Pepsin-mediated inflammation in laryngopharyngeal reflux via the ROS/NLRP3/IL-1ß signaling pathway.

BACKGROUND: Laryngopharyngeal reflux (LPR) is one of the most common disorders in otorhinolaryngology, affecting up to 10% of outpatients visiting otolaryngology departments. In addition, 50% of hoarseness cases are related to LPR. Pepsin reflux-induced aseptic inflammation is a major trigger of LPR; however, the underlying mechanisms are unclear. The nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome has become an important bridge between stimulation and sterile inflammation and is activated by intracellular reactive oxygen species (ROS) in response to danger signals, leading to an inflammatory cascade. In this study, we aimed to determine whether pepsin causes LPR-associated inflammatory injury via mediating inflammasome activation and explore the potential mechanism. METHODS: We evaluated NLRP3 inflammasome expression and ROS in the laryngeal mucosa using immunofluorescence and immunohistochemistry. Laryngeal epithelial cells were exposed to pepsin and analyzed using flow cytometry, western blotting, and real-time quantitative PCR to determine ROS, NLRP3, and pro-inflammatorycytokine levels. RESULTS: Pepsin expression was positively correlated with ROS as well as caspase-1 and IL-1ß levels in laryngeal tissues. Intracellular ROS levels were elevated by increased pepsin concentrations, which were attenuated by apocynin (APO)-a ROS inhibitor-in vitro. Furthermore, pepsin significantly induced the mRNA and protein expression of thioredoxin-interacting protein, NLRP3, caspase-1, and IL-1ß in a dose-dependent manner. APO and the NLRP3 inhibitor, MCC950, inhibited NLRP3 inflammasome formation and suppressed laryngeal epithelial cell damage. CONCLUSION: Our findings verified that pepsin could regulate the NLRP3/IL-1ß signaling pathway through ROS activation and further induce inflammatory injury in LPR. Targeting the ROS/NLRP3 inflammasome signaling pathway may help treat patients with LPR disease.

Role of rs873601 Polymorphisms in Prognosis of Lung Cancer Patients Treated with Platinum-Based Chemotherapy.

BACKGROUND: Lung cancer is still the most lethal malignancy in the world, according to the report of Cancer Statistics in 2021. Platinum-based chemotherapy combined with immunotherapy is the first-line treatment in lung cancer patients. However, the 5-year survival rate is always affected by the adverse reactions and drug resistance caused by platinum-based chemotherapy. DNA damage and repair system is one of the important mechanisms that can affect the response to chemotherapy and clinical outcomes in lung cancer patients. OBJECTIVE: The objective of this study is to find the relationship between the polymorphisms of DNA repair genes with the prognosis of platinum-based chemotherapy in lung cancer patients. PATIENTS AND METHODS: We performed genotyping in 17 single nucleotide polymorphisms (SNPs) of Excision Repair Cross-Complementation group (ERCC) genes and X-ray Repair Cross-Complementing (XRCC) genes of 345 lung cancer patients via Sequenom MassARRAY. We used Cox proportional hazard models, state, and plink to analyze the associations between SNPs and the prognosis of lung cancer patients. RESULTS: We found that the ERCC5 rs873601 was associated with the overall survival time in lung cancer patients treated with platinum-based chemotherapy (p = 0.031). There were some polymorphisms that were related to the prognosis in specific subgroups of lung cancer. Rs873601 showed a great influence on the prognosis of patients more than 55 years, Small Cell Lung Cancer (SCLC), and smoking patients. Rs2444933 was associated with prognosis in age less than 55 years, SCLC, metastasis, and stage III/IV/ED patients. Rs3740051 played an important role in the prognosis of SCLC and metastasis patients. Rs1869641 was involved in the prognosis of SCLC patients. Rs1051685 was related to the prognosis in non-metastasis patients. CONCLUSION: The ERCC5 rs873601 (G>A) was a valuable biomarker for predicting the prognosis in lung cancer patients treated with platinum-based chemotherapy.

Disruption of Iron Homeostasis to Induce Ferroptosis with Albumin-Encapsulated Pt(IV) Nanodrug for the Treatment of Non-Small Cell Lung Cancer.

Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer , accounting for approximately 85% of lung cancers. For more than 40 years, platinum (Pt)-based drugs are still one of the most widely used anticancer drugs even in the era of precision medicine and immunotherapy. However, the clinical limitations of Pt-based drugs, such as serious side effects and drug resistance, have not been well solved. This study constructs a new albumin-encapsulated Pt(IV) nanodrug (HSA@Pt(IV)) based on the Pt(IV) drug and nanodelivery system. The characterization of nanodrug and biological experiments demonstrate its excellent drug delivery and antitumor effects. The multi-omics analysis of the transcriptome and the ionome reveals that nanodrug can activate ferroptosis by affecting intracellular iron homeostasis in NSCLC. This study provides experimental evidence to suggest the potential of HSA@Pt(IV) as a nanodrug with clinical application.

Cost-effectiveness analysis of sintilimab plus IBI305 versus sorafenib for unresectable hepatic cell carcinoma in China.

BACKGROUND: Sintilimab combined with IBI305 treatment regimen had potential clinical benefits than sorafenib in the first-line treatment of patients with unresectable hepatic cell carcinoma (HCC). However, whether sintilimab plus IBI305 has economic benefits in China remains unclear. METHODS: From the perspective of Chinese payers, we used the Markov model to simulate patients with HCC receiving treatment with sintilimab plus IBI305 and sorafenib. The transition probability between health states was estimated using the parametric survival model, and the cumulative medical costs and utility of the two treatment methods were estimated. Considering the incremental cost-effectiveness ratios (ICERs) as the evaluation index, sensitivity analyses were performed to explore the impact of uncertainty on the results. RESULTS: Compared to sorafenib, sintilimab plus IBI305 generated an additional $17552.17 and 0.33 quality-adjusted life years, resulting in an ICER of $52817.89. The analysis outcomes were most sensitive to the total cost of sintilimab plus IBI305. With a willingness-to-pay threshold of $38,334, sintilimab plus IBI305 showed a 1.28% probability of being cost-effective. The total cost of sintilimab plus IBI305 should be reduced by at least 31.9% to be accepted by Chinese payers. CONCLUSIONS: Regardless of whether the price of sintilimab plus IBI305 and sorafenib is covered by Medicare, sintilimab plus IBI305 is unlikely to be cost-effective for first-line treatment of patients with unresectable HCC.

Research advances in immune checkpoint drugs for non-small cell lung cancer.

Background: Non-Small Cell Lung Cancer (NSCLC) is one of the most prevalent malignancies globally, accounting for 85% of lung cancer cases. The rapid advancements in immunotherapy have significantly improved the prognosis of NSCLC patients.Methods: This article provides a comprehensive review of the clinical applications and latest research on commonly used immune checkpoint inhibitors as well as emerging immune checkpoint inhibitors and agonists in NSCLC treatment, providing valuable clinical guidance.Results: Immune checkpoint inhibitors, including PD-1/PD-L1 inhibitors and CTLA-4 inhibitors, have been widely utilized in NSCLC treatment, leading to substantial increases in patient survival and improvements in quality of life. However, challenges persist in terms of tumor complexity, interindividual variability, drug resistance, and adverse reactions. The emergence of novel immune checkpoints, such as LAG-3, TIM-3, OX-40, and ICOS, opens up new research directions to address these issues.Conclusion: Immune checkpoint inhibitors play a crucial role in the treatment of NSCLC, and the investigation of emerging immune checkpoint inhibitors and agonists presents promising therapeutic opportunities. A comprehensive evaluation of the efficacy and safety of these drugs contributes to the development of personalized treatments, ultimately enhancing treatment outcomes and prognosis for NSCLC patients.

Association of variations in the CAT and prognosis in lung cancer patients with platinum-based chemotherapy.

