Objective:To analyze the factors affecting delayed chemotherapy in children with Burkitt lymphoma (BL) and their influence on prognosis.Methods:Retrospective cohort study. Clinical data of 591 children aged ≤18 years with BL from May 2017 to December 2022 in China Net Childhood Lymphoma (CNCL) was collected. The patients were treated according to the protocol CNCL-BL-2017. According to the clinical characteristics, therapeutic regimen was divided into group A, group B and group C .Based on whether the total chemotherapy time was delayed, patients were divided into two groups: the delayed chemotherapy group and the non-delayed chemotherapy group. Based on the total delayed time of chemotherapy, patients in group C were divided into non-delayed chemotherapy group, 1-7 days delayed group and more than 7 days delayed group. Relationships between delayed chemotherapy and gender, age, tumor lysis syndrome before chemotherapy, bone marrow involvement, disease group (B/C group), serum lactate dehydrogenase (LDH) > 4 times than normal, grade Ⅲ-Ⅳ myelosuppression after chemotherapy, minimal residual disease in the interim assessment, and severe infection (including severe pneumonia, sepsis, meningitis, chickenpox, etc.) were analyzed. Logistic analysis was used to identify the relevant factors. Kaplan-Meier method was used to analyze the patients' survival information. Log-Rank was used for comparison between groups.Results:Among 591 patients, 504 were males and 87 were females, the follow-up time was 34.8 (18.6,50.1) months. The 3-year overall survival (OS) rate was (92.5±1.1)%,and the 3-year event-free survival (EFS) rate was (90.5±1.2)%. Seventy-three (12.4%) patients were in delayed chemotherapy group and 518 (87.6%) patients were in non-delayed chemotherapy group. The reasons for chemotherapy delay included 72 cases (98.6%) of severe infection, 65 cases (89.0%) of bone marrow suppression, 35 cases (47.9%) of organ dysfunction, 22 cases (30.1%) of tumor lysis syndrome,etc. There were 7 cases of chemotherapy delay in group B, which were seen in COPADM (vincristine+cyclophosphamide+prednisone+daunorubicin+methotrexate+intrathecal injection,4 cases) and CYM (methotrexate+cytarabine+intrathecal injection,3 cases) stages. There were 66 cases of chemotherapy delay in group C, which were common in COPADM (28 cases) and CYVE 1 (low dose cytarabine+high dose cytarabine+etoposide+methotrexate, 12 cases) stages. Multinomial Logistic regression analysis showed that the age over 10 years old ( OR=0.54,95% CI 0.30-0.93), tumor lysis syndrome before chemotherapy ( OR=0.48,95% CI 0.27-0.84) and grade Ⅲ-Ⅳ myelosuppression after chemotherapy ( OR=0.55,95% CI 0.33-0.91)were independent risk factors for chemotherapy delay.The 3-year OS rate and the 3-year EFS rate of children with Burkitt lymphoma in the delayed chemotherapy group were lower than those in the non-delayed chemotherapy group ((79.4±4.9)% vs. (94.2±1.1)%, (80.2±4.8)% vs. (92.0±1.2)%,both P<0.05). The 3-year OS rate of the group C with chemotherapy delay >7 days (42 cases) was lower than that of the group with chemotherapy delay of 1-7 days (22 cases) and the non-delay group (399 cases) ((76.7±6.9)% vs. (81.8±8.2)% vs. (92.7±1.3)%, P=0.002).The 3-year OS rate of the chemotherapy delay group (9 cases) in the COP (vincristine+cyclophosphamide+prednisone) phase was lower than that of the non-chemotherapy delay group (454 cases) ((66.7±15.7)% vs. (91.3±1.4)%, P=0.005). Similarly, the 3-year OS rate of the chemotherapy delay group (11 cases) in the COPADM1 phase was lower than that of the non-chemotherapy delay group (452 cases) ((63.6±14.5)% vs. (91.5±1.3)%, P=0.001). Conclusions:The delayed chemotherapy was related to the age over 10 years old, tumor lysis syndrome before chemotherapy and grade Ⅲ-Ⅳ myelosuppression after chemotherapy in pediatric BL. There is a significant relationship between delayed chemotherapy and prognosis of BL in children.

