Repeatedly next-generation sequencing during treatment follow-up of patients with small cell lung cancer.

Somatic alterations in tumors are a frequent occurrence. In small cell lung cancer (SCLC), these include mutations in the tumor suppressors TP53 and retinoblastoma (RB1). We used next generation sequencing (NGS) to study specific genetic variants and compare genetic and clinicopathological features of SCLC with healthy control genome. Ten SCLC patients receiving standard chemotherapy, between 2018 and 2019, from the First Hospital of Jilin University were included in this study. Prior patient treatment, NGS was performed using DNA isolated from blood plasma. New NGS analyses were performed after 2 and 4 treatment cycles. Four patients presented with different metastases at diagnosis. Overall, most genes tested presented missense or frameshift variants. TP53, RB1, CREBBP, FAT1 genes presented gain of stop codons. At the single-gene level, the most frequently altered genes were TP53 (8/10 patients, 80%) and RB1 (4/10 patients, 40%), followed by bromodomain containing 4 (BRD4), CREBBP, FAT1, FMS-like tyrosine kinase 3 (FLT3), KDR, poly ADP-ribose polymerase (PARP1), PIK3R2, ROS1, and splicing factor 3b subunit 1 (SF3B1) (2/10 patients, 20%). We identified 5 genes, which have not been previously reported to bear mutations in the context of SCLC. These genes include BRD4, PARP1, FLT3, KDR, and SF3B1. We observed that among the studied individuals, patients with a high number of genetic events, and in which such mutations were not eradicated after treatment, showed a worse prognosis. There has not yet been given enough attention to the above-mentioned genes in SCLC, which will have great clinical prospects for treatment.

A Multi-hospital Study in Wuhan, China：Protective Effects of Non-menopause and Female Hormones on SARS-CoV-2 infection

ImportanceHow to explain the better prognosis of female coronavirus disease 2019 (COVID-19) patients than that of males? ObjectiveTo determine the correlation between menstruation status/sex hormones and prognosis of COVID-19, and to identify potential protective factors for female patients. Design, Setting, and ParticipantsA cross-sectional study of COVID-19 patients who were hospitalized at Tongji and Mobile Cabin Hospitals from Jan 28, 2020 to March 8, 2020. ExposuresConfirmed SARS-CoV-2 infection. Main Outcomes and MeasuresSex differences in severity and composite endpoints (admission to intensive care unit (ICU), use of mechanical ventilation, or death) of COVID-19 patients were compared. The correlation analysis and cox/logistic regression modeling of menstruation status/sex hormones and prognosis were conducted. Correlation between cytokines related to immunity and inflammation and disease severity or estradiol (E2) was revealed. ResultsChi square test indicated significant differences in distribution of composite endpoints (p<0.01) and disease severity (p=0.05) between male and female patients (n=1902). 435 female COVID-19 patients with menstruation records were recruited. By the end of Mar 8, 111 patients recovered and discharged (25.3%). Multivariate Cox regression model adjusted for age and severity indicated that post-menopausal patients show the greater risk of hospitalization time than non-menopausal patients (relative hazard [RH], 1.91; 95% confidence interval [CI], 1.06-3.46) Logistic regression model showed that higher anti-mullerian hormone (AMH) as a control for age increases the risk of severity of COVID-19 (HR=0.146,95%CI = (0.026-0.824) p=0.029). E2 showed protective effect against disease severity (HR= 0.335, 95%CI = (0.105-1.070), p= 0.046). In the Mann-Whitney U test, the higher levels of IL6 and IL8 were found in severe group (p= 0.040, 0.033). The higher levels of IL2R, IL6, IL8 and IL10 were also observed in patients with composite end points (p<0.001, <0.001, 0.009, 0.040). E2 levels were negatively correlated with IL2R, IL6, IL8 and TNF in luteal phase (Pearson Correlation=-0.592, -0.558, -0.545, -0.623; p=0.033, 0.048, 0.054, 0.023) and with C3 in follicular phase (Pearson Correlation=-0.651; p=0.030). Conclusions and RelevanceMenopause is an independent risk factor for COVID-19. E2 and AMH are negatively correlated with COVID-19s severity probably due to their regulation of cytokines related to immunity and inflammation. Key PointsO_ST_ABSQuestionC_ST_ABSAny differences in the outcomes between hospitalized female and male COVID-19 patients? If so, why? FindingsFemale patients display better prognosis than male patients. Non-menopausal women have shorter length of hospital stays, and AMH and E2 are negatively correlated with COVID-19s severity. There is a negative correlation between E2 and the levels of IL6, IL8, IL2R and TNF-, which are significantly correlated with disease severity or composite endpoint. MeaningNon-menopause and female sex hormones, especially E2 and AMH, are potential protective factors for females COVID-19 patients. E2 supplements could be potentially used for COVID-19 patients.

