Early identification of adolescent depression requires objective biomarkers. This study investigated the functional near-infrared spectroscopy (fNIRS) activation patterns and mismatch negativity (MMN) characteristics in adolescents with first-episode mild-to-moderate depression. We enrolled 33 patients and 33 matched healthy controls, measuring oxyhemoglobin (Oxy-Hb) concentration in the frontal cortex during verbal fluency tasks via fNIRS, and recording MMN latency/amplitude at Fz/Cz electrodes using event-related potentials (ERP). Compared with healthy controls, the depression group showed significantly prolonged MMN latency [Fz: (227.88 ± 31.08) ms vs. (208.70 ± 25.35) ms, P < 0.01; Cz: (223.73 ± 29.03) ms vs. (204.18 ± 22.43) ms, P < 0.01], and obviously reduced Fz amplitude [(2.42 ± 2.18) μV vs. (5.65 ± 5.59) μV, P = 0.03]. A significant positive correlation was observed between MMN latencies at Fz and Cz electrodes ( P < 0.01). Oxy-Hb in left frontopolar prefrontal channels (CH15/17) was significantly decreased in patient group ( P < 0.05). Our findings suggest that adolescents with depression exhibit hypofunction in the left prefrontal cortex and impaired automatic sensory processing. The combined application of fNIRS and ERP techniques may provide an objective basis for early clinical identification.
Humans ; Spectroscopy, Near-Infrared/methods* ; Adolescent ; Prefrontal Cortex/physiopathology* ; Evoked Potentials/physiology* ; Depression/physiopathology* ; Female ; Male ; Oxyhemoglobins ; Electroencephalography

OBJECTIVE: To analyze the correlation between the expression levels of Tim-3, C-myc and the proportion of T lymphocyte subsets and prognosis in patients with acute lymphoblastic leukemia (ALL). METHODS: The research group selected 60 ALL patients admitted to our hospital from December 2019 to December 2021, while the control group selected 55 healthy volunteers who underwent physical examination in our hospital. The expression levels of Tim-3, C-myc mRNA and the proportion of T lymphocyte subsets in the two groups were detected. The mortality rate of ALL patients was calculated, and the correlation between the expression levels of Tim-3, C-myc, and the proportion of T lymphocyte subsets and pathological features and prognosis was analyzed. RESULTS: Compared with the control group, the levels of Tim-3, C-myc and CD8⁺ in the research group were increased, while the levels of CD3⁺ , CD4⁺ and CD4⁺ /CD8⁺ were decreased (all P < 0.001). The levels of Tim-3, C-myc mRNA, CD3⁺ , CD4⁺ , CD8⁺ , CD4⁺ /CD8⁺ were correlated with risk classification and extramedullary infiltration (all P < 0.05). The survival rate of patients with low expression of Tim-3, C-myc, and CD8⁺ was higher than that of patients with high expression, while the survival rate of patients with high expression of CD3⁺ , CD4⁺ , and CD4⁺ /CD8⁺ was higher than that of patients with low expression (all P < 0.05). Univariate analysis showed that the deceased patients had higher proportions of extramedullary infiltration and high-risk classification, as well as higher levels of Tim-3, C-myc, and CD8⁺ , while lower levels of CD3⁺ , CD4⁺ , and CD4⁺ /CD8⁺ compared with surviving patients (all P < 0.01). Multivariate logistic regression analysis showed that extramedullary invasion, risk classification, Tim-3, C-myc, CD3⁺ , CD4⁺ , CD8⁺ , CD4⁺ /CD8⁺ were the main factors affecting the prognosis of ALL patients (all P < 0.05). ROC curve analysis showed that the combination of Tim-3, C-myc, and T lymphocyte subsets had higher sensitivity and accuracy in predicting prognosis of ALL patients compared with the single diagnosis of Tim-3, C-myc, CD3⁺ , CD4⁺ , CD8⁺ , and CD4⁺ /CD8⁺ (P < 0.05). CONCLUSION ALL patients show higher levels of Tim-3, C-myc mRNA and CD8⁺ but lower levels of CD3⁺ , CD4⁺ and CD4⁺/CD8⁺. Moreover, the expression levels of Tim-3, C-myc, CD3⁺ , CD4⁺ , CD8⁺ and CD4⁺/CD8⁺ are correlated with extramedullary invasion, high-risk classification and prognosis.
Humans ; Hepatitis A Virus Cellular Receptor 2/metabolism* ; Prognosis ; Proto-Oncogene Proteins c-myc/metabolism* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis* ; T-Lymphocyte Subsets ; Male ; Female ; Adult ; Middle Aged ; Adolescent ; RNA, Messenger

