Objective: To explore the application and efficacy of paclitaxel liposome in the treatment of advanced breast cancer among Chinese population in the real world. Methods: The clinical characteristics of patients with advanced breast cancer who received paclitaxel liposome as salvage treatment from January 1, 2016 to August 31, 2019 in 11 hospitals were collected and retrospectively analyzed. The primary outcome was progression free survival (PFS), and the secondary outcome included objective response rate (ORR) and safety. The survival curve was drawn by Kaplan-Meier analysis and the Cox regression model were used for the multivariate analysis. Results: Among 647 patients with advanced breast cancer who received paclitaxel liposome, the first-line treatment accounted for 43.3% (280/647), the second-line treatment accounted for 27.7% (179/647), and the third-line and above treatment accounted for 29.1% (188/647). The median dose of first-line and second-line treatment was 260 mg per cycle, and 240 mg in third line and above treatment. The median period of paclitaxel liposome alone and combined chemotherapy or targeted therapy is 4 cycles and 6 cycles, respectively. In the whole group, 167 patients (25.8%) were treated with paclitaxel liposome combined with capecitabine±trastuzumab (TX±H), 123 patients (19.0%) were treated with paclitaxel liposome alone (T), and 119 patients (18.4%) were treated with paclitaxel liposome combined with platinum ± trastuzumab (TP±H), 108 patients (16.7%) were treated with paclitaxel liposome combined with trastuzumab ± pertuzumab (TH±P). The median PFS of first-line and second-line patients (5.5 and 5.5 months, respectively) were longer than that of patients treated with third line and above (4.9 months, P<0.05); The ORR of the first line, second line, third line and above patients were 46.7%, 36.8% and 28.2%, respectively. Multivariate analysis showed that event-free survival (EFS) and the number of treatment lines were independent prognostic factors for PFS. The common adverse events were myelosuppression, gastrointestinal reactions, hand foot syndrome and abnormal liver function. Conclusion: Paclitaxel liposomes is widely used and has promising efficacy in multi-subtype advanced breast cancer.
Humans ; Female ; Breast Neoplasms/chemically induced* ; Paclitaxel/adverse effects* ; Liposomes/therapeutic use* ; Retrospective Studies ; Treatment Outcome ; Trastuzumab/therapeutic use* ; Capecitabine/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects*

OBJECTIVE: To investigate the anti-coronavirus potential and the corresponding mechanisms of the two ingredients of Reduning Injection: quercetin and luteolin. METHODS: A pseudovirus system was designed to test the efficacy of quercetin and luteolin to inhibit SARS-CoV-2 infection and the corresponding cellular toxicity. Luteolin was tested for its activities against the pseudoviruses of SARS-CoV-2 and its variants. Virtual screening was performed to predict the binding sites by Autodock Vina 1.1.230 and PyMol. To validate docking results, surface plasmon resonance (SPR) was used to measure the binding affinity of the compounds with various proteins of the coronaviruses. Quercetin and luteolin were further tested for their inhibitory effects on other coronaviruses by indirect immunofluorescence assay on rhabdomyosarcoma cells infected with HCoV-OC43. RESULTS: The inhibition of SARS-CoV-2 pseudovirus by luteolin and quercetin were strongly dose-dependent, with concentration for 50% of maximal effect (EC₅₀) of 8.817 and 52.98 µmol/L, respectively. Their cytotoxicity to BHK21-hACE2 were 177.6 and 405.1 µmol/L, respectively. In addition, luetolin significantly blocked the entry of 4 pseudoviruses of SARS-CoV-2 variants, with EC₅₀ lower than 7 µmol/L. Virtual screening and SPR confirmed that luteolin binds to the S-proteins and quercetin binds to the active center of the 3CLpro, PLpro, and helicase proteins. Quercetin and luteolin showed over 99% inhibition against HCoV-OC43. CONCLUSIONS The mechanisms were revealed of quercetin and luteolin inhibiting the infection of SARS-CoV-2 and its variants. Reduning Injection is a promising drug for COVID-19.
Humans ; SARS-CoV-2 ; COVID-19 ; Luteolin ; Quercetin

