Given the current ethical issues such as unknown high risks in the clinical application of new biomedical technology， thus， medical institutions need to establish new technology management systems， including clarifying the concept， the assessment and admission mechanism， and ethical management systems of new technology. According to the direction of the development of new technology in the medical institution， the ethics review committee should also perfect the management system of ethics committees and the professional composition of ethics review committee members， improve the ability of ethics committee members to evaluate new biomedical technology， increase the assessment of ethical risks of new technology in the preliminary review stage， strengthen the requirements for emergency plan formulation， as well as set the frequency of the follow-up review based on the risk level of new technology. The ethics review committee should work together with the medical management department to formulate an ethical standardization training system for the clinical application of medical technology in the institution， and regularly conduct training for all staff， to promote medical workers’ understanding of the management requirements of biomedical technologies. Different types of new biomedical technology have different ethical risks. Therefore， the medical management departments and ethics review committees of medical institutions should formulate specific management rules based on the characteristics of new technology types. However， it should be noted that when new biomedical technology generally is first introduced into clinical practice， there are often issues regarding fairness and justice in the use of the technology.

ObjectiveTo investigate the feasibility and safety of endoscopic retrograde cholangiopancreatography （ERCP） combined with oral cholangiopancreatography in the treatment of major duodenal papilla gallbladder polyps. MethodsA retrospective analysis was performed for the clinical data of eight patients with choledocholithiasis and gallbladder polyps who underwent ERCP and combined with oral cholangiopancreatography for major duodenal papilla cholecystectomy in Center of Digestive Endoscopy， Jilin People’s Hospital， from May 2022 to June 2024， and related data were collected， including the success rate of surgery， the technical success rate of gallbladder polyp removal， the superselective method of cystic duct， the time of operation， the time of gallbladder polyp removal， and surgical complications. ResultsBoth the success rate of surgery and the technical success rate of gallbladder polyp removal reached 100%， and of all eight patients， three patients used guide wire to enter the gallbladder under direct view， while five patients received oral cholangiopancreatography to directly enter the gallbladder. The time of operation was 51.88±12.34 minutes， and the time of gallbladder polyp removal was 23.13±10.94 minutes. The diameter of gallbladder polyp was 2‍ ‍—‍ ‍8 mm， and pathological examination showed inflammatory polyps in three patients， adenomatous polyps in one patient， and cholesterol polyps in four patients. There were no complications during or after surgery. The patients were followed up for 2‍ ‍—‍ ‍27 months after surgery， and no recurrence of gallbladder polyp was observed. ConclusionOral cholangiopancreatography is technically safe and feasible in endoscopic major duodenal papilla cholecystectomy.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

ObjectiveTo explore the potential mechanism of Dingchuan Granule （定喘颗粒， DG） in the treatment of respiratory syncytial virus （RSV） pneumonia. MethodsA total of 60 male Sprague Dawley （SD） rats were randomly divided into control group， model group， ribavirin group， DG low-dose group， DG middle-dose group， and DG high-dose group， with 10 rats in each group. Except for the control group， rats were administrated with RSV via intranasal drip. After model establishment， the DG low-， middle-， and high-dose groups were administrated via oral gavage with DG at 3.47， 6.93， and 13.86 g/（kg·d） respectively， while the ribavirin group was administrated via oral gavage with ribavirin at 15.75 mg/（kg·d）. The drug was given once daily for one week. The rats in the control group and the model group were not given any drug， only subjected to the grasping action. Twenty-four hours after the last administration， the pathological changes of lung tissues were observed and scored using HE staining. The levels of serum inflammatory factors， including tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6）， were detected by colorimetry. The protein levels of nuclear factor （erythroid derived 2）-like 2 （Nrf2）， Kelch-like ECH-associated protein 1 （Keap1）， heme oxygenase 1 （HO-1）， and NAD（P）H quinone dehydrogenase 1 （NQO1） in lung tissues were measured by Western Blot. The RSV load as well as the gene expression levels of Nrf2， Keap1， HO-1， and NQO1 in lung tissues were determined by qRT-PCR. The level of reactive oxygen species （ROS） in rat lung tissues was detected using chemiluminescence. The levels of glutathione （GSH） and malondialdehyde （MDA） in rat lung tissues were measured by a microassay. ResultsCompared with the control group， other groups had significant increases in pathological score of lung tissue， RSV load， levels of ROS， MDA， serum TNF-α， IL-1β， and IL-6； decrease in GSH level， increases in expression level of Keap1 protein and its mRNA in lung tissue， and significant decrease in levels of Nrf2， HO-1， expression level of NQO1 protein and its mRNA （P＜0.05）. Compared with the model group， all the above-mentioned indicators in the DG low-， middle-， and high-dose groups and the ribavirin group were improved to varying degree （P＜0.05）. The levels of serum TNF-α， IL-1β， and IL-6 in rats of DG dose groups showed a dose-dependent pattern， the DG high-dose group exhibiting the best effect （P＜0.05）. The DG high-dose group was superior to the DG low- and middle-dose groups in reducing the levels of ROS and MDA， and increasing the level of GSH in lung tissues （P＜0.05）. The DG high-dose group and the ribavirin group had better effect than the DG middle-dose group in reducing the RSV load （P＜0.05）. The DG high-dose group was superior to the ribavirin group in improving the protein levels of Nrf2， Keap1， HO-1， and NQO1 （P＜0.05）. ConclusionDG could inhibit oxidative stress by regulating the Nrf2/Keap1/HO-1/NQO1 signaling pathway to improve pulmonary inflammation and treat RSV pneumonia， with the DG high-dose group showing the best effect.