PURPOSE: To explore the relationship between ATM, ATR and CAT polymorphisms and prognosis of lung cancer patients received platinum-based chemotherapy. METHODS: 404 patients with lung cancer who received platinum-chemotherapy were enrolled and DNA typing was performed. Cox regression analysis and stratification analyses was performed to assess relationships between OS and PFS with SNPs genotypes. The prognosis of lung adenocarcinomaand squamous cell carcinomapatients was analyzed with The Cancer Genome Atlas (TCGA) database according to the grouping of CAT expression. RESULTS: CAT rs769217 was significantly related to PFS of patients with lung cancer who received platinum-chemotherapy. In the Additive model, rs769217 was associated with PFS (HR = 0.747, 95% CI = 0.581-0.960, p = 0.023). In the Dominant model, CT and TT genotypes led to lung cancer progression 0.738 times more than CC genotype. In stratification analyses of association between CAT rs769217 polymorphisms and PFS, the HR of patients at stage IV in additive model was 0.73, and HR was 0.745 (p = 0.034) in dominant model. For OS analyses, HR was 0.672 in the older lung cancer patients (>55 years old) in additive model. Meanwhile, in the Dominant model, it was found that the older patients with CT and TT genotypes had better prognosis, and the risk of death after receiving platinum-based chemotherapy was 0.692 times that of patients with CC genotype (p = 0.037). TCGA data shows that LUAD patients with high CAT expression have longer OS (p = 0.020). CONCLUSION: CAT rs769217 is significantly related to PSF of platinum-based chemotherapy in lung cancer patients and may be a biomarker for predicting the prognosis of lung cancer patients with platinum-based chemotherapy.

The Emerging Role of Super-enhancers as Therapeutic Targets in The Digestive System Tumors.

Digestive system tumors include malignancies of the stomach, pancreas, colon, rectum, and the esophagus, and are associated with high morbidity and mortality. Aberrant epigenetic modifications play a vital role in the progression of digestive system tumors. The aberrant transcription of key oncogenes is driven by super-enhancers (SEs), which are characterized by large clusters of enhancers with significantly high density of transcription factors, cofactors, and epigenetic modulatory proteins. The SEs consist of critical epigenetic regulatory elements, which modulate the biological characteristics of digestive system tumors including tumor cell identity and differentiation, tumorigenesis, environmental response, immune response, and chemotherapeutic resistance. The core transcription regulatory loop of the digestive system tumors is complex and a high density of transcription regulatory complexes in the SEs and the crosstalk between SEs and the noncoding RNAs. In this review, we summarized the known characteristics and functions of the SEs in the digestive system tumors. Furthermore, we discuss the oncogenic roles and regulatory mechanisms of SEs in the digestive system tumors. We highlight the role of SE-driven genes, enhancer RNAs (eRNAs), lncRNAs, and miRNAs in the digestive system tumor growth and progression. Finally, we discuss clinical significance of the CRISPR-Cas9 gene editing system and inhibitors of SE-related proteins such as BET and CDK7 as potential cancer therapeutics.

Laryngeal contact granuloma after radiotherapy in patients with nasopharyngeal carcinoma: a case series.

Background: Laryngeal contact granuloma (LCG) is a benign hypertrophic lesion and phonatory injury after abnormal vocal behavior is regarded as its major etiology. Patients receiving radiation for non-laryngeal head and neck tumors are troubled by persistent voice impairment. The occurrence of LCG after radiotherapy for nasopharyngeal carcinoma (NPC) in our practice has implored us to re-exam their underlying etiology. We hypothesize that a proportion of LCG results from voice change caused by non-laryngeal head and neck cancer radiotherapy and firstly describe a distinct LCG population originated after radiotherapy for NPC with respect to the clinical profile, presentation, prognosis and response to treatment of patients. Methods: We retrospectively reviewed the laryngoscopic examination and tumor study findings to elucidate the common clinical features of patients who presented with LCG after radiotherapy for NPC. All patients were regularly monitored with telescopic examination until lesions disappeared. Data on age, sex, clinical presentation, telescopic findings, management, latency time of lesion formation, remission time and clinical outcome were reviewed. Results: The medical review identified 27 cases of LCG secondary to radiotherapy for NPC. All lesions had been diagnosed during routine endoscopy following radiation. The interval between radiation onset and endoscopic diagnosis was 3.77 months (range, 0.67-11 months). 20 cases were resolved through simple observation, 4 cases were resolved with the administration of proton pump inhibitors (PPIs), and 3 cases with a poor response to PPI therapy required subsequent surgical resection. The mean remission time in the observation and PPI groups was 4.42 months (range, 0.73-18.9 months) and 5.78 months (range, 2.17-14.63 months), respectively. All patients recovered completely and none experienced recurrence during a mean follow-up of 32.44 months (range, 5.6-71.67 months). Conclusions: Iatrogenic granulomas of vocal process are presenting after radiation for non-laryngeal head and neck cancers. In contrast with spontaneous granulomas, these granulomas can be cured at high remission rates and low recurrence trend without specific intervention. Thus, simple observation may be sufficient for radiation-induced LCG.

