sample processing,instruments,energy consumed,and the quantities of hazardous materials and waste generated during analytical procedures,need to be considered in the evaluation of the greenness of analytical assays.In this study,we propose a greenness evaluation metric for analytical methods(GEMAM).The new greenness metric is simple,flexible,and comprehensive.The evaluation criteria are based on both the 12 principles of GAC(SIGNIFICANCE)and the 10 factors of sample prep-aration,and the results are presented on a 0-10 scale.The GEMAM calculation process is easy to perform,and its results are easy to interpret.The output of GEMAM is a pictogram that can provide both qualitative and quantitative information based on color and number.

Objective:To investigate the clinical efficacy and safety of ultrasonic bone scalpel in nasal osteotomy.Methods:A retrospective analysis was conducted on clinical data from the patients who received ultrasonic bone scalpel-assisted nasal osteotomy in the Nasal Plastic & Reconstructive Surgery Department, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 2023 and April 2024. All patients underwent open lateral approach osteotomy using an ultrasonic bone scalpel under direct vision, combined with augmentation rhinoplasty using autologous costal cartilage grafting. Intraoperatively, the nasal dorsum was fully exposed, and the lateral nasal cartilage was separated from the nasal septum, followed by precise bone tissue incision using the ultrasonic bone scalpel. Parameters recorded included operative time, and postoperative complications. Based on the standardized photographs taken before the operation and during the 6-month follow-up after the operation, the observer global aesthetic improvement scale (GAIS) was evaluated by a third-party doctor, with a score ranging from 1 to 5. The smaller the score, the more significant the improvement compared to before the operation. The satisfaction of patients with the surgical outcome was evaluated and classified into four levels: very satisfied, satisfied, dissatisfied, and very dissatisfied.Results:A total of 25 female patients were enrolled, aged 20 to 38 years, with an average age of 27.1 years. All procedures were completed successfully, with a mean operative time of (25.4±4.2) minutes. Postoperative localized swelling of varying degrees was observed. Follow-up ranged from 6 to 18 months, with nasal contour and curvature stabilizing by 6 months postoperatively. No complications, such as infection, nasolacrimal duct, lacrimal sac, medial canthal ligament, nerve injuries, or sensory disturbances, were reported. Two cases exhibited mild nasal bone widening at the 6-month follow-up, though no surgical revision was requested. Significant improvement in external nasal morphology was achieved in all patients, with high satisfaction rates. The patients satisfaction survey showed that 18 cases (72%) were very satisfied and 7 cases (28%) were satisfied with the surgical outcome. GAIS scores reflected positive evaluations [(1.24±0.51) points].Conclusion:The ultrasonic bone scalpel for nasal osteotomy offers the advantages of high-precision cutting and efficient hemostasis. It is highly effective in reshaping the nasal contour, with shorter osteotomy time, reduced intraoperative bleeding, and a lower postoperative complication rate. This study provides some insights into plastic surgeons in optimizing nasal bone modification strategies.

Hydrosalpinx is one of the common causes of female infertility and a more common type of chronic tubal inflammation. Hydrosalpinx may reduce the success of assisted reproductive technology (ART) through a variety of mechanisms, including mechanical flushing of the embryo, embryo toxicity, reduced endometrial receptivity, and suppression of ovarian function. The effect of hydrosalpinx and its treatment strategy on ovarian response during controlled superovulation is controversial in existing studies, and there are fewer studies on the effect of hydrosalpinx on embryo quality. In this article, we clarify the pathophysiological mechanisms of hydrosalpinx, analyze its potential impact on ovarian response and embryo quality, and further explore the impact of therapeutic strategies for tubal hydrosalpinx on ART outcomes.