Lung cancer is the most common malignant tumor worldwide, ranking first in both incidence and mortality rates. According to the latest statistics from the International Agency for Research on Cancer (IARC), approximately 2.5 million new cases and around 1.8 million deaths from lung cancer occurred in 2022, placing a tremendous burden on global healthcare systems. The high mortality rate of lung cancer is closely linked to its subtle early symptoms, which often lead to diagnosis at advanced stages. This not only complicates treatment but also results in substantial economic losses. Current treatment options for lung cancer include surgery, radiotherapy, chemotherapy, targeted drug therapy, and immunotherapy. Among these, immunotherapy has emerged as the most groundbreaking advancement in recent years, owing to its unique antitumor mechanisms and impressive clinical benefits. Unlike traditional therapies such as radiotherapy and chemotherapy, immunotherapy activates or enhances the patient’s immune system to recognize and eliminate tumor cells. It offers advantages such as more durable therapeutic effects and relatively fewer toxic side effects. The main approaches to lung cancer immunotherapy include immune checkpoint inhibitors, tumor-specific antigen-targeted therapies, adoptive cell therapies, cancer vaccines, and oncolytic virus therapies. Among these, immune checkpoint inhibitors and tumor-specific antigen-targeted therapies have received approval from the U.S. Food and Drug Administration (FDA) for clinical use in lung cancer, significantly improving outcomes for patients with advanced non-small cell lung cancer. Although other immunotherapy strategies are still in clinical trials, they show great potential in improving treatment precision and efficacy. This article systematically reviews the latest research progress in lung cancer immunotherapy, including the development of novel immune checkpoint molecules, optimization of treatment strategies, identification of predictive biomarkers, and findings from recent clinical trials. It also discusses the current challenges in the field and outlines future directions, such as the development of next-generation immunotherapeutic agents, exploration of more effective combination regimens, and the establishment of precise efficacy prediction systems. The aim is to provide a valuable reference for the continued advancement of lung cancer immunotherapy.

Objective:To investigate the safety and efficacy of laparoscopic simultaneous bilateral adrenalectomy in treating ectopic ACTH syndrome (ACTH)caused by medullary thyroid carcinoma(MTC).Methods:A 56-year-old male patient was admitted after MTC surgery and 7 months of general fatigue. The patient had a history of two open thyroid surgeries for medullary thyroid carcinoma, with previous pathological reports indicating lymph node metastasis in the upper mediastinum and mediastinum, accompanied by weak cytoplasmic expression of ACTH and negative CRH staining. After the operation, the patient developed diabetes, hypertension, and hypokalemia. Upon admission, the patient presented with a blood pressure reading of 200/95 mmHg (1 mmHg = 0.133 kPa), a weight of 61.5 kg, a height of 160 cm, a body mass index (BMI)of 24.02 kg/cm 2, and a waist circumference of 83 cm. Laboratory tests revealed the following: blood potassium level of 2.71 mmol/L, blood calcium level of 1.47 mmol/L, parathyroid hormone level of 6.0 pg/ml, fasting blood glucose level of 10.51 mmol/L, glycated hemoglobin level of 8.2%, blood calcitonin level exceeding 2 000 pg/ml, and blood CEA level of 70.8 μg/L. The plasma ACTH levels at 8∶00, 16∶00, and 24∶00 were 189.0, 125.0, and 65.0 pg/ml, respectively. Serum cortisol levels at 08∶00, 16∶00, and 24∶00 were 429.30, 408.14, and 446.61 μg/L, respectively. The 24-hour urine free cortisol measurement was 1 200 μg, and after the midnight 1mg dexamethasone suppression test at 8∶00, the plasma ACTH level was 183.0 pg/ml, and the serum cortisol level was 538.27 μg/L. The aldosterone level in standing position after 2 hours was 8.2 pg/ml. There were no significant abnormality in catecholamine hormone detection or thyroid function in blood and urine samples. An 18F-FDG-PET/CT examination showed multiple lymph node metastases in the neck, while an abdominal CT scan revealed bilateral adrenal hyperplasia. Enhanced MRI revealed pituitary gland thinning, and lung CT and sputum culture examinations showed scattered multiple lung infections. After a multidisciplinary discussion, the patient was diagnosed with EAS, postoperative MTC metastasis, diabetes, hypertension, hypokalemia, pulmonary infection, mild anemia, liver dysfunction, hypoparathyroidism, and hypocalcemia. The patient were accepted laparoscopic bilateral adrenalectomy via an abdominal approach under general anesthesia. The left adrenal gland was removed first, followed by the right adrenal gland after repositioning. Results:The surgery was successful with a surgical duration of approximately 60 minutes and an intraoperative bleeding volume of about 20 ml. No surgical complications occurred during the perioperative period. Pathological examination confirmed nodular hyperplasia of the adrenal cortex and bilateral adrenal medullary hyperplasia with negative ACTH staining. After a 3-month postoperative follow-up, blood calcitonin levels remained above 2000 pg/ml. The blood ACTH levels at 1 week, 1 month, and 3 months after surgery were 183.0, 220.0, and 731.0 pg/ml, respectively. However, hypertension, diabetes, and hypokalemia rapidly improved. One month after surgery, blood pressure was 100/80 mmHg, fasting blood glucose was 4.4 mmol/L, and blood potassium was 3.87 mmol/L. Pulmonary infection showed improvement, and no adrenal crisis occurred. Glucocorticoid replacement therapy consisted of 20 mg of hydrocortisone tablets in the morning and 10 mg in the afternoon, and thyroid hormone replacement therapy involved daily administration of 100 μg of levothyroxine. Genetic testing revealed heterozygous mutations in the Ret gene. The patient is currently undergoing clinical trial treatment with Ret inhibitors.Conclusions:Based on the data from this case and existing literature reports, laparoscopic simultaneous bilateral adrenalectomy might be safe and effective treatment option for EAS caused by unresectable MTC metastasis. It can correct hypertension, diabetes, and hypokalemia and increase the opportunity for MTC treatment.