Cost-effectiveness analysis of pembrolizumab plus chemotherapy versus chemotherapy as the first-line treatment for advanced esophageal cancer.

OBJECTIVE: The KEYNOTE-590 trial showed that individuals with advanced esophageal cancer who received Pembrolizumab in combination with chemotherapy as a first-line regimen achieved a significant extension of survival. However, this treatment option increases the financial burden on patients and the economic benefits remain to be further evaluated. METHODS: A Markov model was used to simulate 10-year survival of patients with esophageal cancer from the perspective of United States (US) Medicare payers. We evaluated the economics of Pembrolizumab plus chemotherapy in the PD-L1 positive score (CPS ≥10) and any PD-L1 expression groups, respectively. We estimated total costs, quality-adjusted life years (QALYs), and calculated incremental cost effectiveness ratios (ICERs). Sensitivity analyses were conducted to explore the impact of uncertainties on the results. Subgroup analysis was also performed. RESULTS: The analysis results showed that the ICER for pembrolizumab plus chemotherapy versus chemotherapy alone was $293,513.17/QALYs in the any PD-L1 expression group. This exceeded the threshold of willingness to pay ($150,000/QALYs). ICERs were most sensitive to the cost of pembrolizumab and the ICERs exceeded $150,000/QALYs in all subgroups. CONCLUSIONS: Evidence suggests that first-line pembrolizumab in combination with chemotherapy is not a cost-effective option for advanced esophageal cancer in the US, regardless of PD-L1 expression status.

The Roles of EXO1 and RPA1 Polymorphisms in Prognosis of Lung Cancer Patients Treated with Platinum-Based Chemotherapy.

Background: Lung cancer is one of the major causes of cancer-related mortality worldwide. DNA repair and damage response contribute to genomic instability that accompanies tumor progression. In this study, we focus on evaluating association between DNA repair polymorphisms of EXO1, RPA1, and prognosis in lung cancer patients whom received platinum-based chemotherapy. Methods: 593 lung cancer patients were recruited in this study. We performed genotyping of 19 single nucleotide polymorphisms (SNPs) by Sequenom MassARRAY. Cox regression analysis was used to assess overall survival (OS) and progression-free survival (PFS) among SNP genotypes. Results: Significant differences in PFS and OS were observed in RPA1 rs5030740, EXO1 rs1776148, and rs1047840. Results showed that patients with CC genotype in rs5030740 (recessive model: P = 0.034) had a better PFS. Patients with AA or/and AG genotypes in rs1776148 (additive model: P = 0.004; dominant model: P = 0.048) and AA genotype in rs1047840 (recessive model: P = 0.023) had longer OS. We also demonstrated differences in subgroup analysis between rs5030740, rs1776148, rs1047840, and prognosis. Conclusions: Our results indicated that EXO1 rs1776148, rs1047840, and RPA1 rs5030740 were significantly associated with prognosis of lung cancer. Rs1776148, rs1047840, and rs5030740 may act as prognosis markers in lung cancer patients with platinum-based chemotherapy.

The Association Between Genetic Polymorphisms of Transporter Genes and Prognosis of Platinum-Based Chemotherapy in Lung Cancer Patients.