Objective To analysize the temporal trends in the disease burden of major human parasitic diseases in China from 1990 to 2019, so as to provide the evidence for improving the parasitic disease control strategy in China.. Methods The disability-adjusted life years (DALYs) of malaria, intestinal nematode infections, schistosomiasis, food-borne trematodiases, cysticercosis and echinococcosis in China from 1990 to 2019 were captured from the Global Burden of Disease Study 2019 (GBD 2019), and age- and gender-specific DALYs of parasitic diseases were estimated. The temporal trends in DALYs of malaria, intestinal nematode infections, schistosomiasis, food-borne trematodiases, cysticercosis and echinococcosis were evaluated in China from 1990 to 2019 using average annual percent change (AAPC) with Joinpoint regression analysis. Results The DALYs were 643 836.42 person-years due to food-borne trematodiases, 156 853.03 person-years due to cysticercosis, 79 764.62 person-years due to schistosomiasis, 70 989.73 person-years due to intestinal nematode infections, 4 258.61 person-years due to echinococcosis and 264.86 person-years due to malaria in China in 2019, respectively. The overall DALYs of six parasitic diseases were higher among men (546 441.93 person-years) than among women (409 525.33 person-years), and were greater among adults at ages of 14 to 65 years (684 780.84 person-years) than among children at 14 years and lower (35 437.38 person-years) and the elderly at ages of 65 years and older (235 749.04 person-years). During the period from 1990 to 2019, food-borne trematodiases were the leading cause of DALYs among the six parasitic diseases, and cysticercosis shifted from the fourth leading cause in 1990 to the second leading cause of DALYs in China in 2019, while intestinal nematode infections shifted from the second leading cause in 1990 to the fourth leading cause of DALYs in 2019. The DALYs of major human parasitic diseases appeared an overall tendency towards a decline in China from 1990 to 2019, with the fastest drop seen in DALYs due to malaria (AAPC = −19.6%, P = 0.003), followed by due to intestinal nematode infections (AAPC = −8.2%, P < 0.001) and schistosomiasis (AAPC = −3.1%, P < 0.001), and a slow decline was seen in the DALYs of food-borne trematodiases (AAPC = −1.0%, P < 0.001), while there were no significant decrease in the DALYs of echinococcosis (AAPC = −0.5%, P = 0.264) and the DALYs of cysticercosis appeared a tendency towards a rise (AAPC = 0.7%, P < 0.001). Conclusions The disease burden of major human parasitic diseases appeared an overall tendency towards a decline in China from 1990 to 2019, with a high disease burden seen due to food-borne parasitic diseases, no remarkable reduction seen in echinococcosis, and a tendency towards a rise seen in cysticercosis. It is recommended to focus on echinococcosis control, and continue to consolidate the control achievements of other major human parasitic diseases in China; meanwhile, the surveillance and prevention of food-borne parasitic diseases should be reinforced.

Objective:To analyze the gene variants in patients with primary distal renal tubular acidosis (dRTA), and explore the correlation between the genotype and phenotype.Methods:The Sanger direct sequencing or whole-exome sequencing was used to identify causal variants and the variation pathogenicity was evaluated according to 2015 American College of Medical Genetics and Genomics (ACMG) standards and guidelines in 44 dRTA patients (37 families) diagnosed in the Affiliated Qingdao Municipal Hospital of Qingdao University and the Affiliated Hospital of Qingdao University from April 2010 to September 2020. The clinical features of the patients were summarized, and the correlation between the genotype and phenotype was investigated.Results:Seven variants of SLC4A1 gene, 17 variants of ATP6V0A4 gene, and 15 variants of ATP6V1B1 gene were identified in 44 patients with dRTA, and of which 11 variants were new ones. According to ACMG guidelines, the pathogenic, likely pathogenic, benign variants among the 39 variants were 22, 16 and 1, respectively. Nine patients were autosomal dominant hereditary dRTA caused by SLC4A1 gene mutation, 4 patients with autosomal recessive hereditary dRTA complicated with Southeast Asian ovalocytosis and anemia were caused by SLC4A1 gene mutation, and 14 patients caused by ATP6V0A4 gene mutation and 8 patients caused by ATP6V1B1 gene mutation were autosomal recessive hereditary dRTA; Two children with dRTA were found to carry one monoallelic defect in ATP6V1B1, and no causal gene mutation was identified in 7 patients. One patient showed incomplete dRTA, and the other 43 patients showed complete dRTA. The prevalence of sensory neural hearing loss caused by ATP6V0A4 and ATP6V1B1 mutation were 2/14 and 6/10 respectively. The frequency of chronic kidney disease in adults, children and infants were 4/4, 2/4, and 1/36, separately. After the drug treatment based on potassium citrate and sodium citrate, the growth and development (28/40) and electrolyte disturbance (41/44) of most patients were significantly improved. Conclusions:The present study has identified 39 variants of SLC4A1, ATP6V0A4 and ATP6V1B1 genes in 44 patients with dRTA, including 11 novel ones. There is a close relationship between genotype and phenotype in dRTA patients and most patients' conditions were improved after proper treatment. This study enriches the human gene mutation database and provides valuable references for diagnosis, treatment and genetic counseling in patients with dRTA.

