Objective To establish mice models of Kawasaki disease by Lcatobacillus casei cell wall extract(LCWE) ,in order to provide experimental materials for follow-up study .Methods LCWE group was given LCWE 0 .1 mL per mouse(containing 200 mg LCWE) via abdominal intramuscular injection .PBS group was given 0 .1 mL PBS per mouse .Orbital blood samples were collected respectively at the 1st ,3rd and 28th day after administration .The heart ,lung ,liver ,kidney ,spleen and other organs tissue samples were collected for pathological section ,HE staining .The histopathological changes were investigated ,and the routine blood test was proceeded .Results The WBC of LCWE group showed a trend of rising at the 1st ,3rd and 28th day after administration .PLT and MPV of LCWE group increased at the 3rd day after administration ,which returned to normal levels at the 28th day after adminis-tration .The pathological section showed the blood vessel walls of heart tissue enlargement ,surrounded and infiltrated by inflamma-tory cells infiltration ,the atheromatous plaque in blood vessels occasionally .Conclusion The study established mice model of Ka-wasaki disease successfully .

OBJECTIVETo summarize the clinicopathologic features of neuroblastic tumors (NT), and to explore the prognostic significance of MYCN amplification in NT.

METHODSThe clinicopathologic data of 267 NT were reviewed. MYCN gene amplification was detected by fluorescence in situ hybridization (FISH) in 119 cases and the relationship with pathological characteristics and prognostic significance were analyzed.

RESULTSThe study included 267 cases of children NT from patients aged from 1 day to 13 years (median 27 months). The male to female ratio was 1.43. There were 38 cases (14.2%), 43 cases (16.1%), 71 cases (26.6%), and 115 cases (43.1%) of INSS stages I, II, III and IV respectively.Favorable histology group had 157 cases (59.9%); unfavorable histology group had 110 cases (40.1%).Of the 119 NT cases with MYCN FISH performed, 18 cases (15.1%) showed amplification and the signal ratio of MYCN to CEP2 was 4.08-43.29. One hundred and one cases of non-amplified MYCN included MYCN gain in 79 cases (66.3%) and MYCN negative in 22 cases (18.5%). MYCN expression showed significant difference (P = 0.000) between ages, gender, NT type and MKI, but not INPC and clinical stage (P > 0.05).Of the 18 cases with MYCN amplification, 3 were undifferentiated, and 15 poorly differentiated; 17 had high MKI and one moderate MKI. All 18 cases were in unfavorable histology group; the overall survival rate was 3/18, with an average survival time of (17.9 ± 2.4) months.Of the 101 MYCN non-amplification cases, the overall survival rate was 68.3% (69/101), with an average survival time of (29.8 ± 1.3) months. Survival analysis showed the cases with MYCN amplification had worse prognosis (P < 0.05).

CONCLUSIONSNT were commonly diagnosed in early ages and easily to metastasize. Most of cases with favorable histology. The cases of MYCN amplification showed unfavorable histology, and the majority cases with high MKI; The patients with MYCN gene amplification had poor prognosis.

Adolescent ; Cell Differentiation ; Child ; Child, Preschool ; Female ; Gene Amplification ; Humans ; In Situ Hybridization, Fluorescence ; Infant ; Male ; N-Myc Proto-Oncogene Protein ; Neuroblastoma ; genetics ; mortality ; pathology ; Nuclear Proteins ; genetics ; Oncogene Proteins ; genetics ; Prognosis ; Survival Analysis ; Survival Rate