Objective: Platinum-based chemotherapy is the first-line treatment of lung cancer. However, different individual and genetic variation effect therapy for lung cancer. The purpose of this study was to evaluate the association between transport genes genetic polymorphisms and the prognosis of platinum-based chemotherapy in lung cancer patients. Methods: A series of 593 patients with treatment of platinum-based chemotherapy were recruited for this study. A total of 21 single-nucleotide polymorphisms in nine transporter genes were selected to investigate their associations with platinum-based chemotherapy prognosis. Results: Patients with ABCG2 rs1448784 CC genotype had a significantly shorter PFS than CT or TT genotypes (Additive model: HR = 1.54, 95% CI = 1.02-2.35, P = 0.040). In stratification analysis, SLC22A2 rs316003, SLC2A1 rs4658 were related to PFS and AQP9 rs1867380, SLC2A1 rs3820589, SLC22A2 rs316003 indicated were related to OS of platinum-based chemotherapy prognosis. Conclusion: Genetic polymorphisms of rs1448784 in ABCG2 might be potential clinical marker for predicting the prognosis of lung cancer patients treated with platinum-based chemotherapy.

Reprogramming the tumor microenvironment by genome editing for precision cancer therapy.

The tumor microenvironment (TME) is essential for immune escape by tumor cells. It plays essential roles in tumor development and metastasis. The clinical outcomes of tumors are often closely related to individual differences in the patient TME. Therefore, reprogramming TME cells and their intercellular communication is an attractive and promising strategy for cancer therapy. TME cells consist of immune and nonimmune cells. These cells need to be manipulated precisely and safely to improve cancer therapy. Furthermore, it is encouraging that this field has rapidly developed in recent years with the advent and development of gene editing technologies. In this review, we briefly introduce gene editing technologies and systematically summarize their applications in the TME for precision cancer therapy, including the reprogramming of TME cells and their intercellular communication. TME cell reprogramming can regulate cell differentiation, proliferation, and function. Moreover, reprogramming the intercellular communication of TME cells can optimize immune infiltration and the specific recognition of tumor cells by immune cells. Thus, gene editing will pave the way for further breakthroughs in precision cancer therapy.

TGF-ß1-Mediated PD-L1 Glycosylation Contributes to Immune Escape via c-Jun/STT3A Pathway in Nasopharyngeal Carcinoma.

Immunotherapy targeting programmed death ligand-1/programmed cell death protein-1 (PD-L1/PD-1) has achieved great success in multiple cancers, but only a small subset of patients showed clinical responses. Recent evidences have shown that post-translational modification of PD-L1 protein could regulate its protein stability and interaction with cognate receptor PD-1, thereby affecting anticancer immunotherapy in several solid tumors. However, the molecular mechanisms underlying how PD-1/PD-L1 expression is regulated still remain unclear in nasopharyngeal carcinoma (NPC). Here, we found N-glycosylation of PD-L1 in NPC cells and tissues. Mechanistically, we showed that STT3A transferred N-linked glycans to PD-L1, and TGF-ß1 could positively regulate STT3A expression through activating c-Jun to bind to STT3A promoter. Functional assays showed that inhibition of TGF-ß1 resulted in a decrease of glycosylated PD-L1 and enhanced cytotoxic T-cell function against NPC cells. Analysis of clinical specimens revealed that the expression of STT3A was positively correlated with TGF-ß1 and c-Jun, and high STT3A expression was positively correlated with a more advanced clinical stage. Altogether, TGF-ß1 activated c-Jun/STT3A signaling pathway to promote N-glycosylation of PD-L1, thus further facilitating immune evasion and reducing the efficacy of cancer immunotherapy. As such, all these data suggested that targeting TGF-ß1 pathway might be a promising approach to enhance immune checkpoint blockade, and simultaneous blockade of PD-L1 and TGF-ß1 pathways might elicit potent and superior antitumor activity relative to monotherapies.

Application of the Mathieu combined tunnel technique for repairing glans dehiscence after failed hypospadias repair.

