Objective:To explore the clinical characteristics of interleukin-6 (IL-6) and interleukin-8 (IL-8) in cerebrospinal fluid (CSF) of children with bacterial meningitis (BM) and provide reference for clinical diagnosis and treatment of BM.Methods:The clinical data of BM children hospitalized in Women and Children′s Medical Center Affiliated to Guangzhou Medical University from December 2019 to March 2022 were collected and retrospectively analyzed in this case series study.Cytokines in CSF of these children were detected at least twice during the treatment. t test, Mann-Whitney test or analysis of variance were carried out for statistical analysis. Results:There were 40 patients included in this study.The age of onset was 2(1, 8) months, ranging from 2 days to 8 years, and the length of time from onset to hospitalization was (15±17) days, ranging from 1 day to 69 days.The main symptoms at the onset were fever (40 cases, 100%), poor mental state (16 cases, 35.0%), convulsion (9 cases, 22.5%), and vomiting (9 cases, 22.5%).According to pathogens, the patients were divided into the Streptococcus agalactia group (GBS group, 9 cases), Streptococcus pneumoniae group (SP group, 9 cases), other bacteria group (9 cases), and unknown bacteria group (13 cases).The levels of cytokines in the CSF of BM children were increased, along with significantly elevated levels of IL-6 and IL-8 within 1 st week of BM, followed by the peak at 2 nd-3 rd weeks, and then levels of IL-6 and IL-8 presented an overall decreasing trend with the progression of BM.The level of IL-6 in CSF of 10 cases significantly decreased in the 4 th week of BM [within 2 weeks: 773.5(164.1, 1 781.2) ng/L vs. 4 th week: 10.8(2.2, 21.1) ng/L, P=0.005].Such statistical differences didn′t occur to the level of IL-8 [within 2 weeks 182.9(33.6, 657.7) ng/L vs. 4 th week: 92.9(22.6, 226.6) ng/L, P=0.303].After effective antibiotic therapy, 6 patients had elevated white blood cell count in CSF during the 4 th-20 th weeks, with or without repeating intermittent fever.Among them, 4 cases of GBS and 1 case of SP were negative for pathogens in CSF during the retest after treatment, and the levels of IL-6 and IL-8 [(149.1-4 218.6) ng/L and (124.2-1 890.3) ng/L, respectively] in CSF were elevated.Low-dose glucocorticoid was administered for anti-inflammatory treatment, with additional gamma globulin for 1 case and Ibuprofen instead for 1 case.Subsequently, the fever completely subsided.The white blood cell count in CSF decreased significantly ( P=0.024). Conclusions:The levels of IL-6 and IL-8 in CSF increase significantly in the acute phase of BM and generally decrease with the progression of BM.If they are still significantly elevated in the later course of BM, it should be noted that an intracranial hyperinflammatory response may occur, especially when the pathogenic bacteria are GBS or SP.

Purpose: The risk stratification of pediatric anaplastic large cell lymphoma (ALCL) has not been standardized. In this study, new risk factors were included to establish a new risk stratification system for ALCL, and its feasibility in clinical practice was explored. Materials and Methods: On the basis of the non-Hodgkin’s lymphoma Berlin–Frankfurt–Munster 95 (NHL-BFM-95) protocol, patients with minimal disseminated disease (MDD), high-risk tumor site (multiple bone, skin, liver, and lung involvement), and small cell/lymphohistiocytic (SC/LH) pathological subtype were enrolled in risk stratification. Patients were treated with a modified NHL-BFM-95 protocol combined with an anaplastic lymphoma kinase inhibitor or vinblastine (VBL). Results: A total of 136 patients were enrolled in this study. The median age was 8.8 years. The 3-year event-free survival (EFS) and overall survival of the entire cohort were 77.7% (95% confidence interval [CI], 69.0% to 83.9%) and 92.3% (95% CI, 86.1% to 95.8%), respectively. The 3-year EFS rates of low-risk group (R1), intermediate-risk group (R2), and high-risk group (R3) patients were 100%, 89.5% (95% CI, 76.5% to 95.5%), and 67.9% (95% CI, 55.4% to 77.6%), respectively. The prognosis of patients with MDD (+), stage IV cancer, SC/LH lymphoma, and high-risk sites was poor, and the 3-year EFS rates were 45.3% (95% CI, 68.6% to 19.0%), 65.7% (95% CI, 47.6% to 78.9%), 55.7% (95% CI, 26.2% to 77.5%), and 70.7% (95% CI, 48.6% to 84.6%), respectively. At the end of follow-up, one of the five patients who received maintenance therapy with VBL relapsed, and seven patients receiving anaplastic lymphoma kinase inhibitor maintenance therapy did not experience relapse. Conclusion This study has confirmed the poor prognostic of MDD (+), high-risk site and SC/LH, but patients with SC/LH lymphoma and MDD (+) at diagnosis still need to receive better treatment (ClinicalTrials.gov number, NCT03971305).