Objective: To investigate the pathologic features of gonadal tissues of disorders of sexual development (DSD) in children. Methods: Fifty-three cases of gonadal developmental disorders were collected from July 2015 to August 2017 at Guangzhou Women and Children′s Medical Center. Clinical manifestations, karyotypes, sex hormone levels, ultrasound imaging, histology and immunophenotype of gonadal tissues were analyzed. Results: The age of patients ranged from 7 months to 17 years with an average of (50.7 ± 47.1) months. Social genders of the patients included 32 males and 21 females. Forty-eight patients had abnormal sex hormone levels. Clinical presentations included: toward female genitalia in 25 cases, male genitalia tendency in 17 cases and ambiguous external genitalia in 11 cases. Hypospadias was seen in 31 cases and short stature was seen in 8 cases. Chromosomal karyotyping of peripheral blood revealed 23 cases of sex chromosome disorders, 22 cases of 46 XY disorders, of which 3 cases were 5α-reductase deficiency and 8 cases of 46 XX disorders. Ultrasound examination showed cryptorchidism in 30 cases, including 16 cases of unilateral, 14 cases of bilateral and 1 case presenting a huge pelvic tumor. A total of 97 gonadal tissues from 53 cases of DSD were examined, including 9 cases of unilateral and 44 cases of bilateral gonads. Microscopically, 55 gonads (56.7%) showed dysplastic testes including 17 unilateral and 19 bilateral gonads. Fourteen were streak gonads (14.4%) including 8 unilateral and 3 bilateral gonadal tissues. Nine streak gonad with epithelial cord-like structures (9.3%) were found, of which 5 were unilateral and 2 were bilateral lesions. Seven gonads were ovotestis (7.2%), unilateral in 5 cases (the other side of the gonads of ovary in 4 cases, 1 case of dysplastic testes) and bilateral in 1 case. Seven gonads showed follicular-rich ovarian tissue (7.2%). One case showed bilateral dysplastic testes with gonadoblastoma and ectopic adrenal cortex. One case of streak gonad showed epithelial cord-like structures and undifferentiated glandular tissue embedded in malignant mixed germ cell tumors (mixed gonadoblastoma, dysgerminoma, mature teratoma and yolk sac tumor). One case had testicular microlithiasis. Uterus and fallopian tube structures were found in 11 cases. Immunohistochemical stains were performed in 15 cases. D2-40, PLAP and CKIT were expressed in germ cells and Calretinin, WT1 and inhibin were positive in Setoli cells. SALL4 and OCT3/4 were positive in 3 cases. Inhibin highlighted interstitial Leydig cells in 2 cases. GPC3 was positive in yolk sac tumor component. Conclusions Gonadal dysgenesis presents a broad spectrum of gonadal phenotypes with variable degrees of differentiation. The development of bilateral gonadal tissues has certain variability. Chromosomal karyotypes have no correlation with gonadal phenotypes. Accurate histopathologic diagnosis of gonadal dysgenesis plays an important role in the treatment and prognosis of the patient.

Objective To study the clinicopathologic features of pediatric vascular anomalies and application of ISSVA classification. Methods The clinical features, histopathologic findings and immunohistochemical results were analyzed in 117 cases of pediatric vascular anomalies encountered during the period from May 2014 to May 2015.Results A total of 117 cases of vascular anomalies were studied. The age of patients ranged from 18 hours after birth to 11 years ( mean age =34 months and median age =27 months) .There were 73 male patients and 44 female patients, with the male-to-female ratio being 1.7∶1.0.Congenital skin lesions were found in 37 cases ( 31.6%) .The common sites of involvement included head and neck region (46 cases, 39.3%), trunk (28 cases, 23.9%), extremities (14 cases, 12.0%) and internal viscera (31 cases, 26.5%).According to the new ISSVA classification, there were 74 cases of vascular malformations and 43 cases of vascular neoplasms ( ratio=1.7∶1.0 ) .The commonest vascular tumor encountered was infantile hemangioma ( 21 cases, 48.8%) , including 17 cases in proliferative phase and 4 cases in involutive phase.Thirteen cases (23.3%) of congenital hemangioma were found, with 8 cases of rapidly involuting congenital hemangioma and 5 cases of non-involutive congenital hemangioma.Three of the congenital hemangioma occurred in liver. There were 5 cases ( 11.6%) of pyogenic granuloma, 3 cases ( 7.0%) of tufted angioma and 1 case ( 2.3%) of Kaposiform hemangioendothelioma.Amongst the 74 cases of vascular malformations encountered, lymphatic malformation was found in 47 cases ( 63.5%) , venous malformation in 15 cases ( 20.2%) , lymphatic-venous malformation in 11 cases (14.9%) and arteriovenous malformation in 1 case (1.4%).All cases of vascular anomalies were all positive for CD31 on immunostaining.Glut1 and CD15 were positive both in proliferative and involutive phases of the 21 cases of infantile hemangioma, while other vascular tumors and vascular malformations were negative.Forty-seven cases of lymphatic malformation and 11 cases of lymphatic-venous malformation showed D2-40 expression.Focal positivity for D2-40 was demonstrated in 3 cases of tufted angioma and 1 case of Kaposiform hemangioendothelioma.Conclusions Vascular anomalies affecting infants and children include tumors and malformations. Accurate histopathologic diagnosis and ISSVA classification of the various types of vascular anomalies play an important role in clinical management.