Cancer stem cells (CSCs) are proposed to account for the progression, metastasis, and recurrence of diverse malignancies. However, the disorganized vasculars in tumors hinder the accumulation and penetration of nanomedicines, posing a challenge in eliminating CSCs located distantly from blood vessels. Herein, a pair of twin-like small-sized nanoparticles, sunitinib (St)-loaded ROS responsive micelles (RM@St) and salinomycin (SAL)-loaded GSH responsive micelles (GM@SAL), are developed to normalize disordered tumor vessels and eradicate CSCs. RM@St releases sunitinib in response to the abundant ROS in the tumor extracellular microenvironment for tumor vessel normalization, which improved intratumor accumulation and homogeneous distribution of small-sized GM@SAL. Sequentially, GM@SAL effectively accesses CSCs and achieves reduction-responsive drug release at high GSH concentrations within CSCs. More importantly, RM@St significantly extends the window of vessel normalization and enhances vessel integrity compared to free sunitinib, thus further amplifying the anti-tumor effect of GM@SAL. The combination therapy of RM@St plus GM@SAL produces considerable depression of tumor growth, drastically reducing CSCs fractions to 5.6% and resulting in 78.4% inhibition of lung metastasis. This study offers novel insights into rational nanomedicines designed for superior therapeutic effects by vascular normalization and anti-CSCs therapy.

This study was aimed at understanding the relationships among the drug resistance and genome characteristics of group A Streptococcus in Jiangsu Province.A total of 149 group A Streptococcus strains were collected from hospitals between 2016 and 2023.Thirteen antimicrobial minimal inhibitory concentrations were detected with the micro-dilution broth method.The GAS strains were typed with emm genotyping analysis and whole genome sequencing,to determine the carriage rates of drug resistance genes and the evolutionary relationships among strains.The resistance rates of 149 GAS strains to erythromy-cin,tetracycline,and clindamycin exceeded 90％,whereas the strains showed sensitivity to 8 different antibiotics,including penicillin.Notably,the resistance rates to erythromycin,tetracycline,and clindamycin consistently increased over time.All strains were classified into 9 emm types,among which emm12 accounted for the highest proportion(77/149;51.68％).Signifi-cant statistical differences were observed among emm types,in terms of the drug resistance rate,number of resistant species,and prevalence of drug resistance genes.Furthermore,SNP evolutionary tree analysis revealed 3 distinct clusters within the GAS strains:emm12,emm1,and other emm types.emm 12 and emm1 were the dominant GAS strains in Jiangsu Province.Most isolates were resistant to erythromycin,tetracycline,and clindamycin.Differences in phenotypes and genomic characteris-tics were observed among emm types.

Objective:To clarify the safety, repair rate, durability, and risk factors for recurrent mitral regurgitation(MR) in patients with Barlow disease(BD) who total thoracoscopic minimally invasive mitral valvuloplasty(TMVP).Methods:Clinical data, mid-term and long-term outcomes of BD patients who underwent TMVP at Guangdong Provincial People's Hospital from January 2009 to June 2022 were retrospectively analyzed. Patients were divided into a group with no MR recurrence(group A) and a group with MR recurrence(group B) according to whether recurrent MR appeared in the postoperative period, and the data of the two groups of patients were compared with each other for the risk factor analysis.Results:The repair rate of TMVP was 98.4%, and no patient died perioperatively. The median follow-up time was 3.1(1.7, 5.2) years, the follow-up rate was 95.8%, and there was no patient died. As of March 2023, 112 patients developed no recurrent MR(group A), 11 patients developed recurrent MR(group B), and 2 patients in group B underwent repeated mitral valve surgery. The left atrial diameter(LAD) and left ventricular end-systolic diameter(LVESD) were higher in group B than in group A patients[LAD: (50.9±7.7)mm vs.(43.7±8.7)mm, P=0.009; LVESD: (37.1±5.5)mm vs.(33.2±4.7)mm, P=0.011], and the percentage of tendon cord rupture was higher in group B than in group A( P=0.022), while the rest of the baseline data were not statistically significant. There was no statistically significant difference between two groups in terms of the use of different surgical techniques, aortic cross-clamp time, cardiopulmonary bypass time, and operative time. Postoperative LAD, postoperative LVESD, and postoperative left ventricular end-diastolic diameter of group B patients were higher than those of group A( P<0.05). There was no statistically significant difference in perioperative and long-term complication rates between the two groups. Multifactorial Cox regression analysis revealed that advanced age( HR=1.049, 95% CI: 0.997-1.103, P=0.066) and large preoperative LVESD( HR=1.168, 95% CI: 1.053-1.295, P=0.003) were the risk factors for postoperative recurrence MR. Conclusion:Total thoracoscopic minimally invasive BD repair is safe, which has a high success rate and good long-term results. Advanced age and large preoperative LVESD are risk factors for recurrent MR in the long term.

