BACKGROUND: This study aimed to investigate programmed death-ligand 1 tumor proportion score in predicting the safety and efficacy of PD-1/PD-L1 antibody-based therapy in treating patients with advanced non-small cell lung cancer (NSCLC) in a real-world setting. METHODS: This retrospective, multicenter, observational study enrolled adult patients who received PD-1/PD-L1 antibody-based therapy in China and met the following criteria: (1) had pathologically confirmed, unresectable stage III-IV NSCLC; (2) had a baseline PD-L1 tumor proportion score (TPS); and (3) had confirmed efficacy evaluation results after PD-1/PD-L1 treatment. Logistic regression, Kaplan-Meier analysis, and Cox regression were used to assess the progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) as appropriate. RESULTS: A total of 409 patients, 65.0% ( n = 266) with a positive PD-L1 TPS (≥1%) and 32.8% ( n = 134) with PD-L1 TPS ≥50%, were included in this study. Cox regression confirmed that patients with a PD-L1 TPS ≥1% had significantly improved PFS (hazard ratio [HR] 0.747, 95% confidence interval [CI] 0.573-0.975, P = 0.032). A total of 160 (39.1%) patients experienced 206 irAEs, and 27 (6.6%) patients experienced 31 grade 3-5 irAEs. The organs most frequently associated with irAEs were the skin (52/409, 12.7%), thyroid (40/409, 9.8%), and lung (34/409, 8.3%). Multivariate logistic regression revealed that a PD-L1 TPS ≥1% (odds ratio [OR] 1.713, 95% CI 1.054-2.784, P = 0.030) was an independent risk factor for irAEs. Other risk factors for irAEs included pretreatment absolute lymphocyte count >2.5 × 10 9 /L (OR 3.772, 95% CI 1.377-10.329, P = 0.010) and pretreatment absolute eosinophil count >0.2 × 10 9 /L (OR 2.006, 95% CI 1.219-3.302, P = 0.006). Moreover, patients who developed irAEs demonstrated improved PFS (13.7 months vs. 8.4 months, P <0.001) and OS (28.0 months vs. 18.0 months, P = 0.007) compared with patients without irAEs. CONCLUSIONS A positive PD-L1 TPS (≥1%) was associated with improved PFS and an increased risk of irAEs in a real-world setting. The onset of irAEs was associated with improved PFS and OS in patients with advanced NSCLC receiving PD-1/PD-L1-based therapy.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Lung Neoplasms/metabolism* ; Aged ; B7-H1 Antigen/metabolism* ; Programmed Cell Death 1 Receptor/metabolism* ; Adult ; Aged, 80 and over ; Immune Checkpoint Inhibitors/therapeutic use*

