BACKGROUND: Peripheral helper T (T PH ) cells are uniquely positioned within pathologically inflamed non-lymphoid tissues to stimulate B-cell responses and antibody production. However, the phenotype, function, and clinical relevance of T PH cells in hepatocellular carcinoma (HCC) are currently unknown. METHODS: Blood, tumor, and peritumoral liver tissue samples from 39 HCC patients (Sep 2016-Aug 2017) and 101 HCC patients (Sep 2011-Dec 2012) at the Third Affiliated Hospital of Sun Yat-sen University were used. Flow cytometry was used to quantify the expression, phenotype, and function of T PH cells. Log-rank tests were performed to evaluate disease-free survival and overall survival in samples from 39 patients and 101 patients with HCC. T PH cells, CD19 + B cells, and T follicular helper (T FH ) cells were cultured separately in vitro or isolated from C57/B6L mice in vivo for functional assays. RESULTS: T PH cells highly infiltrated tumor tissues, which was correlated with tumor size, early recurrence, and shorter survival time. The tumor-infiltrated T PH cells showed a unique ICOS hi CXCL13 + IL-21 - MAF + BCL-6 - phenotype and triggered naïve B-cell differentiation into regulatory B cells. Triggering programmed cell death protein 1 (PD-1) induced the production of C-X-C motif chemokine ligand 13 (CXCL13) by T PH cells, which then suppressed tumor-specific immunity and promoted disease progression. CONCLUSION Our study reveals a novel regulatory mechanism of T PH cell-regulatory B-cell-mediated immunosuppression and provides an important perspective for determining the balance between the differentiation of protumorigenic T PH cells and that of antitumorigenic T FH cells in the HCC microenvironment.
Carcinoma, Hepatocellular/metabolism* ; Liver Neoplasms/metabolism* ; Humans ; T-Lymphocytes, Helper-Inducer/metabolism* ; Animals ; Mice ; Male ; Female ; Mice, Inbred C57BL ; Middle Aged ; B-Lymphocytes, Regulatory/metabolism* ; Flow Cytometry ; Interleukin-21 ; Aged ; Chemokine CXCL13/metabolism*

Sennoside A (SA), a typical prodrug, exerts its laxative effect only after its transformation into rheinanthrone catalyzed by gut microbial hydrolases and reductases. Hydrolases have been identified, but reductases remain unknown. By linking a photoreactive group to the SA scaffold, we synthesized a photoaffinity probe to covalently label SA reductases and identified SA reductases using activity-based protein profiling (ABPP). From lysates of an active strain, Bifidobacterium pseudocatenulatum (B. pseudocatenulatum), 397 proteins were enriched and subsequently identified using mass spectrometry (MS). Among these proteins, chromate reductase/nicotinamide adenine dinucleotide (NADH) phosphate (NADPH)-dependent flavin mononucleotide (FMN) reductase/oxygen-insensitive NADPH nitroreductase (nfrA) was identified as a potent SA reductase through further bioinformatic analysis and The Universal Protein Resource (UniProt) database screening. We also determined that recombinant nfrA could reduce SA. Our study contributes to further illuminating mechanisms of SA transformation to rheinanthrone and simultaneously offers an effective method to identify gut bacterial reductases.

OBJECTIVE To evaluate the pharmacodynamics of Wujiashen Gejiejing on rats with deficiency of lung qi. METHODS The rat model of deficiency of lung qi was established by sawdust fumigation. By comparing the general activity state, blood acid-alkali indexes, biochemical indexes related to chronic bronchitis and airway histological characteristics of rats in each group, the pharmacodynamics of Wujiashen Gejiejing on rats with deficiency of lung qi was evaluated. RESULTS Compared with model group, after the Wujiashen Gejiejing intervention, the body weight of the rats significantly increased; the levels of p(O2) and SaO2 in blood were significantly increased(P<0.001), p(CO2) was significantly decreased(P<0.05), and pH had a tendency to increase; the levels of endothelin(ET) and IL-1β in serum were significantly decreased(P<0.01 or P<0.05), and the levels of TNF-α in serum had a decreasing trend. The damaged lung structures were significantly improved. CONCLUSION Wujiashen Gejiejing can significantly improve the activity state and improve hypoxemia and hypercapnia of lung qi deficiency syndrome, improve the damaged lung structure and the function of lung ventilation, and has obvious anti-inflammatory effect. Its mechanism may be related to regulating the expression of inflammatory cytokines IL-1β, TNF-α and ET.

