BACKGROUND: Pancreatic cancer is a lethal malignancy prone to gemcitabine resistance. The single-strand selective monofunctional uracil DNA glycosylase (SMUG1), which is responsible for initiating base excision repair, has been reported to predict the outcomes of different cancer types. However, the function of SMUG1 in pancreatic cancer is still unclear. METHODS: Gene and protein expression of SMUG1 as well as survival outcomes were assessed by bioinformatic analysis and verified in a cohort from Fudan University Shanghai Cancer Center. Subsequently, the effect of SMUG1 on proliferation, cell cycle, and migration abilities of SMUG1 cells were detected in vitro . DNA damage repair, apoptosis, and gemcitabine resistance were also tested. RNA sequencing was performed to determine the differentially expressed genes and signaling pathways, followed by quantitative real-time polymerase chain reaction and Western blotting verification. The cancer-promoting effect of forkhead box Q1 (FOXQ1) and SMUG1 on the ubiquitylation of myelocytomatosis oncogene (c-Myc) was also evaluated. Finally, a xenograft model was established to verify the results. RESULTS: SMUG1 was highly expressed in pancreatic tumor tissues and cells, which also predicted a poor prognosis. Downregulation of SMUG1 inhibited the proliferation, G1 to S transition, migration, and DNA damage repair ability against gemcitabine in pancreatic cancer cells. SMUG1 exerted its function by binding with FOXQ1 to activate the Protein Kinase B (AKT)/p21 and p27 pathway. Moreover, SMUG1 also stabilized the c-Myc protein via AKT signaling in pancreatic cancer cells. CONCLUSIONS SMUG1 promotes proliferation, migration, gemcitabine resistance, and c-Myc protein stability in pancreatic cancer via protein kinase B signaling through binding with FOXQ1. Furthermore, SMUG1 may be a new potential prognostic and gemcitabine resistance predictor in pancreatic ductal adenocarcinoma.
Humans ; Pancreatic Neoplasms/pathology* ; Forkhead Transcription Factors/genetics* ; Signal Transduction/genetics* ; Animals ; Cell Line, Tumor ; Proto-Oncogene Proteins c-akt/metabolism* ; Cell Proliferation/physiology* ; Mice ; Uracil-DNA Glycosidase/genetics* ; Female ; Male ; Gemcitabine ; Mice, Nude ; Apoptosis/physiology* ; Deoxycytidine/analogs & derivatives* ; Cell Movement/genetics*

Objective:To learn about the clinical characteristics of patients with neurobrucellosis (NB) and provide references for clinical diagnosis and treatment of NB.Methods:The clinical data of 22 NB patients diagnosed and treated at Beidahuang Industry Group General Hospital from January 2018 to November 2024 and 178 healthy individuals undergoing physical examinations during the same period were retrospectively collected. The epidemiological characteristics, clinical manifestations, laboratory tests, treatment and prognosis of NB patients were analyzed.Results:Among the 22 NB patients, 12 were males (54.55%) and 10 were females (45.45%). The age was (51.77 ± 12.75) years old, ranging from 27 to 80 years old. Most of the patients were farmers (95.45%, 21/22), and 16 cases (72.73%) had contacted with cattle/sheep. The onset seasons were mainly in summer (40.91%, 9/22) and spring (31.82%, 7/22). Among all NB patients, there were 10 cases of encephalitis/meningoencephalitis, 9 cases of myelitis, and 3 cases of meningitis. The general symptoms were mainly fever (68.18%, 15/22), the neurological symptoms were mainly nausea and vomiting (36.36%, 8/22), and the physical signs were mainly muscle weakness (50.00%, 11/22) and pathological signs (45.45%, 10/22). The laboratory test results showed that the levels of hemoglobin, hematocrit, C-reactive protein, total protein, albumin, γ-glutamyl transpeptidase, α-hydroxybutyric acid dehydrogenase, lactate dehydrogenase, and glutathione reductase in NB patients were significantly different from those in healthy individuals ( P < 0.001). Brain magnetic resonance imaging revealed ischemic changes in 5 cases (22.73%), abnormal brain signals in 2 cases (9.09%), and demyelinating lesions in white matter in 1 case (4.55%). After treatment, 18 NB patients were followed up and showed good prognosis, with only 2 cases exhibiting varying degrees of sequelae (walking disorders or memory impairment). Conclusions:The clinical manifestations of NB patients are diverse. A comprehensive judgment should be made by combining epidemiological characteristics, clinical manifestations, laboratory tests and imaging examinations.

