ObjectiveTo explore the relationship between negative life events and depression severity in adolescent patients with depressive disorder， as well as the chain mediating role of insomnia symptoms and quality of life. Methods374 outpatient patients and hospitalized patients with adolescent depressive disorders were enrolled. The Adolescent Life Event Scale （ASLEC）， the Insomnia Severity Index （ISI）， the World Health Organization Quality of Life Questionnaire Short Form （WHOQOL-BREF）， and the Center for Epidemiology Depression Scale （CES-D） were used to evaluate the negative life event situation， insomnia symptoms， quality of life level and depression severity of the subjects， respectively. In addition， the PROCESS 4.0 macroprogram was used to analyze the chain mediating effect of insomnia symptoms and quality of life between negative life events and depression severity in patients with adolescent depressive disorder. ResultsThe results of correlation analysis showed that there was a significant correlation between negative life events and insomnia symptoms， quality of life， and depression severity （all P<0.05）. In addition， the results of chain mediation showed that negative life events had a significant direct effect on depression severity， with an effect size of 0.12 （P<0.001）. Insomnia symptoms and quality of life played a mediating role in the relationship between negative life events and depression severity in patients with adolescent depressive disorders， with indirect effect sizes of 0.062 （95%CI： 0.040-0.087） and 0.091 （95%CI： 0.059-0.123）， respectively. It could also play a chain mediation role， and the effect size was 0.039 （95%CI： 0.024-0.057）. ConclusionNegative life events experienced by patients with adolescent depressive disorder not only directly affect the severity of depressive symptoms， but may also indirectly exacerbate depression through insomnia symptoms and quality of life.

Objective:To construct a Boston matrix-based management model for operational quality of hospital's equipment for diagnosis and treatment,so as to achieve management with comprehensive process for operational quality of them.Methods:Combining evaluation indicators of operational quality of equipment for diagnosis and treatment,the stability and safety were quantified to construct the management model for operational quality of the safety of hospital's equipment for diagnosis and treatment by using the Boston matrix.From January 2023 to January 2024,a total of 300 equipment for diagnosis and treatment in clinical use of JuYe County People's Hospital were enrolled.Using a random number table method,150 equipment adopted conventional management mode,while the other 150 equipment adopted the Boston matrix-based management model for operational quality of hospital's equipment for diagnosis and treatment(Boston matrix management mode)to conduct management.The standardization of test for equipment performance,management quality of operation,and multi-dimensional efficacy scores were compared between the two management modes.A self-designed questionnaire was adopted to investigate satisfactions of engineers,doctors,nurses,and patients for two kinds of management modes,who involved in using equipment.Results:In 150 tests for performance,which adopted Boston matrix-based management mode,the standardization degrees of environmental management,parameter settings,equipment operation and record feedback were respectively 94%,93.33%,92.67%and 92.67%,all of them were significantly higher than those of conventional management mode(x2=12.997,14.361,13.830,12.891,P<0.05).The scores of resource allocation,technical support,information infrastructure,and management performance for equipment were(92.36±3.57),(91.69±4.36),(92.54±3.69)and(93.54±4.36)points in Boston matrix management mode,respectively,and all of them were significantly higher than those in conventional management mode,and the differences were significant(t=18.673,12.439,12.377,12.509,P<0.05).The scores of utilization efficacy,maintenance efficacy,and repair efficacy in using equipment under Boston matrix management mode were all significantly higher than those in conventional management mode,and the differences were significant(t=13.149,12.344,12.864,P<0.05).Satisfaction scores from engineers for equipment,doctors,nurses,and patients for operation of equipment for diagnosis and treatment,which adopted Boston matrix management mode,were all higher than those of adopting conventional management mode,and the differences were significant(t=13.1504,16.064,11.139,13.605,P<0.05).Conclusion:The Boston matrix-based management model for operational quality of hospital's equipment for diagnosis and treatment can be used in the quantitative analysis of safety and stability of equipment,and realize safe management with comprehensive process for equipment,and enhance medical service quality,and improve utilization efficacy of equipment.

