Objective:To investigate the clinical characteristics of a family with maturity-onset diabetes of the young type 3(MODY3) and assess its association with the novel HNF1A-c.47T>A variant.Methods:A genetic pedigree of the MODY3 family was constructed, and clinical data were collected. Whole-exome sequencing combined with Sanger sequencing was used, followed for familial co-segregation analysis. Bioinformatics tools, including multiple sequence alignment–based conservation analysis and protein structural prediction, were conducted to validate the association between the novel HNF1A-c.47T>A variant and MODY3.Results:Seven MODY3 patients were diagnosed in this family, all harboring the HNF1A-c.47T>A heterozygous variant. AlphaFold2 protein structure prediction indicated that the HNF1A-c.47T>A variant altered the conformation of the first pair of α-helices within the protein dimerization domain.Conclusion:Based on co-segregation analysis, sequence conservation assessment, protein structure prediction, and classification based on American College of Medical Genetics and Genomics(ACMG) Guidelines, the HNF1A-c.47T>A variant was determined to be pathogenic for MODY3. This study reports this novel pathogenic variant, expanding the mutational spectrum of MODY3. By revealing its disruptive effect on the protein dimerization domain, the findings provide a potential molecular basis for the diagnosis and management of patients carrying similar variants.

Type 2 diabetes mellitus(T2DM)is an insulin resistance disease.Improving insulin resis-tance and controlling blood glucose are the main means of clinical treatment for T2DM.Empa-gliflozin is a highly selective sodium-dependent glu-cose transporters(SGLT)2 inhibitor,which is inde-pendent of insulin.It can effectively control blood glucose levels,reduce blood pressure and body weight,protect heart and kidney function,reduce the rehospitalization rate and the risk of death in patients with heart failure(HF),and does not in-crease the risk of hypoglycemia.Empagliflozin can be used alone or in combination with other hypo-glycemic drugs to control blood glucose.This arti-cle reviews the mechanism of action,clinical bene-fits,and combination with other drugs of empa-gliflozin,aiming to provide reference for the clinical use of empagliflozin.

Type 2 diabetes mellitus(T2DM)is an insulin resistance disease.Improving insulin resis-tance and controlling blood glucose are the main means of clinical treatment for T2DM.Empa-gliflozin is a highly selective sodium-dependent glu-cose transporters(SGLT)2 inhibitor,which is inde-pendent of insulin.It can effectively control blood glucose levels,reduce blood pressure and body weight,protect heart and kidney function,reduce the rehospitalization rate and the risk of death in patients with heart failure(HF),and does not in-crease the risk of hypoglycemia.Empagliflozin can be used alone or in combination with other hypo-glycemic drugs to control blood glucose.This arti-cle reviews the mechanism of action,clinical bene-fits,and combination with other drugs of empa-gliflozin,aiming to provide reference for the clinical use of empagliflozin.

Objective:To investigate the clinical characteristics of a family with maturity-onset diabetes of the young type 3(MODY3) and assess its association with the novel HNF1A-c.47T>A variant.Methods:A genetic pedigree of the MODY3 family was constructed, and clinical data were collected. Whole-exome sequencing combined with Sanger sequencing was used, followed for familial co-segregation analysis. Bioinformatics tools, including multiple sequence alignment–based conservation analysis and protein structural prediction, were conducted to validate the association between the novel HNF1A-c.47T>A variant and MODY3.Results:Seven MODY3 patients were diagnosed in this family, all harboring the HNF1A-c.47T>A heterozygous variant. AlphaFold2 protein structure prediction indicated that the HNF1A-c.47T>A variant altered the conformation of the first pair of α-helices within the protein dimerization domain.Conclusion:Based on co-segregation analysis, sequence conservation assessment, protein structure prediction, and classification based on American College of Medical Genetics and Genomics(ACMG) Guidelines, the HNF1A-c.47T>A variant was determined to be pathogenic for MODY3. This study reports this novel pathogenic variant, expanding the mutational spectrum of MODY3. By revealing its disruptive effect on the protein dimerization domain, the findings provide a potential molecular basis for the diagnosis and management of patients carrying similar variants.