Objective To explore the improvements of high-fat intake on lung injury induced by Paragonimus proliferus infection in rats, and to preliminarily explore the mechanisms underlying the role of cytochrome P450 4A1 (CYP 4A1) in the improve ments. Methods SD rats were randomly assigned into three groups, including the normal control group (n = 10), the infection and normal diet group (n = 12) and the infection and high-fat diet group (n = 12). Rats in the normal control group were fed with normal diet and without any other treatments, and animals in the infection and normal diet group were subcutaneously injected with 8 excysted metacercariae of P. proliferus via the abdominal wall, followed by feeding with normal diet, while rats in the infection and high-fat diet group were subcutaneously injected with 8 excysted metacercariae of P. proliferus via the abdominal wall, followed by feeding with high-fat diet. All rats were sacrificed 28 weeks post-infection, and serum samples and lung specimens were collected. Following hematoxylin-eosin (HE) staining of rat lung specimens, the rat lung injury was observed under an optical microscope, and alveolitis was evaluated using semi-quantitative scoring. Serum interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α) levels were measured using enzyme-linked immunosorbent assay (ELISA), and the cytochrome P450 4A1 (CYP 4A1) expression was quantified in rat lung specimens at transcriptional and translational levels using quantitative real-time PCR (qPCR) and Western blotting assays. Results Alveolar wall thickening, edema and inflammatory cell infiltration were alleviated 28 weeks post-infection with P. proliferus in rats in the infection and high-fat diet group relative to the infection and normal diet group, and no alveolar consolidation was seen in the infection and high-fat diet group. The semi-quantitative score of alveolitis was significantly higher in the infection and normal diet group [(2.200 ± 0.289) points] than in the normal control group [(0.300 ± 0.083) points] and the infection and high-fat diet group [(1.300 ± 0.475) points] (both P values < 0.05), and higher serum IL-1β [(151.586 ± 20.492)] pg/mL and TNF-α levels [(180.207 ± 23.379) pg/mL] were detected in the infection and normal diet group than in the normal control group [IL-1β: (103.226 ± 3.366) pg/mL; TNF-α: (144.807 ± 1.348) pg/mL] and the infection and high-fat diet group [IL-1β: (110.131 ± 12.946) pg/mL; TNF-α: (131.764 ± 27.831) pg/mL] (all P values < 0.05). In addition, lower CYP 4A1 mRNA (3.00 ± 0.81) and protein expression (0.40 ± 0.02) was quantified in lung specimens in the infection and normal diet group than in the normal control group [(5.03 ± 2.05) and (0.84 ± 0.14)] and the infection and high-fat diet group [(11.19 ± 3.51) and (0.68 ± 0.18)] (all P values < 0.05). Conclusion High-fat intake may alleviate lung injuries caused by P. proliferus infection in rats through up-regulating CYP 4A1 expression in lung tissues at both translational and transcriptional levels.