Clinical features and sexual transmission potential of SARS-CoV-2 infected female patients: a descriptive study in Wuhan, China

BackgroundAs of March 2, 2020, SARS-CoV-2 has infected more than 80174 people and caused 2915 deaths in China. This virus rapidly spreads to 56 countries worldwide. Thus, in order to effectively block its transmission, it is urgent to uncover all the possible transmission routes of SARS-CoV-2. MethodsFrom January 28 to February 18, 2020, 35 female patients diagnosed with COVID-19 in Tongji Hospital were included in this descriptive study. The gynecologic history, clinical characteristics, laboratory findings and chest computed tomography (CT) of all patients were recorded in detail. To examine whether there is sexual transmission through vaginal from female to her partner, we employed real-time polymerase chain reaction testing (RT-PCR) to detect SARS-CoV-2 in vaginal environment (including vaginal discharge, cervical or vaginal residual exfoliated cells) and anal swab samples, and inquired recent sexual behaviors from the patients. FindingsThe age range of the 35 patients with COVID-19 was 37-88 years. Over 50% patients infected with SARS-CoV-2 had chronic diseases. We tested the vaginal environment and anal swabs from the 35 female patients with COVID-19 and found that only an anal swab sample from one patient was positive for SARS-CoV-2. All the samples from vaginal environment were negative for SARS-CoV-2. The infection rate of the patients sexual partner was 42{middle dot}9%. Additionally, two female patients admitted having sex with their partners during a possible infection incubation period, while one patients partner was uninfected and the other patients partner was diagnosed with COVID-19 (after the diagnosis of the female patient). ConclusionNo positive RT-PCR result was found in the vaginal environment perhaps due to the lack of ACE2 expression, which is the receptor of SARS-CoV-2, in the vagina and cervix tissues (human protein atlas). The results from this study show no evidence of transmission of SARS-CoV-2 through vaginal sex from female to her partner. However, the risk of infection of non vaginal sex and other intimate contacts during vaginal sex should not be ignored. FundingThis work was financially supported by the Clinical Research Pilot Project of Tongji hospital, Huazhong University of Science and Technology (No. 2019CR205).

Folate-conjugated polyspermine for lung cancer-targeted gene therapy

Biodegradable polyamines have long been studied as potential recombinant viral gene vectors. Spermine (SPE) is an endogenous tetra-amine with excellent biocompatibility yet poor gene condensation capacity. We have previously synthesized a polyspermine based on SPE and poly(ethylene glycol) (PEG) diacrylate (SPE-alt-PEG) for enhanced transfection performance, but the synthesized SPE-alt-PEG still lacked specificity towards cancer cells. In this study, folic acid (FA) was incorporated into SPE-alt-PEG to fabricate a targeted gene delivery vector (FA-SPE-PEG) via an acylation reaction. FA-SPE-PEG exhibited mild cytotoxicity in both cancer cells and normal cells. FA-SPE-PEG possessed higher transfection efficiency than PEI 25 K and Lipofectamine(®) 2000 in two tested cancer cell lines at functional weight ratios, and its superiority over untargeted SPE-alt-PEG was prominent in cells with overexpressed folate receptors (FRs). Moreover, in vivo delivery of green fluorescent protein (GFP) with FA-SPE-PEG resulted in highest fluorescent signal intensity of all investigated groups. FA-SPE-PEG showed remarkably enhanced specificity towards cancer cells both in vivo and in vitro due to the interaction between FA and FRs. Taken together, FA-SPE-PEG was demonstrated to be a prospective targeted gene delivery vector with high transfection capacity and excellent biocompatibility.

A comparative study on two different biopsy techniques in the diagnosis of pancreatic cancer / 中华普通外科杂志

Objective To compare wedge biopsy and disposable automatic biopsy gun biopsy for the diagnosis of pancreatic cancer. Methods The clinical data of 217 patients with unresectable pancreatic cancer undergoing palliative operation and biopsy were retrospectively analyzed in our hospital from March 25,2006 to March 25,2011.Group A(wedge biopsy) consisted of 120 cases and B( disposable automated biopsy gun biopsy) of 97 cases.The success rate of biopsy,the positive rate of biopsy,the accuracy of diagnosis and the incidence of postoperative complications were calculated. Results The success rate,positive rate,diagnostic accuracy and the incidence of postoperative hemorrhage of group A and B were 100％,97.5％,97.5％,1.7％ and 100％,99％,99％,1.0％,respectively ( all P ＞ 0.05 ).The incidence of postoperative pancreatic leakage in group A and B were 11.7％ and 2.1％ (P =0.007 ).Conclusions Intra-operative biopsy for the diagnosis of pancreatic cancer using disposable automated biopsy gun biopsy has significantly decreased the incidence of post-biopsy pancreatic leakage as compared with wedge biopsy.