Objective:To learn about the clinical characteristics of patients with neurobrucellosis (NB) and provide references for clinical diagnosis and treatment of NB.Methods:The clinical data of 22 NB patients diagnosed and treated at Beidahuang Industry Group General Hospital from January 2018 to November 2024 and 178 healthy individuals undergoing physical examinations during the same period were retrospectively collected. The epidemiological characteristics, clinical manifestations, laboratory tests, treatment and prognosis of NB patients were analyzed.Results:Among the 22 NB patients, 12 were males (54.55%) and 10 were females (45.45%). The age was (51.77 ± 12.75) years old, ranging from 27 to 80 years old. Most of the patients were farmers (95.45%, 21/22), and 16 cases (72.73%) had contacted with cattle/sheep. The onset seasons were mainly in summer (40.91%, 9/22) and spring (31.82%, 7/22). Among all NB patients, there were 10 cases of encephalitis/meningoencephalitis, 9 cases of myelitis, and 3 cases of meningitis. The general symptoms were mainly fever (68.18%, 15/22), the neurological symptoms were mainly nausea and vomiting (36.36%, 8/22), and the physical signs were mainly muscle weakness (50.00%, 11/22) and pathological signs (45.45%, 10/22). The laboratory test results showed that the levels of hemoglobin, hematocrit, C-reactive protein, total protein, albumin, γ-glutamyl transpeptidase, α-hydroxybutyric acid dehydrogenase, lactate dehydrogenase, and glutathione reductase in NB patients were significantly different from those in healthy individuals ( P < 0.001). Brain magnetic resonance imaging revealed ischemic changes in 5 cases (22.73%), abnormal brain signals in 2 cases (9.09%), and demyelinating lesions in white matter in 1 case (4.55%). After treatment, 18 NB patients were followed up and showed good prognosis, with only 2 cases exhibiting varying degrees of sequelae (walking disorders or memory impairment). Conclusions:The clinical manifestations of NB patients are diverse. A comprehensive judgment should be made by combining epidemiological characteristics, clinical manifestations, laboratory tests and imaging examinations.

Nonalcoholic fatty liver disease (NAFLD), especially nonalcoholic steatohepatitis (NASH), is a common hepatic manifestation of metabolic syndrome. However, there are no effective therapy to treat this devastating disease. Accumulating evidence suggests that the generation of elastin-derived peptides (EDPs) and the inhibition of adiponectin receptors (AdipoR)1/2 plays essential roles in hepatic lipid metabolism and liver fibrosis. We recently reported that the AdipoR1/2 dual agonist JT003 significantly degraded the extracellular matrix (ECM) and ameliorated liver fibrosis. However, the degradation of the ECM lead to the generation of EDPs, which could further alter liver homeostasis negatively. Thus, in this study, we successfully combined AdipoR1/2 agonist JT003 with V14, which acted as an inhibitor of EDPs-EBP interaction to overcome the defect of ECM degradation. We found that combination of JT003 and V14 possessed excellent synergistic benefits on ameliorating NASH and liver fibrosis than either alone since they compensate the shortage of each other. These effects are induced by the enhancement of the mitochondrial antioxidant capacity, mitophagy, and mitochondrial biogenesis via AMPK pathway. Furthermore, specific suppression of AMPK could block the effects of the combination of JT003 and V14 on reduced oxidative stress, increased mitophagy and mitochondrial biogenesis. These positive results suggested that this administration of combination of AdipoR1/2 dual agonist and inhibitor of EDPs-EBP interaction can be recommended alternatively for an effective and promising therapeutic strategy for the treatment of NAFLD and NASH related fibrosis.