OBJECTIVE: To explore the feasibility and effectiveness of repairing surgical defect in pharyngo-laryngeal malignant tumor with free rectus femoris flap. METHODS: The clinical data of 34 patients with surgical defects in pharyngo-laryngeal malignant tumor who met the selection criteria between July 2014 and August 2024 were retrospectively analyzed. There were 25 males and 9 females, aged 25-82 years, with a median age of 54 years. The disease duration ranged from 2 months to 2 years, with a median of 7 months. The tumor locations included the oropharynx, hypopharynx, cervical esophagus, and larynx. Pathological types included squamous cell carcinoma (29 cases), myoepithelial carcinoma (2 cases), adenoid cystic carcinoma (1 case), and diffuse large B-cell lymphoma (2 cases). TNM staging: 16 cases of T ₄N ₁M ₀, 3 cases of T ₄N ₂M ₀, 3 cases of T ₄N ₀M ₀, 10 cases of T ₃N ₁M ₀, and 2 cases of T ₃N ₀M ₀. The 2017 American Joint Committee on Cancer (AJCC) staging was stage Ⅲ in 2 cases and stage Ⅳ in 32 cases. The blood supply of the proximal rectus femoris muscle was observed by enhanced CT of the lower limb vessels before operation, and the surgical defects ranged from 3.0 cm×2.0 cm to 12.0 cm×8.5 cm. The blood supply and perforators of rectus femoris muscle were explored during operation, and the free rectus femoris flap pedicled with the direct vascular stem of rectus femoris muscle was used to repair the defect. For the patients with pharyngeal fistula or obvious neck swelling after operation, the blood supply of the flap was analyzed by vascular enhanced CT to determine the corresponding strategies of nutritional support, anti-infection, dressing change and drainage. Radiotherapy and chemotherapy were supplemented in 27 patients with lymph node metastasis after operation. RESULTS: All the 34 patients were followed up 1-10 years, with an average of 3 years. The flap was found to be necrotic by fibrolaryngoscopy at 1 week after operation in 2 cases, and the incision healed after dressing change and nutritional support, and no reoperation was performed. The flap was in good condition at 1 week after operation in 4 cases, and the signs of gradual necrosis of the flap were found within 1 month after operation, of which 2 cases were healed after dressing change, 1 case was removed the necrotic tissue by reoperation, and 1 case was healed after pectoralis major myocutaneous flap was used to repair the pharyngeal tissue defect. The flaps survived in 28 cases, including 4 cases of pharyngeal fistula, which healed by dressing change. Twenty-two cases achieved satisfactory results in swallowing or phonation. Two patients with total laryngectomy and voice reconstruction underwent reoperation to seal the voice tube because of postoperative aspiration. During the follow-up, 1 case had tracheal stomal recurrence, 2 cases had bone metastasis, and 1 case had bone and lung metastasis. CONCLUSION The free rectus femoris flap has good flexibility, the volume of the flap is easy to adjust, and the incision of the donor site is concealed, which is expected to become a new choice for the repair of the surgical defect in pharyngo-laryngeal malignant tumor.
Humans ; Male ; Middle Aged ; Female ; Aged ; Adult ; Plastic Surgery Procedures/methods* ; Retrospective Studies ; Laryngeal Neoplasms/pathology* ; Aged, 80 and over ; Pharyngeal Neoplasms/pathology* ; Free Tissue Flaps/blood supply* ; Quadriceps Muscle/transplantation* ; Surgical Wound/surgery* ; Treatment Outcome

Epidermal growth factor receptor (EGFR) exon 20 mutations represent a rare subset of genetic alterations in non-small cell lung cancer (NSCLC). Among them, the complex mutation H773_V774delinsLM is exceedingly uncommon, accounting for only 0.2%-1% of all EGFR mutations. It is currently believed that rare EGFR mutations are generally resistant to the first- and second-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Although the third-generation EGFR-TKIs have shown some efficacy in certain rare mutations, clinical evidence regarding their use in NSCLC patients with the H773_V774delinsLM mutation remains sparse, and their efficacy and safety are yet to be clarified. Here, we present the first documented case of a patient with EGFR H773_V774delinsLM-mutant lung adenocarcinoma who experienced remarkable tumor regression following treatment with furmonertinib. This case highlights the potential utility of furmonertinib in treating patients with this rare EGFR mutation and may provide valuable insight into emerging treatment strategies for similarly affected patients.
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Humans ; Adenocarcinoma/genetics* ; Adenocarcinoma of Lung ; ErbB Receptors/genetics* ; Exons/genetics* ; Lung Neoplasms/enzymology* ; Mutation ; Protein Kinase Inhibitors/therapeutic use*

Aiming at the current situation of insufficient integration of medical humanities teaching and clinical practice,as well as the need for further research and improvement in the teaching system,guided by the concept of medicine and humanistic literacy integration advocated by the new medical science,this paper deeply discussed the construction of clinical medical humanities teaching system from four aspects,including the selection of clinical medical humanities teachers and team building;the teaching path that combines theoretical education,narrative medicine,and clinical skill training infused with medical humanities content;curriculum ideological and political construction with the goal of establishing the core concept and value orientation of"patient-centered";the teaching assessment and evaluation method characterized by formative evaluation.The clinical medical humanities teaching system emphasizes the practicality,experiential,and emotional aspects of medical humanities teaching,deeply integrating medical humanities with clinical practice teaching content throughout the clinical internship period of medical education,with a view to enhancing the humanistic practice ability and literacy of medical students.