Conventional cancer therapies, such as radiotherapy and chemotherapy, often damage normal cells and may induce new tumors. Oncolytic viruses (OVs) selectively target tumor cells while sparing normal cells. Most OVs used in clinical trials have been genetically engineered to enhance their ability to target tumor cells and activate immune responses. To develop a specific OV-based approach for treating cervical cancer, this study constructed an oncolytic adenovirus that delivered a base editor targeting oncogenes to achieve efficient killing of tumor cells through inhibiting tumor growth and directly lysing tumor cells. We utilized the human telomerase reverse transcriptase (TERT) promoter to drive the expression of adenovirus early region 1A (E1A) and successfully constructed the P-hTERT-E1A-GFP vector, which was validated for its activity in cervical cancer cells. Given the critical role of the MYC oncogene in the research of oncology, identifying efficient editing sites for the MYC oncogene is a key step in this study.Three MYC-targeting gRNAs were engineered and co-delivered with ABE8e base editor plasmids into HEK293T cells. Following puromycin selection, Sanger sequencing demonstrated differential editing efficiencies: MYC-1 (43%), MYC-2 (25%), and MYC-3 (35%), identifying MYC-1 as the most efficient editing locus. By constructing the P-ABEs-hTERT-E1A-GFP and P-MYC gRNA-hTERT-E1A-GFP vectors, we successfully packaged the virus and confirmed its specificity and efficacy. The experimental results demonstrate that this novel oncolytic adenovirus effectively inhibits the growth of HeLa cells in vitro, providing new experimental evidence and potential strategies for treating cervical cancer based on the HeLa cell model.
Humans ; Uterine Cervical Neoplasms/pathology* ; Oncolytic Viruses/genetics* ; Female ; HEK293 Cells ; Oncolytic Virotherapy/methods* ; Adenoviridae/genetics* ; Gene Editing/methods* ; Telomerase/genetics* ; Adenovirus E1A Proteins/genetics* ; Genetic Vectors/genetics* ; HeLa Cells

Objective:To summarize the genotype and clinical phenotype characteristics of children with epilepsy associated with the SCN1B gene encoding the sodium channel β1 subunit. Methods:The genotypes and clinical phenotypes of patients with SCN1B variants among suspected genetic epilepsy cases treated at the Children′s Medical Center of Peking University First Hospital between May 2016 and July 2024 were analyzed. These variants were identified using next-generation sequencing and subsequently validated by Sanger sequencing or quantitative polymerase chain reaction methods. Results:A total of 17 patients were analyzed, including 8 males and 9 females. Ten cases of missense variations (including 2 with the same variations), 4 cases of deletion variations, and 1 case each of nonsense variations, splice site variations, and exons 4-5 deletions were identified. Among them, 6 cases had novel SCN1B variations. The variants in 11 cases were inherited from 1 parent. Eleven types of gene variants have not been reported yet. Onset of epilepsy ranged from 3 months to 5 years and 3 months old (median age: 14 months). Types of seizures included generalized tonic-clonic seizures (GTCS) in 14 cases, focal seizures in 9 cases, myoclonic seizures in 3 cases, atypical absence seizures in 2 cases and epilepsy spasms, tonic seizures and atonic seizures in 1 case each. Eleven cases had diverse seizure types. Fourteen cases (14/17) demonstrated fever sensitivity. Electroencephalography revealed focal discharges in 3 cases, coinciding with focal and generalized discharges in 3 additional cases, and multifocal discharges in 6 cases. Seizures were identified in 4 cases: 1 case of myoclonic seizures, 1 case of GTCS, 1 case of atypical absence seizures, and 1 case exhibiting both myoclonic and tonic seizures. Nine cases (9/17) were diagnosed with genetic epilepsy with febrile seizures plus, 1 case diagnosed with myoclonic epilepsy in infancy and 1 diagnosed with infant epileptic spasms syndrome. There were 2 cases of nonspecific developmental epileptic encephalopathy, while the remaining 4 cases could not be diagnosed with a specific epileptic syndrome. Effective antiseizure medications (ASMs) included valproate in 8 cases, levetiracetam in 5 cases, topiramate in 3 cases, clobazam in 2 cases, clonazepam and vigabatrin in 1 case each. Sodium channel blockers exacerbated seizures in 3 cases, specifically oxcarbazepine in 2 cases and lamotrigine in 1 case. At the last follow-up, seizures were controlled for at least 6 months in 14 patients (14/17), while seizures remained uncontrolled in 3 patients despite trialing 2 or more ASMs. Thirteen patients exhibited normal development, while 4 experienced developmental delays. Conclusions:The heterozygous variants in children with SCN1B gene-related epilepsy include missense, deletion, nonsense, splice site variants, and exon deletions. The correlation between different genetic variants and clinical phenotypes remains unclear. These variants are associated with epilepsy onset from infancy to early childhood, presenting with various seizure types, with GTCS being the most common. Phenotypic manifestations can vary significantly in severity, ranging from benign febrile seizures or febrile seizures plus to developmental epileptic encephalopathy. Valproic acid demonstrates the highest effectiveness rate, while the use of sodium channel blockers may worsen seizures in certain patients, necessitating cautious administration.

