Background::The incidence rate of lung cancer in women has significantly increased over the past decade, and previous evidence has indicated a significant relationship between the elevated levels of sex hormones and the risk of lung cancer. Therefore, we hypothesized that female hormone-related cancer (FHRC) patients, including breast, endometrial, cervical, and ovarian cancer patients, may experience a higher risk of developing subsequent lung cancer. This meta-analysis aimed to identify the risk of lung cancer among FHRC patients compared to the general population.Methods::The PubMed, Web of Science, EMBASE, Cochrane Library, and CNKI databases were searched up to May 11, 2022. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were used to identify the risk of subsequent lung cancer after FHRC. Subgroup analyses based on the follow-up time and tumor type were also conducted.Results::A total of 58 retrospective cohort studies involving 4,360,723 FHRC participants were included. The pooled results demonstrated that FHRC patients had a significantly increased risk of developing subsequent primary lung cancer (SIR = 1.61, 95% CI: 1.48-1.76, P <0.001). Subgroup analysis revealed an obvious trend of increasing lung cancer risk over time (SIRs for <5 years, ≥5 years, ≥10 years, ≥20 years, and ≥30 years after FHRC: 1.32, 1.59, 1.57, 1.68, and 1.95, respectively). In addition, subgroup analysis stratified by tumor type indicated an increased risk of developing subsequent lung cancer after breast (SIR = 1.25, P <0.001), endometrial (SIR = 1.40, P = 0.019), cervical (SIR = 2.56, P <0.001), and ovarian cancer (SIR = 1.50, P = 0.010). Conclusion::FHRC patients are more likely to develop lung cancer than the general population. Furthermore, the increased risk of subsequent primary lung cancer is more obvious with a longer survival time and is observed in all types of hormone-related cancer.Registration::International Platform of Registered Systematic Review and Meta-analysis Protocols: No. INPLASY202270044; https://inplasy.com/

Objective To explore the role and mechanism of RNA demethylase fat mass and obesity-associated protein(FTO)in the ferroptosis in testicular interstitial cells induced by di(2-ethylhexyl)phthalate(DEHP).Methods Forty 3-week-old C57BL/6 male mice were randomly divided into a control group(corn oil)and 3 dosed DEHP treatment groups(5,250 and 500 mg/kg),and received an intragastric infusion of corresponding agents for 35 d,respectively.After mouse testicular interstitial TM3 cells was treated with 0,100,200 and 400 μmol/L mono-2-ethylhexyl phthalate(MEHP)for 24 h,corresponding plasmids were transfected to construct Fto overexpressing TM3 cells.Serum testosterone level was detected by ELISA,expression of testicular proteins was detected with immunohistochemical assay,and contents of Fe2+,malondialdehyde(MDA)and lipid peroxides in the testicle were detected by colorimetry.Methylated RNA immunoprecipitation,RT-PCR,and Western blotting were used to detect the level of N6-methyladenosine(m6A)modification.Results In the mice exposed to 250 and 500 mg/kg DEHP,the serum testosterone level was significantly reduced(P＜0.01),contents of Fe2+,MAD and lipid peroxides in testicular tissue were obviously increased(P＜0.01),and protein levels of RNA demethylase FTO,and ferroptosis related molecules ferritin heavy chain 1(FTH1)and glutathione peroxidase 4(GPX4)were significantly down-regulated(P＜0.05),while those of transferrin receptor(TFRC),ferroportin(FPN),cyclooxygenase-2(COX-2),and acyl-CoA synthetase long-chain family member 4(ACSL4)were notably up-regulated(P＜0.05).MEHP treatment for 24 h resulted in remarkably decreased cell viability in the TM3 cells,increased production of intracellular reactive oxygen species(ROS),reduced mitochondrial membrane potential(MMP)(P＜0.01),down-regulated mRNA and protein levels of Fto(P＜0.01),and the changes in other ferroptosis related proteins were consistent with the trend in testicular tissue,indicating ferroptosis in testicular interstitial cells.Intervention with ferroptosis inhibitor Fer-1 or overexpression of Fto significantly inhibited MEHP-induced toxicity and ferroptosis in TM3 cells(P＜0.05),and overexpression of Fto reduced the m6A modification of Gpx4 and Fth1 mRNA(P＜0.05).Conclusion Abnormal m6A modification of Gpx4 and Fth1 caused by inhibiting FTO expression may be the mechanism of ferroptosis in testicular interstitial cells induced by DEHP.

Abstract As a new type of pollutant, microplastics have attracted extensive attention. Children in a critical stage of growth and development are vulnerable to microplastics. Summarzing the relevant laws and regulations and the source of microplastics, the paper demonstrates the ways of microplastics entering human body, some toxic effects of microplastics found in recent experimental studies and their potential hazards to children s health are introduced in detail.