Objective To verify that lncRNA-C21orF96 regulates the expression of miRNA-875-5p and USF2 genes and promotes the invasion and metastasis of gastric cancer.Methods RT-PCR was used to measure the expression of lncRNA-C21orF96 related miRNA in gastric cancer cells.pcDNA3.1 plasmid was used to over-express lncRNA-C21orF96 in KATO-Ⅲ and siRNA was used to knockdown the expression of lncRNA-C21orF96 in SGC-7901,and RT-PCR was used to measure the expression of miRNA-875-5p and USF2 genes;By overexpressing lncRNA-C21orF96 in MKN45,transwell was used to observe changes of cells invasion and migration.Results LncRNA-C21orF96 showed a significant inverse relationship with miR-875-5p,(SGC-7901:21.19 ±1.09 vs.3.28 ±0.06,P＜0.01;SNU-16:24.76 ±2.09 vs.8.16 ±0.07,P ＜ 0.01).In KATO-Ⅲ over-expressing lncRNA-C21 orF96,miR-875-5p expression decreased significantly while USF2 expression increased (P ＜0.01);In SGC-7901 with lncRNA-C21orF96 knockdown,miR-875-5p expression increased significantly while USF2 expression decreased (P ＜ 0.05).The number of cells passing through the artificial basement membrane in the experimental group was significantly different from that in the control group (migration:216.19 ± 2.30 vs.89.19 ± 4.60,P＜0.001;invasion:146.18 ±5.3 vs.59.18 ± 2.60,P ＜ 0.001).Conclusions The overexpression of lncRNA-C21orF96 significantly reduces the expression of miR-875-5p and promotes the expression of USF2,hence promoting the invasion and metastasis of gastric cancer.

Objective:To evaluate the effect of imatinib on growth impairment in children with chronic myeloid leukemia (CML-CP) in the chronic phase.Methods:From July 2018 to July 2019, questionnaires were distributed to CML children aged <18 years at the time of diagnosis who were receiving imatinib for at least 3 months or to their parents in China. The height-for-age standard deviation score (HtSDS) and the difference of standard deviation integral (△HtSDS) were used to explore the change in height with imatinib therapy.Results:The data of 238 respondents were included; 138 (58.0% ) respondents were men. The median age at the first diagnosis of CML was 11.0 years (range, 1.4-17.9 years) , and 93 (39.0% ) respondents were at the prepuberty stage. At the time of completing the questionnaires, the median age was 15.0 years (range, 2.0-34.0 years) . The median duration of imatinib therapy was 28 months (range, 3-213 months) . Among all the respondents, the mean HtSDS when completing the questionnaires (-0.063±1.361) was significantly lower than that at the time of starting imatinib treatment (0.391±1.244) ( P<0.001) . Total 71.0% respondents showed growth impairment that was more common in those starting imatinib therapy at prepubertal age than in those starting at pubertal age. Multivariate analysis showed that younger at the start of imatinib therapy ( P<0.001) and longer duration of imatinib therapy ( P<0.001) were significantly associated with severe growth impairment on imatinib therapy. Conclusions:Imatinib induced growth impairment in children with CML-CP. Younger the age of initiation and longer the duration of imatinib therapy, more obvious the effect of imatinib on growth impairment.