Objective To compare the efficacy,economic burden,psychological impact,and quality of life between surgical and medical castration following radical prostatectomy(RP)in patients with very high-risk prostate cancer(VHR PCa).Methods Clinical data of 167 patients with VHR PCa who underwent RP in the Department of Urology,the First Affiliated Hospital of Anhui Medical University during Jul.2019 and Mar.2024 were retrospectively collected.Patients were divided into two groups:the surgical castration group(n=44)and medical castration group(n=123).The effects of different castration methods on the biochemical recurrence(BCR)were analyzed with Cox proportional hazards models.The survival curves of BCR-free and progress to castration-resistant prostate cancer(CRPC)were plotted with the Kaplan-Meier method.The differences in functional assessment of cancer therapy-prostate(FACT-P)and hospital anxiety and depression scale(HADS)between the two groups were evaluated with linear regression model.Results The total costs were significantly lower in the surgical castration group than in the medical castration group[(47 422.0±3 998.3)yuan vs.(59 017.2±8 014.1)yuan,P＜0.001].One month postoperatively,the surgical castration group had significantly lower prostate-specific antigen(PSA)level[0.028(0.010,0.159)ng/mL vs.0.100(0.029,0.895)ng/mL,P=0.002].However,no significant differences were observed in the PSA level between the two groups at 3,6,and 12 months postoperatively,or in PSA nadir and time to nadir(P＞0.05).Cox regression analysis suggested a potentially higher risk of BCR in the medical castration group(HR=2.23),but the difference was not statistically significant(P=0.112).The 1-and 3-year BCR-free survival rates were higher in the surgical castration group(90.9％vs.85.4％;86.4％vs.70.7％,respectively),whereas 1-and 3-year progression-free survival rates were comparable between the two groups(97.7％vs.97.6％;95.5％vs.91.9％),with no significant differences(P＞0.05).No significant differences were found in FACT-P[(57.3±10.2)vs.(57.3±7.6)]or HADS[(12.6±5.1)vs.(11.3±4.8)]scores between the two groups(P＞0.05).Conclusion In VHR PCa patients,surgical castration performed following RP is not inferior to drug castration in terms of PSA control,and potential delay of BCR.It had a lower cost and does not significantly increase the psychological burden.As an underutilized strategy,surgical castration can become an optional option for individualized treatment.