Objective    To explore the relationship between metformin use and the risk and prognosis of esophageal cancer in patients with diabetes. Methods    The PubMed, Web of Science, EMbase, VIP, WanFang and CNKI databases were searched by computer to identify relevant studies from inception to August 21, 2021. Newcastle-Ottawa scale (NOS) was used to evaluate research quality. The STATA 12.0 software was used to conduct the statistical analysis. Results    A total of 14 studies involving 5 605 218 participants were included finally. NOS of all researches were≥6 points. The pooled results indicated that metformin use could decrease the risk of esophageal cancer in diabetics (OR=0.84, 95%CI 0.71-1.00, P=0.045), and could also prolong the overall survival of diabetics with esophageal cancer (HR=0.89, 95%CI 0.80-0.99, P=0.025). Conclusion    Metformin use can not only decrease the risk of esophageal cancer in patients with diabetes, but also improve the prognosis of diabetics with esophageal cancer significantly. However, more prospective high-quality studies are still needed to verify the conclusion.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutations are often associated with non-EGFR genetic alterations, which may be a reason for the poor efficacy of EGFR tyrosine kinase inhibitors (TKIs). Here we conducted this study to explore whether EGFR-TKIs combined with chemotherapy would benefit advanced lung adenocarcinoma patients with both sensitive EGFR mutation and concomitant non-EGFR genetic alterations. METHODS: Cases of advanced lung adenocarcinoma with EGFR mutation combined with concomitant non-EGFR genetic alterations were retrospectively collected. And the patients were required to receive first-line EGFR-TKIs and chemotherapy combination or EGFR-TKIs monotherapy. Demographic, clinical and pathological data were collected, and the electronic imaging data were retrieved to evaluate the efficacy and time of disease progression. Survival data were obtained through face-to-face or telephone follow-up. The differences between the two groups in objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were investigated. RESULTS 107 patients were included, including 63 cases in the combination group and 44 cases in the monotherapy group. The ORR were 78% and 50% (P=0.003), and DCR were 97% and 77% (P=0.002), respectively. At a median follow-up of 13.7 mon, a PFS event occurred in 38.1% and 81.8% of patients in the two groups, with median PFS of 18.8 mon and 5.3 mon, respectively (P<0.000,1). Median OS was unreached in the combination group, and 27.8 mon in the monotherapy group (P=0.31). According to the Cox multivariate regression analysis, combination therapy was an independent prognostic factor of PFS CONCLUSIONS: In patients with EGFR-mutant advanced lung adenocarcinoma with concomitant non-EGFR genetic alterations, combination of TKIs and chemotherapy was significantly superior to EGFR-TKIs monotherapy, which should be the preferred treatment option.
Adenocarcinoma of Lung/genetics* ; ErbB Receptors/genetics* ; Humans ; Lung Neoplasms/pathology* ; Mutation ; Protein Kinase Inhibitors/therapeutic use* ; Retrospective Studies

Conventional therapies for hemophilia A (HA) are prophylactic or on-demand intravenous FVIII infusions. However, they are expensive and inconvenient to perform. Thus, better strategies for HA treatment must be developed. In this study, a recombinant FVIII cDNA encoding a human/rat hybrid FVIII with an enhanced procoagulant potential for adeno-associated virus (AAV)-delivered gene therapy was developed. Plasmids containing human FVIII heavy chain (hHC), human light chain (hLC), and rat light chain (rLC) were transfected into cells and hydrodynamically injected into HA mice. Purified AAV viruses were intravenously injected into HA mice at two doses. Results showed that the hHC + rLC protein had a higher activity than the hHC + hLC protein at comparable expression levels. The specific activity of hHC + rLC was about 4- to 8-fold higher than that of their counterparts. Hydrodynamic injection experiments obtained consistent results. Notably, the HA mice undergoing the AAV-delivered hHC + rLC treatment exhibited a visibly higher activity than those treated with hHC + hLC, and the therapeutic effects lasted for up to 40 weeks. In conclusion, the application of the hybrid FVIII (hHC + rLC) via an AAV-delivered gene therapy substantially improved the hemorrhagic diathesis of the HA mice. These data might be of help to the development of optimized FVIII expression cassette for HA gene therapy.
Animals ; Dependovirus/genetics* ; Factor VIII/metabolism* ; Genetic Therapy/methods* ; Hemophilia A/therapy* ; Humans ; Mice ; Rats

