OBJECTIVE To evaluate the cost-effectiveness of rezivertinib versus gefitinib as first-line treatment for epidermal growth factor receptor （EGFR） mutation-positive advanced non-small cell lung cancer （NSCLC） from the perspective of the Chinese healthcare system. METHODS A Markov model was constructed based on the REZOR trial data， with a cycle length of 3 weeks and a study duration of 5 years. Both costs and health outcomes were discounted at an annual rate of 5%. A cost-utility analysis was conducted using 3 times China’s 2024 per capita gross domestic product as the willingness-to-pay （WTP） threshold. The economic differences between the rezivertinib regimen versus the gefitinib regimen were evaluated using the incremental cost- effectiveness ratio （ICER） and incremental net monetary benefit （INMB）. Sensitivity and scenario analyses were performed to verify the robustness of the model. RESULTS Compared to the gefitinib regimen， the rezivertinib regimen saved 225 310.47 yuan and gained an additional 0.57 quality- adjusted life years （QALYs）， resulting in an ICER of －395 562.80 yuan/QALY， which was much lower than the WTP threshold of this study， indicating that rezivertinib had an absolute economic advantage. The INMB analysis （389 041.26 yuan） further validated this conclusion. One-way and probabilistic sensitivity analyses confirmed the robustness of the model. Scenario analysis， incorporating a 15% reduction in drug prices and adjustments to the utility values for progression free survival and progression disease， yielded consistent results with the base case analysis. CONCLUSIONS Compared to gefitinib， rezivertinib as a first-line treatment for EGFR mutation-positive advanced NSCLC has an absolute economic advantage.

Metabolic associated fatty liver disease (MAFLD) is fundamentally driven by an imbalance in hepatic fatty-acid flux: the influx of fatty acids exceeds the liver’s capacity for disposal, resulting in excessive hepatic lipid accumulation, predominantly in the form of triglycerides (TGs). The occurrence and progression of MAFLD depend on disordered regulation across multiple metabolic steps, including fatty-acid uptake, de novo lipogenesis (DNL), fatty-acid oxidation (FAO), and very low-density lipoprotein (VLDL) export. Forkhead box protein O1 (FOXO1) is a key transcriptional regulator within the hepatic network coordinating glucose and lipid metabolism. Under metabolic stress and insulin resistance (IR), FOXO1 expression is frequently increased, whereas its inhibitory phosphorylation is reduced. These changes enhance FOXO1 nuclear localization and transcriptional activity, thereby reprogramming the expression of genes related to metabolism in the liver. Because hepatic lipid deposition is the central pathological feature of MAFLD, the functional status of FOXO1 directly influences hepatic lipid homeostasis. Growing evidence suggests that FOXO1 can exert bidirectional, environment-dependent effects on hepatic lipid accumulation; however, the molecular basis for this functional switch remains incompletely understood. This review systematically summarizes the biological functions and regulatory mechanisms of FOXO1 and its roles in hepatic lipid metabolism, with a particular focus on its crosstalk with insulin signaling. FOXO1 expression is shaped by RNA modifications and epigenetic regulation mediated by non-coding RNAs. Its transcriptional output is precisely governed by post-translational modifications—such as phosphorylation and acetylation—as well as by coordinated nucleocytoplasmic shuttling. Notably, these regulatory patterns vary markedly across nutritional states, degrees of insulin resistance, and stages of disease. In the fed state, insulin/IGF-1 signaling activates the PI3K-AKT pathway, promoting the inhibitory phosphorylation of FOXO1 and facilitating additional modifications, including acetylation, methylation, and ubiquitination. Together, these events drive FOXO1 export from the nucleus and dampen its transcriptional activity, suppressing gluconeogenesis and constraining lipogenic programs. Conversely, during fasting or when insulin signaling is weakened, FOXO1 inhibition is relieved. FOXO1 accumulates in the nucleus, binds to DNA, and regulates the transcription of downstream target genes. Mechanistically, FOXO1 can aggravate hepatic lipid accumulation by activating genes involved in TG synthesis while repressing FAO-related pathways, thereby favoring storage over oxidation. However, under specific conditions, FOXO1 may also alleviate the hepatic lipid burden by promoting TG hydrolysis and enhancing VLDL secretion, thereby reducing the net hepatic lipid load. In addition, lipotoxic signals mediated by ceramides and diacylglycerols (Cer/DAG) activate atypical protein kinase C (aPKC), further exacerbating the disruption of the AKT-FOXO1 axis. This vicious cycle ultimately produces a metabolic paradox in which increased hepatic glucose output coexists with persistent, insulin-independent lipogenesis, accelerating MAFLD progression. Importantly, FOXO1 regulation is not uniform: during early metabolic overload, insulin-mediated suppression may remain effective, whereas in advanced insulin resistance, the loss of AKT control permits sustained FOXO1 activity. Such stage-dependent dynamics may help explain why FOXO1 can either promote steatosis or, in certain contexts, support programs that facilitate lipid turnover. Accordingly, interventions should be liver-specific and tuned to the disease stage, aiming to curb maladaptive FOXO1 signaling while preserving its capacity to promote triglyceride hydrolysis and VLDL secretion when advantageous. Overall, this review offers an important perspective on MAFLD pathogenesis, emphasizing FOXO1 as a potential therapeutic target and providing a theoretical basis for developing liver-specific, disease-course-dependent precision interventions.