Repairing glans dehiscence after failed hypospadias repair is challenging for pediatric surgeons. Here, we introduced and evaluated a newly modified Mathieu technique, Mathieu combined tunnel (MCT), which involves multiple custom-designed flaps for the shortage of flap source material after repeated operations; we also constructed a tunnel to avoid the glans incision that may carry new risks of dehiscence. This retrospective study included 26 patients who were consecutively admitted to the First Affiliated Hospital of Sun Yat-Sen University (Guangzhou, China) for glans dehiscence repair after failed hypospadias repair from October 2014 to October 2020; sixteen patients underwent surgery using the MCT (MCT group) and ten patients underwent surgery using the tubularized incised plate (TIP) technique (TIP group). The operative time, blood loss, postoperative complications, normal urethral meatus rate, success rate, and Hypospadias Objective Penile Evaluation (HOPE) score were compared between the two groups. The MCT group achieved an overall satisfactory penile appearance and voiding function, with a higher rate of normal urethral meatus (15/16, 93.8%) and a lower rate of glans dehiscence (1/16, 6.2%), compared with the TIP group (70.0% and 30.0%, respectively). However, these differences were not statistically significant, possibly because of the limited number of patients (all P > 0.05). Mean postoperative HOPE scores were similar in the MCT group (mean ± standard deviation: 8.83 ± 0. 89) and TIP group (8.94 ± 0.57) (P > 0.05). No significant differences were found between the two groups in terms of blood loss and success rate, nor in the rates of various complications (e.g., fistula, urethral stricture, and glans dehiscence). In conclusion, the MCT technique appears to be feasible and reliable for repairing glans dehiscence after failed hypospadias repair.

High-resolution laser induced excitation spectroscopy and decay dynamics of YNbO4:Er3.

The rare earth materials have attracted intensive attention due to their strong luminescent characteristic. However, the split fine Stark levels are difficult to be determined. Here we report a room-temperature detection for Stark levels of YNbO4: Er3+ using established laser-induced spectroscopy system with dye laser of superhigh resolution of wavelength at 0.005 nm. From excitation spectra, six split Stark levels of 4G11/2 (Er3+) were directly detected. Moreover, nonradiative relaxations of 4G9/2→4G11/2 and 4G11/2→2H11/2/ 4S3/2 have been observed with weighed lifetimes of 0.70 µs and 6.15 µs, and characteristic green emission of Er3+ (@555 nm) yields lifetime of 31.78 µs.

Familial Temperature-Sensitive Auditory Neuropathy: Distinctive Clinical Courses Caused by Variants of the OTOF Gene.

Objective: To investigate the clinical course and genetic etiology of familial temperature-sensitive auditory neuropathy (TSAN), which is a very rare subtype of auditory neuropathy (AN) that involves an elevation of hearing thresholds due to an increase in the core body temperature, and to evaluate the genotype-phenotype correlations in a family with TSAN. Methods: Six members of a non-consanguineous Chinese family, including four siblings complaining of communication difficulties when febrile, were enrolled in this study. The clinical and audiological profiles of the four siblings were fully evaluated during both febrile and afebrile episodes, and the genetic etiology of hearing loss (HL) was explored using next-generation sequencing (NGS) technology. Their parents, who had no complaints of fluctuating HL due to body temperature variation, were enrolled for the genetics portion only. Results: Audiological tests during the patients' febrile episodes met the classical diagnostic criteria for AN, including mild HL, poor speech discrimination, preserved cochlear microphonics (CMs), and absent auditory brainstem responses (ABRs). Importantly, unlike the pattern observed in previously reported cases of TSAN, the ABRs and electrocochleography (ECochG) signals of our patients improved to normal during afebrile periods. Genetic analysis identified a compound heterozygous variant of the OTOF gene (which encodes the otoferlin protein), including one previously reported pathogenic variant, c.5098G > C (p.Glu1700Gln), and one novel variant, c.4882C > A (p.Pro1628Thr). Neither of the identified variants affected the C2 domains related to the main function of otoferlin. Both variants faithfully cosegregated with TSAN within the pedigree, suggesting that OTOF is the causative gene of the autosomal recessive trait segregation in this family. Conclusion: The presence of CMs with absent (or markedly abnormal) ABRs is a reliable criterion for diagnosing AN. The severity of the phenotype caused by dysfunctional neurotransmitter release in TSAN may reflect variants that alter the C2 domains of otoferlin. The observations from this study enrich the current understanding of the phenotype and genotype of TSAN and may lay a foundation for further research on its pathogenesis.

The Effects of WISP1 Polymorphisms on the Prognosis of Lung Cancer Patients with Platinum-Based Chemotherapy.