This study was aimed at understanding the relationships among the drug resistance and genome characteristics of group A Streptococcus in Jiangsu Province.A total of 149 group A Streptococcus strains were collected from hospitals between 2016 and 2023.Thirteen antimicrobial minimal inhibitory concentrations were detected with the micro-dilution broth method.The GAS strains were typed with emm genotyping analysis and whole genome sequencing,to determine the carriage rates of drug resistance genes and the evolutionary relationships among strains.The resistance rates of 149 GAS strains to erythromy-cin,tetracycline,and clindamycin exceeded 90％,whereas the strains showed sensitivity to 8 different antibiotics,including penicillin.Notably,the resistance rates to erythromycin,tetracycline,and clindamycin consistently increased over time.All strains were classified into 9 emm types,among which emm12 accounted for the highest proportion(77/149;51.68％).Signifi-cant statistical differences were observed among emm types,in terms of the drug resistance rate,number of resistant species,and prevalence of drug resistance genes.Furthermore,SNP evolutionary tree analysis revealed 3 distinct clusters within the GAS strains:emm12,emm1,and other emm types.emm 12 and emm1 were the dominant GAS strains in Jiangsu Province.Most isolates were resistant to erythromycin,tetracycline,and clindamycin.Differences in phenotypes and genomic characteris-tics were observed among emm types.

Objective:To clarify the safety, repair rate, durability, and risk factors for recurrent mitral regurgitation(MR) in patients with Barlow disease(BD) who total thoracoscopic minimally invasive mitral valvuloplasty(TMVP).Methods:Clinical data, mid-term and long-term outcomes of BD patients who underwent TMVP at Guangdong Provincial People's Hospital from January 2009 to June 2022 were retrospectively analyzed. Patients were divided into a group with no MR recurrence(group A) and a group with MR recurrence(group B) according to whether recurrent MR appeared in the postoperative period, and the data of the two groups of patients were compared with each other for the risk factor analysis.Results:The repair rate of TMVP was 98.4%, and no patient died perioperatively. The median follow-up time was 3.1(1.7, 5.2) years, the follow-up rate was 95.8%, and there was no patient died. As of March 2023, 112 patients developed no recurrent MR(group A), 11 patients developed recurrent MR(group B), and 2 patients in group B underwent repeated mitral valve surgery. The left atrial diameter(LAD) and left ventricular end-systolic diameter(LVESD) were higher in group B than in group A patients[LAD: (50.9±7.7)mm vs.(43.7±8.7)mm, P=0.009; LVESD: (37.1±5.5)mm vs.(33.2±4.7)mm, P=0.011], and the percentage of tendon cord rupture was higher in group B than in group A( P=0.022), while the rest of the baseline data were not statistically significant. There was no statistically significant difference between two groups in terms of the use of different surgical techniques, aortic cross-clamp time, cardiopulmonary bypass time, and operative time. Postoperative LAD, postoperative LVESD, and postoperative left ventricular end-diastolic diameter of group B patients were higher than those of group A( P<0.05). There was no statistically significant difference in perioperative and long-term complication rates between the two groups. Multifactorial Cox regression analysis revealed that advanced age( HR=1.049, 95% CI: 0.997-1.103, P=0.066) and large preoperative LVESD( HR=1.168, 95% CI: 1.053-1.295, P=0.003) were the risk factors for postoperative recurrence MR. Conclusion:Total thoracoscopic minimally invasive BD repair is safe, which has a high success rate and good long-term results. Advanced age and large preoperative LVESD are risk factors for recurrent MR in the long term.

