ObjectiveTo construct a novel KPC mouse model of type 2 diabetes mellitus （T2DM） comorbid with spontaneous pancreatic cancer based on the gene editing-metabolic intervention dual-driven strategy， and to compare it with traditional models. MethodsA total of 14 male KPC mice were randomly divided into novel model group （T2DM-KPC group with 7 mice） and control group （KPC group with 7 mice）， and 14 male BALB/c-nu nude mice were randomly divided into traditional model group （T2DM-pancreatic cancer group with 7 mice） and control group （pancreatic cancer group with 7 mice）. The mice in the KPC group and the pancreatic cancer group were fed with normal diet， and those in the T2DM-KPC group and the T2DM-pancreatic cancer group were fed with a high-fat diet. After 4 weeks， the mice in the T2DM-KPC group and the T2DM-pancreatic cancer group were given intraperitoneal injection of streptozotocin. Subsequently， the mice in the KPC group and the T2DM-KPC group developed primary pancreatic tumor spontaneously over time， while those in the T2DM-pancreatic cancer group and the pancreatic cancer group were inoculated with tumor cells to form subcutaneous tumor xenograft at 2 weeks after stabilization of blood glucose. The 4 groups were observed in terms of tumor formation rate， tumor formation time， body weight， and the change in blood glucose； RNA sequencing was performed for tumors from the KPC group and the T2DM-KPC group， and then molecular subtyping was performed； HE staining， Masson staining， and immunohistochemical staining were used to assess the histopathological features and tumor microenvironment of pancreatic tumor from the T2DM-KPC group， which were compared with those of the T2DM-pancreatic cancer group. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups； the Fisher’s exact test was used for comparison of categorical data between multiple groups. ResultsThe T2DM-KPC group had a tumor formation rate of 85.71% and a tumor formation time of 104.40±2.87 days， while the T2DM-pancreatic cancer group had a tumor formation rate of 71.43% and a tumor formation time of 95.20±9.47 days， and there were no significant differences between the two groups in tumor formation rate， tumor formation time， body weight， and blood glucose （all P>0.05）. Molecular subtyping showed that the model in the KPC group highly resembled the pancreatic progenitor subtype of human pancreatic ductal adenocarcinoma （PDAC）， and the model in the T2DM-KPC group highly resembled the immunogenic subtype of PDAC. HE staining showed that tumor cells in the T2DM-KPC group were arranged into glandular tubular structures of varying shapes， exhibiting significant cellular atypia， and this model faithfully recapitulated the pathological features of primary pancreatic cancer and showed greater invasiveness than the KPC group. Immunohistochemical staining and Masson staining showed that compared with the T2DM-pancreatic cancer group， the T2DM-KPC group had significantly higher degrees of tumor proliferation （assessed by Ki-67 expression） and fibrosis （assessed by α-SMA and Masson） （all P<0.05）， suggesting that the mouse model in the T2DM-KPC group could better recapitulate the features of hyperproliferation and pronounced desmoplasia in human pancreatic cancer. ConclusionA novel KPC mouse model of T2DM comorbid with spontaneous pancreatic cancer is successfully constructed in this study. This model can accurately mimic the histopathological architecture and stromal microenvironment of T2DM comorbid with pancreatic cancer， realize the longitudinal simulation of the progression of pancreatic tissue from intraepithelial neoplasia to invasive carcinoma and metastasis in the presence of T2DM， and support the translational research on immunotherapy， thereby providing a novel experimental carrier for in vivo studies on spontaneous pancreatic cancer in T2DM.