The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.How-ever,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive rela-tionship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met's anti-proliferative effects were blocked by AMPK inhibitor or YAP1 over-expression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

OBJECTIVE To explore the intracellular expression changes of p38 and Erk1/2 under three phototoxic conditions, compare three detection methods, and further investigate their molecular mechanisms. METHODS The methods involved using three testing approaches to assess the phototoxicity of chlorpromazine(CPZ) and tiaprofenic acid(TA). Subsequently, whole-cell lysates from the biological samples used in the three testing methods were collected, and the changes in the expression levels of intracellular p38 and Erk1/2 were evaluated using Western blotting. RESULTS All three testing methods accurately identified CPZ and TA as phototoxic compounds. In the 3T3 NRU phototoxicity assay, compared to the control group, the expression of p38 significantly increased under phototoxic doses of TA and CPZ(P<0.05), a phenomenon not observed in other testing methods. In phototoxicity assays using guinea pig and artificial skin models, similar expression pattern changes were observed for p38 and Erk1/2. CONCLUSION p38 and Erk1/2 have obvious dose dependence and high sensitivity in the 3T3 NRU phototoxicity test, and can be considered as potential molecular markers for evaluating the phototoxicity of 3T3 NRU. However, they have not been feasible in guinea pig tests and EpiKutis artificial skin tests. Guinea pigs and EpiKutis artificial skin exhibit more similar changes in p38 and Erk1/2 expression, suggesting that the EpiKutis artificial skin model test method may be a better alternative to animal testing than the 3T3 NRU method.

Objective:To analyze the correlation between drug-induced sleep endoscopy (DISE), results, polysomnography (PSG) indicators, and clinical parameters in patients with obstructive sleep apnea (OSA), and to establish and validate a predictive model for tongue base plane obstruction.Methods:This retrospective study analyzed 117 OSA patients diagnosed via PSG and treated at the Department of Otolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical University, between October 2014 and March 2022. The cohort comprised of 114 males and 3 females, with an age range of 20 to 54 years (mean age 38.1±8.4 years). Data on DISE results, PSG results, and clinical indicators were collected for all 117 patients. Logistic regression analysis was performed to identify relevant indicators, and a predictive model for tongue base plane obstruction was constructed and internally validated using the R programming language.Results:Univariate logistic regression analysis identified four independent risk factors for predicting tongue root plane obstruction: tonsil grading, N2, N3, and rapid eye movement sleep(REM) stage [ OR:0.412(0.260~0.652),1.045(1.012~1.079),0.943(0.903~0.984),0.961(0.925~0.998), P <0.05]. Multivariate logistic regression analysis confirmed tonsil grading and N3 sleep stage (12.48±12.22%) as significant predictors. A nomogram model incorporating these factors demonstrated good predictive performance, with an area under curve(AUC) of 0.82 (95% CI: 0.548-1.000), an optimal cutoff of 0.519, a specificity of 80.0%, and a sensitivity of 86.7%. Internal validation of the model in the validation cohort yielded an AUC of 0.751 (95% CI: 0.625-0.876). Conclusions:Tongue base plane obstruction observed during DISE in OSA patients is associated with tonsil grading and N3 sleep stage duration. The predictive model developed for tongue base plane obstruction based on DISE demonstrates good efficacy, as evidenced by its internal validation.

Benign prostatic hyperplasia(BPH)is one of the major chronic complications of type 2 diabetes mellitus(T2DM),and sex steroid hormones are common risk factors for the occurrence of T2DM and BPH.The profiles of sex steroid hormones are simultaneously quantified by LC-MS/MS in the clinical serum of patients,including simple BPH patients,newly diagnosed T2DM patients,T2DM complicated with BPH patients and matched healthy individuals.The G protein-coupled estrogen receptor(GPER)inhibitor G15,GPER knockdown lentivirus,the YAP1 inhibitor verteporfin,YAP1 knockdown/overexpression lentivirus,targeted metabolomics analysis,and Co-IP assays are used to investigate the molecular mechanisms of the disrupted sex steroid hormones homeostasis in the pathological process of T2DM complicated with BPH.The homeostasis of sex steroid hormone is disrupted in the serum of patients,accompanying with the proliferated prostatic epithelial cells(PECs).The sex steroid hormone metabolic profiles of T2DM patients complicated with BPH have the greatest degrees of separation from those of healthy individuals.Elevated 17β-estradiol(E2)is the key contributor to the disrupted sex steroid hormone homeostasis,and is significantly positively related to the clinical characteristics of T2DM patients complicated with BPH.Activating GPER by E2 via Hippo-YAP1 signaling exacerbates high glucose(HG)-induced PECs prolifer-ation through the formation of the YAP1-TEAD4 heterodimer.Knockdown or inhibition of GPER-mediated Hippo-YAP1 signaling suppresses PECs proliferation in HG and E2 co-treated BPH-1 cells.The anti-proliferative effects of verteporfin,an inhibitor of YAP1,are blocked by YAP1 overexpression in HG and E2 co-treated BPH-1 cells.Inactivating E2/GPER/Hippo/YAP1 signaling may be effective at delaying the progression of T2DM complicated with BPH by inhibiting PECs proliferation.