PURPOSE: To investigate the relationships between Wnt1 inducible signaling pathway protein 1 (WISP1) polymorphisms and the prognosis of platinum-based chemotherapy in lung cancer patients. PATIENTS AND METHODS: A total of 363 lung cancer patients were recruited in this study. All of them received at least two cycles of platinum-based chemotherapy. We used unconditional logistic regression analysis to assess the associations of 39 single nucleotide polymorphisms in WISP1 gene with platinum-based chemotherapy prognosis. RESULTS: The results indicated that patients carried rs2929973 GT or GG genotypes had increased risk of disease progression (HR = 0.712, 95% CI = 0.553-0.916, P = 0.015). Patients with rs2977551 TT genotype had a significantly decreased risk of progression-free survival than patients carrying CT or CC genotype (HR = 0.723, 95% CI = 0.561-0.932, P = 0.032) and overall survival (HR = 0.725, 95% CI = 0.552-0.913, P = 0.045). For rs2977549, patients carrying TT genotype had a significantly longer progression-free survival than patients with CC or CT genotypes (HR = 0.708, 95% CI = 0.550-0.912, P = 0.017). Among of them, rs16904853, rs10956697, rs2929965, rs2929973, rs7828685, rs2977551 and rs2977549 were related to progression-free survival, and rs10956697 and rs2977551 were related to overall survival in subgroup analyses, respectively. CONCLUSION: WISP1 rs2929973, rs2977551 and rs2977549 may be contributed to a potential candidate biomarker for prediction of platinum-based chemotherapy prognosis in lung cancer patients.

Personalized bioconversion of Panax notoginseng saponins mediated by gut microbiota between two different diet-pattern healthy subjects.

BACKGROUND: Panax notoginseng saponins (PNS) as the main effective substances from P. notoginseng with low bioavailability could be bio-converted by human gut microbiota. In our previous study, PNS metabolic variations mediated by gut microbiota have been observed between high fat, high protein (HF-HP) and low fat, plant fiber-rich (LF-PF) dietary subjects. In this study, we aimed to correspondingly characterize the relationship between distinct gut microbial species and PNS metabolites. METHODS: Gut microbiota were collected from HF-HP and LF-PF dietary healthy adults and profiled by 16S rRNA gene sequencing. PNS were incubated with gut microbiota in vitro. A LC-MS/MS method was developed to quantify the five main metabolites yields including ginsenoside F1 (GF1), ginsenoside Rh2 (GRh2), ginsenoside compound K (GC-K), protopanaxatriol (PPT) and protopanaxadiol (PPD). The selected microbial species, Bifidobacterium adolescentis and Lactobacillus rhamnosus, were employed to metabolize PNS for the corresponding metabolites. RESULTS: The five main metabolites were significantly different between the two diet groups. Compared with HF-HP group, the microbial genus Blautia, Bifidobacterium, Clostridium, Corynebacterium, Dorea, Enhydrobacter, Lactobacillus, Roseburia, Ruminococcus, SMB53, Streptococcus, Treponema and Weissella were enriched in LF-PF group, while Phascolarctobacterium and Oscillospira were relatively decreased. Furthermore, Spearman's correlative analysis revealed gut microbials enriched in LF-PF and HF-HP groups were positively and negatively associated with the five metabolites, respectively. CONCLUSIONS: Our data showed gut microbiota diversity led to the personalized bioconversion of PNS.

COVID-19 one year later: a retrospect of CRISPR-Cas system in combating COVID-19.

Coronavirus disease 2019 (COVID-19), an infectious disease caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has posed a persistent global threat. The transmission of SARS-CoV-2 is wide and swift. Rapid detection of the viral RNA and effective therapy are imperative to prevent the worldwide spread of the new infectious disease. Clustered Regularly-Interspaced Short Palindromic Repeats (CRISPR)- CRISPR-associated protein (Cas) system is an RNA-directed adaptive immune system, and it has been transformed into a gene editing tool. Applications of CRISPR-Cas system involves in many fields, such as human gene therapy, drug discovery and disease diagnosis. Under the background of COVID-19 pandemic, CRISPR-Cas system shows hidden capacity to fight the emergency in many aspects. This review will focus on the role of gene editing in COVID-19 diagnosis and treatment. We will describe the potential use of CRISPR-Cas-based system in combating COVID-19, from diagnosis to treatment. Furthermore, the limitation and perspectives of this novel technology are also evaluated.