Objective: To investigate the clinical features, treatment and prognosis of the children with malignancy-associated hemophagocytic syndrome (MAHS) in Beijing in recent decade. Methods: The clinical data of the patients with MAHS under 18 years old from July 2007 to February 2018 collected by the Society of Beijing hemophagocytic syndrome were analyzed retrospectively. Results: There were 46 patients under 18 years old with MAHS in all(male 27, female 19). The patients with MAHS took up 8.9% of the patients with hemophagocytic lymphohistiocytosis (HLH)(46/519 cases) from the area during that period.The median age of onset had 13.5 years (0.9-18.0 years). Thirty-five patients had lymphoma (76.0%), 9 cases had leukemia (19.6%), 1 case had myelodysplastic syndrome with refractory anemia with excess blast(RAEB-T), and 1 case had Epstein-Barr virus(EBV) associated lymphoproliferative disease (borderline tumor stage). All the patients had a fever.A half of them suffered from hepatosplenomegaly and 7 patients(15.2%) had neurological symptoms.The common laboratory abnormalities included cytopenias, hemophagocytosis in bone marrow (81.8%, 36/44 cases), elevated serum ferritin (87.8%, 36/41 cases), and elevated sCD₂₅ (100.0%, 15/15 cases), decreased nature killer(NK) activity (61.1%, 11/18 cases), and plasma EBV-DNA positive (57.9%). Four patients did not receive treatment, the rest were treated by several chemotherapy protocols including the HLH-94/2004 protocol.Five patients (10.8%) received the allogeneic hematopoietic stem cell transplantation, and 1 case received the splenectomy therapy.The mortality was 58.7%.Four heterozygous mutations of SH2D1A, UNC13D and PRF1 genes were found in 2 patients. Conclusions MAHS in children progresses rapidly, with poor prognosis, and it is often complicated with EBV infection.The children with MAHS may develop genetic defects similar to primary hemophagocytic syndrome.Nowadays, there is no standard treatment for MAHS, so the individualized treatment is to be explored.

On September 7th, 2017, one female patient, aged 48 years with deep partial-thickness flame burn on face, upper limbs, trunk, and lower limbs of 40% total body surface area was admitted to the First People′s Hospital of Foshan City. After admission, active fluid replacement, anti-infection, nutritional support, and other treatments were performed. After debridement and skin grafting for 3 times and blood transfusion for 2 times, the patient recovered well. On the 20th day post admission, sudden heartbeat and respiratory arrest happened, and the patient died after ineffective rescue. Autopsy showed that thrombus formed in right internal jugular vein and deep veins of lower extremities, and vascular lumina of the bilateral pulmonary artery. The direct cause of death was acute pulmonary thromboembolism, but whether the embolus originated from deep vein of lower extremity or right internal jugular vein was not clear. This case suggests that clinician should not only pay attention to the prevention of deep venous thrombosis of lower extremities of burn patients, but also the possibility of internal jugular vein thrombosis, especially for patients with internal jugular vein access.

OBJECTIVE: To analyze the morphological features and forensic pathological characteristics of cardiac ruptures of different causes for their differential diagnosis. METHODS: We analyzed the data of 44 autopsy cases of cardiac rupture from 2014 to 2017 in our institute, including 11 cases caused by blunt violence with intact pericardium, 4 caused by cardiopulmonary resuscitation (CPR), 9 by myocardial infarction, and 20 by aorta dissection rupture.The gross features and histopathological characteristics of cardiac rupture and pericardial effusion were analyzed and compared. RESULTS: Cardiac ruptures caused by blunt violence varied in both morphology and locations, and multiple ruptures could be found, often accompanied with rib or sternum fractures; the volume of pericardial effusion was variable in a wide range; microscopically, hemorrhage and contraction band necrosis could be observed in the cardiac tissue surrounding the rupture.Cardiac ruptures caused by CPR occurred typically near the apex of the right ventricular anterior wall, and the laceration was often parallel to the interventricular septum with frequent rib and sternum fractures; the volume of pericardial blood was small without blood clots; microscopic examination only revealed a few hemorrhages around the ruptured cardiac muscular fibers.Cardiac ruptures due to myocardial infarction caused massive pericardial blood with blood clots, and the blood volume was significantly greater than that found in cases of CPR-induced cardiac rupture ( < 0.05);lacerations were confined in the left ventricular anterior wall, and the microscopic findings included myocardial necrosis, inflammatory cell infiltration, and mural thrombus.Cardiac tamponade resulting from aorta dissection rupture was featured by massive pericardial blood with blood clots, and the blood volume was much greater than that in cases of cardiac ruptures caused by blunt violence, myocardial infarction and CPR ( < 0.05). CONCLUSIONS Hemorrhage, inflammatory cell infiltration, and lateral thrombi around the cardiac rupture, along with pericardial blood clots, are all evidences of antemortem injuries.
Aneurysm, Dissecting ; complications ; Aortic Aneurysm ; complications ; Cardiopulmonary Resuscitation ; adverse effects ; Forensic Pathology ; Heart Rupture ; etiology ; pathology ; Heart Rupture, Post-Infarction ; pathology ; Humans ; Myocardial Contusions ; complications