Objective:To analyze the clinical and immunological characteristics of children with acute viral infection-related encephalopathy.Methods:Case-control study.A retrospective analysis was conducted on the clinical data of children diagnosed with acute viral infection-related encephalopathy during hospitalization at the Children′s Hospital, Capital Institute of Pediatrics from January 2020 to January 2023.According to the last follow-up modified Rankin scale (mRS) score, these children were divided into a good prognosis group (mRS score ≤2) and a poor prognosis group (mRS score >2), and the clinical and immunological characteristics of the children with different prognoses were analyzed.The binary Logistic regression was used to analyze the risk factors for poor prognosis.Results:A total of 28 children with acute viral infection-related encephalopathy aged 4 months to 11 years were included.There were 16 males (57%) and 12 females (43%). Among the preinfection viruses, there were 16 children of Corona virus disease 2019, 8 children of influenza A virus, 3 children of influenza B virus, and 1 child of norovirus.Among them, there were 21 children with acute necrotizing encephalopathy, 4 children with acute encephalopathy with biphasic seizures and late reduced diffusion, 2 children with mild encephalitis with a reversible splenial lesion, and 1 child with hemorrhagic shock and encephalopathy syndrome.Among the first symptoms, 24 children (85.7%) had consciousness disorders, 23 children (82.1%) had seizures, 17 children (60.7%) had speech disorders, 11 children (39.3%) had involuntary movements, and 10 children (35.7%) had abnormal mental behavior.For the site of lesion, the cranial nuclear magnetic resonance imaging revealed 17 in the thalamus, 10 in the brainstem, 9 in the basal ganglia, 8 in the cerebellar hemisphere, and 4 in the corpus callosum.In the last follow-up evaluation, 17 children had a mRS score of >2, and 11 children had a mRS score of ≤2.Univariate analysis showed that disturbance of consciousness, seizure cluster, brain stem lesion, absolute value of serum T lymphocytes, cerebrospinal fluid(CSF) protein, CSF cytokines [interleukin(IL)-1β, IL-6 and IL-8]were higher in the poor prognosis group than those in the good prognosis group.Multivariate Logistic regression analysis indicated that brain stem disease, CSF IL-1β and T lymphocyte absolute number were independent risk factors for poor prognosis.Conclusions:Brain stem lesions, cerebrospinal fluid IL-1β and the absolute number of T lymphocytes have predictive value for the prognosis of acute viral infection-associated encephalopathy.The more severe the conditions, the lower the T lymphocytes, and the higher the cytokines in some cerebrospinal fluid.

Objective:To summarize the clinical manifestations, diagnosis, treatment and prognosis of acute flaccid myelitis (AFM) in children.Methods:Clinical characteristics of 4 AFM cases from Department of Neurology, Children′s Hospital Affiliated to Capital Institute of Pediatrics, from September 2018 to November 2022, were analyzed retrospectively.Results:The age of 4 children with AFM was 7 years, 4 years and 3 months, 7 years and 1 month, 6 years and 5 months, respectively. There were 2 boys and 2 girls. Prodromal infection status showed 3 children of respiratory tract infection and 1 child of digestive tract infection. The main manifestation was asymmetrical limb weakness after infection, and the affected limb range was from monoplegia to quadriplegia. Cranial nerve injury was involved in 1 child, no encephalopathy. Magnetic resonance imaging in the spinal cord of all 4 children showed long T1 and T2 signals, mainly involving gray matter. Cerebrospinal fluid cell-protein separation was observed in 2 children. Pathogen detected in 1 child pharyngeal swab was enterovirus D68. Antibody IgM to adenovirus was positive in the blood of 1 child. Antibody IgG against Echo and Coxsackie B virus were positive in the blood of another child. After glucocorticoid, human immunoglobulin or simple symptomatic treatment and at the same time under later rehabilitation training, muscle strength recovered to different degrees, but there were disabilities left in 3 children.Conclusions:AFM should be considered in children with acute and asymmetrical flaccid paralysis accompanied by abnormal magnetic resonance imaging signal in the central region of spinal cord, especially post-infection. The effective treatment is limited and the prognosis is poor.