AIM: To evaluate the safety and efficacy of low-dose transscleral cyclophotocoagulation(TSCP)in the management of persistent ocular hypertension after an acute attack of angle-closure glaucoma(AACG).METHODS:This retrospective study enrolled patients diagnosed with persistent ocular hypertension after an acute AACG attack at the No.988 Hospital of the Joint Logistics Support Force of the Chinese PLA between September 2023 and September 2024. All patients underwent low-dose TSCP using a semiconductor diode laser. Subsequent cataract surgery combined with goniosynechialysis was performed once intraocular pressure(IOP)was stabilized. Changes in anterior chamber depth(ACD), best-corrected visual acuity(VA), and IOP were compared before and after TSCP, as well as before and after phacoemulsification. Post-TSCP complications were also documented.RESULTS: A total of 21 patients(21 eyes)were enrolled, including 8 males and 13 females, with a mean age of 67.95±7.25 y. Compared with pre-cyclophotocoagulation values, ACD increased significantly at 3 d post-TSCP(1.49±0.18 vs 1.22±0.21 mm; P<0.001). BCVA and IOP decreased significantly at 1 d post-TSCP, pre-phacoemulsification, 1 wk post-phacoemulsification, and 1 mo post-phacoemulsification compared with pre-TSCP IOP(all P<0.01). Regarding postoperative complications, 2 eyes experienced pain on the day of the procedure, 5 eyes developed mild corneal endothelial folds, 2 eyes exhibited moderate anterior chamber inflammatory reaction, and 12 eyes showed shallow ciliary body detachment. No serious complications occurred during the 1-month follow-up period.CONCLUSION:Low-dose TSCP appears to be an effective bridging therapy for patients with persistent ocular hypertension following an AACG attack. It facilitates rapid IOP reduction, alleviates symptoms, and helps preserve visual function with a favorable safety profile, thereby reducing the risks associated with subsequent intraocular surgery.

