Aim To investigate the effects of Cartham-us tinctorius L.extract(CTLE)on oxidative stress,lipid metabolism,and apoptosis levels of mice with al-cohol-induced liver injury and its mechanism of action.Methods The mouse model of alcohol-associated liver disease was established by chronic alcohol feeding and acute alcohol gavage.Mice were randomly divided into four groups.During the modeling period,the state changes of mice were observed every day,and their weight was recorded.At the end of modeling,blood and liver tissues were collected from each group of mice.The blood of mice was analyzed biochemically,and HE staining and Oil Red O staining were used to evaluate further the degree of pathological damage in the liver of mice.Quantitative real-time PCR(qPCR)and Western blot were applied to detect the mRNA and protein expression levels of p-PI3K,PI3K,p-Akt,Akt,p-mTOR,mTOR,p-FoxO1,FoxO1,p-FoxO3a,FoxO3a,p-FoxO4,FoxO4,BCL and BAX factors.Results Compared to the model group,the CTLE administration group showed improved hepatic patho-logical injury and reduced lipid deposition.The bio-chemical indexes in serum and liver,such as ALT,AST,TG,TC,and MDA levels were reduced,while GSH and SOD levels increased.Regulating the PI3K/Akt/FoxO pathway resulted in increased production of SOD,which reduced damage and apoptosis caused by reactive oxygen species(ROS).Conclusions CTLE can exert anti-oxidative stress and anti-apoptotic effects through the PI3K/Akt/FoxO pathway and attenuates alcoholic liver injury in mice,providing new ideas for the treatment of alcoholic liver disease and the develop-ment of related drugs.

Objective To investigate the effect of reactive oxygen species(ROS)/silent information regulator 1(SIRT1)on hyperoxia-induced mitochondrial injury in BEAS-2B cells.Methods The experiment was divided into three parts.In the first part,cells were divided into H0,H6,H12,H24,and H48 groups.In the second part,cells were divided into control group,H48 group,H48 hyperoxia+SIRT1 inhibitor group(H48+EX 527 group),and H48 hyperoxia+SIRT1 agonist group(H48+SRT1720 group).In the third part,cells were divided into control group,48-hour hyperoxia+N-acetylcysteine group(H48+NAC group),and H48 group.The ROS kit was used to measure the level of ROS.Western blot and immunofluorescent staining were used to measure the expression levels of SIRT1 and mitochondria-related proteins.Transmission electron microscopy was used to observe the morphology of mitochondria.Results Compared with the H0 group,the H6,H12,H24,and H48 groups had a significantly increased fluorescence intensity of ROS(P<0.05),the H48 group had significant reductions in the expression levels of SIRT1 protein and mitochondria-related proteins(P<0.05),and the H24 and H48 groups had a significant reduction in the fluorescence intensity of mitochondria-related proteins(P<0.05).Compared with the H48 group,the H48+SRT1720 group had significant increases in the expression levels of mitochondria-related proteins and the mitochondrial aspect ratio(P<0.05),and the H48+EX 527 group had a significant reduction in the mitochondrial area(P<0.05).Compared with the H48 group,the H48+NAC group had a significantly decreased fluorescence intensity of ROS(P<0.05)and significantly increased levels of SIRT1 protein,mitochondria-related proteins,mitochondrial area,and mitochondrial aspect ratio(P<0.05).Conclusions The ROS/SIRT1 axis is involved in hyperoxia-induced mitochondrial injury in BEAS-2B cells.

Abstract Allergic diseases can occur in all systems of the body, covering the whole life cycle, from children to adults and to old age, can be lifelong onset and even fatal in severe cases. Children account for the largest proportion of the victims of allergic disease, Children s allergies start from scratch, ranging from mild to severe, from less to more, from single to multiple systems and systemic performance, so the prevention and treatment of allergic diseases in children is of great importance, which can not only prevent high risk allergic conditions from developing into allergic diseases, but also further block the process of allergy. At present, there is no consensus on the management system of allergic children in kindergartens and primary schools. The "Consensus on Allergy Management and Prevention in Kindergartens and Primary Schools", which includes the organizational structure, system construction and management of allergic children, provides evidence informed recommendations for the long term comprehensive management of allergic children in kindergartens and primary schools, and provides a basis for the establishment of the prevention system for allergic children.

