Objective To investigate the effect of vecuronium bromide on the malignant biological behavior of gastric cancer cells and its molecular mechanism.Methods Gastric cancer cells HGC-27 were divided into control group,experimental-L,-M,-H groups,si-NC group,si-FGD5-AS1 group,pcDNA-FGD5-AS1 group,pcDNA group,experimental-H+pcDNA group,experimental-H+pcDNA-FGD5-AS1 group.The control group was cultured conventionally;experimental-L,-M,-H groups were treated with 5,10 and 20μmol·mL-1 vecuronium bromide,respectively;si-FGD5-AS1 group and the si-NC group were transfected with lncRNA FGD5-AS1 interference expression vector and negative control plasmid,respectively;pcDNA-FGD5-AS1 group and pcDNA group were transfected with lncRNA FGD5-AS1 overexpression vector and negative control plasmid,respectively;lncRNA FGD5-AS1 overexpression vector and negative control plasmid were transfected into HGC-27 cells in the experimental-H+pcDNA-FGD5-AS1 group and experimental-H+pcDNA group,and then treated with 20 μmuol·mL-1 vecuronium bromide.Methyl thiazolyl tetrazolium(MTT),flow cytometry and real-time fluorescent quantitative polymerase chain reaction(RT-qPCR)were applied to dectect cell viability,apoptosis and lncRNA FGD5-AS1 expression.Results The cell activity of control group,experimental-L,-M,-H groups,si-NC group,si-FGD5-AS1 group,pcDNA group,PCDNA-FGD5-AS1 group,experimental-H+pcDNA group and experimental-H+PCDNA-FGD5-AS1 group were 1.31±0.07,0.58±0.03,1.31±0.06,0.51±0.03,1.29±0.08,1.68±0.15,0.59±0.03 and 1.16±0.06;the apoptosis rates were(6.49±0.44)％,(23.52±0.98)％,(6.42±0.44)％,(26.75±0.97)％,(6.72±0.38)％,(2.56±0.19)％,(23.56±1.04)％and(11.65±0.47)％;the expression levels of lncRNA FGD5-AS1 were 1.00±0.05,0.37±0.02,0.99±0.05,0.21±0.02,1.00±0.03,2.98±0.12,0.38±0.02 and 0.87±0.05,respectively.The above indexes were compared with the control group and experimental-H group,those in the si-FGD5-AS1 group were compared with the si-NC group,those in the pcDNA-FGD5-AS1 group were compared with the pcDNA group,and those in the experimental-H+pcDNA-FGD5-AS1 group were compared with the experimental-H+pcDNA group,the differences were statistically significant(all P＜0.05).Conclusion Vecuronium bromide may inhibit the proliferation of HGC-27 cells and promote cell apoptosis by down-regulating lncRNA FGD5-AS1.

