Objective To determine the role of SCN1A gene variation in the development of familial febrile seizures (FS).Methods Clinical data were collected from 8 familial FS pedigrees, and peripheral venous blood samples were collected from the probands and other available family members. All 26 coding exons and exon-intron boundaries at least 50 bases of the human SCN1A gene were amplifled by polymerase chain reaction, the products were subsequently sequenced. To novo variation, other family members were screened for the corresponding exons. Two hundred age-matched healthy children were served as normal controls. ResultsA total of 33 variations in the SCN1A gene were identifled in these families. Of these variations, one was a missense mutation; the remaining 32 variations were previously submitted as single nucleotide polymorphisms (SNPs). A c.2650G>A heterozygous missense mutation in exon 15 of the SCN1A gene found in the proband of family 4 was inherited from his father who had seizures with fever in early childhood. The c.2650G>A mutation was absent in the 400 alleles of normal controls. To the best of our knowledge, the SCN1A c.2650G>A mutation has neither been reported in the NCBI SNP database nor in the literature to date. The c.2650G>A mutation changes a glycine at amino acid 884 in the SCN1A protein to a serine (p.Gly884Ser). Protein sequence analysis showed that the p.Gly884Ser is located at a highly conserved region between the 4th and 5th transmembrane segment of the homologous domain Ⅱ of voltage-gated sodium channel 1 subunit (DIIS4-S5). ConclusionsThe pathogenesis of familial febrile seizures was related to the SCN1A variation, the mutation outside the region of the voltage sensor (S4) and ion channel pore (S5-S6) of the voltage gated sodium channelα-subunit may be an important factor to cause mild phenotype epilepsy syndrome.

Objective To probe the mechanism of Warlker-256 cell apoptosis resulted from permanent and strong magnetic field. Method The amplification, rearrangement, deletion, transcription and expression of P53 were detected in 320 rats treated by magnetic field and 80 controls, using Dot Blot of DNA and RNA, Southern and Northern blot, and immunohistochemical technologies. Results P53 is wild type in Warlker-256 cells, no amplification, rearrangement and deletion were found in either magnetic treated group or control group. The transcription and expression of P53 is significantly enhanced in the treated group versus the control(P

OBJECTIVE: To study the mechanism and clinical significance of specific immunotherapy (SIT) on the expression changes of GM-CSF and IL-5 in the tissue samples of recurrent nasal polyps. METHOD: Perennial allergic rhinitis patients with recurrent nasal polyps were randomly divided into 2 groups. The experimental group of 19 patients was treated by SIT and standardized treatment (glucocorticoid nasal spray) , and the control group of 17 patients was only treated by standardized treatment (glucocorticoid nasal spray). We measured the expression levels of GM-CSF and IL-5 in the tissue samples of the nasal polyps by ELISA, and compared the results obtained before treatment with expression levels detected at 6 months and 1 year after the treatment. RESULT: The expression of GM-CSF and IL-5 in the recurrent nasal polyps reduced significantly (P < 0.05) in both groups after 6 months and 1 year post-treatment compared with pre-treatment, and the expression of GM-CSF and IL-5 in the experimental group was much lower than that of the control group. CONCLUSION SIT decreases the expression of GM-CSF and IL-5 and reduces the inflammatory reaction in the tissue samples of recurrent nasal polyps.
Enzyme-Linked Immunosorbent Assay ; Granulocyte-Macrophage Colony-Stimulating Factor ; metabolism ; Humans ; Immunotherapy ; Inflammation ; drug therapy ; Interleukin-5 ; metabolism ; Nasal Mucosa ; pathology ; Nasal Polyps ; drug therapy ; metabolism ; Rhinitis, Allergic, Perennial ; drug therapy ; metabolism

Objective To build the linear models for exploring relations between behavior data and functional magnetic resonance image(fMRI) signals of brain during cognitive task and to validate whether it is reasonable.Methods The linear models of behavior data and fMRI signals were built,and the functional regions of brain were detected by tests of corresponding parameters.Experimental data of Stroop tasks were used to study the effects of the models by comparing with the results of SPM.Results The results of Stroop data showed that dorsal lateral prefrontal cortex(Brodmann 9/46),and superior frontal median cortex(Brodmann 8/9) were associated with response time of Stroop tasks,and accorded with SPM results and other reports.Conclusion The models can quantitatively analyze the relations of response time and fMRI signals,providing a new way to explore functional images of cognition.

