BACKGROUND: Molecular subtyping is an essential complementarity after pathological analyses for targeted therapy. This study aimed to investigate the consistency of next-generation sequencing (NGS) results between circulating tumor DNA (ctDNA)-based and tissue-based in non-small cell lung cancer (NSCLC) and identify the patient characteristics that favor ctDNA testing. METHODS: Patients who diagnosed with NSCLC and received both ctDNA- and cancer tissue-based NGS before surgery or systemic treatment in Lung Cancer Center, Sichuan University West China Hospital between December 2017 and August 2022 were enrolled. A 425-cancer panel with a HiSeq 4000 NGS platform was used for NGS. The unweighted Cohen's kappa coefficient was employed to discriminate the high-concordance group from the low-concordance group with a cutoff value of 0.6. Six machine learning models were used to identify patient characteristics that relate to high concordance between ctDNA-based and tissue-based NGS. RESULTS: A total of 85 patients were enrolled, of which 22.4% (19/85) had stage III disease and 56.5% (48/85) had stage IV disease. Forty-four patients (51.8%) showed consistent gene mutation types between ctDNA-based and tissue-based NGS, while one patient (1.2%) tested negative in both approaches. Patients with advanced diseases and metastases to other organs would be suitable for the ctDNA-based NGS, and the generalized linear model showed that T stage, M stage, and tumor mutation burden were the critical discriminators to predict the consistency of results between ctDNA-based and tissue-based NGS. CONCLUSION ctDNA-based NGS showed comparable detection performance in the targeted gene mutations compared with tissue-based NGS, and it could be considered in advanced or metastatic NSCLC.
Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Circulating Tumor DNA/blood* ; High-Throughput Nucleotide Sequencing/methods* ; Female ; Male ; Lung Neoplasms/pathology* ; Middle Aged ; Mutation/genetics* ; Aged ; Adult ; Aged, 80 and over

OBJECTIVES: To assess the efficacy and safety of Tiaozhou Ziyin (TZZY) recipe for treatment of premature ovarian insufficiency (POI) and explore the possible mechanisms. METHODS: We used bioinformatics analyses and network pharmacology to identify the main active ingredients in TZZY recipe and their core targets, which were verified by Western blotting. We tested the efficacy and safety of the recipe in 60 POI patients, who were randomized into control group (n=30) with Femoston treatment and TZZY group (n=30) with additional TZZY recipe treatment for 3 menstrual cycles. RESULTS: The core active ingredients of TZZY recipe included kaempferol, β-sitosterol, luteolin, and quercetin. The core targets included SRC, TP53, STAT3, PIK3CA, and MAPK3, which were involved in positive regulation of cell movement and protein phosphorylation, the cancer pathways and the PI3K-Akt signaling pathway. Molecular docking showed that the core active ingredients had good binding ability with the core targets. In female rat models of POI, TZZY recipe treatment significantly up-regulated ovarian expressions of p-PI3K and p-Akt proteins. In the clinical trial, treatment with Femoston and Femoston plus TZZY recipe both significantly increased E₂ levels and reduced FSH and LH levels and Kupperman scores of the patients, and the combined treatment produced significantly stronger effects. Both treatments increased the number of antral follicles of the patients, but the combined treatment also significantly increased the levels of AMH. CONCLUSIONS The therapeutic mechanism of TZZY recipe for POI involves multiple active ingredients, multiple therapeutic targets and multiple pathways, and activating the PI3K /Akt pathway is one of its main mechanisms of action, to improve ovarian reserve function, alleviate clinical symptoms, and enhance clinical efficacy in POI patients.
Female ; Primary Ovarian Insufficiency/drug therapy* ; Humans ; Drugs, Chinese Herbal/therapeutic use* ; Animals ; Rats ; Molecular Docking Simulation ; Signal Transduction ; Sitosterols/therapeutic use* ; Kaempferols/therapeutic use*

OBJECTIVE To investigate the effect of Guanxinning tablets(GXN) on early heart failure model rats, and to explore the protective mechanism of GXN on heart failure rats from the perspective of intestinal flora. METHODS Six rats who underwent sham operation were set as sham operation group. Took 80 SD rats to undergo aortic arch stenosis and established a heart failure rat model. The surviving rats were divided into 4 groups, namely the model control group, the positive control group(captopril tablets 12.5 mg·kg–1), high-dose and low-dose of GXN group(600, 1 200 mg·kg–1). The 4 groups were administered continuously for 8 weeks. Cardiac ultrasonography was performed every 4 week. Serum NT-proBNP, hs-CRP, IL-6, TNF-α, SOD and MDA levels were measured. The effects of GXN on the structure and function of intestinal flora were observed based on the high-throughput sequencing technology and bioinformatics analysis of 16S gut microbiome. RESULTS Compared to the model control group, after giving different doses of GXN, the survival rate of rats increased, and the thickness of the ventricular wall decreased to varying degrees. The weight of the heart and coefficient of the heart were all reduced. GXN could also reduce the level of inflammatory factors, inhibit the level increase of NT-proBNP in rats, and increase the activity of serum SOD. In addition, GXN intervention could significantly improve the intestinal flora diversity of rats with heart failure, the possible target genera of GXN were Akkermansia genera, Phascolarctobacterium genera and Oxalobacter genera. The effect of GXN on intestinal function in rats with heart failure might be concentrated in non-homologous end-joining, influenza A, carotenoid synthesis, indole alkaloids biosynthesis, betalain biosynthesis, renin-angiotensin system and other biological pathways. CONCLUSION The protective effect of GXN on early heart failure rats may be related to the regulation of intestinal flora pathway.