Allyl isothiocyanate (AITC) is a natural product commonly used in food preservation and pharmaceutical applications. Toxoplasmosis, caused by the protozoan pathogen Toxoplasma gondii, is prevalent globally while the impact of AITC on toxoplasmosis is unclear. We explored the effect of AITC on acute toxoplasmosis. We infected C57BL/6 mice with T. gondii type I RH strain following AITC administration. On the 4th day after infection, which corresponds to the initial stage of infection, we collected serum for the determination of inflammatory cytokine levels. The mice serum of the AITC-administered group contained significantly lower levels of granulocyte colony-stimulating factor, interferon-gamma, interleukin (IL)-23 subunit p19, IL-4, IL-6, and monocyte chemoattractant protein-1. The lifespan of the mice in the AITC-administered group was significantly reduced. In vitro experiments showed that AITC promoted the proliferation of intracellular T. gondii accompanied by the inhibition of IL-4, IL-1β, and IL-6 production in RAW264.7 macrophages. Our results showed that AITC facilitated T. gondii infection in the early stage by inhibiting the production of several inflammatory cytokines.

Allyl isothiocyanate (AITC) is a natural product commonly used in food preservation and pharmaceutical applications. Toxoplasmosis, caused by the protozoan pathogen Toxoplasma gondii, is prevalent globally while the impact of AITC on toxoplasmosis is unclear. We explored the effect of AITC on acute toxoplasmosis. We infected C57BL/6 mice with T. gondii type I RH strain following AITC administration. On the 4th day after infection, which corresponds to the initial stage of infection, we collected serum for the determination of inflammatory cytokine levels. The mice serum of the AITC-administered group contained significantly lower levels of granulocyte colony-stimulating factor, interferon-gamma, interleukin (IL)-23 subunit p19, IL-4, IL-6, and monocyte chemoattractant protein-1. The lifespan of the mice in the AITC-administered group was significantly reduced. In vitro experiments showed that AITC promoted the proliferation of intracellular T. gondii accompanied by the inhibition of IL-4, IL-1β, and IL-6 production in RAW264.7 macrophages. Our results showed that AITC facilitated T. gondii infection in the early stage by inhibiting the production of several inflammatory cytokines.