The comprehensive detection and identification of active ingredients in complex matrices is a crucial challenge.Liquid chromatography coupled with high-resolution mass spectrometry(LC-HRMS)is the most prominent analytical platform for the exploration of novel active compounds from complex matrices.However,the LC-HRMS-based analysis workflow suffers from several bottleneck issues,such as trace content of target compounds,limited acquisition for fragment information,and uncertainty in interpreting relevant MS2 spectra.Lycibarbarspermidines are vital antioxidant active ingredients in Lycii Fructus,while the reported structures are merely focused on dicaffeoylspermidines due to their low content.To comprehensively detect the new structures of lycibarbarspermidine derivatives,a"depict"strategy was developed in this study.First,potential new lycibarbarspermidine derivatives were designed according to the biosynthetic pathway,and a comprehensive database was established,which enlarged the coverage of lycibarbarspermidine derivatives.Second,the polarity-oriented sample prep-aration of potential new compounds increased the concentration of the target compounds.Third,the construction of the molecular network based on the fragmentation pathway of lycibarbarspermidine derivatives broadened the comprehensiveness of identification.Finally,the weak response signals were captured by data-dependent scanning(DDA)followed by parallel reaction monitoring(PRM),and the efficiency of acquiring MS2 fragment ions of target compounds was significantly improved.Based on the integrated strategy above,210 lycibarbarspermidine derivatives were detected and identified from Lycii Fructus,and in particular,170 potential new compounds were structurally characterized.The integrated strategy improved the sensitivity of detection and the coverage of low-response components,and it is expected to be a promising pipeline for discovering new compounds.

Cancer genomics has led to the discovery of numerous oncogenes and tumor suppressor genes that play critical roles in cancer development and progression.Oncogenes promote cell growth and proliferation,whereas tumor suppressor genes inhibit cell growth and division.The dysregulation of these genes can lead to the development of cancer.Recent studies have focused on non-coding RNAs(ncRNAs),including circular RNA(circRNA),long non-coding RNA(lncRNA),and microRNA(miRNA),as therapeutic targets for cancer.In this article,we discuss the oncogenes and tumor suppressor genes of ncRNAs associated with different types of cancer and their potential as therapeutic targets.Here,we highlight the mechanisms of action of these genes and their clinical applications in cancer treatment.Understanding the molecular mechanisms underlying cancer development and identifying specific therapeutic targets are essential steps towards the development of effective cancer treatments.

Objective To analyze and study the prescriptions of Chief Physician Chang Yalin for treating breast hyperplasia patients in the outpatient department,explores and summarizes the medication patterns for treating breast hyperplasia,and provides reference and dialectical medication ideas for clinical treatment of breast hyperplasia by using data mining technology.Methods Collect the prescriptions of Dr.Chang Yalin for treating breast hyperplasia patients at the Outpatient Department of Jiuquan Traditional Chinese Medicine Hospital from January 1,2017 to December 31,2022.After induction and organization,establish a data table,use Excel 2019 to statistically analyze the drug frequency and gender,taste,and meridian.Use SPSS Modoler 18.0 software April algorithm to analyze the association rules of the drugs,and use SPSS Statistics for cluster analysis.Results A total of 184 prescriptions were included,covering 140 types of traditional Chinese medicine,with a total frequency of use of 4059 times.Among them,Cornus officinalis,dried ginger,roasted licorice,Poria cocos,and jujube are commonly used drugs for the treatment of breast hyperplasia.The top three types of Chinese medicine that are commonly used are tonifying deficiency,warming internal medicine,and relieving external symptoms.The medicinal properties are mainly warm and mild;The medicinal taste is characterized by sweetness,bitterness,and bitterness;The main meridians of drugs are spleen,lung,and heart meridians.Association rule analysis shows that roasted licorice white peony,poria cocos,licorice,and cornus flesh white peony,jujube,and ginger are equivalent.Classify commonly used drugs into 4 categories using Euclidean distance clustering and segmentation with 5.Conclusion Dr.Chang Yalin has always implemented the core idea of treating breast hyperplasia through the coordination of liver and spleen,the simultaneous application of attack and tonifying,and the simultaneous treatment of phlegm and blood stasis.In terms of the combination of latent drugs,the main focus is on tonifying qi and spleen,tonifying yin/blood and regulating liver,and resolving stasis/resolving phlegm and dispersing stagnation.In terms of the combination of"cold phlegm"and"blood stasis and toxin",as well as the combination of"eighteen contraindications"and"nineteen contraindications",his principles and methods are more distinctive and worthy of further research and promotion.