Objective:To investigate the clinicopathological features of gonadal neoplastic related lesions in children with disorders of sexual development (DsD).Methods:The clinical manifestations, chromosomal karyotype, histology and immunophenotype of 12 cases of neoplastic related lesions from Guangzhou Women and Children′s Medical Center, Guangzhou were analyzed during Jan 2015 to May 2020.Results:Twelve cases of neoplastic related lesions were screened in 205 cases of DsD, and 6 patients with gonadal germ cell neoplasia aged 3-13 years with an average age of 8.3 years. There were 2 males and 4 females. Clinical features showed malformation of external genitalia in 2 cases, short stature in 2 cases, clitoral enlargement in 1 case, lower abdominal pain and a huge pelvic mass in 1 case. Chromosomal karyotyping of peripheral blood showed 2 cases of 46XY and 4 cases of 45X/46XY. Fourteen gonadal specimens were examined. Microscopically, 1 case showed dysgerminoma in left ovary, and malignant mixed germ cell tumors in right ovary, as well as gonadoblastoma (GB) and undifferentiated gonadal tissue (UGT). The remaining 5 cases were all precursor lesions of germ cell tumor. Six specimens showed GB, 3 of UGT, and 3 specimens showed germ cell neoplasia in situ (GCNIS), one of which was accompanied by intratubular seminoma and 1 was GB with GCNIS. The other 6 patients with DsD were aged from 8 months to 2 years and 5 months, including 5 males and 1 females. Clinical manifestations showed 5 cases of hypospadias and 1 case of bilateral indirect inguinal hernia. Microscopically, 6 cases showed maturation delay of gonocytes in seminiferous tubules. Immunohistochemically, the primordial germ cells/gonocytes expressed OCT3/4, PLAP and c-KIT in the 12 cases.Conclusion:Gonadal neoplasia in children with DsD is mainly precursor lesions of germ cell tumor and improved understanding of these lesions is of great significance.

Objective:To summarize the clinical, pathological and molecular characteristics of various types of pediatric glioma, and to explore the differences in the morphology and clinical significance among various types of pediatric glioma.Methods:Based on the fifth edition of the World Health Organization classification of central nervous system tumors, this study classified or reclassified 111 pediatric gliomas that were diagnosed at Guangzhou Medical University Affiliated Women and Children′s Medical Center from January 2020 to June 2023. The clinical manifestations, imaging findings, histopathology, and molecular characteristics of these tumors were analyzed. Relevant literature was also reviewed.Results:The 111 patients with pediatric glioma included 56 males and 55 females, with the age ranging from 10 days to 13 years (average age, 5.5 years). Clinically, manifestations presented from 5 days to 8 years before the diagnosis, including epilepsy in 16 cases, increased intracranial pressure in 48 cases and neurological impairment in 66 cases. MRI examinations revealed tumor locations as supratentorial in 43 cases, infratentorial in 65 cases, and spinal cord in 3 cases. There were 73 cases presented with a solid mass and 38 cases with cystic-solid lesions. The largest tumor diameter ranged from 1.4 to 10.6 cm. Among the 111 pediatric gliomas, there were 6 cases of pediatric diffuse low-grade glioma (pDLGG), 63 cases of circumscribed astrocytoma glioma (CAG), and 42 cases of pediatric diffuse high-grade glioma (pDHGG). Patients with pDLGG and CAG were younger than those with pDHGG. The incidence of pDLGG and CAG was significantly lower in the midline of the infratentorial region compared to that of pDHGG. They were more likely to be completely resected surgically. The pDLGG and CAG group included 4 cases of pleomorphic xanthoastrocytoma, showing histological features of high-grade gliomas. Among the high-grade gliomas, 13 cases were diffuse midline gliomas and also showed histological features of low-grade glioma. Immunohistochemical studies of H3K27M, H3K27ME3, p53, ATRX, BRAF V600E, and Ki-67 showed significant differences between the pDLGG and CAG group versus the pDHGG group ( P<0.01). Molecular testing revealed that common molecular variations in the pDLGG and CAG group were KIAA1549-BRAF fusion and BRAF V600E mutation, while the pDHGG group frequently exhibited mutations in HIST1H3B and H3F3A genes, 1q amplification, and TP53 gene mutations. With integrated molecular testing, 2 pathological diagnoses were revised, and the pathological subtypes of 35.3% (12/34) of the pediatric gliomas that could not be reliably classified by histology were successfully classified. Conclusions:There are significant differences in clinical manifestations, pathological characteristics, molecular variations, and prognosis between the pDLGG, CAG and pDHGG groups. The integrated diagnosis combining histology and molecular features is of great importance for the accurate diagnosis and treatment of pediatric gliomas.