Objective:To investigate the construction effects of the graduate biochemistry technology courses based on the outcome-based education (OBE) concept, analyze the technical needs of graduate students, and further integrate and optimize the teaching methods.Methods:A self-compiled questionnaire with good reliability and validity was used to conduct an overall sampling survey on the graduate students who took the elective courses in Batch 2021 in a medical college in Shanghai. Excel and GraphPad Prism software were used for data analysis.Results:According to this survey, the courses gain good effects in terms of teaching framework, course facilities, teaching forms, teaching contents and comprehensive evaluation of teaching. A total of 112 students (95.2%) thought that the course was very helpful to the expansion of experimental technology and experimental operation ability. However, there were still some teaching needs, such as expanding the types of experiments and increasing experimental operations.Conclusions:Under the guidance of OBE concept, the construction of the graduate biochemistry technology courses has gradually achieved good results. Later, the online-offline hybrid teaching form will be further improved and the curriculum teaching arrangement will be optimized further.

Objective:To investigate the effects of sodium-glucose cotransporter 2 inhibitor dapagliflozin on myocardial remodeling in mice with diabetic cardiomyopathy and related mechanisms.Methods:Between January and December 2021, 60 6-week-old male C57BL/6J mice were chosen for the study, 40 were used to establish a diabetic cardiomyopathy model and the model was established in 28 mice, of whom, 14 were assigned to a non-intervention group and 14 to a dapagliflozin treatment group(intervention group).The rest of the 20 mice were in the control group.The mice in the intervention group were treated with dapagliflozin via oral gavage for 12 weeks.Cardiac structure and function were measured by ultrasound, the degree of myocardial fibrosis was evaluated by histology and electron microscopy, the concentrations of inflammatory factors were detected by enzyme-linked immunosorbent assays, apoptosis of myocardial cells was examined by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling(TUNEL), and the level of myocardial oxidative stress was evaluated by dihydroethidium fluorescence.Results:At the end of the experiments, the body weight and fasting blood glucose in the intervention group were slightly lower than in the non-intervention group, but the difference was not statistically significant, while values from cardiac function parameters such as left ventricular ejection fraction were more favorable than in the non-intervention group[(61.07±4.66)% vs.(45.8±4.80)%, t=-5.24, P<0.05].Compared with the non-intervention group, the intervention group had alleviated myocardial hypertrophy, less myocardial disarray, and reduced collagen volume fraction[(18.4±1.9)% vs.(31.8±3.7)%, t=-12.0, P<0.05].Furthermore, the concentrations of inflammatory factors in the intervention group were lower than in the control group[interleukin-6: (82.19±10.90)ng/L vs.(291.02±31.02)ng/L, t=23.8, P<0.05; tumor necrosis factor-α: (70.45±12.13)ng/L vs.(201.31±27.10)ng/L( t=16.5), P<0.05; perforin 3: (13.05±2.04)μg/L vs.(42.40±1.26)μg/L( t=45.8), P<0.05; the index of myocardial apoptosis: 1.736±0.247 vs.0.864±0.129, t=11.7, P<0.05].The level of myocardial oxidative stress in the non-intervention group was higher than in the intervention group(2.655±0.252 vs.1.274±0.298, t=-13.3, P<0.05). Conclusions:Dapagliflozin can reduce myocardial hypertrophy and inhibit myocardial fibrosis through mitigating myocardial oxidative stress and inflammatory response, thus suppressing myocardial remodeling and ultimately protecting cardiac function in diabetic cardiomyopathy mice.