Objective: To investigate the genetic and genomic profiling of juvenile myelomonocytic leukemia (JMML) and factors affecting its survival rate. Methods: Clinical characteristics, cytogenetics, molecular biology results and survival status of children with 27 JMML cases admitted to the Hematology Department of Children's Hospital, Capital Institute of Pediatrics from December 2012 to December 2021 were analyzed retrospectively, and the outcomes of the children were followed up. Kaplan-Meier method was used for survival analysis. Univariate analysis was used for analyzing factors affecting the overall survival (OS) rates of patients who received hematopoietic stem cell transplantation (HSCT). Log-Rank test was used for comparison of survival curves. Results: Among 27 JMML cases, there were 11 males and 16 females. The age of disease onset was 28 (11,52) months. There are 20 cases of normal karyotype, 4 cases of monosomy 7, 1 case of trisomy 8,1 case of 11q23 rearrangement and 1 case of complex karyotype. A total of 39 somatic mutations were detected.Those involved in RAS signal pathway were the highest (64%(25/39)), among which PTPN11 mutation was the most frequent (44% (11/25)). A total of 17 cases (63%) received HSCT, 8 cases (30%) did not receive HSCT, and 2 cases (7%) lost follow-up. For children receiving transplantation, the follow-up time after transplantation was 47 (11,57) months. The 1-year OS rate of high-risk transplantation group (17 cases) and high-risk non transplantation group (6 cases) was (88±8)% and (50±20)% respectively, with a statistically significant difference (χ²=5.01, P=0.025). The 5-year OS rate of the high-risk transplantation group was (75±11)%. The survival time of those who relapsed or progressed to acute myeloid leukemia after transplantation was significantly shorter than that of those who did not relapse (χ²=6.80, P=0.009). The OS rate of patients with or without PTPN11 mutation was (81±12) % and (67±19)% respectively (χ²=0.85, P=0.356). Conclusions: The main pathogenesis involved in JMML is gene mutation related to RAS signaling pathway, and the most common driver gene of mutation is PTPN11. Allogeneic HSCT can significantly improve the survival rate of high-risk JMML patients. The recurrence or progression after transplantation was related to poor prognosis.
Male ; Female ; Child ; Humans ; Child, Preschool ; Leukemia, Myelomonocytic, Juvenile/therapy* ; Retrospective Studies ; Survival Analysis ; Mutation ; Hematopoietic Stem Cell Transplantation

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans ; Female ; Blood Platelets/pathology* ; Biomarkers, Tumor/genetics* ; Ovarian Neoplasms/pathology* ; China

Objective: To analyze the clinicopathologic characteristics and prognosis of testicular diffuse large B-cell lymphoma (DLBCL) . Methods: A retrospective analysis was performed on 68 patients with testicular DLBCL admitted to Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine from October 2001 to April 2020. The gene mutation profile was evaluated by targeted sequencing (55 lymphoma-related genes) , and prognostic factors were analyzed. Results: A total of 68 patients were included, of whom 45 (66.2% ) had primary testicular DLBCL and 23 (33.8% ) had secondary testicular DLBCL. The proportion of secondary testicular DLBCL patients with Ann Arbor stage Ⅲ-Ⅳ (P<0.001) , elevated LDH (P<0.001) , ECOG score ≥ 2 points (P=0.005) , and IPI score 3-5 points (P<0.001) is higher than that of primary testicular DLBCL patients. Sixty-two (91% ) patients received rituximab in combination with cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP) -based first-line regimen, whereas 54 cases (79% ) underwent orchiectomy prior to chemotherapy. Patients with secondary testicular DLBCL had a lower estimated 5-year progression-free survival (PFS) rate (16.5% vs 68.1% , P<0.001) and 5-year overall survival (OS) rate (63.4% vs 74.9% , P=0.008) than those with primary testicular DLBCL, and their complete remission rate (57% vs 91% , P=0.003) was also lower than that of primary testicular DLBCL. The ECOG scores of ≥2 (PFS: P=0.018; OS: P<0.001) , Ann Arbor stages Ⅲ-Ⅳ (PFS: P<0.001; OS: P=0.018) , increased LDH levels (PFS: P=0.015; OS: P=0.006) , and multiple extra-nodal involvements (PFS: P<0.001; OS: P=0.013) were poor prognostic factors in testicular DLBCL. Targeted sequencing data in 20 patients with testicular DLBCL showed that the mutation frequencies of ≥20% were PIM1 (12 cases, 60% ) , MYD88 (11 cases, 55% ) , CD79B (9 cases, 45% ) , CREBBP (5 cases, 25% ) , KMT2D (5 cases, 25% ) , ATM (4 cases, 20% ) , and BTG2 (4 cases, 20% ) . The frequency of mutations in KMT2D in patients with secondary testicular DLBCL was higher than that in patients with primary testicular DLBCL (66.7% vs 7.1% , P=0.014) and was associated with a lower 5-year PFS rate in patients with testicular DLBCL (P=0.019) . Conclusion: Patients with secondary testicular DLBCL had worse PFS and OS than those with primary testicular DLBCL. The ECOG scores of ≥2, Ann Arbor stages Ⅲ-Ⅳ, increased LDH levels, and multiple extra-nodal involvements were poor prognostic factors in testicular DLBCL. PIM1, MYD88, CD79B, CREBBP, KMT2D, ATM, and BTG2 were commonly mutated genes in testicular DLBCL, and the prognosis of patients with KMT2D mutations was poor.
Male ; Adult ; Humans ; Prognosis ; Retrospective Studies ; Myeloid Differentiation Factor 88 ; China/epidemiology* ; Testicular Neoplasms/drug therapy* ; Cyclophosphamide ; Rituximab/therapeutic use* ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; Prednisone/therapeutic use* ; Doxorubicin/therapeutic use* ; Vincristine/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Immediate-Early Proteins/therapeutic use* ; Tumor Suppressor Proteins