AIM To study the chemical constituents from the n-butanol fraction of Siegesbeckiae glabrescens Makino.METHODS The n-butanol fraction from S.glabrescens was isolated and purified by silica gel,ODS and preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.RESULTS Seventeen compounds were isolated and identified as orientalin B(1),ent-2-oxo-15,16,19-trihydroxypimar-8(14)-ene(2),ent-12α,16-epoxy-2β,15α,19-trihydroxypimar-8-ene(3),ent-12α,16-epoxy-2β,15α,19-trihydroxy-pimar-8(14)-ene(4),kirenol(5),benzyl-O-β-D-glucopyranoside(6),hexyl-β-glucopyranoside(7),(Z)-3-hexenyl-β-D-glucopyranoside(8),phenylethyl-O-β-D-glucopyranoside(9),(6R,9S)-3-oxo-α-ionol-β-D-glucopyranoside(10),2-methoxy-4-(2-propenyl)phenyl-β-D-glucoside(11),4-allyl-2,6-dimethoxyphenyl glucoside(12),2-hydroxy-methylphenyl-1-O-β-D-glucopyranoside(13),icarside B2(14),everlastoside D(15),(2S,4R,5S,7S,9S,10R,13S,15R)-2,7,15,16,19-pentahydroxypimar-8(14)-ene(16),and benzyl-β-D-apiofuranosyl-(1″→6′)-β-D-glucopy-ranoside(17).Compound 9 showed weak ABTS radical scavenging capability,and compound 15 had strong DPPH and ABTS radicals scavenging activities.CONCLUSION Compounds 7-9,14-15 are isolated from genus Siegesbeckia for the first time.Compounds 2-4,7-17 are first isolated from this plant.Compound 9 and 15 exhibit antioxidant activities.

Objective To explore the age-related biological properties of bone-derived mesenchymal stem cells(BMSCs)from mice of different age groups and their osteogenic differentiation induced by bone morphogenetic protein 2(BMP2).Methods Eight C57BL/6J mice were divided into a young group(4 weeks old,weighing 10～15 g,n=4)and an old group(12 months old,weighing 20～25 g,n=4),with half male and half female.MSCs were extracted from the whole bones of the 2 groups of mice.After the obtained cells were identified with flow cytometry for the surface markers,β-galactosidase staining was employed to compare the senescence level of BMSCs,MTT and EdU incorporation assays were conducted to compare the proliferation and self-renewal abilities of between the 2 groups.Western blotting was employed to analyze the expression of CyclinD1 and P21 in BMSCs.Then ALP staining,Alizarin Red staining and RT-qPCR were used to evaluate the osteogenic differentiation ability of the cells.RNA sequencing was performed to compare the differential gene expression in BMP2-induced BMSCs.Lastly,the sequencing results were re-confirmed by using flow cytometry.Results Flow cytometry showed that the sorted and cultured mouse BMSCs met the criteria for MSCs.The results of β-galactosidase staining indicated that the senescence level of BMSCs in the old group was significantly higher than that in the young group(P＜0.05).MTT and EdU doping experiments revealed that the cell viability and proliferation ability of BMSCs were significantly lower in the old group than the young group(P＜0.05).Western blotting displayed that the expression level of cell cycle protein CyclinD1 was lower,whereas that of cell cycle inhibitory factor P21 was significantly higher in the BMSCs from the old group than the cells from the young group(P＜0.05).ALP/Alizarin Red staining and RT-qPCR demonstrated that the BMSCs from the young group had stronger osteogenic differentiation capacity after BMP2 treatment when compared the cells of the old group(P＜0.05).RNA sequencing results displayed that the changing profile of CD51 expression was in opposite trends in the young and old BMSCs after BMP2 treatment.Finally,flow cytometry revealed that the percentage of CD51+cells within the CD45-cells was significantly higher in the young group than the old group.Conclusion The decrease in the percentage of CD51+cells among CD45-cells in aged BMSCs is closely associated with their decreased responsiveness to BMP2-induced osteogenic differentiation.