Objective:To summarize the relevant evidence for the prevention of contrast-associated acute kidney injury (CA-AKI) after enhanced CT examination in patients with nephropathy.Methods:The literature on prevention of CA-AKI in patients with nephropathy who underwent enhanced CT examination in relevant websites and medical literature databases at home and abroad were systematically searched, the quality of the literature was evaluated, and the relevant evidence was extracted and summarized. The retrieval period was from January 1, 2013 to December 1, 2023.Results:A total of 17 literature was included, including 6 guidelines, 5 expert consensuses, 2 clinical decisions, 2 cohort studies, 1 evidence summary and 1 systematic review. Evidence was extracted from these literature. After summary and analysis of these evidence, 10 evidence topics were sorted out, including threshold of estimated glomerular filtration rate and high-risk population, screening, hydration prevention, drug prevention, use of nephrotoxic drugs, use of metformin, precautions for dialysis patients, alternative imaging strategies, choice of iodine contrast agents, and points for attention after enhanced CT examination, forming 47 pieces of evidence.Conclusion:The relevant evidence for the prevention of CA-AKI can provide a more systematic evidence-based basis for medical staffs in screening high-risk population and preventing and managing CA-AKI in patients with chronic kidney disease before enhanced CT examination.

Objective:To summarize the relevant evidence for the prevention of contrast-associated acute kidney injury (CA-AKI) after enhanced CT examination in patients with nephropathy.Methods:The literature on prevention of CA-AKI in patients with nephropathy who underwent enhanced CT examination in relevant websites and medical literature databases at home and abroad were systematically searched, the quality of the literature was evaluated, and the relevant evidence was extracted and summarized. The retrieval period was from January 1, 2013 to December 1, 2023.Results:A total of 17 literature was included, including 6 guidelines, 5 expert consensuses, 2 clinical decisions, 2 cohort studies, 1 evidence summary and 1 systematic review. Evidence was extracted from these literature. After summary and analysis of these evidence, 10 evidence topics were sorted out, including threshold of estimated glomerular filtration rate and high-risk population, screening, hydration prevention, drug prevention, use of nephrotoxic drugs, use of metformin, precautions for dialysis patients, alternative imaging strategies, choice of iodine contrast agents, and points for attention after enhanced CT examination, forming 47 pieces of evidence.Conclusion:The relevant evidence for the prevention of CA-AKI can provide a more systematic evidence-based basis for medical staffs in screening high-risk population and preventing and managing CA-AKI in patients with chronic kidney disease before enhanced CT examination.

OBJECTIVE：To provid e reference for hospital decision-maker to select and use repaglinide and naglinide reasonably. METHODS ：Through reviewing literautre ，guideline and instruction ，full score system was estalished for comunni- cation between pharmacists and physicians ；from the aspects of clinical necessity ，effectiveness，safety，economy，medical insu- rance attribute ，essential medicine attribute ，original research attribute ，drug packaging attribute ，drug market and enterprise attributes，the Mini health technology assessment （Mini HTA ）was carried out for repaglinide and nateglinide ，and scored on the basis of weight value. RESULTS ：Repaglinide and naglinide ’s final score were 77 and 74，respectively. For type 2 diabetes，both of them could reduce postprandial blood glucose ，and had less side effect and good safety. They were both included in the medical insurance list. Both of them were original varieties ，easy to store and had a long period of validity. Although they were expensive in the treatment of type 2 diabetes，their manufacturers had a good reputation and were widely used in the world ，which was a good choice for patients with type 2 diabetes. But they were different to certain extent ；repaglinide could be used in patients with poor renal function [eGFR ＜30 mL/min] without dose adjustment ；nateglinide should be adjusted according to eGFR for renal excretion. Repaglinide was essential medicine but nateglinide wasn ’t；repaglinide didn ’t need shading storage but nateglinide did. In addition ， a variety of liver drug enzyme inducers or inhibitors may interact with the two drugs ，and special groups should be used with. CONCLUSIONS ：Mini HTA provide reference for the selection and rational use of repaglinide and nateglinide ；patients with type 2 diabetes can select suitable drug according to their own conditions and needs. When combined with other drugs ，blood glucose should be closely monitored to prevent the occurrence of hypoglycemia.