OBJECTIVE: To explore the clinical characteristics and genetic basis of a child with Mental retardation autosomal dominant 51 (MRD51). METHODS: A child with MRD51 who was hospitalized at Guangzhou Women and Children's Medical Center on March 4, 2022 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and her parents were collected and subjected to whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a 5-year-and-3-month-old girl, had manifested autism spectrum disorder (ASD), mental retardation (MR), recurrent febrile convulsions and facial dysmorphism. WES revealed that she has harbored a novel heterozygous variant of c.142G>T (p.Glu48Ter) in the KMT5B gene. Sanger sequencing confirmed that neither of her parents has carried the same variant. The variant has not been recorded in the ClinVar, OMIM and HGMD, ESP, ExAC and 1000 Genomes databases. Analysis with online software including Mutation Taster, GERP++ and CADD indicated it to be pathogenic. Prediction with SWISS-MODEL online software suggested that the variant may have a significant impact on the structure of KMT5B protein. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be pathogenic. CONCLUSION The c.142G>T (p.Glu48Ter) variant of the KMT5B gene probably underlay the MRD51 in this child. Above finding has expanded the spectrum of KMT5B gene mutations and provided a reference for clinical diagnosis and genetic counseling for this family.
Humans ; Female ; Child, Preschool ; Intellectual Disability/genetics* ; Autism Spectrum Disorder/genetics* ; Mutation

Objective:To survey treatment and prognosis of hyperkalemia patients in the emergency department and to analyze factors associated with all-cause in-hospital mortality.Methods:We implemented electronic hospital information system, extracted demographic characteristics, underlying diseases, laboratory findings, potassium lowering therapy and prognosis of hyperkalemia patients [age ≥ 18 years, serum potassium (K +) concentration ≥ 5.5 mmol/L] in the emergency department of Peking Union hospital in Beijing between June 1st 2019 to May 31st 2020. The enrolled subjects were divided into the non-survival group and the survival group according to their prognosis. Univariate analysis and Cox regression model were adopted to analyze factors affecting all-cause in-hospital mortality of hyperkalemia patients. Results:A total of 579 patients [median age 64 (22) years; 310 men (53.5%) and 269 women (46.5%)] with hyperkalemia were enrolled, among which, 317 (54.7%), 143 (24.7%) and 119 (20.6%) were mild, moderate, and severe hyperkalemia, respectively. 499 (86.20%) patients received potassium-lowering therapy, forty-four treatment regimens were administered. Insulin and glucose (I+G, 61.3%), diuretics (Diu, 57.2%), sodium bicarbonate (SB, 41.9%) and calcium gluconate/chloride (CA, 44.4%) were commonly used for the treatment of hyperkalemiain the emergency department. The combination of insulin and glucose, calcium gluconate/chloride, diuretics and sodium bicarbonate (I+G+CA+Diu+SB) was the most favored combined treatment regimen of hyperkalemia in the emergency department. The higher serum potassium concentration, the higher proportion of administrating combined treatment regimen and/or hemodialysis (HD) (the proportion of administrating combined treatment regimen in mild, moderate, and severe hyperkalemia patients were 58.4%, 82.5% and 94.8%; the proportion of administrating HD in mild, moderate, and severe hyperkalemia patients were 9.7%, 13.3% and 16.0%, respectively). The proportion of achievement of normokalaemia elevated as the kinds of potassium lowering treatment included in the combined treatment regimen increased. The proportion of achievement of normokalaemia was 100% in the combined treatment regimen including 6 kinds of potassium lowering therapy. Among various potassium lowering treatments, HD contributed to the highest rate of achievement of normokalaemia (93.8%). 111 of 579 (19.20%) hyperkalemia patients died in hospital. Cox regression model revealed that complicated with cardiac dysfunction predicted higher mortality [hazard ratio ( HR) = 1.757, 95% confidence interval (95% CI) was 1.155-2.672, P = 0.009]. Achievement of normokalaemia and administration of diuretics attributed to lower mortality ( HR = 0.248, 95% CI was 0.155-0.398, P = 0.000; HR = 0.335, 95% CI was 0.211-0.531, P = 0.000, respectively). Conclusions:Treatment of hyperkalemia in the emergency department were various. Complicated with cardiac dysfunction were associated with higher mortality. Achieving normokalaemia was associated with decreased mortality.