ObjectiveTo explore the protective effects of Dahuang Tangluo pills on early diabetic kidkdey disease （DKD） in db/db mice. MethodEight db/m mice were selected as the control group. Forty male db/db mice were selected and blood samples were collected via tail vein to measure fasting blood glucose （FBG）. Mice with FBG ≥ 16.7 mmol·L^-1， increased urine output， and persistent albuminuria were considered successful in model establishment. After successful modeling， they were randomly divided into a model group， a dapagliflozin group （1.5 mg·kg^-1·d^-1）， and high， medium， and low dose groups of Dahuang Tangluo pills （3.6， 1.8， 0.9 g·kg^-1·d^-1， respectively）， with eight mice in each group. All medication groups were administered orally， while the control and model groups were given an equal amount of distilled water by gavage daily. After continuous administration for 10 weeks， the survival status of the mice was observed， and their body weight， FBG， and kidney function-related indicators were measured. Inflammatory indicators in renal tissues were determined by enzyme-linked immunosorbent assay （ELISA）. Hematoxylin-eosin （HE） staining， Masson staining， and electron microscopy were used to observe the pathological changes in renal tissues in each group. Immunofluorescence was employed to examine the expression of advanced glycation end products （AGEs） and receptors for advanced glycation end products （RAGE） proteins. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were utilized to detect the gene and protein expression levels of AGEs， RAGE， inhibitor of nuclear factor-κB （NF-κB） kinase （IKK）， and NF-κB in the renal tissues of mice in each group. ResultCompared with control group， the model group showed a significant increase in body weight， FBG， serum creatinine （SCr）， urinary microalbumin/urine creatinine ratio （ACR）， total cholesterol （TC）， and triglycerides （TG） （P<0.05）. The levels of intercellular adhesion molecule-1 （ICAM-1）， interleukin-6 （IL-6）， and tumor necrosis factor-alpha （TNF-α） in renal tissues were significantly elevated （P<0.05）. Renal histopathological staining and electron microscopy revealed loose arrangement， gaps， structural disarray， mesangial proliferation， and significant fibrosis in renal tissues. Real-time PCR results showed a significant increase in the expression of RAGE， IKK， and NF-κB genes in renal tissues （P<0.05）. Immunofluorescence results demonstrated a significant increase in the expression of AGEs and RAGE proteins in renal tissues （P<0.05）. Western blot results showed a significant increase in the expression of AGEs， RAGE， IKK， and NF-κB proteins in renal tissues （P<0.05）. After drug intervention， compared with model group， the dapagliflozin group and the high-dose Dahuang Tangluo pills group showed significant reductions in body weight， FBG， SCr， and ACR （P<0.05）， and a significant decrease in TC in mouse serum （P<0.05）， while the high-dose Dahuang Tangluo pills group showed a significant decrease in TG in mouse serum （P<0.05）. All treatment groups showed a significant reduction in ICAM-1， IL-6， and TNF-α in renal tissues （P<0.05）. Renal histopathological staining and electron microscopy showed improved kidney injury， decreased collagen fiber deposition， and reduced mesangial proliferation in all treatment groups. Real-time PCR results showed a significant decrease in the expression of RAGE， IKK， and NF-κB genes in the dapagliflozin group and the high- and medium-dose Dahuang Tangluo pills groups （P<0.05）. Immunofluorescence results demonstrated a significant decrease in the expression of AGEs and RAGE proteins in the dapagliflozin group and the high- and medium-dose Dahuang Tangluo pills groups （P<0.05）. Western blot results showed a significant decrease in the expression of AGEs， RAGE， IKK， and NF-κB proteins in the dapagliflozin group and the high- and medium-dose Dahuang Tangluo pills groups （P<0.05）. ConclusionDahuang Tangluo pills can improve the pathological structure of the kidneys and reduce renal inflammation in DKD mice， possibly through inhibiting the AGEs/RAGE/IKK/NF-κB pathway.