Allyl isothiocyanate (AITC) is a natural product commonly used in food preservation and pharmaceutical applications. Toxoplasmosis, caused by the protozoan pathogen Toxoplasma gondii, is prevalent globally while the impact of AITC on toxoplasmosis is unclear. We explored the effect of AITC on acute toxoplasmosis. We infected C57BL/6 mice with T. gondii type I RH strain following AITC administration. On the 4th day after infection, which corresponds to the initial stage of infection, we collected serum for the determination of inflammatory cytokine levels. The mice serum of the AITC-administered group contained significantly lower levels of granulocyte colony-stimulating factor, interferon-gamma, interleukin (IL)-23 subunit p19, IL-4, IL-6, and monocyte chemoattractant protein-1. The lifespan of the mice in the AITC-administered group was significantly reduced. In vitro experiments showed that AITC promoted the proliferation of intracellular T. gondii accompanied by the inhibition of IL-4, IL-1β, and IL-6 production in RAW264.7 macrophages. Our results showed that AITC facilitated T. gondii infection in the early stage by inhibiting the production of several inflammatory cytokines.

Allyl isothiocyanate (AITC) is a natural product commonly used in food preservation and pharmaceutical applications. Toxoplasmosis, caused by the protozoan pathogen Toxoplasma gondii, is prevalent globally while the impact of AITC on toxoplasmosis is unclear. We explored the effect of AITC on acute toxoplasmosis. We infected C57BL/6 mice with T. gondii type I RH strain following AITC administration. On the 4th day after infection, which corresponds to the initial stage of infection, we collected serum for the determination of inflammatory cytokine levels. The mice serum of the AITC-administered group contained significantly lower levels of granulocyte colony-stimulating factor, interferon-gamma, interleukin (IL)-23 subunit p19, IL-4, IL-6, and monocyte chemoattractant protein-1. The lifespan of the mice in the AITC-administered group was significantly reduced. In vitro experiments showed that AITC promoted the proliferation of intracellular T. gondii accompanied by the inhibition of IL-4, IL-1β, and IL-6 production in RAW264.7 macrophages. Our results showed that AITC facilitated T. gondii infection in the early stage by inhibiting the production of several inflammatory cytokines.

Allyl isothiocyanate (AITC) is a natural product commonly used in food preservation and pharmaceutical applications. Toxoplasmosis, caused by the protozoan pathogen Toxoplasma gondii, is prevalent globally while the impact of AITC on toxoplasmosis is unclear. We explored the effect of AITC on acute toxoplasmosis. We infected C57BL/6 mice with T. gondii type I RH strain following AITC administration. On the 4th day after infection, which corresponds to the initial stage of infection, we collected serum for the determination of inflammatory cytokine levels. The mice serum of the AITC-administered group contained significantly lower levels of granulocyte colony-stimulating factor, interferon-gamma, interleukin (IL)-23 subunit p19, IL-4, IL-6, and monocyte chemoattractant protein-1. The lifespan of the mice in the AITC-administered group was significantly reduced. In vitro experiments showed that AITC promoted the proliferation of intracellular T. gondii accompanied by the inhibition of IL-4, IL-1β, and IL-6 production in RAW264.7 macrophages. Our results showed that AITC facilitated T. gondii infection in the early stage by inhibiting the production of several inflammatory cytokines.