OBJECTIVE To investigate the effects of multiple doses of Shugan jieyu capsules on the pharmacokinetics of voriconazole,rivaroxaban and apixaban in rats.METHODS Male SD rats were randomly divided into voriconazole group(30 mg/kg),rivaroxaban group(2 mg/kg),apixaban group(0.5 mg/kg),Shugan jieyu capsules+voriconazole group(145 mg/kg+30 mg/kg),Shugan jieyu capsules+rivaroxaban group(145 mg/kg+2 mg/kg),Shugan jieyu capsules+apixaban group(145 mg/kg+0.5 mg/kg),with 6 rats in each group.After the rats in each group were consecutively administered solvent(0.5%sodium carboxymethyl cellulose solution)or Shugan jieyu capsules by intragastric gavage for 8 days,they were respectively given voriconazole,rivaroxaban and apixaban solution by intragastric gavage on the 8th day.Blood samples were then collected at different time points(in voriconazole group,rivaroxaban group and corresponding drug combination groups,blood was collected before administration and at 0.17,0.34,0.5,0.75,1,1.5,2,3,4,5,6,8,10 and 12 hours post-administration;in apixaban group and corresponding drug combination group,blood was collected before administration and at 0.08,0.17,0.25,0.34,0.5,0.75,1,3,5,7,10 and 12 hours post-administration).Ultra-high performance liquid chromatography-tandem mass spectrometry method was employed to determine the mass concentrations of voriconazole,rivaroxaban and apixaban in rat plasma.The main pharmacokinetic parameters of these drugs were calculated using a non-compartmental model,and the comparisons were made between groups.RESULTS Compared with single drug group,after multiple administrations of Shugan jieyu capsules,AUC0-t,AUC0-∞ and cmax of voriconazole were significantly decreased,while CLz/F was significantly increased,and tmax was also significantly prolonged(P＜0.05).For rivaroxaban and apixaban,their tmax values were both significantly prolonged(P＜0.05).However,there were no statistically significant differences in the other pharmacokinetic parameters between the two groups(P＞0.05).CONCLUSIONS The combination of Shugan jieyu capsules can decrease the exposure,increase the clearance,and delay the peak concentration of oral voriconazole.However,it does not affect the exposure levels of rivaroxaban and apixaban,but it does delay the time to reach peak concentration for both drugs.