Background: Androgenetic alopecia (AGA) leads to thinning of scalp hair and affects 60%~70% of the adult population worldwide. Developing more effective treatments and studying its mechanism are of great significance. Previous clinical studies have revealed that hair growth is stimulated by 650-nm red light. Objective: This study aimed to explore the effect and mechanism of 650-nm red light on the treatment of AGA by using ex vivo hair follicle culture. Methods: Human hair follicles were obtained from hair transplant patients with AGA. Hair follicles were cultured in Williams E medium and treated with or without 650-nm red light.Real-time RT-PCR and immunofluorescence staining were used to detect the expression level of genes and proteins in hair follicles, respectively. RNA-sequencing analysis was carried out to reveal the distinct gene signatures upon 650 nm treatment. Results: Low-level 650 nm red light promoted the proliferation of human hair follicles in the experimental cultured-tissue model. Consistently, 650 nm red light significantly delayed the transition of hair cycle from anagen to catagen in vitro. RNA-seq analysis and gene clustering for the differentially expressed genes suggests that leukocyte transendothelial migration, metabolism, adherens junction and other biological process maybe involved in stimulation of hair follicles by 650-nm red light treatment. Conclusion The effect of 650-nm red light on ex vivo hair follicles and the transcriptome set which implicates the role of red light in promoting hair growth and reversing of miniaturization process of AGA were identified.

This study analyzed the current status of the cultivation process of professional postgraduates of clinical medicine, combining with the case of the auxiliary teaching model of Academic Salons on the WeChat platform in Xiangya Hospital of Central South University. We collected students' satisfaction evaluation of this auxiliary teaching model by questionnaire survey. Through analyzing the results and feedback, we found that the overall satisfaction of this auxiliary teaching model is 71.43%, and the model has a remarkable effect in broadening knowledge, inspiring thinking of clinical diagnosis and treatment, improving ability of scientific research, increasing learning interest, enhancing the ability to link theory with practice, and using the knowledge flexibly. However, there are still some shortcomings in early publicity, understanding students' interests and needs, and improving students' autonomous learning ability. Therefore, using the WeChat platform to carry out academic salons is a good auxiliary teaching model for cultivating the scientific research ability of professional postgraduates of clinical medicine.

Objective: To investigate the single nucleotide polymorphisms (SNPs) of rs600231A/G and rs4102217 G/C in the promoter region of MALAT1 (metastasis associated in lung adenocarcinoma transcript 1) gene in the healthy population of Guangxi district and analyze the differences in the population among different regions. Methods: The genotypes of rs600231A/G and rs4102217G/C of 207 healthy individuals in Guangxi were detected by SNPscan high-throughput technique. The genotype and allele frequency distributions were analyzed statistically with the data of HapMap-CEU (European population), HapMap-HCB (Beijing Han population), HapMap-JPT (Japanese population) and HapMap-YRI (African population) published by Human genome Haplotype Map (HapMap). Results: There were three genotypes of AA (38.2%), AG (46.4%) and GG (15.4%) in rs600231A/G, and the differences were significantly different compared with the polymorphism of Japan and Africa population (HapMap-JPT and HapMap-YRI) (P＜0.05). Compared with HapMap-CEU, the genotype difference was not statistically significant (P＞0.05), but the allele distribution was statistically different (P＜0.05). The rs4102217 G/C polymorphism contained GG(75.4%), CG(23.2%) and CC(1.4%), and the polymorphisms were significantly different from those in European and Japanese populations (P＜0.05). There was no significant difference between gender in the polymorphisms of the two loci (P＞0.05). Conclusion The polymorphisms of rs600231A/G and rs4102217G/C in the MALAT1 promoter region were found in Guangxi healthy population, and the distribution of polymorphisms may be different in the population of various regions.