OBJECTIVE: To investigate the anti-coronavirus potential and the corresponding mechanisms of the two ingredients of Reduning Injection: quercetin and luteolin. METHODS: A pseudovirus system was designed to test the efficacy of quercetin and luteolin to inhibit SARS-CoV-2 infection and the corresponding cellular toxicity. Luteolin was tested for its activities against the pseudoviruses of SARS-CoV-2 and its variants. Virtual screening was performed to predict the binding sites by Autodock Vina 1.1.230 and PyMol. To validate docking results, surface plasmon resonance (SPR) was used to measure the binding affinity of the compounds with various proteins of the coronaviruses. Quercetin and luteolin were further tested for their inhibitory effects on other coronaviruses by indirect immunofluorescence assay on rhabdomyosarcoma cells infected with HCoV-OC43. RESULTS: The inhibition of SARS-CoV-2 pseudovirus by luteolin and quercetin were strongly dose-dependent, with concentration for 50% of maximal effect (EC₅₀) of 8.817 and 52.98 µmol/L, respectively. Their cytotoxicity to BHK21-hACE2 were 177.6 and 405.1 µmol/L, respectively. In addition, luetolin significantly blocked the entry of 4 pseudoviruses of SARS-CoV-2 variants, with EC₅₀ lower than 7 µmol/L. Virtual screening and SPR confirmed that luteolin binds to the S-proteins and quercetin binds to the active center of the 3CLpro, PLpro, and helicase proteins. Quercetin and luteolin showed over 99% inhibition against HCoV-OC43. CONCLUSIONS The mechanisms were revealed of quercetin and luteolin inhibiting the infection of SARS-CoV-2 and its variants. Reduning Injection is a promising drug for COVID-19.

Purpose: The aim of this study was to compare the efficacy of liver transplantation (LT) and liver resection (LR) for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) and to investigate risk factors affecting prognosis. Materials and Methods: A total of 94 HCC patients with PVTT type I (segmental PVTT) and PVTT type II (lobar PVTT) were involved and divided into LR (n=47) and LT groups (n=47). Recurrence-free survival (RFS) and overall survival (OS) were compared before and after inverse probability of treatment weighting (IPTW). Prognostic factors for RFS and OS were explored. Results: Two treatment groups were well-balanced using IPTW. In the entire cohort, LT provided a better prognosis than LR. Among patients with PVTT type I, RFS was better with LT (p=0.039); OS was not different significantly between LT and LR (p=0.093). In subgroup analysis of PVTT type I patients with α-fetoprotein (AFP) levels >200 ng/mL, LT elicited significantly longer median RFS (18.0 months vs. 2.1 months, p=0.022) and relatively longer median OS time (23.6 months vs. 9.8 months, p=0.065). Among patients with PVTT type II, no significant differences in RFS and OS were found between LT and LR (p=0.115 and 0.335, respectively). Multivariate analyses showed treatment allocation (LR), tumor size (>5 cm), AFP and aspartate aminotransferase (AST) levels to be risk factors of RFS and treatment allocation (LR), AFP and AST as risk factors for OS. Conclusion LT appeared to afford a better prognosis for HCC with PVTT type I than LR, especially in patients with AFP levels >200 ng/mL.

Background:The role of local treatment in oligometastatic prostate cancer (PCa) is gaining interest with the oligometastases hypothesis proposed and the improvement of various surgical methods and techniques.This study aimed to compare the short-term therapeutic outcomes of robotic-assisted laparoscopic radical prostatectomy (RALP) for oligometastatic prostate cancer (OPC) vs.localized PCa using propensity score matching.Methods:Totally 508 consecutive patients underwent RALP as a first-line treatment.The patients were divided into two groups according to oligometastatic state:the OPC group (n =41) or the localized PCa group (n =467).Oligometastatic disease was defined as the presence of two or fewer suspicious lesions.The association between the oligometastatic state and therapeutic outcomes of RALP was evaluated,including biochemical recurrence (BCR) and overall survival (OS).A Cox proportional hazards model was used to assess the possible risk factors for BCR.Results:Totally 41 pairs of patients were matched.The median operative time,the median blood loss,the overall positive surgical margin rate,the median post-operative hospital stays,and the post-operative urinary continence recovery rate between the two groups showed no statistical significance.The 4-year BCR survival rates of the OPC group and localized PCa group were 56.7％ and 60.8％,respectively,without a significant difference (P=0.804).The 5-year OS rates were 96.3％ and 100％,respectively (P =0.326).Additionally,the results of Cox regression showed that oligometastatic state was not an independent risk factor for BCR (P =0.682).Conclusions:Our findings supported the safety and effectiveness of RALP in OPC.Additionally,oligometastatic state and sites did not have an adverse effect on BCR independently.