BACKGROUND: Patients with pulmonary nodules are treated by minimally invasive surgery, and postoperative symptoms have become the main factors affecting patients' emotion and quality of life. This study aimed to analyze the changes of postoperative symptoms in lung cancer patients with pulmonary nodules. METHODS: The clinical data of eighty-eight lung cancer patients admitted to the same medical group of Department of Thoracic Surgery, West China Hospital of Sichuan University from June 2021 to September 2021 were prospectively collected and analyzed. The types and severity of clinical symptoms before operation, on discharge day, 30-day and 90-day after operation were analyzed. RESULTS: The incidence of postoperative symptoms in lung cancer patients was 79.5%, and most patients suffered from mild (54.3%) and moderate (32.9%) symptoms. The main postoperative symptoms of lung cancer patients were pain (55.7%) and cough (37.2%). The incidence of pain at discharge (55.7%) was significantly higher than that at 30-day (23.7%, P=0.01) and 90-day (12.0%, P=0.01) after discharge. The incidence of cough was significantly higher at 30-day (66.1%) and 90-day (66.0%) than that at discharge (37.2%) (P=0.01, P=0.04). CONCLUSIONS The main postoperative symptoms of lung cancer patients with pulmonary nodules are pain and cough. The incidence and severity of pain decreases with time, and the incidence of cough increases but the severity decreased gradually.
Cough/etiology* ; Humans ; Lung Neoplasms/surgery* ; Pain/etiology* ; Pneumonectomy/adverse effects* ; Quality of Life ; Thoracic Surgery, Video-Assisted/adverse effects*

Liver transplantation is one of the main treatments of early hepatocellular carcinoma (HCC). The recurrence of HCC after liver transplantation severely affects the long-term survival rate of the recipients. Targeted therapy and immunotherapy play a critical role in HCC downstaging, preventing disease progression, reducing recurrence rate, prolonging the survival and improving the quality of life. However, no consensus has been reached on the application of targeted therapy and immunotherapy in recipients undergoing liver transplantation for HCC, including indications, timing and dosage. In this article, clinical research progresses on the indications and timing of targeted therapy and immunotherapy before and after liver transplantation for HCC were reviewed, aiming to provide reference for prolonging the survival of recipients after liver transplantation for HCC.

Objective To investigate the effects of cholesterol-lowering agents on the proliferation, stemness characters, migration, invasion, and neutrophil extracellular traps formation (NETs) formation in liver cancer cells. Methods ASPP2 or HMGCR gene was knocked down in mouse liver cancer cell Hepa1-6 to establish cells with high or low cholesterol, respectively. Simvastatin and berberine were used to reduce cholesterol synthesis. CCK-8 and plate cloning assays were conducted to detect the proliferation ability of liver cancer cells. Sphere formation assay and qRT-PCR were used to analyze the stemness character and expression of related genes. Wound-healing assay and Transwell assay were used to analyze the ability of cell migration and invasion. Immunofluorescence staining was carried out to analyze the effect of lipid-lowering agent on NETs formation. Results Cholesterol-lowering agents significantly inhibited the proliferation and stemness-related gene expression of Hepa1-6 cells (P < 0.001), significantly inhibited the migration and invasion of Hepa1-6 cells (P < 0.001), and significantly inhibited the neutrophil-induced invasion and formation of NETs (P < 0.001). Conclusion Cholesterol-lowering agents suppress the proliferation and invasion via inhibiting the stemness characters and NETs formation in liver cancer cells. It is a potential strategy for the treatment of liver cancer metastasis.

Objective    To explore the correlation of preoperative D-dimer (DD) level with prognosis in Chinese esophageal cancer patients. Methods    PubMed, EMbase, Web of Science, Cochrane Library, CNKI, VIP, Wanfang, SinoMed databases were searched to identify potential studies which assessed prognostic value of preoperative DD level in Chinese esophageal cancer patients from the establishment date of each database to March 20, 2019. The Stata 12.0 software was applied to conduct the meta-analysis and the hazard ratio (HR) with 95% confidence interval (CI) was combined to evaluate the relation between preoperative DD level and survival of Chinese esophageal cancer patients. Results    A total of 5 studies involving 1 277 patients were included. The quality score of each study was ≥6 points. The results showed that the elevated preoperative DD level was significantly associated with poor overall survival (OS, HR=1.49, 95%CI 1.05-2.10, P=0.025) and cancer-specific survival (CSS, HR=1.83, 95%CI 1.39-2.42, P<0.001). However, no significant relation of preoperative DD with disease-free survival (DFS) was observed (HR=1.55, 95%CI 0.89-2.70, P=0.125). Conclusion    High preoperative DD level may be an independent prognostic factor for Chinese patients with esophageal cancer. More prospective studies with bigger sample sizes are still needed to verify our results.