Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) block downstream signaling pathways by inhibiting receptor tyrosine kinase activity, consequently suppressing proliferation, invasion and metastasis of tumor cells. EGFR-TKIs have been proven to be highly effective in patients with late non-small cell lung cancer (NSCLC) harboring EGFR sensitive mutations, significantly better than chemotherapy. Third-generation EGFR-TKIs, such as osimertinib, have emerged as the first-line treatment for advanced NSCLC patients with sensitive EGFR mutations. However, there are still some patients who exhibit primary resistance upon initial treatment with EGFR-TKIs. The exact mechanism of primary resistance remains unknown, and may be related to factors such as the structure of EGFR mutation subtypes, concurrent mutations, BIM deletion polymorphism, and high expression of programmed cell death-ligand 1. This review summarizes the molecular mechanisms of primary resistance to EGFR-TKIs and discusses potential therapeutic strategies, with the goal of optimizing precision targeted therapy for NSCLC patients.

Objective: To investigate the status of condom use and its influencing factors among men who have sex with men (MSM), so as to provide a basis for improving condom utilization rates and AIDS prevention and control in this population. Methods: From May to October 2024, a snowball sampling method was employed to recruit MSM in Songjiang District, Shanghai Municipality. Self-administered questionnaires were used to collect data on demographic characteristics, AIDS-related knowledge, sexual behaviors, pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP), and condom use in the past six months. Multivariable logistic regression model was used to analyze the influencing factors for consistent condom use. Results: A total of 921 MSM were surveyed, with a median age of 29.00 (interquartile range, 9.00) years. Among them, 697 (75.68%) were aware of AIDS-related knowledge, 826 (89.69%) expressed willingness to use PrEP, and 835 (90.66%) were willing to use PEP. Additionally, 787 (85.45%) MSM reported their age at first homosexual intercourse as ≥18 years, while 519 (56.35%) reported consistent condom use in the past six months. Multivariable logistic regression analysis revealed that MSM who were aware of AIDS-related knowledge (OR=0.582, 95% CI: 0.423-0.801), willing to use PrEP (OR =0.611, 95% CI: 0.385-0.969), and whose age at first homosexual intercourse was <18 years (OR=0.480, 95% CI: 0.330-0.700) were less likely to consistent use condoms. Conclusion The proportion of consistent condom use among the MSM remains relatively low, which is primarily associated with AIDS-related knowledge, willingness to use PrEP, and the age at first homosexual intercourse.

ObjectiveTo observe the clinical effectiveness and safety of Qingfei Shenshi Decoction （清肺渗湿汤） combined with western medicine for patients with bronchial asthma of heat wheezing syndrome， and to explore its potential mechanism of action. MethodsEighty-six participants with bronchial asthma of heat wheezing syndrome were randomly divided into treatment group and control group， each group with 43 participants. The control group received conventional western medicine， and the treatment group was additionally administered Qingfei Shenshi Decoction orally on the basis of the control group， 1 dose per day. Both groups were treated for 14 days. The primary outcome measure was clinical effectiveness； secondary outcome measures included traditional Chinese medicine （TCM） syndrome score， asthma control test （ACT） score， pulmonary function indices such as forced expiratory volume in 1 second （FEV₁）， forced vital capacity （FVC）， peak expiratory flow （PEF）， serum inflammatory factor levels including interleukin-4 （IL-4）， tumour necrosis factor-α （TNF-α）， and high-sensitivity C-reactive protein （hs-CRP）， and immune function indices including CD3⁺， CD4⁺， CD8⁺， CD4⁺/CD8⁺. All outcome measures were evaluated before and after treatment. Vital signs were monitored， and electrocardiography， blood routine， urine routine， liver function， and renal function tests were performed before and after treatment. Adverse events and reactions during the study were recorded. ResultsA total of 80 patients completed the trial with 40 in each group. The total clinical effective rate of the treatment group was 97.5% （39/40）， which was significantly higher than that of the control group （85.0%， 34/40， P＜0.05）. After treatment， both groups showed decreased TCM syndrome scores， IL-4， TNF-α， hs-CRP， and CD8⁺ levels， as well as increased ACT scores， CD3⁺， CD4⁺， CD4⁺/CD8⁺， FEV₁， FVC， and PEF levels （P＜0.05 or P＜0.01）. Moreover， the improvements in these indices were more significant in the treatment group than in the control group （P＜0.05 or P＜0.01）. No significant abnormalities in safety indicators were observed in either group， and no adverse events or reactions occurred. ConclusionQingfei Shenshi Decoction combined with conventional western medicine for patients with bronchial asthma of heat wheezing syndrome can effectively improve the clinical symptoms， pulmonary function， and clinical effectiveness， with good safety. Its mechanism may be related to reducing inflammatory factor levels and regulating T lymphocyte subsets to improve immune function.