Objective To investigate the seasonal Aedes population fluctuation and the resistance of Aedes populations to common insecticides in Jiangsu Province in 2020, so as to provide insights into vector-borne infectious diseases control.. Methods One village was randomly sampled from each of Xinbei District of Changzhou City and Zhangjiagang County of Suzhou City in southern Jiangsu Province, Hai’an County of Nantong City and Yandu District of Yancheng City in Central Jiangsu Province, and Suining County of Xuzhou City and Sihong County of Suqian City in northern Jiangsu Province during the period between May and October, 2020. A small ponding container was sampled, and larval Aedes mosquitoes were collected using straws once each in early and late stages of each month. All larvae were bred in laboratory to adults for population identification. In addition, larval breeding were observed in all small ponding containers in and out of 30 households that were randomly sampled from six surveillance sites, and the larval mosquito density was estimated using Breteau index. Larval A. albopictus mosquitoes were sampled around Cuiyuan New Village in Jintan District of Changzhou City, and bred in laboratory to the first offspring generation, and the susceptibility of adult female mosquitoes to deltamethrin, lambda-cyhalothrin, malathion, and propoxur was tested using the filter-paper bioassay recommended by WHO. Results A total of 1 165 larval Aedes mosquitoes were captured from small ponding containers in six surveillance sites of Jiangsu Province in 2020, and all were identified as A. albopictus following eclosion. The largest number of Aedes larvae captured was found in July. A total of 1 152 households were investigated in six surveillance sites, and the mean Breteau indexes were 9.58, 13.20, 13.71, 13.20, 12.18 and 5.58 from May to October, respectively, while a high Aedes transmission risk was seen in Xinbei District of Changzhou City, with a higher Breteau index than in Suining (H = 23.667, P_adjusted = 0.001) and Sihong (H = 22.500, P_adjusted = 0.003) counties. The field-captured A. albopictus from Cuiyuan New Village in Jintan District of Changzhou City remained sensitive to malathion, but was resistant to propoxur, and developed high-level resistance to deltamethrin and lambda-cyhalothrin. Conclusions A. albopictus was present in southern, central and northern Jiangsu Province in 2020, and the larval density peaked in July. A. albopictus captured from Cuiyuan New Village in Jintan District of Changzhou City has developed high-level resistance to pyrethroid pesticides.

Objective:The results of the three lipid detection systems were compared to analyze their influence on risk stratification and clinical treatment in lipid management, especially the target goal cut-off point determination, and to find ways to reduce the impact on target goal determination of various lipid measurement system.Methods:A total of 196 serum samples with triglyceride TG <4.5 mmol/L were collected from people undergoing physical examinations and in-patients in the Second Xiangya Hospital of Central South University from August to October 2022. Triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were directly detected with Hitachi-Woke (HW), Roche and Mindray detection systems, respectively. The non high-density lipoprotein cholesterol (non HDL-C) was calculated by formula (TC-HDL-C) and LDL-C (F-LDL-C) was calculated by Friedewald formula, and results from various methodology were compared. The coefficient of variation ( CV) of these six indicators derived from the three detection systems were calculated to evaluate the consistency of the obtained results from different venders. In addition, the Pearson correlation coefficient was analyzed to evaluate the correlation of each indicator among different systems. According to the Chinese Guidelines for Blood Lipid Management, samples were divided into groups with LDL-C levels of <1.4, 1.4-<1.8, 1.8-<2.6, 2.6-<3.4 and ≥3.4 mmol/L according to the recommended LDL-C levels for different risk stratification levels. The sample size and percentage of LDL-C test results from different systems in the same group were counted to evaluate the impact of LDL-C differences between systems on clinical decision-making of blood lipid management. The correction factor was calculated through two methods: (1) The average deviation of LDL-C between systems was estimated by EP9-A3 method; (2) Multiple linear stepwise regression was used to establish the regression model of LDL-C difference and related indexes between systems. The two correction factors were used to correct the deviation of LDL-C value obtained from various systems, and Chi-square test was used to compare the difference of LDL-C grouping consistency rate before and after correction. Result:The average CV values of TG, TC, LDL-C, F-LDL-C, HDL-C, and non HDL-C among the three detection systems were 4.84%, 1.92%, 11.96%, 3.81%, 5.82% and 2.61%, respectively. Correlation analysis showed that when comparing the three systems in pairs, except for LDL-C derived from HW and Roche′s, and Mindray and Roche′s LDL-C ( R 2=0.938 and 0.947), the R 2 of other indicators were all greater than 0.97. The consistency rates of the three systems on LDL-C and F-LDL-C were 51.0% (100/196) and 90.8% (178/196), respectively, according to the risk stratification standard values and the difference was statistically significant ( P<0.05). When comparing in pairs, the consistency rates of Roche and HW, Mindray and HW, Mindray and Roche system LDL-C grouping were 60.7% (119/196), 82.7% (162/196), and 54.1% (106/196), respectively. After adjusting for mean deviation, the group consistency rate of Roche and HW increased to 73.7%-79.4% ( P<0.05), and the group consistency rate of Roche and Mindray increased to 72.3%-79.0% ( P<0.05). After adjusting for difference regression model, the group consistency rate of Roche and HW increased to 82.5%-84.0%, and the group consistency rate of Roche and Mindray increased to 81.0%-89.2%. However, there was no significant change in the group consistency rate of Mindray and HW after adjusting for both correction methods ( P>0.05) .Conclusions:There are significant differences in LDL-C derived from different detection systems, and the consistency rate of grouping according to the lipid-lowering standard value is relatively low, which may affect clinical decision-making in lipid management. Adjusted by the correction factor, the consistency rate of grouping between Roche and HW, Roche and Mindray systems with large differences in LDL-C can be improved. Using the difference multiple linear regression model as a correction factor is superior to the average deviation.