BACKGROUND: At present, there is no available delirium translated assessment method for 3.3 million Tibetans. This study aimed to provide a method for delirium assessment for Tibetan patients speaking this language by validating a translation of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). METHODS: The study was conducted between July 2018 and November 2018. Patients were screened for delirium by a neurologist using the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV). Patients were subsequently screened by two nurses using Tibetan translations of the CAM-ICU. With DSM-IV criterion as the reference standard, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated to assess the validity of the CAM-ICU criterion. Interrater reliability was determined by comparing the CAM-ICU ratings of nurse 1 vs. nurse 2 using the κ coefficient. RESULTS: Ninety-six patients were assessed independently by two nurses and one neurologist. According to DSM-IV standard, 42 out of 96 (43.8%) patients developed delirium. The sensitivities of Tibetan CAM-ICU were 90.5% for nurse 1 and 92.9% for nurse 2, respectively. Their specificities were 85.2% and 90.7%, respectively. The PPV were 82.6% for nurse 1 and 88.6% for nurse 2. Their NPV were 92.0% and 94.2%, respectively. The Tibetan CAM-ICU was done with good interrater reliability between nurse 1 and nurse 2 (κ = 0.91, P < 0.001). CONCLUSION The Tibetan CAM-ICU shows good validity and might be incorporated into clinical practice in Tibetan Intensive Care Units. CLINICAL TRAIL REGISTRY:: www.chictr.org.cn (No. ChiCTR1800018231).

Background:: At present, there is no available delirium translated assessment method for 3.3 million Tibetans. This study aimed to provide a method for delirium assessment for Tibetan patients speaking this language by validating a translation of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Methods:: The study was conducted between July 2018 and November 2018. Patients were screened for delirium by a neurologist using the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV). Patients were subsequently screened by two nurses using Tibetan translations of the CAM-ICU. With DSM-IV criterion as the reference standard, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated to assess the validity of the CAM-ICU criterion. Interrater reliability was determined by comparing the CAM-ICU ratings of nurse 1 vs. nurse 2 using the κ coefficient. Results:: Ninety-six patients were assessed independently by two nurses and one neurologist. According to DSM-IV standard, 42 out of 96 (43.8%) patients developed delirium. The sensitivities of Tibetan CAM-ICU were 90.5% for nurse 1 and 92.9% for nurse 2, respectively. Their specificities were 85.2% and 90.7%, respectively. The PPV were 82.6% for nurse 1 and 88.6% for nurse 2. Their NPV were 92.0% and 94.2%, respectively. The Tibetan CAM-ICU was done with good interrater reliability between nurse 1 and nurse 2 (κ= 0.91, P < 0.001). Conclusion:: The Tibetan CAM-ICU shows good validity and might be incorporated into clinical practice in Tibetan Intensive Care Units. Clinical Trail Registry: www.chictr.org.cn (No. ChiCTR1800018231)

Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease with cellular and molecular mechanisms yet to be fully described. Mutations in a number of genes including SOD1 and FUS are associated with familial ALS. Here we report the generation of induced pluripotent stem cells (iPSCs) from fibroblasts of familial ALS patients bearing SOD1 and FUS mutations, respectively. We further generated gene corrected ALS iPSCs using CRISPR/Cas9 system. Genome-wide RNA sequencing (RNA-seq) analysis of motor neurons derived from SOD1 and corrected iPSCs revealed 899 aberrant transcripts. Our work may shed light on discovery of early biomarkers and pathways dysregulated in ALS, as well as provide a basis for novel therapeutic strategies to treat ALS.
Amyotrophic Lateral Sclerosis ; genetics ; metabolism ; therapy ; Cell Line ; Clustered Regularly Interspaced Short Palindromic Repeats ; Genetic Therapy ; Genome-Wide Association Study ; Humans ; Induced Pluripotent Stem Cells ; metabolism ; Mutation, Missense ; RNA-Binding Protein FUS ; genetics ; metabolism ; Superoxide Dismutase-1 ; genetics ; metabolism

Xeroderma pigmentosum (XP) is a group of genetic disorders caused by mutations of XP-associated genes, resulting in impairment of DNA repair. XP patients frequently exhibit neurological degeneration, but the underlying mechanism is unknown, in part due to lack of proper disease models. Here, we generated patient-specific induced pluripotent stem cells (iPSCs) harboring mutations in five different XP genes including XPA, XPB, XPC, XPG, and XPV. These iPSCs were further differentiated to neural cells, and their susceptibility to DNA damage stress was investigated. Mutation of XPA in either neural stem cells (NSCs) or neurons resulted in severe DNA damage repair defects, and these neural cells with mutant XPA were hyper-sensitive to DNA damage-induced apoptosis. Thus, XP-mutant neural cells represent valuable tools to clarify the molecular mechanisms of neurological abnormalities in the XP patients.
DNA Damage ; DNA Repair ; DNA-Binding Proteins ; genetics ; metabolism ; Female ; Humans ; Induced Pluripotent Stem Cells ; metabolism ; pathology ; Male ; Models, Biological ; Mutation ; Neural Stem Cells ; metabolism ; pathology ; Xeroderma Pigmentosum ; genetics ; metabolism ; pathology

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Cell Culture Techniques ; methods ; Child ; Female ; Humans ; Induced Pluripotent Stem Cells ; cytology ; metabolism ; Male ; Middle Aged