OBJECTIVE: To explore the clinical characteristics and genetic etiology of a child with multiple pterygium syndrome (MPS). METHODS: A child with MPS who was treated at the Orthopedics Department of Guangzhou Women and Children's Medical Center Affiliated to Guangzhou Medical University on August 19, 2020 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and her parents were also collected. Whole exome sequencing (WES) was carried out for the child. Candidate variant was validated by Sanger sequencing of her parents and bioinformatic analysis. RESULTS: The child, an 11-year-old female, had a complain of "scoliosis found 8 years before and aggravated with unequal shoulder height for 1 year". WES results revealed that she has carried a homozygous c.55+1G>C splice variant of the CHRNG gene, for which both of her parents were heterozygous carriers. By bioinformatic analysis, the c.55+1G>C variant has not been recorded by the CNKI, Wanfang data knowledge service platform and HGMG databases. Analysis with Multain online software suggested that the amino acid encoded by this site is highly conserved among various species. As predicted with the CRYP-SKIP online software, the probability of activation and skipping of the potential splice site in exon 1 caused by this variant is 0.30 and 0.70, respectively. The child was diagnosed with MPS. CONCLUSION The CHRNG gene c.55+1G>C variant probably underlay the MPS in this patient.
Humans ; Child ; Female ; Abnormalities, Multiple/genetics* ; Malignant Hyperthermia/genetics* ; Skin Abnormalities/genetics* ; Heterozygote ; Mutation ; Receptors, Nicotinic/genetics*

Objective:To investigate the clinic opathological features, treatment and prognosis of children newly diagnosed with ependymoma.Methods:Clinical data of 127 pediatric ependymoma (EPN) patients (0-16 years old) treated with tumor resection and postoperative radiotherapy at Xinhua Hospital Affiliated to Shanghai Jiao Tong University between 2001 and 2021 were retrospectively analyzed. Among them, 53 children were female and 74 were male. Local control (LR), event-free survival (EFS) and overall survival (OS) rates were analyzed by Kaplan-Meier method. The relationship between clinic opathological factors and clinical prognosis, and the effect of treatment on clinical prognosis of patients were analyzed by Cox proportional hazards model.Results:At a median follow-up time of 29 months (3-251 months), the 3-year OS and EFS rates were 89.5% and 71.5%, respectively. For patients undergoing incomplete resection followed by postoperative adjuvant radiotherapy, the 3-year LR, OS and EFS rates were 78.3%, 65.8% and 85.7%, respectively. A total of 43 children were aged <3 years old when diagnosed and 84 aged ≥3 years old. The interval time between surgery and radiotherapy in children aged <3 years old was 91 d, and 35.5 d in those aged ≥3 years old ( P<0.001). For patients <3 years old, the median EFS was 90 months when initiating radiotherapy within ≤70 d after surgery, compared to 43 months for those who initiated radiotherapy at >70 d after surgery ( P=0.053). According to fifth edition of the WHO classification of tumors of the central nervous system (WHO CNS5), 39 children were classified as posterior fossa ependymoma group A (PFA group). The OS and EFS rates in the PFA group were significantly less than those in other groups (3-year OS rate were 69.2% vs. 94.6%, P<0.001; 3-year EFS rate were 46.9% vs. 79.1%, P<0.001). In the PFA group, 12 patients received postoperative adjuvant chemotherapy, 14 did not receive chemotherapy, and whether chemotherapy was given was unknown in 13 cases. No significant differences were observed in OS and EFS between patients treated with and without chemotherapy ( P=0.260, P=0.730). Univariate Cox analysis showed that tumor location and WHO CNS5 molecular classification were significantly associated with EFS, and WHO CNS5 molecular classification was significantly correlated with OS. Multivariate Cox analysis showed that tumor location in the posterior fossa was an independent risk factor for EFS ( HR=2.72, 95% CI=1.1~6.71, P=0.03). Conclusions:Patients newly diagnosed with pediatric ependymoma can obtain favorable survival after surgery combined with postoperative adjuvant radiotherapy. Patients with residual tumors can achieve favorable LC and survival after postoperative adjuvant radiotherapy. Delaying of radiotherapy tends to lead to poor survival for patients aged <3 years old when diagnosed. Children in the PFA group obtain worse prognosis compared to their counterparts in other groups. The tumor location in the posterior fossa is an independent risk factor for pediatric ependymoma.