Objective To construct Raji-Luc lymphoma cells with CD19 knockout using CRISPR/Cas9 technology and preliminarily validate their immune escape ability.Methods PB-CRISPR-CD19 small guide RNA(sgRNA)plasmids was constructed,the optimal sgRNA sequence was screened,and Raji-Luc cells with pCAG-PBase,PB-CD19 sgRNA,and PB-CRISPR-Cas9 were co-transfected.Stable knockout monoclonal cell lines were screened by flow sorting and limit dilution method and the knockout effect was verified through gene sequence testing.The expression of luciferase on the surface of the cell line was detected by microplate reader,CD19 CAR-T and CD38 CAR-T previously constructed in the laboratory were used as effector cells,and the immune escape ability of Raji-Luc CD19 KO cell line was verified by universal luciferase chemiluminescence method.Results The transfection efficiency of Raji-Luc CD19 KO cells prepared by electro transfection was high,and the knockout efficiency of the two monoclonal cells was more than 99%.There was no significant difference in luciferase expression compared to the original Raji-Luc cells,and CD19 CAR-T cells could not be activated to the kill them.Conclusion Successfully constructed Raji-Luc CD19 KO lymphoma cell line.

Objective To explore EEG characteristics and the therapeutic effect in children with electrical status epilepticus during slow sleep(ESES).Methods The eligible ESES cases in our center from 2014 to 2020 were included.The age at diagnosis of ESES,the duration of ESES,spike wave index(SWI)during wakefulness and the distribution of spike wave during the period of ESES,age at seizure onset,the clinical syndromes and the outcomes after treatment were analyzed.The ESES cases were divided into 4 groups according to the distribution of spike wave:focal ESES,unilateral ESES,bilateral asymmetric ESES,multiple foci ESES.The SWI during the awake stage were divided into 3 groups based on the different rates:≤20%,21%～49%,≥50%.The therapeutic outcomes were classified into three groups:satisfactory response,seizure control and ineffective.Results 50 cases were included,with 32 males and 18 females.The average onset age of ESES was 6 years and 7 months,and the average duration of ESES was 28 months.A significant correlation between the distribution of ESES and the thera-peutic effects was found,bilateral asymmetric ESES had a good therapeutic effects,while multiple foci ESES showed a poor therapeutic effects.The duration of ESES was significantly correlated with therapeutic effects,and the efficacy was worse when the duration was longer than 1 year.A significant relationship between the SWI during wakefulness of ESES and the therapeutic effects was detected,the patient with SWI≤20%during wakefulness had a good therapeutic effect.There was a negative correlation between the onset age of ESES and the duration of ESES and SWI index during wakefulness.There was a positive correlation between the duration of ESES and SWI index during wakefulness.Conclusion Our results suggest that onset age,distribution,duration and SWI during wake-fulness of ESES were correlated with therapeutic outcomes,The patient with SWI≤20%during wakefulness had a good therapeutic effect and have unfavorable outcomes with ESES last more than 1 year.The earlier onset of ESES,the longer duration of ESES and higher SWI during wakefulness will be showed..

Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.