Objective To compare the efficacy,economic burden,psychological impact,and quality of life between surgical and medical castration following radical prostatectomy(RP)in patients with very high-risk prostate cancer(VHR PCa).Methods Clinical data of 167 patients with VHR PCa who underwent RP in the Department of Urology,the First Affiliated Hospital of Anhui Medical University during Jul.2019 and Mar.2024 were retrospectively collected.Patients were divided into two groups:the surgical castration group(n=44)and medical castration group(n=123).The effects of different castration methods on the biochemical recurrence(BCR)were analyzed with Cox proportional hazards models.The survival curves of BCR-free and progress to castration-resistant prostate cancer(CRPC)were plotted with the Kaplan-Meier method.The differences in functional assessment of cancer therapy-prostate(FACT-P)and hospital anxiety and depression scale(HADS)between the two groups were evaluated with linear regression model.Results The total costs were significantly lower in the surgical castration group than in the medical castration group[(47 422.0±3 998.3)yuan vs.(59 017.2±8 014.1)yuan,P＜0.001].One month postoperatively,the surgical castration group had significantly lower prostate-specific antigen(PSA)level[0.028(0.010,0.159)ng/mL vs.0.100(0.029,0.895)ng/mL,P=0.002].However,no significant differences were observed in the PSA level between the two groups at 3,6,and 12 months postoperatively,or in PSA nadir and time to nadir(P＞0.05).Cox regression analysis suggested a potentially higher risk of BCR in the medical castration group(HR=2.23),but the difference was not statistically significant(P=0.112).The 1-and 3-year BCR-free survival rates were higher in the surgical castration group(90.9％vs.85.4％;86.4％vs.70.7％,respectively),whereas 1-and 3-year progression-free survival rates were comparable between the two groups(97.7％vs.97.6％;95.5％vs.91.9％),with no significant differences(P＞0.05).No significant differences were found in FACT-P[(57.3±10.2)vs.(57.3±7.6)]or HADS[(12.6±5.1)vs.(11.3±4.8)]scores between the two groups(P＞0.05).Conclusion In VHR PCa patients,surgical castration performed following RP is not inferior to drug castration in terms of PSA control,and potential delay of BCR.It had a lower cost and does not significantly increase the psychological burden.As an underutilized strategy,surgical castration can become an optional option for individualized treatment.

Objective:To construct a Boston matrix-based management model for operational quality of hospital's equipment for diagnosis and treatment,so as to achieve management with comprehensive process for operational quality of them.Methods:Combining evaluation indicators of operational quality of equipment for diagnosis and treatment,the stability and safety were quantified to construct the management model for operational quality of the safety of hospital's equipment for diagnosis and treatment by using the Boston matrix.From January 2023 to January 2024,a total of 300 equipment for diagnosis and treatment in clinical use of JuYe County People's Hospital were enrolled.Using a random number table method,150 equipment adopted conventional management mode,while the other 150 equipment adopted the Boston matrix-based management model for operational quality of hospital's equipment for diagnosis and treatment(Boston matrix management mode)to conduct management.The standardization of test for equipment performance,management quality of operation,and multi-dimensional efficacy scores were compared between the two management modes.A self-designed questionnaire was adopted to investigate satisfactions of engineers,doctors,nurses,and patients for two kinds of management modes,who involved in using equipment.Results:In 150 tests for performance,which adopted Boston matrix-based management mode,the standardization degrees of environmental management,parameter settings,equipment operation and record feedback were respectively 94%,93.33%,92.67%and 92.67%,all of them were significantly higher than those of conventional management mode(x2=12.997,14.361,13.830,12.891,P<0.05).The scores of resource allocation,technical support,information infrastructure,and management performance for equipment were(92.36±3.57),(91.69±4.36),(92.54±3.69)and(93.54±4.36)points in Boston matrix management mode,respectively,and all of them were significantly higher than those in conventional management mode,and the differences were significant(t=18.673,12.439,12.377,12.509,P<0.05).The scores of utilization efficacy,maintenance efficacy,and repair efficacy in using equipment under Boston matrix management mode were all significantly higher than those in conventional management mode,and the differences were significant(t=13.149,12.344,12.864,P<0.05).Satisfaction scores from engineers for equipment,doctors,nurses,and patients for operation of equipment for diagnosis and treatment,which adopted Boston matrix management mode,were all higher than those of adopting conventional management mode,and the differences were significant(t=13.1504,16.064,11.139,13.605,P<0.05).Conclusion:The Boston matrix-based management model for operational quality of hospital's equipment for diagnosis and treatment can be used in the quantitative analysis of safety and stability of equipment,and realize safe management with comprehensive process for equipment,and enhance medical service quality,and improve utilization efficacy of equipment.