Objective:To investigate the clinical features of pediatric patients with intracranial primary non-germinomatous germ cell tumors (NGGCT) and evaluate the treatment outcomes and prognostic factors of NGGCT.Methods:Clinical data of 40 children with NGGCT who were treated with radiotherapy (RT) at our department between November 2008 and June 2019 were retrospectively analyzed. Ninety percent of them received craniospinal irradiation (CSI). All children received platinum-based chemotherapy. Survival analysis was conducted using the Kaplan-Meier estimate. The prognostic factors were analyzed by log-rank test.Results:The primary sites were pineal gland, sellar / suprasellar region and basal ganglia. The median age of onset was 108 months (20-204 months). The median follow-up time was 33 months (8-131 months), and the 3-year and 5-year overall survival (OS) rates were 82.0%. The 3-year and 5-year progression-free survival (PFS) rates were 78.6% and 73.0%. Univariate analysis showed that increased alpha-fetoprotein (AFP) ( P=0.02), age at first diagnosis>10 years ( P=0.006), metastasis at first diagnosis ( P<0.001), and the pathological type (choriocarcinoma, yolk sac tumor and / or embryonal carcinoma) ( P=0.036) were independent adverse prognostic factors. Conclusions:Increased AFP, age>10 years at first diagnosis, tumor metastasis and pathological type were independent adverse prognostic factors of NGGCT. The overall prognosis of NGGCT children is worse than that of their counterparts with germinoma, and multidisciplinary intensive therapy is needed to improve survival.

Objective:To examine the effects of heart rate control during hospitalization on short-term prognosis of heart failure in elderly patients.Methods:As a prospective study, 150 elderly patients with heart failure were selected from the Department of Geriatrics, Qilu Hospital of Shandong University.The subjects were divided into an experimental group and a control group by digitally generated random numbers, with 75 individuals in each group.Both groups received conventional anti-heart failure therapy during hospitalization, but patients from the control group had doses of heart rate control drugs adjusted every 2-4 weeks, with no special requirement for the heart rate before hospital discharge.In contrast, patients from the experimental group were given heart rate control drugs with timely dose adjustment to achieve more proactive heart rate control, aiming for a rate <70 beat/min, as long as heart failure symptom improvement and good volume management could be maintained.Values of cardiac function indexes were compared between the two groups at discharge and 6 months after discharge.Heart failure readmission rates within 6 months, cardiovascular disease mortality rates and the incidences of composite endpoint events after readmission due to heart failure aggravation were compared between the two groups.Treatment safety was also evaluated.Results:There was no statistical difference in blood pressure, heart rate, N-terminal pro-B-type natriuretic peptide(NT-pro-BNP), left ventricular ejection fraction(LVEF), left ventricular end systolic diameter(LVESD), or left ventricular end diastolic diameter(LVEDD)between the two groups at admission( P>0.05), and there was no statistical difference in the average length of hospitalization between the two groups( P>0.05). The experimental group had a lower average heart rate and diastolic pressure than the control group at discharge and 6 months latter[at discharge: (61.6±4.2)beat/min(1 mmHg=0.133 kPa) vs.(78.0±7.1)beat/min, (62.1±10.4)mmHg vs.(66.1±10.2)mmHg; at 6 months: (64.7±12.1)beat/min vs.(71.8±11.2)beat/min, (62.8±11.2)mmHg vs.(68.6±10.2)mmHg; P<0.05 or P<0.01]. NT-pro-BNP in the experimental group was significantly lower than that in the control group at discharge[(1 706±1 408)ng/L vs.(2 806±3 812)ng/L, P<0.05]. The absolute values of changes in LVEF(ΔLVEF), LVESD(ΔLVESD)and LVEDD(ΔLVEDD)after 6 months in the experimental group were significantly higher than those in the control group[ΔLVEF: (0.08±0.09) vs.(0.02±0.09), P<0.05; ΔLVESD: (-5.82±7.44)mm vs.(-1.63±6.07)mm, P<0.01; ΔLVEDD: (-2.76±5.52)mm vs.(-0.86±4.44)mm, P<0.05]. The rate of readmission and the incidence of composite endpoint events within 6 months in the experimental group were significantly lower than those in the control group[21.3%(16 cases) vs.36.0%(27 cases), P<0.05]; 25.3%(19 cases) vs.44.0%(33 cases), P<0.05.There was no significant difference in all-cause mortality between the two groups( P>0.05). Conclusions:For elderly patients with heart failure, proactive active heart rate control during hospitalization and a rate <70 beat/min before discharge will improve cardiac function indexes and lower the rate of readmission with exacerbation of heart failure, cardiovascular disease mortality and the incidence of composite end-point events after readmission.This strategy has good safety and is beneficial for short-term prognosis.