Hepatotoxicity induced by bioactive constituents in traditional Chinese medicines or herbs,such as bavachin(BV)in Fructus Psoraleae,has a prolonged latency to overt drug-induced liver injury in the clinic.Several studies have described BV-induced liver damage and underlying toxicity mechanisms,but little attention has been paid to the deciphering of organisms or cellular responses to BV at no-observed-adverse-effect level,and the underlying molecular mechanisms and specific indicators are also lacking during the asymptomatic phase,making it much harder for early recognition of hepatotoxicity.Here,we treated mice with BV for 7 days and did not detect any abnormalities in biochemical tests,but found subtle steatosis in BV-treated hepatocytes.We then profiled the gene expression of hepatocytes and non-parenchymal cells at single-cell resolution and discovered three types of hepatocyte subsets in the BV-treated liver.Among these,the hepa3 subtype suffered from a vast alteration in lipid metabolism,which was characterized by enhanced expression of apolipoproteins,carboxylesterases,and stearoyl-CoA desaturase 1(Scd1).In particular,increased Scd1 promoted monounsaturated fatty acids(MUFAs)syn-thesis and was considered to be related to BV-induced steatosis and polyunsaturated fatty acids(PUFAs)generation,which participates in the initiation of ferroptosis.Additionally,we demonstrated that mul-tiple intrinsic transcription factors,including Srebf1 and Hnf4a,and extrinsic signals from niche cells may regulate the above-mentioned molecular events in BV-treated hepatocytes.Collectively,our study deciphered the features of hepatocytes in response to BV insult,decoded the underlying molecular mechanisms,and suggested that Scd1 could be a hub molecule for the prediction of hepatotoxicity at an early stage.

OBJECTIVE: To explore the brain effect mechanism and the correlation between brain functional imaging and cognitive function in treatment of depressive disorder (DD) with transcutaneous auricular vagus nerve stimulation (taVNS) based on the resting-state functional magenetic reasonance imaging (rs-fMRI). METHODS: Thirty-two DD patients were included in a depression group and 32 subjects of healthy condition were enrolled in a normal group. In the depression group, the taVNS was applied to bilateral Xin (CO₁₅) and Shen (CO₁₀), at disperse-dense wave, 4 Hz/20 Hz in frequency and current intensity ≤20 mA depending on patient's tolerance, 30 min each time, twice daily. The duration of treatment consisted of 8 weeks. The patients of two groups were undertaken rs-fMRI scanning. The scores of Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA) and Wisconsin card sorting test (WCST) were observed in the normal group at baseline and the depression group before and after treatment separately. The differential brain regions were observed before and after treatment in the two groups and the value of degree centrality (DC) of fMRI was obtained. Their correlation was analyzed in terms of HAMD, HAMA and WCST scores. RESULTS: The scores of HAMD and HAMA in the depression group were all higher than those in the normal group (P<0.05). After treatment, the scores of HAMD and HAMA were lower than those before treatment in the depression group; the scores of total responses, response errors and perseverative errors of WCST were all lower than those before treatment (P<0.05). The brain regions with significant differences included the left inferior temporal gyrus, the left cerebellar peduncles region 1, the left insula, the right putamen, the bilateral supplementary motor area and the right middle frontal gyrus. After treatment, the value of DC in left supplementary motor area was negatively correlated to HAMD and HAMA scores respectively (r=-0.324, P=0.012; r=-0.310, P=0.015); the value of DC in left cerebellar peduncles region 1 was negatively correlated to the total responses of WCST (r=-0.322, P=0.013), and the left insula was positively correlated to the total responses of WCST (r=0.271, P=0.036). CONCLUSION The taVNS can modulate the intensity of the functional activities of some brain regions so as to relieve depressive symptoms and improve cognitive function.
Humans ; Depression/therapy* ; Magnetic Resonance Imaging/methods* ; Vagus Nerve Stimulation/methods* ; Brain/diagnostic imaging* ; Transcutaneous Electric Nerve Stimulation/methods* ; Vagus Nerve