Objective:To analyze the clinical characteristics and diagnosis and treatment of children with Kasabach-Merritt phenomenon (KMP).Methods:A retrospective analysis was conducted on the clinical data and follow-up data of 8 patients diagnosed KMP in Beijing Children′s Hospital, Capital Medical University from January 2016 to January 2019.The clinical data included laboratory examination, diagnosis, treatment and prognosis.Results:Among the 8 children with KMP, 6 cases were male and 2 cases were female.The median onset age was 4 (0-17) months, 2 cases of neonatal onset.The median onset to the diagnosis time was 59 (34-140) days; 6 cases with bone destruction; 6 cases had misdiagnosis and mistreatment history, they were misdiagnosed as idiopathic thrombocytopenic purpura, Evans syndrome, abnormal bone and joint development; 4 cases were Kaposiform hemangioendothelioma; 8 cases were used alone or combined with the application of hormones, Sirolimus, and Vincristine, 7 patients underwent interventional therapy.All patients survived with a median follow-up period of 487 (112-1 033) days.Median time of platelet count returned to normal was 24.5 (7-60) days, and median time of fibrinogen returned to normal was 20 (7-30) days.Median time of D-dimer dropped to a normal was 105 (40-240) days.Conclusions:Children with concurrent platelet count and coagulation abnormalities should be considered with KMP.Doctors need to identify the potential visceral vascular lesions.Early diagnosis and treatment are important, which can improve the clinical prognosis of patients.

The clinical and laboratory data of a patient with chronic refractory immune thrombocytopenia (ITP) who had a significant increase in the proportion of inhibitory T cells in the hematological oncology center of Beijing Children′s Hospital Affiliated to Capital Medical University in February 2018 and regularly followed up in the outpatient department received a retrospective analysis.This 8-year-old patient′s clinical features were 6 years of skin and mucous membrane bleeding spots and petechiae recurring, with occasionally nasal epistaxis.Physical examination: cardiopulmonary abdomen and nervous system examinations are normal, and no superficial lymphadenopathy is touched.Blood routine indicated that the platelets were 2.00×10 9/L, and white blood cell count and hemoglobin level were normal.Bone marrow suggested that hyperplasia was significantly active, with more than 300 megakaryocytes.The patient was diagnosed with ITP, and he was treated with first-line treatment with gamma globulin and oral Corticosteroids.The first-line treatment with high-dose Dexamethasone therapy was repeated, and the second-line treatment was low-dose Rituximab combined with high-dose Dexamethasone.Evaluations had been conducted with every relapsed course, and Cyclosporine was administered orally on the basis of the highly suppressive T cells.After half a month, the child achieved partial remission and continued for 3 months, and then reached a complete remission of 6 months (till this paper). It is suggested that, with ITP as an immunological disease with high heterogeneity, the immune abnormality index is expected to become a breakthrough in the development of precise treatment.