Objective:To summarize the genotype and clinical phenotype characteristics of children with epilepsy associated with the SCN1B gene encoding the sodium channel β1 subunit. Methods:The genotypes and clinical phenotypes of patients with SCN1B variants among suspected genetic epilepsy cases treated at the Children′s Medical Center of Peking University First Hospital between May 2016 and July 2024 were analyzed. These variants were identified using next-generation sequencing and subsequently validated by Sanger sequencing or quantitative polymerase chain reaction methods. Results:A total of 17 patients were analyzed, including 8 males and 9 females. Ten cases of missense variations (including 2 with the same variations), 4 cases of deletion variations, and 1 case each of nonsense variations, splice site variations, and exons 4-5 deletions were identified. Among them, 6 cases had novel SCN1B variations. The variants in 11 cases were inherited from 1 parent. Eleven types of gene variants have not been reported yet. Onset of epilepsy ranged from 3 months to 5 years and 3 months old (median age: 14 months). Types of seizures included generalized tonic-clonic seizures (GTCS) in 14 cases, focal seizures in 9 cases, myoclonic seizures in 3 cases, atypical absence seizures in 2 cases and epilepsy spasms, tonic seizures and atonic seizures in 1 case each. Eleven cases had diverse seizure types. Fourteen cases (14/17) demonstrated fever sensitivity. Electroencephalography revealed focal discharges in 3 cases, coinciding with focal and generalized discharges in 3 additional cases, and multifocal discharges in 6 cases. Seizures were identified in 4 cases: 1 case of myoclonic seizures, 1 case of GTCS, 1 case of atypical absence seizures, and 1 case exhibiting both myoclonic and tonic seizures. Nine cases (9/17) were diagnosed with genetic epilepsy with febrile seizures plus, 1 case diagnosed with myoclonic epilepsy in infancy and 1 diagnosed with infant epileptic spasms syndrome. There were 2 cases of nonspecific developmental epileptic encephalopathy, while the remaining 4 cases could not be diagnosed with a specific epileptic syndrome. Effective antiseizure medications (ASMs) included valproate in 8 cases, levetiracetam in 5 cases, topiramate in 3 cases, clobazam in 2 cases, clonazepam and vigabatrin in 1 case each. Sodium channel blockers exacerbated seizures in 3 cases, specifically oxcarbazepine in 2 cases and lamotrigine in 1 case. At the last follow-up, seizures were controlled for at least 6 months in 14 patients (14/17), while seizures remained uncontrolled in 3 patients despite trialing 2 or more ASMs. Thirteen patients exhibited normal development, while 4 experienced developmental delays. Conclusions:The heterozygous variants in children with SCN1B gene-related epilepsy include missense, deletion, nonsense, splice site variants, and exon deletions. The correlation between different genetic variants and clinical phenotypes remains unclear. These variants are associated with epilepsy onset from infancy to early childhood, presenting with various seizure types, with GTCS being the most common. Phenotypic manifestations can vary significantly in severity, ranging from benign febrile seizures or febrile seizures plus to developmental epileptic encephalopathy. Valproic acid demonstrates the highest effectiveness rate, while the use of sodium channel blockers may worsen seizures in certain patients, necessitating cautious administration.

ObjectiveTo observe the effect of twelve-week aerobic exercise on inhibitory control abilities and the change of brain activation in overweight children. MethodsFrom October to December, 2021, 20 overweight children from a primary school in Changping District were selected for a twelve-week aerobic exercise intervention. Their inhibitory control abilities were measured by Flanker task before and after intervention, while their brain activation levels during the task were detected by functional near infrared spectroscopy (fNIRS). ResultsThe interactions between task type and time of accuracy and reaction time in inconsistent tasks Flanker task were significant (F > 9.277, P < 0.05), with higher accuracy and lower reaction time of after intervention (P < 0.05). After intervention, ch1, ch2, ch3, ch6, and ch8 channels were activated by inconsistent tasks (P < 0.05). ConclusionA twelve-week aerobic exercise intervention could improve the inhibitory control ability, and increase the prefrontal cortex activation during inconsistent tasks in overweight children.

Maintaining normal physical activity level is one of the goals of asthma treatment in children with asthma.In order to better understand the relationship between asthma and exercise, it is necessary to summarize the related studies on exercise in children with asthma.This paper overviews the related researches on the benefits of exercise to patients with asthma, the current situation of exercise in children with asthma, exercise-induced bronchoconstriction, and the formulation of exercise prescription in children with asthma, so that clinicians can have a deeper understanding of exercise-related content in children with asthma, in order to better guide children with asthma in exercise.