OBJECTIVE: To investigate the efficacy and safety of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in combination of ATG and post-transplant cyclophosphamide (PTCy) -induced immune tolerance after transplantation in treatment of childhood myelodysplastic syndromes(MDS）. METHODS: From July 2016 to November 2020, a total of 8 children with MDS receiving the haploidentical allo-HSCT combined with ATG and PTCy-induced immune tolerance after transplantation in our hospital were enrolled, whose clinical data were retrospected and analyzed. RESULTS: Median age at diagnosis of the 8 children (1 male and 7 females) was 6.4 (range, 10 months to 15 years) years old. The median medical history of MDS was 2.7 years (range, 3 months to 8 years). Among the 8 patients, 7 cases were diagnosed with refractory cytopenia of childhood and one with refractory anemia with excess of blasts. The HSC donors were father, mother or brother of patients and HLA matching in 6-9/12 loci were identical. All the donors were healthy and didn't carry the same pathogenic genes as the recipients. The median age of donors was 36.4 (range, 25 to 49) years old. The median mononuclear cell (MNC) number of the graft was 19.8, ranging in (13.2-47.3)×10⁸/kg, and the median CD34⁺ cell number was 11.8×10⁶/kg, ranging in (5.0-18.3)×10⁶/kg. Graft-versus-host disease prophylactic regimen was started on day 3 and 4 after transplantation, in which cyclophosphamide (50 mg/kg·d) was administered by intravenous infusion. From day 5 after transplantation, low-dose tacrolimus was administered by intravenous infusion and mycophenolate mofetil was administered orally. The median time of neutrophil and platelet engraftment was 12.6 (rang, 11 to 15) days and 13.3 (rang, 11 to 18) days, respectively. All the patients achieved full donor chimerism on neutrophil engraftment after transplantation. The median follow-up time was 1 032 (rang, 747 to 1 536) days. Both overall survival rate and disease-free survival rate were 100%. CONCLUSION Haplo-HSCT combined with ATG and PTCy-induced immune tolerance after transplantation is a safe and effective treatment for children with MDS.
Adult ; Child ; Cyclophosphamide ; Female ; Graft vs Host Disease/drug therapy* ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; Myelodysplastic Syndromes/drug therapy* ; Transplantation Conditioning ; Treatment Outcome

OBJECTIVE: Through showing the full picture of double-arm controlled clinical research and systematic review evidence in the field of orally administrated Chinese herbal medicine (CHM) for treatment of lung cancer, to provide a reference for future clinical research and to indicate a direction for future systematic reviews. METHODS: A comprehensive search of clinical controlled studies was performed regarding orally administered CHM treatment for lung cancer published from January 1970 to September 2020. The language was restricted to Chinese and English. Relevant data were extracted, the quality of systematic reviews was evaluated, and the research evidence was visually displayed. RESULTS: Randomized controlled trials were the most common type of research design. The research sample sizes were typically small. Oral CHM showed certain curative advantages in treating lung cancer. The key stages in oral CHM intervention for lung cancer are chemotherapy, radiotherapy, and late palliative treatment. The advantageous outcomes of oral CHM treatment of lung cancer are the short-term efficacy, quality of life, and adverse reactions. The perioperative stage, overall survival, pharmacoeconomic evaluation, and Chinese medicine decoctions are weak research areas. CONCLUSIONS CHM has staged and therapeutic advantages in treating lung cancer. The overall methodological quality is poor, and the level of evidence requires improvement. It is necessary to carry out large-scale, standardized, and higher-quality research in the superior and weak areas of CHM treatment of lung cancer.
Drugs, Chinese Herbal/adverse effects* ; Humans ; Lung Neoplasms/drug therapy* ; Quality of Life ; Randomized Controlled Trials as Topic ; Systematic Reviews as Topic