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

Objective:To analyze the relationship between 24-hour urinary calcium (24 h UCa) level and the risk of end-stage kidney disease (ESKD), cardiovascular disease (CVD), and all-cause mortality.Methods:In the Chinese Cohort Study of Chronic Kidney Disease, we examined 3 375 patients aged 18-74 years with CKD stages 1-4. Kaplan-Meier survival and Cox proportional hazard regression models were used to test a time-to-event association between levels of 24 h UCa and incidence of ESKD, CVD, and all-cause mortality.Results:During a follow-up of 4.17 (3.37, 5.20) years, 179, 145, 104 and 38 ESKD events occurred in <0.60, 0.60-, 1.20-, ≥2.32 mmol 24 h UCa groups. Higher levels of 24 h UCa (1.20-,≥2.32 mmol) were independently associated with a lower incidence of ESKD events in patients with CKD, with HR (95% CI) of 0.71 (0.54-0.93) and 0.43 (0.29-0.64), respectively. No significant associations with CVD and all-cause mortality endpoints were detected. Conclusion:Among patients with CKD, levels of 24 h UCa displayed an association with the risk of ESKD among patients with CKD stages 1-4.

Objective:To observe changes in peripapillary blood flow before and after combined treatment with anti-vascular endothelial growth factor (VEGF) drugs and Dexamethasone intravitreal implant (DEX) in patients with central retinal vein occlusion (CRVO).Methods:A prospective clinical study. Thirty-three eyes of 33 patients with newly diagnosed non-ischemic CRVO and macular edema (ME) were enrolled from Shanxi Eye Hospital between April 2023 and April 2024. All patients underwent best-corrected visual acuity (BCVA) and swept-source optical coherence tomography angiography (SS-OCTA) examinations. The treatment regimen consisted of three intravitreal injections of ranibizumab and one DEX implant. SS-OCTA was used to scan a 3 mm×3 mm area centered on the optic disc to measure peripapillary retinal nerve fiber layer (RNFL) thickness and blood flow density in the superficial vascular complex (SVC), deep vascular complex (DVC), and radial peripapillary capillaries (RPC). Changes in SVC, DVC, and RPC blood flow density and RNFL thickness were evaluated at 3 and 6 months post-treatment. Shapiro-Wilk test was used to assess normality, and Spearman's rank correlation coefficient was applied for correlation analysis.Results:Compared with before treatment, the blood flow density changes of SVC and RPC showed a downward trend at 3 and 6 months after treatment. Among them, the difference was statistically significant at 6 months after treatment ( Z=?2.592, ?2.070, P=0.012, 0.042), while there was no statistically significant difference at 3 months after treatment ( P>0.05). The blood flow density of DVC showed an upward trend at 3 and 6 months after treatment, but the differences were not statistically significant ( P>0.05). The results of the correlation analysis showed that the thickness of RNFL was negatively correlated with the blood flow density of DVC ( r=?0.768, P<0.001). It was positively correlated with the blood flow densities of SVC and RPC ( r=0.288, 0.398; P=0.040, 0.004). Conclusion:Anti-VEGF drugs combined with DEX treatment can significantly improve the perioptic disc blood flow distribution in eyes with CRVO, manifested as a decrease in blood flow density of SVC and RPC, while a compensatory increase in blood flow of DVC. The thickness variation of RNFL is closely related to the blood flow density of different vascular layers.

Objective To establish a quality control method for Bletilla compound spleen-tonifying Traditional Chinese Medicine(TCM). Methods The content of gallic acid was determined by HPLC. Atractylodes macrocephala Koidz, Codonopsis pilosula Nannf and Pulsatillae Radix were identified by TLC. Results The identification and determination methods showed good specificity. Gallic acid displayed good linearity within the range of 3.6-179.8 µg/ml （r=0.999 9）. The average recovery was 101.12% （RSD 0.98%）. Conclusion The TLC and HPLC could be used as quality control method for Bletilla compound spleen-tonifying TCM.

Objective:To establish the HPLC fingerprints and multi-component content determination method of Yinchen Wuling Powder; To evaluate the quality of Yinchen Wuling Powder combined with chemical pattern recognition technology.Methods:A wavelength-switching HPLC method was used to establish the fingerprint profiles of different batches of Yinchen Wuling Powder and determine the contents of seven components of neochlorogenic acid, chlorogenic acid, isochlorogenic acid B, isochlorogenic acid A, isochlorogenic acid C, cinnamic acid, cinnamaldehyde. Principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were applied to evaluate the quality. Quality difference biomarkers were screened.Results:The fingerprint profiles of 24 batches of Yinchen Wuling Powder were identified with 20 common peaks, and 7 components were recognized. The similarity between the 24 batches of samples and the control profile was 0.966-0.994, and the attribution analysis showed that peaks 1, 2, 3 were common to Artemisia Scoparia and Alismatis Rhizoma. Chromatographic peaks 4 (neochlorogenic acid), 5, 6, 7 (chlorogenic acid), 8, 9, 10, 11, 12, 13, 14 (isochlorogenic acid B), 15 (isochlorogenic acid A), 16 (isochlorogenic acid C), and 19 were from Artemisia Scoparia, and peaks 17, 18 and 20 were from Cinnamomi Ramulus. Principal component analysis classified the 24 batches of samples into 4 categories, and partial least squares discriminant analysis was used to determine 11 quality difference biomarkers, including isochlorogenic acid B and neochlorogenic acid.Conclusions:The established method of determining fingerprint and multi-component content is accurate and with good repeatability. The results can provide a certain basis for the quality evaluation of Yinchen Wuling Powder.