Objective To study the effect of age-related white matter changes (ARWMC) on first symptomatic ischemic stroke events in the oldsters. Methods For the prospective study, a total of 368 eligible oldsters were enrolled in the study from January 2010 to August 2012. The degrees of ARWMC were assessed by ARWMC scale;according to the scores, they were divided into non ARWMC group, mild-moderate ARWMC group and severe ARWMC group. The patients were followed up once every 3 months. The clinical endpoint events and time (first symptomatic ischemic stroke, myocardial infarction and all-cause death) were recorded. Analyses of variance and Chi-square test were used to compare the differences of clinical data among the 3 groups. COX regression was used to assess the risk differences of first symptomatic ischemic stroke in the oldsters of three groups. Results After an average of follow-up for 48.7 months, 50 participants (13.6％) had first symptomatic ischemic stroke;25 (25.8％) were categorized as the severe ARWMC group, 22 (10.9％) were as the mild-medium group, and 3 (4.4％) were as the non ARWMC group. Among the three groups, the differences in age, history of hypertension, systolic blood pressure, incidence of clinical endpoint events and first symptomatic ischemic stroke, and follow-up time of endpoint events were statistically significant (P<0.05); patients from the severe ARWMC group were the oldest, and had the longest history of hypertension, the highest systolic blood pressure, the highest incidence of clinical end events and first symptomatic ischemic stroke, and the shortest follow-up period for clinical end events. COX regression analysis showed that the risk of first symptomatic ischemic stroke in the severe ARWMC group was about 8 times higher than that in the non ARWMC group (hazard ratio=9.012, 95％CI: 2.310-35.154, P=0.002). Conclusion In oldsters, severe ARWMC often accompany hypertension history and poor blood pressure controll, and it is an independent and serious risk factor for long-term first symptomatic ischemic stroke.

This study was aimed to explore the antidepressant effect of Kai-Xin Jie-Yu (KXJY) prescription on depressive model of rats,and to explore the level of inflammatory cytokines in peripheral blood.According to sucrose preference and weight,male SD rats were randomly divided into the normal group,model group and traditional Chinese medicine (TCM) group.The model of depression was established by chronic unpredictable mild stress and separation for @@6 weeks.Body weight,sucrose preference and forced swimming test were used to evaluate the depressive state.The levels of IL-1β,IL-2,IL-6 and TNF-α in the serum of rats were measured by ELISA.The results showed that compared with the normal group,the weight,sucrose preference and total drinking water of rat model gToup were significantly reduced.The immobility time of forced swimming was significantly prolonged.The level of IL-1β,IL-2,IL-6 and TNF-α expression in serum was significantly increased.There was no significant difference between the body weight of rats in the model group and TCM group.The total amount of drinking water and sucrose preference were significantly increased.The immobility time of forced swimming was reduced.Levels of IL-1 β,IL-2,IL-6 and TNF-α expression were decreased significantly.It was concluded that KXJY prescription can improve depression symptoms in depression model of rats.It may be related to regulate the expression level of serum inflammatory cytokines.

This study was aimed to detect the expression of miR-665 in the hippocampal of depression rat model treated with Kai-Xin Jie-Yu (KXJY) decoction and bioinformatic analysis of target genes of miR-665,in order to investigate the role of miR-665 in the pathogenesis of depression and the antidepressant mechanism of KXJY decoction.The rat model of chronic stress depression was established and then treated with KXJY decoction for 42 days.The total RNA from hippocampus tissues was extracted.And the relative expression of miR-665 in hippocampus of rats in each group was detected by RT-qPCR.TargetScan and microRNAorg databases were used to predict target genes for miR-665.DAVID database was used to classify GO function and to analyze KEGG signaling pathway of target genes.The results showed that compared with the normal group,the expression level of miR-665 in hippocampus of the model group was significantly higher with significant difference (P ＜ 0.01).Compared with the model group,the expression level of miR-665 in hippocampus of Chinese medicine group and western medicine group decreased significantly with significant difference (P ＜ 0.01).The biological functions of miR-665 target genes were mainly concentrated in the response to organic substance.The signal pathway was mainly concentrated in N-Glycan biosynthesis.It was concluded that miR-665 may be involved in the pathological process of depression,by correcting the abnormal expression of miR-665,which may be one of the antidepressant mechanisms of KXJY decoction.Through the analysis and prediction of the target genes,it provided a certain direction and theoretical basis for further study on the specific mechanism of KXJY decoction intervention on miR-665.

This article was aimed to investigate the function and mechanism of Kai-Xin Jie-Yu (KXJY) pill on depression.The depression model rats were established by chronic unpredictable mild stress and separation.The sucrose preference test and Morris water maze (MWM) were performed.The regulation effects of neural plasticity-related genes including glycogen synthase kinase-3β (GSK-3β),cAMP-response element binding protein (CREB),5-hydroxytryptamine 2C receptors (HTR2C),and vascular endothelial growth factor (VEGF) were determined.The results showed that among depression model rats,KXJY pill significantly increased the sucrose preference and the escape latency of MWM in a certain extent.The neural plasticity-related genes including GSK-3β and HTR2C mRNA were decreased significantly,whereas CREB and VEGF mRNA were increased significantly with the treatment of KXJY pill.It was concluded that KXJY pill had the function of reducing depression-like behavior,which might be mediated by the regulation of GSK-3β,CREB,HTR2C and VEGF.