A GC-LSTM model is proposed based on the characteristics of global optimization of genetic algorithm.The model automatically and iteratively searches the optimal hyper-parameter configuration of the C-LSTM model through the genetic algorithm of a specific genetic strategy,and it is configured using the genetic iteration results and validated on the MIT-BIH arrhythmia database according to the classification criteria of the Association for the Advancement of Medical Instrumentation.The testing shows that the classification accuracy,sensitivity,accuracy and F1 value of GC-LSTM model are 99.37%,95.62%,95.17%and 95.39%,respectively,higher than those of the manually established model,and it is also advantageous over the existing mainstream methods.Experimental results demonstrate that the proposed method can achieve better classification performance while avoiding a large number of experimental parameters.

Objective To investigate the protective effects of HTD4010 against lipopolysaccharide(LPS)-induced septic cardiomyopathy(SCM)in mice and explore the mechanisms mediating its effect.Methods Forty-five male ICR mice were randomized equally into control group,LPS(10 mg/kg)group,and LPS+HTD4010 group(in which 2.5 mg/kg HTD4010 was injected subcutaneously at 1 h and 6 h after LPS injection).Cardiac function of the mice was evaluated by ultrasound,and pathological changes in the myocardial tissues were observed with HE staining.The levels of IL-6 and TNF-α in serum and myocardial tissues were detected using ELISA,and apoptosis of the cardiomyocytes was detected with TUNEL staining.The expression levels of the key proteins associated with apoptosis,autophagy and the AMPK/mTOR pathway in the myocardial tissues were detected using Western blotting.The ultrastructural changes of cardiac myocardial mitochondria was observed with transmission electron microscopy.Results LPS exposure caused severe myocardial damage in mice,characterized by myocardial fiber rupture,structural disorder,inflammatory cell infiltration,and mitochondrial damage.The LPS-treated mice exhibited significantly decreased cardiac LVEF and FS values,elevated IL-6 and TNF-αlevels in serum and myocardial tissue,and an increased myocardial cell apoptosis rate with enhanced expressions of Bax,p-62 and p-mTOR and lowered expressions of Bcl-2,LC3 Ⅱ/I,Beclin-1 and p-AMPK(P<0.05 or 0.01).Treatment of the septic mice with HTD4010 significantly alleviated myocardial damage,increased LVEF and FS values,reduced IL-6 and TNF-α levels in serum and myocardial tissue,decreased cardiomyocyte apoptosis,lowered myocardial expressions of Bax,p-62 and p-mTOR,and increased Bcl-2,LC3 Ⅱ/I,Beclin-1 and p-AMPK expressions(P<0.05 or 0.01).Conclusion HTD4010 can attenuate myocardial injury in SCM mice possibly by promoting autophagy via modulating the AMPK/mTOR signaling pathway.

Objective:This study is to understand the hot spots and trends in the recruitment of clinical trial subjects in China over the past 20 years, explore the existing problems and countermeasures, and provide scientific ideas for domestic clinical trial institutions to effectively solve the problem of subject recruitment.Methods:Bibliometric analysis was used to study the relevant literature from three major domestic databases from 2001 to 2021, analyzing key indicators such as annual publication volume, journal distribution, institutional distribution, regional distribution, and high-frequency keyword co-occurrence.Results:A total of 162 articles were selected. The results showed that the overall publication volume in this field showed an upward trend, and the research institutions were diversified, with a concentration of medical and pharmaceutical institutions and universities. The current research hotspots in this field focused on quality and efficiency improvement of subject recruitment, with themes of subject protection, ethical review, regulation development, standardized management, etc.Conclusions:The research in this field has made significant progress, but the overall research level is still relatively weak. Therefore, it is suggested that the country should play a role in macro-regulation, on the one hand, starting with top-level design, promoting the construction of a standardized management system for subject recruitment, continuously strengthening subject protection, and enhancing the effectiveness of scientific recruitment. On the other hand, releasing the potential of grassroots institutions and giving full play to the volume advantage by promoting the sinking of advantageous resources. Meanwhile, great importance should be attached to the development of Phase I clinical trials, giving full play to the strong internal energy of traditional medicine and promoting the development of Chinese traditional medicine. These multi-measures should provide a theoretical basis for exploring the transformation of ′clinical research hospitals′, and promote the high-quality development of new drug research and development in China.