Diabetic Peripheral Neuropathy （DPN） is one of the most common and harmful complications of type 2 diabetes. DPN's pathogenesis include high blood sugar-induced oxidative stress， inflammation， and mitochondrial dysfunction. These factors are combined to damage nerve fibers， leading to sensory issues， pain， and numbness. Through a coordinated effect， these factors trigger nerve fiber damage and lead to sensory abnormalities， pain and numbness in limbs， and other symptoms， seriously restricting patients' activities of daily living and mobility. Recent research highlights that cellular senescence plays a critical role in DPN. Cellular senescence is manifested by the loss of cell proliferation ability， and further aggravates nerve damage via oxidative stress， mitochondrial dysfunction， autophagy impairment， inflammatory reaction， and other mechanisms， accelerating DPN occurrence and progression. In terms of medical treatment， current methods focus on blood sugar control， pain relief medicine， and microcirculation improvement， while no therapy has been developed based on cellular senescence. In contrast， traditional Chinese medicine （TCM） shows a unique advantage in DPN prevention and treatment via cellular senescence modulation. TCM emphasizes a holistic approach， as well as syndrome differentiation and treatment， effective in anti-aging and nerve damage repair. Recent studies show that TCM active ingredients， including puerarin， ginsenosides， and berberine， can reduce inflammation， oxidative stress， and apoptosis via signaling pathway regulation， thereby slowing cellular senescence to alleviate nerve damage. Furthermore， TCM compounds such as Buyang Huanwutang， Taohong Siwutang， and Huangqi Guizhi Wuwutang exert synergistic effects on cellular senescence-related pathways to improve nerve health and reduce DPN clinical symptoms. Therefore， this paper reviews the literature related to the interaction between cellular senescence and DPN from the perspective of cellular senescence， summarizing the mechanism of DPN and TCM intervention strategies.

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.

OBJECTIVE To conduct a comprehensive clinical evaluation of phosphate-lowering drugs in the treatment of chronic kidney disease （CKD） with hyperphosphatemia， and to provide evidence-based support for clinical drug decision-making. METHODS Relevant studies meeting the inclusion and exclusion criteria were retrieved， a comprehensive evaluation of efficacy， safety and economics was conducted based on existing study results. Innovation was analyzed from three aspects including filling the clinical gap， and suitability was assessed from two aspects including technical suitability. Accessibility was evaluated based on the survey data from 37 medical institutions in Kunming， combined with information from the National Reimbursement Drug List and national centralized drug procurement. RESULTS A total of 10 meta-analyses and 2 pharmacoeconomic studies were included. In terms of efficacy， all three categories of phosphate-lowering drugs （calcium-based phosphate binders， non-calcium-based phosphate binders， sodium-hydrogen exchanger 3 inhibitors） effectively reduced serum phosphorus levels. Calcium-based phosphate binders elevated serum calcium levels more significantly； sevelamer was superior to calcium-based phosphate binders in reducing intact parathyroid hormone levels； iron-based phosphate binders improved iron metabolism and anemia-related indicators. In terms of safety， iron-based phosphate binders had the highest incidence of gastrointestinal adverse reactions， followed by lanthanum carbonate. In terms of economics， sevelamer demonstrated economic advantages over calcium-based phosphate binders and lanthanum carbonate. In terms of innovation， non-ca lcium-based phosphate binders addressed the clinical limitation of hypercalcemia associated with calcium-based phosphate binders； iron-based phosphate binders met the treatment needs of patients with comorbid iron deficiency anemia； tenapanor exhibited an innovative phosphorus-lowering mechanism. In terms of suitability， all three categories showed good suitability in various aspects. In terms of accessibility， sevelamer had the highest availability rate， while tenapanor was not yet available in medical institutions. All three categories have been included in the National Reimbursement Drug List ； the prices of lanthanum carbonate and sevelamer decreased substantially following centralized procurement with improved affordability. CONCLUSIONS For CKD patients with hyperphosphatemia， non-calcium-based phosphate binders are preferred， among which sevelamer is recommended as the first-line choice. Lanthanum carbonate may be considered for patients with gastrointestinal intolerance； iron-based phosphate binders are preferred for patients with comorbid iron deficiency anemia； tenapanor may be considered for patients with poor response to or intolerance of conventional regimens； calcium-based phosphate binders are not recommended as long-term first-line therapy.