ObjectiveTo explore the efficacy and mechanism of Euphorbia humifusa on acute kidney injury （AKI） based on network pharmacology， molecular docking and experimental verification. MethodsThe active components and targets of E. humifusa were retrieved from TCMSP and SwissTargetPrediction database， and the AKI targets were screened by GeneCards and Online Mendelian Inheritance in Man（OMIM） databases. The drug targets and disease targets were intersected to construct a protein-protein interaction network， and the intersection targets were subjected to gene ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） enrichment analysis. Discover Studio software was used to verify the molecular docking of key components and core targets. Gentamicin （GM） was used to induce AKI rat model. Control group， model group， verapamil （16 mg·kg^-1） group， E. humifusa extract （18， 54， 162 mg·kg^-1·d^-1） group and E. humifusa 70% ethanol extract （423 mg·kg^-1） group were continuously administered for 14 days. Urine volume was detected 24 h after modeling and administration. Serum creatinine （SCr）， Blood urea nitrogen （BUN）， 24-hour urine protein （24 hUTP） and uric acid （UA） content； the contents of malondialdehyde （MDA）， glutathione （GSH）， superoxide dismutase （SOD）， carbon monoxide synthase （NOS） and lactate dehydrogenase （LDH） in kidney were measured. The levels of interleukin （IL）-6 and tumor necrosis factor （TNF）-α in serum were detected by enzyme linked immunosorbent assay（ELISA） kit. The pathological changes of renal tissue were detected by hematoxylin-eosin （HE） and Masson staining. Western blot was used to detect the expression of PI3K/protein kinase B（Akt）/NF-κB signaling pathway-related proteins. ResultsIn this study， 13 active components such as kaempferol， luteolin， apigenin， gallic acid and quercetin were screened and identified from E. humifusa. Through bioinformatics analysis， these components and AKI have a total of 289 targets， of which 62 are core targets， including Akt1， TNF， tumor protein p53（TP53） and IL-1β. These targets are mainly involved in the regulation of biological processes such as NF-κB signaling pathway， HIF-1 signaling pathway， TNF signaling pathway， PI3K/Akt signaling pathway and mitogen-activated protein kinase（MAPK） signaling pathway. In animal experiments， we successfully constructed a GM-induced AKI model in rats. Compared with the model group， E. humifusa extract could significantly reduce the levels of 24 hUTP， BUN and SCr in rats （P<0.01）， indicating its improvement effect on renal function. In addition， the extract of E. humifusa also significantly reduced LDH activity and MDA content in rat kidney tissue （P<0.05， P<0.01）， and significantly increased SOD， NOS activity and GSH content （P<0.05）， indicating that the extract of E. humifusa has the potential of anti-oxidation and protection of renal function. Further analysis of inflammatory factors showed that the levels of IL-6 and TNF-α in serum of rats treated with E. humifusa extract were significantly decreased （P<0.01）， indicating that E. humifusa extract had anti-inflammatory effects. In addition， the extract of E. humifusa can also regulate the protein expression of PI3K/Akt/NF-κB signaling pathway， which further confirmed its mechanism of reducing GM-induced AKI. ConclusionThe extract of E. humifusa has a significant therapeutic effect on acute kidney injury through its multi-component and multi-target mechanism. Its effect is reflected in improving renal function， anti-oxidation， anti-inflammation and regulating immune response. These findings provide a scientific basis for the application of E. humifusa in the treatment of acute kidney injury， and point out the direction for future drug development and clinical research.

Bronchiolar adenoma (BA) is a rare type of lung tumor characterized by bilayered epithelial cells having a continuous basal layer and a luminal layer. It resembles mucinous adenocarcinoma (MA) on frozen section, with difficulty in distinguishing the basal layer. Immunohistochemistry is the best choice for verifying the diagnosis. This study aimed to comprehensively characterize three cases of BA-combined carcinoma using clinical, histopathological, and genetic features. BA and carcinoma sections were subjected to next-generation sequencing, respectively. It was hypothesized that while different mutation forms matched different regions, BA and lung adenocarcinoma shared the same gene mutation when they co-occurred in the same location. BA with extensive carcinoma is extremely rare and presents diagnostic challenges due to its overlap with conditions such as MA. Because of its distinctive morphological characteristics, BA may be regarded as a low-grade malignancy, particularly during a confusing evaluation. A multifaceted examination of clinical, radiological, immunohistochemical, and genetic data is necessary for an accurate diagnosis.