OBJECTIVES: To identify cuproptosis- and ferroptosis-related genes involved in nonalcoholic fatty liver disease and to determine the diagnostic value of hub genes. METHODS: The gene expression dataset GSE89632 was retrieved from the Gene Expression Omnibus database to identify differentially expressed genes (DEGs) between the non-alcoholic steatohepatitis (NASH) group and the healthy group using the 'limma' package in R software and weighted gene co-expression network analysis. Gene ontology, kyoto encyclopedia of genes and genomes pathway, and single-sample gene set enrichment analyses were performed to identify functional enrichment of DEGs. Ferroptosis- and cuproptosis-related genes were obtained from the FerrDb V2 database and available literatures, respectively. A combined signature for cuproptosis- and ferroptosis-related genes, called CRF, was constructed using the STRING database. Hub genes were identified by overlapping DEGs, WGCNA-derived key genes, and combined signature CRF genes, and validated using the GSE109836 and GSE227714 datasets and real-time quantitative polymerase chain reaction. A nomogram of NASH diagnostic model was established utilizing the 'rms' package in R software based on the hub genes, and the diagnostic value of hub genes was assessed using receiver operating characteristic curve analysis. In addition, immune cell infiltration in NASH versus healthy controls was examined using the CIBERSORT algorithm. The relationships among various infiltrated immune cells were explored with Spearman's correlation analysis. RESULTS: Analysis of GSE89632 identified 236 DEGs between the NASH group and the healthy group. WGCNA highlighted 8 significant modules and 11,095 pivotal genes, of which 330 genes constituted CRF. Intersection analysis identified IL6, IL1B, JUN, NR4A1, and PTGS2 as hub genes. The hub genes were all downregulated in the NASH group, and this result was further verified by the NASH validation dataset and real-time quantitative polymerase chain reaction. Receiver operating characteristic curve analysis confirmed the diagnostic efficacy of these hub genes with areas under the curve of 0.985, 0.941, 1.000, 0.967, and 0.985, respectively. Immune infiltration assessment revealed that gamma delta T cells, M1 macrophages, M2 macrophages, and resting mast cells were predominantly implicated. CONCLUSIONS Our investigation underscores the significant association of cuproptosis- and ferroptosis-related genes, specifically IL6, IL1B, JUN, NR4A1, and PTGS2, with NASH. These findings offer novel insights into the pathogenesis of NASH, potentially guiding future diagnostic and therapeutic strategies.
Non-alcoholic Fatty Liver Disease/pathology* ; Humans ; Ferroptosis/genetics* ; Copper/metabolism* ; Gene Ontology ; Gene Expression Profiling

Objective: To describe fertility and explore factors associated with it among pre-conception couples of childbearing age. Methods: Based on the pre-conceptional offspring trajectory study of the School of Public Health of Fudan University, couples of childbearing age who participated in the pre-conception physical examination in Shanghai Jiading District from 2016 to 2021 were recruited and followed up. Couples' time to pregnancy (TTP) was analyzed and Cox proportional hazards regression model was used to explore the factors associated with TTP. Kaplan-Meier was used to calculate each menstrual cycle's cumulative pregnancy rate. Results: A total of 1 095 preconception couples were included in the analysis, the M(Q₁,Q₃)of TTP was 4.33 (2.41, 9.78) menstrual cycles. Age of women (FR=0.90, 95%CI: 0.85-0.95, P<0.001), women who were overweight or obese before pregnancy (FR=0.36, 95%CI: 0.24-0.55, P<0.001), women who were exposed to second-hand smoking (FR=0.63, 95%CI: 0.44-0.92, P=0.016), women whose home or office had been renovated in the past 2 years and had a particular smell (FR=0.46, 95%CI: 0.26-0.81, P=0.008) were risk factors for impaired fertility. Regular menstrual cycles (FR=1.64, 95%CI: 1.16-2.31, P=0.005), females who often drank tea/coffee (FR=1.55, 95%CI: 1.11-2.17, P=0.011) and males who took folic acid before conception (FR=2.35, 95%CI: 1.38-4.23, P=0.002) were associated with better fertility. The cumulative pregnancy rate of 3, 6, and 12 menstrual cycles was 37.6%, 64.4%, and 78.4%, respectively. Conclusion: Older couples, overweight or obesity before pregnancy, irregular menstruation, exposure to secondhand smoke and decoration pollutants in females are associated with impaired fertility. Frequent tea/coffee drinking before pregnancy in females and taking folic acid before pregnancy in males are associated with shortened conception time.
Pregnancy ; Male ; Humans ; Female ; Cohort Studies ; Overweight/complications* ; Coffee ; Intention ; China/epidemiology* ; Fertility ; Obesity/complications* ; Tea

Mitral regurgitation(MR)is a common valvular heart disease in China,the prevalence of which increases with age,and most patients present with a wide range of cardiac or non-cardiac comorbidities.Transcatheter mitral valve edge-to-edge repair(TEER)has become a guideline-recommended,safe and effective treatment option for patients with severe primary or secondary mitral regurgitation.With the rapid development of TEER technology in China,relevant devices have been developed and approved for clinical trials,including the self-designed and manufactured JensClip system,which adopts a unique slider locking design to realize the innovation of mitral clip locking mode.Here we reported a case of JensClip device in treatment of a patient with degenerative mitral regurgitation(DMR).