Erythropoietin-producing hepatoma receptor A2 （EphA2） is a member of the erythropoietin-producing hepatoma （Eph） subfamily of receptor tyrosine kinases. As a critical regulator of cancer development and progression， EphA2 can promote tumor initiation， growth， invasion， metastasis， stemness， and angiogenesis by activating or enhancing the oncogenic signaling pathways. High expression of EphA2 in tumor tissues is closely associated with poor prognosis， thus it is a very promising potential target for cancer treatment. This article reviews the molecular mechanisms by which EphA2 promotes cancer development and progression， aiming to provide clues and theoretical basis for EphA2-targeted cancer treatment.

ObjectiveTo evaluate the clinical efficacy of acupuncture in the treatment of adolescent depression and to explore its potential mechanisms based on functional magnetic resonance imaging （fMRI） and serum proteomics. MethodsA randomized， double-blind， sham acupuncture-controlled trial design was conducted. A total of 100 adolescents with depression were enrolled and randomly assigned to an acupuncture group and a sham acupuncture group， with 50 participants in each group. In addition， 20 healthy subjects were recruited as healthy controls. Participants in the acupuncture group received acupuncture at Baihui （GV 20）， Yintang （GV 29）， Zhongwan （CV 12）， Qihai （CV 6）， bilateral Tianshu （ST 25）， bilateral Neiguan （PC 6）， bilateral Zusanli （ST 36）， and bilateral Taichong （LR3）. The sham acupuncture group received intervention using a blunt placebo needle without skin penetration. Both groups received 30-min treatments three times per week for 4 weeks. The primary outcome was the reduction rate of the 24-item Hamilton Depression Rating Scale （HAMD-24） score. Secondary outcomes included changes in HAMD-24 scores before and after treatment， covering nine factors （anxiety/somatization， cognitive impairment， sleep disturbance， psychomotor retardation， hopelessness， fatigue， weight change， diurnal mood variation， and suicidal ideation）， response rate and remission rate after treatment， and symptom severity before and after treatment. Subgroup analyses of total HAMD-24 scores were performed according to concomitant medication use and the number of medications taken. During the study period， all adverse events were monitored and recorded to evaluate safety. Patients who volunteered and met the eligibility criteria for imaging examinations were selected to undergo brain fMRI scanning and serum proteomic analysis to investigate changes in functional connectivity among brain regions and differential proteins. ResultsA total of 49 participants in the acupuncture group and 50 participants in the sham acupuncture group were included in the efficacy analysis. Among them， 20 participants in the acupuncture group and 21 in the sham acupuncture group completed fMRI scans， while 19 participants in the acupuncture group and 21 in the sham acupuncture group completed serum proteomic analyses. After 4 weeks of treatment， the mean reduction rate of HAMD-24 score in the acupuncture group was significantly higher than that in the sham acupuncture group ［（58±24）% vs.（26±19）%， P＜0.01］. Compared to baseline， scores for anxiety/somatization， cognitive impairment， psychomotor retardation， and hopelessness， and the total HAMD-24 score significantly decreased in both groups. In addition， the acupuncture group showed significant reductions in sleep disturbance， fatigue， and suicidal ideation scores （P＜0.01）. After treatment， the response rate and remission rate were 67.35% （33/49） and 24.48% （12/49） in the acupuncture group， respectively， significantly higher than 6.00% （3/50） and 0 in the sham acupuncture group （P＜0.01）. The proportion of participants with moderate symptoms was lower， whereas the proportion with mild symptoms was higher in the acupuncture group than the sham acupuncture group （P＜0.01）. Among those receiving acupuncture alone， acupuncture combined with medication， or fewer than three medications， the total HAMD-24 scores decreased after treatment in both the acupuncture subgroup and the sham acupuncture subgroup， with significantly lower scores in the acupuncture subgroup （P＜0.01）. During the study period， four mild adverse events were reported， including one case in the acupuncture group and three cases in the sham acupuncture group； none of these events affected the continuation of treatment. fMRI results showed that acupuncture enhanced functional connectivity between the prefrontal cortex and cerebellar-limbic system-related brain regions. Proteomic analysis identified 24 differentially expressed proteins associated with acupuncture treatment， mainly enriched in pathways related to neuroinflammation and energy metabolism. ConclusionAcupuncture can significantly improve depressive symptoms in adolescents with depression. Its therapeutic effects may be achieved by modulating emotion-related brain networks and regulating pathways associated with neuroinflammation and energy metabolism.