Background: and Purpose In patients with large vessel occlusion (LVO), intravenous thrombolysis (IVT) frequently alters thrombus location; however, the clinical impact of this phenomenon remains unclear. We aimed to compare post-IVT thrombus dynamics between tenecteplase and alteplase and to evaluate the association between thrombus dynamics and 3-month outcomes. Methods: This retrospective study analyzed prospectively collected, multicenter data from consecutive patients with LVO who underwent bridging therapy between January 2022 and December 2024. Thrombus dynamics were classified as resolution, migration, or stability. Analyses incorporated propensity score matching with weighting to balance baseline characteristics. Results: Of the 806 initially included patients, 746 were included after matching (373 treated with tenecteplase and 373 treated with alteplase). The incidence of thrombus migration was significantly higher in the tenecteplase group than in the alteplase group (19.3% vs. 11.3%; odds ratio [OR]: 1.92; 95% confidence interval [CI] 1.27–2.91). The advantage of tenecteplase over alteplase was restricted to patients with an IVT-to-puncture time of <60 minutes (18.6% vs. 6.2%; p=0.001) and was no longer significant when the interval ≥60 minutes (19.7% vs. 15.0%; p=0.204; pinteraction=0.043). Additionally, thrombus migration was associated with a better functional outcome (OR: 1.62; 95% CI 1.04–2.53). Finally, tenecteplase was associated with improved functional independence compared with alteplase (OR: 1.43; 95% CI 1.04–1.95). Conclusions Tenecteplase demonstrated superior efficacy in inducing thrombus migration compared with alteplase, particularly within 60 minutes of IVT administration. Thrombus migration independently predicted improved functional independence. These findings support the preferential use of tenecteplase for bridging therapy in patients with LVO.

OBJECTIVE To investigate the current career development status and existing bottlenecks among graduates of clinical pharmacist training bases， and to provide evidence for optimizing the training system， enhancing trainees’ job competency， and promoting the sound development of the clinical pharmacy discipline. METHODS Graduates from a clinical pharmacist training base in a tertiary class A hospital were selected as survey subjects. A six-dimensional questionnaire was designed using “Wenjuanxing” platform， distributed and collected via a mobile APP and E-mail. The survey analyzed participants’ basic characteristics， the impact of training on their professional roles， as well as their satisfaction regarding professional sentiment， competence， career status， professional recognition， the current state of the clinical pharmacist workforce， and the teaching model of the training base. The reliability of the questionnaire responses was assessed using Cronbach’s α coefficient. RESULTS A total of 164 questionnaires were distributed， and 147 valid responses were recovered， yielding a valid response rate of 89.63%. The Cronbach’s α coefficient for the questionnaire content was 0.943. The surveyed trainees were primarily employed at general hospitals （81.63%） and tertiary class A hospitals （72.11%）， with women constituting the majority （79.59%）. Their ages were concentrated between 26 and 35 years old （63.27%）， and most of them were supervising pharmacists（59.86%）. After training， 96.60% of graduates returned to their original institutions， and the proportion working in clinical pharmacist positions increased from 52.38% to 84.35%. Trainees’ overall satisfaction rate with the training model was 84.35%. However， their satisfaction with innovation and research capacity in clinical pharmacy was only 42 .18%， the satisfaction with salary and benefits was 35.37%， and the satisfaction with both occupational recognition and rationality of staffing was less than 50%. CONCLUSIONS Clinical pharmacist training bases can effectively promote trainees’ career transition， enhance job competency， and stabilize the talent pool among trainees. Nonetheless， the profession still faces bottlenecks such as relatively weak research capacity， low compensation， insufficient professional recognition， and unreasonable staffing. These issues require a multi-pronged， collaborative approach involving the optimization of training systems， the enhancement of career support， and the improvement of industry policies.

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

The pharmaceutical industry faces challenges in quality digitization for complex multi-stage processes, especially in small-sample systems. Here, an intelligent quality prediction and diagnostic (IQPD) framework was developed and applied to Tong Ren Tang's Niuhuang Qingxin Pills, utilizing four years of data collected from four production units, covering the entire process from raw materials to finished products. In this framework, a novel path-enhanced double ensemble quality prediction model (PeDGAT) is proposed, which combines a graph attention network and path information to encode inter-unit long-range and sequential dependencies. Additionally, the double ensemble strategy enhances model stability in small samples. Compared to global traditional models, PeDGAT achieves state-of-the-art results, with an average improvement of 13.18% and 87.67% in prediction accuracy and stability on three indicators. Additionally, a more in-depth diagnostic model leveraging grey correlation analysis and expert knowledge reduces reliance on large samples, offering a panoramic view of attribute relationships across units and improving process transparency. Finally, the IQPD framework integrates into a Human-Cyber-Physical system, enabling faster decision-making and real-time quality adjustments for Tong Ren Tang's Niuhuang Qingxin Pills, a product with annual sales exceeding 100 million CNY. This facilitates the transition from experience-driven to data-driven manufacturing.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.