Drugs under special management include narcotic drugs,psychotropic drugs,toxic drugs for medical use,radiopharmaceuticals,and pharmaceutical precursor chemicals.Supervising and guiding the clinical use of drugs under special management is one of the important responsibilities of the Pharmaceutical Management and Drug Therapy Committee(Group)of medical institutions.The standard for drugs under special management is led by the Pharmaceutical Professional Committee of the China Hospital Association,which standardizes 16 key elements of organizational management,process management,and quality control management drugs under special management in medical institutions.It can guide the standardized implementation of Pharmaceuticals under special control work in various levels and types of medical institutions.This article elaborates on the methods and contents of formulating standards for Pharmaceuticals under special management,to provide reference and inspiration for medical institutions to carry out special drug drug management and daily related work.

Objective: To study the pollution status of polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCB), polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in cord blood of newborns in an e-waste dismantling area of Guangdong Province. Methods: We recruited 20 eligible mothers and newborns who could meet the inclusion criteria in local hospitals of Guiyu in 2007. The inclusion criteria included directly engaged in dismantling e-waste during pregnancy and within 1 year before pregnancy; living in the e-waste dismantling workshops or the distance between living place and the e-waste dismantling areas was ≤200 m; the father of newborn was directly engaged in electronic waste dismantling for more than 1 year; the frequency of visiting the e-waste dismantling workshop during pregnancy was ≥3 times in a week. Questionnaires and physical examinations were performed on maternal and neonatal, and cord blood was collected from newborns to detect PCDD/Fs, PCB and PBDE. The concentration level of organic pollutants was corrected by the blood lipid content, and the total toxicity equivalent was calculated. The correlation between three compounds was analyzed by Spearman correlation. Results: The mothers of the 20 newborns were (23.45±3.27) years old and lived for more than 5 years. The number of one parent engaged in e-waste dismantling, the mother or father smoking, and parent engaged in e-waste dismantling work were 3, 13, 15 and 19, respectively. The weight of newborns ranged from 2.5 to 3.6 kilogram and the Apgar score was 10 points. No adverse birth outcomes such as preterm birth, malformation or stillbirth were found. The median (maximum, minimum) concentration of PCBs, PCDD/Fs and PBDEs in cord blood were 263.22 (328.29, 244.19), 38.42 (147.49, 12.68), 39.33 (265.11, 14.81) pg/g lipid, respectively. The median (maximum, minimum) of toxic equivalence concentrations of PCDD/Fs and PCB were 3.94 (9.24, 2.69) and 15.95 (26.64, 9.28) pg TEQ/g lipid. PBDE, the proportion of PBDE, PCB and PCDD/Fs in cord blood was 50.41%, 49.25% and 0.34%, respectively. PCBs and PBDEs were positively correlated (r=0.733, P=0.039). Conclusion The high concentrations of PCDD/Fs, PCB, and PBDE were detected in the e-waste dismantling area. It is recommended that the risk of such substances on the health of local people should be assessed in a timely manner.

Twenty-one protostane-type triterpenoids with diverse structures, including nine new compounds (-), were isolated from the of Linn. Structurally, alisolides A‒F (-), composed of an oxole group coupled to a five-membered ring, represent unusual C-17 spirost protostane-type triterpenoids. Alisolide H () is a novel triterpenoid with an unreported endoperoxide bridge. Alisolide I () represents the first example of 23,24-acetal triterpenoid. Their structures were elucidated based on spectroscopic analysis, wherein the absolute configurations of ‒, were further confirmed by the Mo(OAc)-induced ECD method. Furthermore, all isolates were evaluated for their inhibitory effects on LPS-induced NO production in Caco-2 cells, and all the compounds showed remarkable inhibitory activities, with IC values in the range of 0.76-38.20 μmol/L.