OBJECTIVE To compare the clinical efficacy and safety of Fluticasone furoate/umeclidinium/vilanterol （FF/UMEC/VI） and Budesonide/glycopyrronium/formoterol （BUD/GLY/FOR） in the treatment of stable asthma-chronic obstructive pulmoary disease （COPD） overlap syndrome （ACOS）.METHODS A retrospective analysis was performed on clinical data of 157 patients with stable ACOS who received standardized treatment at the Affiliated Hospital of Xuzhou Medical University from March 2023 to March 2025. Patients were assigned to the FF/UMEC/VI group （ n＝ 80， receiving FF/UMEC/VI in addition to baseline therapy） and the BUD/GLY/FOR group （ n＝ 77， receiving BUD/GLY/FOR in addition to baseline therapy） according to the treatment regimens. The lung function parameters [forced expiratory volume in one second （FEV 1 ）， forced vital capacity （FVC）， FEV 1 /FVC， FEV 1 percentage of predicted value （FEV 1 %pred）， peak expiratory flow （PEF）]， inflammatory markers [peripheral blood eosinophils （EOS） count， fractional exhaled nitric oxide （FeNO） level， serum levels of interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α）]， and clinical symptom assessment indicators [Asthma Control Test （ACT） scores， COPD Assessment Test （CAT） scores， modified Medical Research Council Dyspnea Scale （mMRC） grades] were compared between the two groups at baseline， week 12 and week 24. The occurrences of acute exacerbations and adverse reactions during the 24-week treatment were documented.RESULTS At baseline， there were no statistically significant differences in lung function parameters， inflammatory markers， or clinical symptom assessment indicators between the two groups （ P ＞0.05）. At weeks 12 and 24， all the above indicators in both groups were significantly improved compared with pre-treatment values in the same group （ P ＜0.05）. The FF/UMEC/VI group showed significantly greater improvements in FEV 1 ， FEV 1 %pred and PEF at week 24， as well as IL-6 and TNF-α levels， ACT and CAT scores， and mMRC grades at both weeks 12 and 24， than the BUD/GLY/FOR group at the corresponding time points （ P ＜0.05）. Within the 24-week treatment， the incidence and frequency of acute exacerbations in the FF/UMEC/VI group were significantly lower than those in the BUD/GLY/FOR group （ P ＜0.05）. There was no statistically significant difference in the incidence of adverse reactions between the two groups （ P ＞0.05）.CONCLUSIONS Both FF/UMEC/VI and BUD/GLY/FOR can effectively improve lung function， reduce inflammation， and alleviate symptoms in patients with ACOS， and both demonstrate good safety profiles； FF/UMEC/VI shows more pronounced advantages in improving long-term lung function， reducing levels of systemic inflammatory markers， and preventing and controlling acute exacerbations， making it more suitable for the long-term management of patients with ACOS in the stable phase.

Objective To explore the application value of Laennec's membrane space in dealing with complex anatomical variations and dense adhesions during repeated liver transplantation (Re-LT). Methods The clinical data of 8 cases of Re-LT recipients treated in the Department of Hepatobiliary Surgery of the First Hospital Affiliated to Harbin Medical University were retrospectively analyzed. During the operation, based on the Laennec's membrane anatomical concept, the remaining Laennec space and the free technique within the hepatic portal plate were flexibly applied for dissection. Specifically, the first hepatic portal main ducts (biliary and portal veins) were dissected by lowering the hepatic portal plate inside the Laennec's membrane space, and the second hepatic portal was exposed to perform the modified piggyback liver transplantation to avoid the injury to the right adrenal gland and right kidney caused by the free inferior vena cava below the liver. Moreover, the dense adhesions between the liver and hollow organs were separated by a combination of blunt and sharp dissection within the subcapsular space of the liver capsule (Glisson capsule). Results All 8 cases of recipients successfully completed the surgery. Among them, 7 cases underwent end-to-end biliary anastomosis with a T-tube left in place, and 1 underwent choledochoenteric anastomosis, 2 cases underwent modified piggyback reconstruction, 2 cases used the subcapsular dissection technique to handle organ adhesions. One recipient died of generalized drug-resistant Klebsiella pneumoniae infection combined with septic shock after the operation, while the remaining 7 cases were discharged after the main complications (such as delayed graft function recovery, pulmonary infection, bile leakage, etc.) were cured or significantly improved. Two cases of recipients who used the subcapsular dissection technique effectively avoided the secondary injury of hollow organs, and no digestive tract leakage complications occurred after the operation. Conclusions By flexibly applying Laennec's membrane space and the intrahepatic portal plate free technique in Re-LT, it may effectively cope with the loss of anatomical layers and vascular dense adhesions, reducing the surgical difficulty and the risk of secondary injury, providing important technical support for improving the prognosis of recipients.