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 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 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 investigate the feasibility of using optimized protocol of iodine contrast agent with fixed injection time in triple-rule-out CT examination of acute chest pain patients. Methods A prospective study was conducted. The patients who underwent triple-rule-out CT examination of acute chest pain at the Second Hospital of Shanxi Medical University from September 2017 to June 2018 were enrolled. According to the patient's body mass index (BMI), they were divided into BMI ≤ 23 kg/m2 group and BMI > 23 kg/m2 group. The patients in each group were subdivided into two subgroups according to the random number table, and they were given two iodine contrast injection protocols with fixed injection time (14 s). Protocol 1 was performed with 55 mL of total iodinated contrast media: iodinated contrast media was first injected at 5.0 mL/s for 8 s, followed by the same contrast media injection at 2.5 mL/s for 6 s, finally followed by injection of 40 mL of saline at a rate of 2.5 mL/s. Protocol 2 with 60 mL of total iodinated contrast media: iodinated contrast media was first injected at 5.0 mL/s for 10 s, followed by the same contrast media injection at 2.5 mL/s for 4 s, finally followed by injection of 40 mL of saline at a rate of 2.5 mL/s. The primary and objective evaluation was conducted on the image quality of the patients' blood vessels in different segments. The primary score, CT value and contrast-to-noise ratio (CNR) of the pulmonary artery, coronary artery, aorta and total effective radiation dose for the examination were recorded. Results A total of 92 patients were enrolled in the analysis. There were 44 patients in BMI≤ 23 kg/m2 group, in which 22 patients received in protocol 1 and protocol 2, 48 patients in BMI > 23 kg/m2 group, in which 24 patients in protocol 1 and protocol 2, respectively. There was no significant difference in the effective radiation dose between the two subgroups receiving different injection protocols in different BMI groups (mSv: 6.7±1.1 vs. 6.5±0.8 between protocol 1 and protocol 2 in BMI ≤ 23 kg/m2 group; 7.8±1.0 vs. 8.0±1.1 between protocol 1 and protocol 2 in BMI > 23 kg/m2 group, both P > 0.05). In BMI ≤ 23 kg/m2 group, the CT value, CNR and primary scores of pulmonary artery images in patients receiving protocol 2 were significantly higher than those receiving protocol 1 [CT value (HU): 584±110 vs. 472±86 for main pulmonary artery, 561±93 vs. 467±78 for left pulmonary artery, 555±91 vs. 472±83 for right pulmonary artery; CNR: 24.2±7.5 vs. 18.7±4.6 for main pulmonary artery, 23.2±6.8 vs. 18.6±4.8 for left pulmonary artery, 22.9±6.7 vs. 18.8±4.7 for right pulmonary artery; primary score:4.0 (4.0, 4.0) vs. 3.5 (3.0, 4.0), all P < 0.05]; and there was no statistically significant difference in the primary or objective evaluation of coronary artery or aortic image quality between the two protocols. In BMI > 23 kg/m2 group, the CT value, CNR and primary scores of coronary artery and aortic images in patients receiving protocol 2 were significantly higher than those receiving protocol 1 [CT value (HU): 369±63 vs. 315±61 for proximal right coronary artery (RCA), 388±63 vs. 323±63 for proximal left coronary artery (LCA), 328±83 vs. 272±51 for ascending aorta, 348±82 vs. 272±49 for aortic arch; CNR: 15.0±4.6 vs. 12.3±4.7 for proximal RCA, 15.7±3.8 vs. 12.8±5.2 for proximal LCA, 13.2±5.3 vs. 10.4±4.1 for ascending aorta, 14.1±5.3 vs. 10.4±3.9 for aortic arch; primary score: 4.0 (3.0, 4.0) vs. 3.0 (3.0, 4.0) for coronary, 4.0 (3.0, 4.0) vs. 3.0 (2.0, 4.0) for aorta; all P < 0.05]; and there was no statistically significant difference in the primary or objective evaluation of pulmonary artery image quality between the two protocols. Conclusions The effective radiation dose of triple-rule-out CT examination of acute chest pain is relatively low. The low-dose iodine contrast agent application program with fixed injection time can meet the needs of clinical diagnosis of triple-rule-out CT examination of acute chest pain patients. For patients with BMI ≤ 23 kg/m2, both protocols 1 and 2 can obtain excellent image quality; in order to avoid the influence of superior vena cava artifacts, protocol 1 is recommended. For patients with BMI > 23 kg/m2, application protocol 2 can obtain stable, excellent image quality that is more suitable for clinical applications.

Objective To explore the effect of various information means in the training of newly recruited nurses and to provide a practical basis for comprehensive and thorough development of the training. Methods Nurses who are enrolled in 2015 were chosen as the test group. Its applications can be in the form of Mobile APP,office software,online software and We Chat public platform. Afterwards,the effect of various information means can be judged by comparing the test results with the nurses who are enrolled in 2013 (the control group). The nurses in the test group were surveyed in the form of questionnaires to evaluate the training effect. Results The scores of theory ex amination and nasal feeding in the test group were higher than those of control group(P<0.01). The 93.8 percent of the nurses in test group believe that training is beneficial to the understanding and consolidation of knowledge as well as to improve the ability of self-learning. Also the training effect is prominent. Conclusion The various information means in the training of newly recruited nurses can improve training efficiency and enhance training effectiveness.