Hepatocellular carcinoma （HCC）， an insidious malignant tumor with high incidence and lethality， poses a major threat to physical and mental health of human beings. The pathological mechanism needs to be further studied. Surgery， radiotherapy， chemotherapy， and targeted drugs are effective but induce many adverse reactions. Traditional Chinese medicine （TCM） has unique advantages and abundant clinical experience in the treatment of HCC. There has been an explosion of research on the pathways， targets， and mechanism of TCM against HCC from the perspective of molecular biology. According to previous research， Chinese medicinals or compound Chinese medicine prescriptions， directly or indirectly prevent the occurrence and progression of HCC through multiple pathways and targets， which is closely related to the pathophysiological processes such as cell proliferation， metastasis， apoptosis， autophagy， inflammatory response， and immune response. This paper summarizes and analyzes research on the action pathways and mechanisms of Chinese medicine against HCC. Specifically， isoliquiritigenin， dendrobium candidum and Yexiazhu compound Ⅱ regulate phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway to inhibit the growth， proliferation and metastasis of tumor cells. Toad venom and dioscorea zingiberensis induce and enhance HCC autophagy by modulating mammalian target of rapamycin （mTOR） signaling pathway. Myricetin， asparagus， and Biejiajian Wan regulate mitogen-activated protein kinase （MAPK） signaling pathway to promote HCC cell cycle arrest， inhibit angiogenesis， and induce apoptosis. Polygonum odoratum， tetragonum， and plantainoside modulate nuclear factor-kappa B （NF-κB） to inhibit inflammatory response and HCC metastasis and reduce drug resistance. Quercetin and erigeron breviscapus control the Janus kinase 2/signal transducer and activator of transcription 3 （JAK2/STAT3） signaling pathway to suppress epithelial-mesenchymal transition （EMT） and remodel cytoskeleton. This paper is expected to lay a theoretical basis for the in-depth research on and clinical application of Chinese medicine in the treatment of HCC.

OBJECTIVE: To explore the genetic basis for a girl featuring epilepsy, developmental delay and regression. METHODS: Clinical data of the patient was collected. Activities of hexosaminidase A (Hex A) and hexosaminidase A&B (Hex A&B) in blood leukocytes were determined by using a fluorometric assay. Peripheral blood samples were collected from the proband and six members from her pedigree. Following extraction of genomic DNA, whole exome sequencing was carried out. Candidate variants were verified by Sanger sequencing. RESULTS: Enzymatic studies of the proband have shown reduced plasma Hex A and Hex A&B activities. Genetic testing revealed that she has carried c.1260_1263del and c.1601G>C heterozygous compound variants of the HEXB gene. Her mother, brother and sister were heterozygous carriers of c.1260_1263del, while her father, mother, three brothers and sister did not carry the c.1601G>C variant, suggesting that it has a de novo origin. Increased eosinophils were discovered upon cytological examination of peripheral blood and bone marrow samples. CONCLUSION The compound heterozygous variants of c.1260_1263del and c.1601G>C of the HEXB gene probably underlay the Sandhoff disease in this child. Eosinophilia may be noted in infantile Sandhoff disease.
Child ; Eosinophilia/genetics* ; Female ; Genetic Testing ; Hexosaminidase A/genetics* ; Hexosaminidase B/genetics* ; Humans ; Male ; Mutation ; Pedigree ; Sandhoff Disease/genetics*