OBJECTIVETo summarize the treatment status of gastric gastrointestinal stromal tumor (GIST) in Shandong province,by analyzing the clinicopathological features and prognostic factors.

METHODSClinicopathological and follow-up data of 1 165 patients with gastric GIST between January 2000 and December 2013 from 23 tertiary referral hospitals in Shandong Province were collected to establish a database. The risk stratification of all cases was performed according to the National Institutes of Health(NIH) criteria proposed in 2008. Kaplan-Meier method was used to calculate the survival rate. Log-rank test and Cox regression model were used for univariate and multivariate prognostic analyses.

RESULTSAmong 1 165 cases of gastric GIST, 557 were male and 608 were female. The median age of onset was 60 (range 15-89) years. Primary tumors were located in the gastric fundus and cardia in 623 cases(53.5%), gastric body in 346 cases(29.7%), gastric antrum in 196 cases(16.8%). All the cases underwent resection of tumors, including endoscopic resection (n=106), local resection (n=589), subtotal gastrectomy(n=399), and total gastrectomy(n=72). Based on the NIH risk stratification, there were 256 cases (22.0%) at very low risk, 435 (37.3%) at low risk, 251 cases (21.5%) at intermediate risk, and 223 cases (19.1%) at high risk. A total of 1 116 cases(95.8%) were followed up and the median follow-up period was 40 (range, 1-60) months. During the period, 337 patients relapsed and the median time to recurrence was 34 (range 1-60) months. The 1-, 3-, and 5-year survival rates were 98.6%, 86.1% and 73.4%, respectively. The 5-year survival rates of patients at very low, low, intermediate, and high risk were 93.1%, 85.8%, 63.0% and 42.3% respectively, with a statistically significant difference (P=0.000). Multivariate analysis showed that primary tumor site (RR=0.580, 95%CI:0.402-0.835), tumor size (RR=0.450, 95%CI:0.266-0.760), intraoperative tumor rupture(RR=0.557, 95%CI:0.336-0.924), risk classification (RR=0.309, 95%CI:0.164-0.580) and the use of imatinib after surgery (RR=1.993, 95%CI:1.350-2.922) were independent prognostic factors.

CONCLUSIONSThe choice of surgical procedure for gastric GIST patients should be based on tumor size. All the routine procedures including endoscopic resection, local excision, subtotal gastrectomy and total gastrectomy can obtain satisfactory curative outcomes. NIH classification has a high value for the prediction of prognosis. Primary tumor site, tumor size, intraoperative tumor rupture, risk stratification and postoperative use of imatinib are independent prognostic factors in gastric GIST patients.

China's prevention and control of parasitic diseases has made remarkable achievements. However,the prevalence and transmission of parasitic diseases is impacted by the complicated natural and social factors of environment ,natural disas-ters,population movements,and so on. Therefore,there are still the risks of the outbreak of emergency parasitic diseases af-fairs,which may affect the control effectiveness of parasitic diseases and endanger the social stability seriously. In this article , we aim at the analysis of typical cases of emergency parasitic disease affairs and their impacts on public health security in China in recently years,and we also elaborate the disposal characteristics of emergency parasitic disease affairs,and propose the estab-lishment of response system to emergency parasitic disease affairs in China,including the organizational structure and response flow path,and in addition,point out that,in the future,we should strengthen the system construction and measures of the re-sponse system to emergency parasitic disease affairs,so as to control the risk and harm of parasitic disease spread as much as possible and to realize the early intervention and proper disposal of emergency parasitic disease affairs.