Objective To investigate the protective effects of HTD4010 against lipopolysaccharide(LPS)-induced septic cardiomyopathy(SCM)in mice and explore the mechanisms mediating its effect.Methods Forty-five male ICR mice were randomized equally into control group,LPS(10 mg/kg)group,and LPS+HTD4010 group(in which 2.5 mg/kg HTD4010 was injected subcutaneously at 1 h and 6 h after LPS injection).Cardiac function of the mice was evaluated by ultrasound,and pathological changes in the myocardial tissues were observed with HE staining.The levels of IL-6 and TNF-α in serum and myocardial tissues were detected using ELISA,and apoptosis of the cardiomyocytes was detected with TUNEL staining.The expression levels of the key proteins associated with apoptosis,autophagy and the AMPK/mTOR pathway in the myocardial tissues were detected using Western blotting.The ultrastructural changes of cardiac myocardial mitochondria was observed with transmission electron microscopy.Results LPS exposure caused severe myocardial damage in mice,characterized by myocardial fiber rupture,structural disorder,inflammatory cell infiltration,and mitochondrial damage.The LPS-treated mice exhibited significantly decreased cardiac LVEF and FS values,elevated IL-6 and TNF-αlevels in serum and myocardial tissue,and an increased myocardial cell apoptosis rate with enhanced expressions of Bax,p-62 and p-mTOR and lowered expressions of Bcl-2,LC3 Ⅱ/I,Beclin-1 and p-AMPK(P<0.05 or 0.01).Treatment of the septic mice with HTD4010 significantly alleviated myocardial damage,increased LVEF and FS values,reduced IL-6 and TNF-α levels in serum and myocardial tissue,decreased cardiomyocyte apoptosis,lowered myocardial expressions of Bax,p-62 and p-mTOR,and increased Bcl-2,LC3 Ⅱ/I,Beclin-1 and p-AMPK expressions(P<0.05 or 0.01).Conclusion HTD4010 can attenuate myocardial injury in SCM mice possibly by promoting autophagy via modulating the AMPK/mTOR signaling pathway.

ObjectiveTo understand the current situation and influencing factors of health service demands of new residents in Shanghai. MethodsFrom July to August 2020， a questionnaire survey was conducted in 1 358 new residents from 36 survey points in 7 districts of the city. The questionnaire included the basic medical insurance coverage in the inflow area， the current situation of medical demand and related influencing factors， and the demands for other health services. Results47.1%（562/1 194）of new residents did not choose to seek timely medical treatment when they were not feeling well. The main reason was that the working hours occupied the medical treatment time. Logistic regression analysis showed that the main factors affecting the medical needs in new residents were the average daily working hours， living area and type of residence， health status， physical examination and physical exercise， and the type of basic medical insurance. The demands of new residents for "health consultation of common diseases and frequently occurring diseases"， "health behavior intervention （such as smoking cessation and alcohol restriction）"， "medical guidance and publicity"， "accidental injury prevention （traffic， work， falling， etc.）" and "maintenance of legitimate rights and interests of health" were 57.1%（682/1 194）、41.3%（493/1 194）、34.9%（417/1 194）、32.2%（385/1 194） and 31.9%（381/1 194）， respectively. ConclusionNew residents demands for medical services cannot be met. We should actively improve the working and living conditions of new residents， improve the construction of new residents' health service system， and improve the utilization level of health services.

OBJECTIVE To establish an analytical method based on ultra-performance liquid chromatography-quadrupole-time- of-flight mass spectrometry （UPLC-Q-TOF/MS） combined with UNIFI platform for rapid identification of the chemical constituents in Abrus cantoniensis Hance. METHODS The chromatographic separation was performed on ACQUITY PRM HSS T3 FIT column for gradient elution with the mobile phase consisted of 0.1% formic acid aqueous solution-acetonitrile. The flow rate was 0.3 mL/min， and injection volume was 2 μL. Electrospray ionization was used to collect the mass spectrometry data of the chemical constituents of A. cantoniensis Hance with full information tandem mass spectrometry technology in positive and negative ion modes. The chemical constituent database of A. cantoniensis Hance was established. Targeted and non-targeted analyses were conducted based on UNIFI platform， and chemical constituents were further identified in combination with accurate molecular mass， secondary fragment ion information and equivalence with reference substances and literature data， etc. RESULTS Totally 46 compounds of A. cantoniensis Hance were successfully identified， including 19 flavonoids， 8 triterpenoids， 3 alkaloids， 5 organic acids and 11 other components. Among them， 11 compounds were firstly found in A. cantoniensis Hance， and 9 compounds were confirmed by reference substance. CONCLUSIONS The analytical method based on UPLC-Q-TOF/MS combined with UNIFI platform can quickly identify the chemical constituents of A. cantoniensis Hance. Flavonoids and triterpenes are the main components in A. cantoniensis Hance.