The research on human hepatobiliary development and disorders has been constrained by minimal access to human fetal tissue, and low accuracy of animal models. To overcome this problem, we have established a system for the differentiation of human pluripotent stem cells (hPSCs) into functional hepatobiliary organoids (HBOs). We have previously reported that our 45-d approach closely mimics key stages of hepatobiliary development, starting with the differentiation of hiPSC into endoderm and a small part of mesoderm, and subsequently into hepatoblast-like cells, followed by the parallel generation of hepatocyte-like cells and cholangiocyte-like cells, formation of immature HBO expressing early hepatic and biliary markers, and mature HBO displaying hepatobiliary functionality. In this study, we present an updated version of our previous protocol, which only needs 35 days to achieve maturation in vitro. Furthermore, a hepatobiliary culture medium is developed to functionally maintain the HBOs for more than 1.5 months. The capacity of this approach for producing large amounts of functional HBOs and enabling long-term culture in vitro holds promise for applications on developmental research, disease modeling, as well as screening of therapeutic agents.

Objective:To summarize the effect of Chinese Children′s Cancer Group (CCCG) Wilms tumor (WT)-2015 protocol.Methods:This was a prospective study. CCCG-WT-2015 protocol was revised on the basis of the CCCG-WT-2009 protocol. Clinical data of 288 children diagnosed with newly diagnosed kidney neoplasms in fourteen pediatric centers between September 2015 to December 2018 were summarized. The age of onset, distribution of pathological subtypes, staging, curative effect and prognostic factors of these children were analyzed. Kaplan-Meier method was used for survival curve and Log-Rank method was used for univariate analysis.Results:Among 288 cases with kidney neoplasms, there were 261 cases of WT, including 254 cases (97.3%) with favorable histology (FH) WT and 7 cases (2.7%) with unfavorable histology WT (UFHWT). The 3 year events free survival (EFS) rate for FHWT and UFHWT were (88.9±2.1)% and (80.0±17.9)%, which were better than that in WT-2009 (81.2% and 71.7%). In the 96 cases of stage Ⅲ/Ⅳ FHWT with indications for radiotherapy, 76 cases received radiation, another 20 cases received M protocol chemotherapy (cyclophosphamide, etoposide, gentamycin, vincristine and adriamycin) instead of radiation. The 3 year EFS rate for these two groups were (84.7±4.3)% and (84.7±8.1)%(χ 2=0.015, P=0.902). There were 22 renal clear cell sarcoma and 5 malignant rhabdoid tumor, 3 year EFS rate of them was (94.4±5.4)% and (20.0±17.9)%. Univariate analysis was performed for age, gender, pathological type, stage, whether rupture occurred during operation, whether complete remission (CR) occurred at the end of treatment and radiotherapy. Pathological types (χ 2=44.329, P<0.01) and failure to achieve CR at the end of the treatment (χ 2=49.459, P<0.01) were independent factor for predicting survival. Conclusion:Compared with CCCG-WT-2009, treatment of renal tumors in CCCG-WT-2015 study yielded good survival outcome, which can be further applied.

Objective To discuss the clinical effect of facial contour remodeling using transplantation of the autologous granular fat grafting combined with botulinum toxin A injection.Methods Negative-pressure liposuction was carried out in the inner thigh or abdomen using liposuction needle connected with an injector,to let stand for layered,discharge lower layer water,rinse,extract the fat particles into a 2 ml syringe,inject into facial depression area with multipoint,multiple-tunnel,and multilayer manner,over injection of about 20％-30％ every time.89 patients received the injection;some accepted two injections;13 cases were injected in temple (14.6％),and 16 in forehead (17.98％).30 of them received subcutaneous injection of botulinum toxin A,each side dose was less than 20 U.Results Patients had been followed up for 3-36 months,and obvious improvements were observed in facial contour in the frontal and temporal region as well as the skin texture;the survival rate of fat granule reached to 60％-80％.No hematoma,nodes and infection been observed.Patients combined with botulinum toxin A injection had more ideal facial contour and more satisfaction.Conclusions Autologous fat granules transplantation in the face has stable clinical effect,and combining with botulinum toxin A injection can improve facial contour.It is a safe,ideal treatment in facial rejuvenation and facial contour remodeling and it therefore can be widely recommended in clinical treatment.