Objective To analyze the influencing factors on clinical response to conbercept for diabetic maeular edema (DME).Methods A total of 51 patients (51 eyes) with DME who underwent intravitreal injection of conbercept were included in this retrospective study.The general information (age,sex,body mass index,smoking history,drinking history),blood glucose indicators (duration of diabetes,fasting blood glucose,HbA 1 c),blood pressure indicators (history of hypertension,systolic blood pressure,diastolic blood pressure),lipid indicators [total cholesterol (TC),high-density lipoprotein (HDL),apolipoprotein A (APOA)],biochemical indicators [neutrophil concentration,hemoglobin (HB),serum creatinine (Scr)] were collected.The best corrected visual acuity (BCVA) and macular central macular thickness (CMT) before and after treatment were comparatively analyzed.CMT reduced not less than 20％ and BCVA increased by 2 lines as effective standards.Univariate analysis and multivariate logistic regression analysis were used to determine the factors affecting the efficacy ofintravitreal injection ofconbercept in patients with DME.Results Univariate analysis showed that diastolic blood pressure,HDL,serum neutrophil concentration,baseline CMT and baseline BCVA were associated with edema regression (P＜ 0.05);HbA 1 c was associated with vision improvement (P＜ 0.05).Multivariate logistic regression analysis showed that there was a history of smoking (OR=0.122,95％ CI 0.017-0.887),low diastolic blood pressure (OR=0.850,95％CI 0.748-0.966),low HDL (OR=0.007,95％CI 0.000 1-0.440),thin baseline CMT (OR=0.986,95％CI 0.977-0.995) were independent risk factors for failure outcome of edema regression (P＜0.05);long duration of diabetes (OR=1.191,95％CI 1.011-1.404),high APOA (OR=l.007,95％ CI 1.000-1.013) were independent risk factors for failure outcome of vision improvement.Age,fasting blood glucose,systolic blood pressure,TC,HB,Scr and other indicators had no effect on the efficacy of edema regression and vision improvement after treatment (P＞ 0.05).Conclusions Smoking history,long duration of diabetes,low diastolic blood pressure,low HDL level,high APOA level and thin baseline CMT are independent risk factors for the treatment of DME with intravitreal injection of conbercept.

Raw264.7 cells were incubated with receptor activator of NF-kappa B ligand (RANKL) and α-melanocyte stimulating hormone(α-MSH) for6 d.The amount of osteoclast cells were counted by tartrate resistant acid phosphatase staining and the acid phosphatase activity was assayed.The expressions of 5 melanocortin receptors (MCR) in Raw264.7 cells were determined by RT-PCR.The results showed that the number of osteoclasts in RANKL +α-MSH group was significantly increased compared with RANKL group (P ＜ 0.05),but there was no osteoclast formation in α-MSH group.Compared with control group and α-MSH group,the acid phosphatase activities were significantly increased in RANKL group and α-MSH+RANKL group (P＜0.05).All five MCRs were expressed in the Raw264.7 cells shown by RT-PCR.These results suggest that α-MSH may promote osteoclasts formation through RANK signaling pathway.

Objective:To explore the relationship between the severity of cardiovascular disease with the expression of apolipoprotein(a) [apo(a)] and apolipoprotein B(apoB) in peripheral blood and their location in peripheral blood cells.Methods: In this report,we selected 4 patients with angiography which indicated that three coronary arteries were narrowed and 5 control patients with normal angiography.Arterial blood was collected and analyzed for lipid parameters in plasma.The mRNA expression of apo(a) and apoB in peripheral white blood cells and platelets were determined by RT-PCR and their protein expression by western blot.Moreover,the expression and location of apo(a) and apoB in white blood cells were determined by confocal microscopy and computer 3D analysis.Results: In plasma,levels of high density lipo-protein-cholesterol(HDL-C) and apolipoprotein A-Ⅰ(apoA-Ⅰ) in cardiovascular disease(CVD) patients were significantly less than those in the control patients[(0.62?0.05) mmol/L,(0.78?0.08) mmol/L vs(0.81?0.15) mmol/L,(0.9?0.07) mmol/L,P0.05).Studies with confocal microscopy indicated that proteins of apo(a) and apoB were co-expressed by a few cells of leukocytes and the ratio of apoB/apo(a) in cardiovascular disease patients was significantly less than that in the control patients(optical density value 1.60?0.12 vs 4.40?0.35,P