Objective:To investigate the clinical characteristics and influencing factors of mortality in patients with intra-abdominal candidiasis (IAC).Methods:The retrospective case-control study was conducted. The clinicopathological data of 203 IAC patients who were admitted to 7 medical centers from June 2018 to June 2020 were collected, including 54 cases in Sir Run Run Shaw Hospital of Zhejiang University School of Medicine, 31 cases in Fujian Medical University Union Hospital, 25 cases in Beijing Hospital, 25 cases in the First Affiliated Hospital of Xi'an Jiaotong University, 24 cases in China-Japan Friendship Hospital, 22 cases in General Hospital of Eastern Theater Command of Chinese PLA and 22 cases in Chongqing University Cancer Hospital. There were 130 males and 73 females, aged (64±15)years. Observation indicators: (1) candida infection and treatment of IAC patients; (2) analysis of influencing factors for mortality of IAC patients. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Univariate and multivariate analyses were performed by Logistic regression model. Results:(1) Candida infection and treatment of IAC patients: 134 cases of candida albicans were cultured in the initial abdominal drainage fluid or intraoperative abdominal specimens of 203 patients, and 49 cases were treated with fluconazole. Of 69 cases infected with non candida albicans, 13 cases were treated with fluconazole. The resistance rate of candida albicans to fluconazole was 5.91%(12/203). Of 203 patients, there were 68 cases with infections shock, 53 cases with renal failure, 84 cases with respiratory failure and 63 cases with multiple organ failure, respectively. There were 148 of 203 patients admitted to intensive care unit for 9 days(range, 3-20 days), and the total hospital stay was 28 days(range, 17-50 days). Of 203 patients, 86 cases were cured and discharged, 50 cases were improved and transferred to local hospitals, 32 cases gave up treatment and discharged automatically, 19 cases died, 16 cases had no follow-up data. The mortality was 25.12%(51/203). (2) Analysis of influencing factors for mortality of IAC patients. Results of univariate analysis showed that acute physiology and chronic health evaluation score, sequential organ failure assessment score, the Cr, bilirubin, albumin, procalcitonin, and PLT on the first day of candida positive culture, of the lowest value in a week and the highest in a week, heart disease, diabetes, infections shock, renal failure, respiratory failure, multiple organ failure, anti-fungal therapy were the related factors for mortality of IAC patients ( t=-2.322, Z=-2.550, -2.262, -4.361, t=2.085, Z=-3.734, -5.226, -2.394, -5.542, t=3.462, Z=-4.957, -5.632, 3.670, -5.805, t=3.966, Z=-3.734, -5.727, χ2=4.071, 4.638, 27.353, 18.818, 13.199, 26.251, 13.388, P<0.05). Multivariate analysis showed that the bilirubin, procalcitonin on the first day of candida positive culture and infections shock were independent risk factors for mortality of IAC patients ( odds ratio=1.021, 1.022, 6.864, 95% confidence interval as 1.010-1.033, 1.001-1.044, 1.858-25.353, P<0.05). Conclusions:The common fungus of IAC was candida albicans, and fluconazole can be used as the initial empirical treatment. The prognosis of patients with abdominal candidiasis is poor. Bilirubin, procalcitonin on the first day of candida positive culture and infections shock are indepen-dent risk factors for mortality of IAC patients.

Objective:To investigate the clinical characteristics, treatment and prognosis of children with acquired thrombotic thrombocytopenic purpura (TTP).Methods:The clinical manifestations, laboratory examination, treatment and prognosis of 5 children with acquired TTP hospitalized in Beijing Children′s Hospital, Capital Medical University from January 2016 to July 2019 were analyzed retrospectively.Results:There were 5 children with acquired TTP including 2 males and 3 females, with the onset age of 8.9(0.8-14.5) years, while 11 children with TTP in the same period. Thrombocytopenia and microangiopathic hemolytic anemia were found in all 5 patients. Only one patient had typical pentalogy of TTP, 3 patients had nervous system symptoms and 3 patients had fever, while renal impairment was relatively rare (1 case). Laboratory examination showed severe thrombocytopenia (7(4-14) ×10 9/L) and low level of hemoglobin (70(58-100)g/L) in all 5 children. Blood biochemical examination showed that total bilirubin (mainly indirect bilirubin) increased in 3 patients, lactate dehydrogenase increased in 5 patients, and urea nitrogen increased in 1 patient. Bone marrow smear showed megakaryocyte did not decrease. Plasma ADAMTS13 activity was 0 in all 5 patients while ADAMTS13 inhibitor was positive in 4 patients and negative in 1 patient. All 5 children received glucocorticoid therapy, rituximab was added in the early stage of the disease, and 3 children received plasma exchange. The time of platelet recovery to normal was 19 (9-29) days. One child had TTP recurrence after 9 months of treatment. The condition was stable after being treated with glucocorticoid and rituximab again. This case was finally diagnosed as systemic lupus erythematosus after more than 3 years followed up. By December 1, 2020, the follow-up time was 24(16-57) months.The clinical symptoms of all patients disappeared and the platelet level was stable at 159(125-269) ×10 9/L. Conclusions:Childhood acquired TTP is relatively rare, which can occur in all age groups. The clinical manifestations are mainly thrombocytopenia and microangiopathic hemolytic anemia, the plasma ADAMTS 13 activity and inhibitor test are helpful for the diagnosis of acquired TTP. Plasma exchange and rituximab are effective treatment. This disease requires long-term follow-up.