Objective:To analyze the relationship between 24-hour urinary calcium (24 h UCa) level and the risk of end-stage kidney disease (ESKD), cardiovascular disease (CVD), and all-cause mortality.Methods:In the Chinese Cohort Study of Chronic Kidney Disease, we examined 3 375 patients aged 18-74 years with CKD stages 1-4. Kaplan-Meier survival and Cox proportional hazard regression models were used to test a time-to-event association between levels of 24 h UCa and incidence of ESKD, CVD, and all-cause mortality.Results:During a follow-up of 4.17 (3.37, 5.20) years, 179, 145, 104 and 38 ESKD events occurred in <0.60, 0.60-, 1.20-, ≥2.32 mmol 24 h UCa groups. Higher levels of 24 h UCa (1.20-,≥2.32 mmol) were independently associated with a lower incidence of ESKD events in patients with CKD, with HR (95% CI) of 0.71 (0.54-0.93) and 0.43 (0.29-0.64), respectively. No significant associations with CVD and all-cause mortality endpoints were detected. Conclusion:Among patients with CKD, levels of 24 h UCa displayed an association with the risk of ESKD among patients with CKD stages 1-4.

Objective:To observe changes in peripapillary blood flow before and after combined treatment with anti-vascular endothelial growth factor (VEGF) drugs and Dexamethasone intravitreal implant (DEX) in patients with central retinal vein occlusion (CRVO).Methods:A prospective clinical study. Thirty-three eyes of 33 patients with newly diagnosed non-ischemic CRVO and macular edema (ME) were enrolled from Shanxi Eye Hospital between April 2023 and April 2024. All patients underwent best-corrected visual acuity (BCVA) and swept-source optical coherence tomography angiography (SS-OCTA) examinations. The treatment regimen consisted of three intravitreal injections of ranibizumab and one DEX implant. SS-OCTA was used to scan a 3 mm×3 mm area centered on the optic disc to measure peripapillary retinal nerve fiber layer (RNFL) thickness and blood flow density in the superficial vascular complex (SVC), deep vascular complex (DVC), and radial peripapillary capillaries (RPC). Changes in SVC, DVC, and RPC blood flow density and RNFL thickness were evaluated at 3 and 6 months post-treatment. Shapiro-Wilk test was used to assess normality, and Spearman's rank correlation coefficient was applied for correlation analysis.Results:Compared with before treatment, the blood flow density changes of SVC and RPC showed a downward trend at 3 and 6 months after treatment. Among them, the difference was statistically significant at 6 months after treatment ( Z=?2.592, ?2.070, P=0.012, 0.042), while there was no statistically significant difference at 3 months after treatment ( P>0.05). The blood flow density of DVC showed an upward trend at 3 and 6 months after treatment, but the differences were not statistically significant ( P>0.05). The results of the correlation analysis showed that the thickness of RNFL was negatively correlated with the blood flow density of DVC ( r=?0.768, P<0.001). It was positively correlated with the blood flow densities of SVC and RPC ( r=0.288, 0.398; P=0.040, 0.004). Conclusion:Anti-VEGF drugs combined with DEX treatment can significantly improve the perioptic disc blood flow distribution in eyes with CRVO, manifested as a decrease in blood flow density of SVC and RPC, while a compensatory increase in blood flow of DVC. The thickness variation of RNFL is closely related to the blood flow density of different vascular layers.

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.

Objective:To evaluate the clinical value of a capillary electrophoresis-based method for gene diagnosis of hyperphenylalaninemia.Methods:In this single-center prospective study, 40 newborns with suspected hyperphenylalaninemia detected by neonatal liquid chromatography-tandem mass spectrometry screening at Nanjing Maternity and Child Health Care Hospital from February 2021 to February 2023 were included, with 22 males, 18 females and a mean age at diagnosis of 21.93 days.Capillary electrophoresis was used to detect 85 variants of the phenylalanine hydroxylase ( PAH) gene in 40 newborns with suspected hyperphenylalaninemia.The PAH gene of undiagnosed patients was further analyzed by Sanger sequencing.The detection rate, sensitivity and specificity of capillary electrophoresis were calculated. Results:Among these 40 newborns with suspected hyperphenylalaninemia, 71 PAH variants were detected by capillary electrophoresis, 32 patients were clearly diagnosed, only 1 pathogenic variant was found in 5 patients, and no pathogenic variant was found in the last 3 patients.Therefore, the detection rate, sensitivity and specificity of capillary electrophoresis for analysis of the PAH gene were 80.00%, 88.75% and 100%, respectively. Conclusions:The capillary electrophoresis-based method can rapidly, efficiently and accurately detect PAH gene variants at lower cost and is a promising gene detection method for hyperphenylalaninemia in clinical practice.

Objective To understand the distribution of ecological suitability of Scutellaria baicalensis Georgi;To screen the main ecological factors affecting its distribution;To predict its suitable planting area in China.Methods A total of 231 batches of Scutellaria baicalensis Georgi were collected through the fourth national survey of TCM resources.The environment information of sampling points were recorded,and 55 ecological factors were analyzed by MaxEnt model and GIS.Results Rainfall,vegetation type and soil types had a greater influence on the distribution of Scutellaria baicalensis Georgi.The ecological suitable areas of Scutellaria baicalensis Georgi mainly concentrated in the eastern part of Shaanxi Province,the western part of Hebei Province and most areas of Chengde,the most part of Shanxi Province,the western part of Beijing,the western part of Liaoning Province,the central and eastern part of Shandong Province,the junction of Jiangsu and Anhui Province,the northern part of Yunnan Province,and the eastern and southern part of Sichuan Province.Conclusion The ecological suitability areas of Scutellaria baicalensis Georgi were classified in this study,and the results could provide reference for the selection of cultivation areas of Scutellaria baicalensis Georgi.