Objective To investigate the distribution of traditional Chinese medicine(TCM)syndromes and related risk factors in children with mycoplasma pneumoniae pneumonia(MPP).Methods The clinical data of 420 children with MPP admitted to the First Affiliated Hospital of Guangzhou University of Chinese Medicine were collected.The clinical data included gender,age,history of respiratory tract diseases,TCM syndromes,MPP classification,cough duration,fever duration,fever peak value,laboratory indicators of C-reactive protein(CRP),procalcitonin(PCT)and lactate dehydrogenase(LDH),and the complication of infection.SPSS 26.0 software was used for data statistics,and then the distribution of TCM syndromes in children with MPP and its correlation with various clinical data,as well as the related risk factors of MPP with different classification and various TCM syndromes were explored.Results(1)Among the 420 children with MPP,there were 283 cases(67.4％)of mild MPP,76 cases(18.1％)of refractory MPP,and 61 cases(14.5％)of severe MPP.For the distribution of TCM syndromes,there were 152 cases(36.2％)of wind-heat obstructing the lung syndrome,141 cases(33.6％)of phlegm-heat obstructing the lung syndrome,77 cases(18.3％)of damp-heat obstructing the lung syndrome,25 cases(6.0％)of toxin-heat obstructing the lung syndrome,16 cases(3.8％)of lung-spleen qi deficiency syndrome,and 9 cases(2.1％)of yin deficiency and lung heat syndrome.For the classification of infection,there were 295 cases(70.2％)of simple mycoplasma pneumoniae(MP)infection and 125 cases(29.8％)of mixed infection.(2)There were statistically significant differences in age stratification and visit season among MPP children with different TCM syndromes(P＜0.01),while no significant differences were shown in the gender,history of respiratory tract diseases,and the complication of infection(P＞0.05).(3)There were statistically significant differences in the visit season,history of respiratory tract diseases,and the complication of infection among the children with various MPP types(P＜0.05),while no significant differences were shown in the gender and age stratification(P＞0.05).(4)There were statistically significant differences in laboratory indicators of CRP and PCT and in the symptoms of cough duration,fever duration and fever peak among MPP children with different TCM syndromes(P＜0.05 or P＜0.01).(5)Significant differences were presented in laboratory indicators of PCT and LDH and in the symptoms of cough duration,fever duration and fever peak value among the children with different MPP types(P＜0.05 or P＜0.01).(6)Multivariate logistic regression analysis showed that CRP level ≥10.5 mg/L and wind-heat obstructing the lung syndrome were the independent risk factors for mild MPP(P＜0.05 or P＜0.01);fever duration≥7 days,cough duration ≥ 12 days and phlegm-heat obstructing the lung syndrome were the independent risk factors for refractory MPP(P＜0.05 or P＜0.01);cough duration ≥ 12 days,mixed infection and toxin-heat obstructing the lung syndrome were the independent risk factors for severe MPP(P＜0.01).Conclusion The results indicated that the classification MPP in children is predominated by mild MPP,and their TCM syndrome types is predominated by wind-heat obstructing the lung syndrome.The proportions of refractory MPP and damp-heat obstructing the lung syndrome increase significantly in autumn,which may be related to the characteristics of regional environment and circuit qi.The increase of CRP level and fever peak may be related to phlegm-heat obstructing the lung syndrome and toxin-heat obstructing the lung syndrome.In clinic,attention should be paid to the early use of heat-clearing and phlegm-resolving drugs or heat-clearing and toxin-removing drugs;children with the history of respiratory tract diseases and mixed infections are more likely to develop into severe MPP,and the physicians should be alert clinically.Wind-heat obstructing the lung syndrome,phlegm-heat obstructing the lung syndrome and toxin-heat obstructing the lung syndrome are the independent risk factor separately for mild MPP,refractory MPP and severe MPP,which requires timely intervention to prevent mild MPP from developing into refractory MPP or severe MPP in clinic.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Interleukin-1 receptor associated kinase 4 (IRAK-4), acting as a serine threonine kinase, is considered as a key signal node for the transduction of IL-1R family and TLRs signal pathway. Studies have found that IRAK-4 has a hand in many signal pathways, involving the inflammatory response of human joints, intestines, liver and nervous system, as well as other autoimmune diseases. It is also one of the causes of drug resistance of some cancer cells. Therefore, IRAK-4 tends to be an effective therapeutic target for inflammatory diseases and cancer. The prospects for the development of drugs in this pathway is to develop novel IRAK-4 small molecule inhibitors and investigate their safety and effectiveness, enrich the clinical treatment of inflammatory and cancer diseases finally. This paper classified and summarized the latest research progress on small molecule inhibitors of IRAK-4 signaling pathway according to structures of the compounds, in order to provide assistances and references for the research and development of related drugs.

The stomatognathic system is an organic combination of bone, dentition, joints, masticatory muscles and innervation nerves. It is an organ system for the human body to perform mastication, speech, swallowing and other important functions. Due to the complex anatomical structure of stomatognathic system and ethical limitations, it is difficult to directly measure the movement and force by using the biomechanical experimental methods. Multi-body system dynamics is an important tool to study the kinetics and force of a multi-body system, which consists of several objects with relative motion. We can use the method of multi-body system dynamics simulation in engineering to study the movement, soft tissue deformation and force transfer of this complex stomatognathic system. This paper briefly introduces the history and application methods of multi-body system dynamics and the commonly used modeling methods. The application and research progress of multi-body system dynamics modeling methods in the field of stomatology was emphatically summarized, development prospects of current research and difficulties were put forward.

About 8 dental schools were founded by Chinese dentists during modern times (1909-1949) in China. Only one still worked after the founding of the People's Republic of China, which was one of the three dental schools founded by dentist Situ Bo. There were no systematic researches on Situ Bo's participation in dentistry education. This paper analyzes the founder's experience in dentistry and in the two schools he founded at the beginning, focusing on the background and process of the schools' construction, management, teaching, teachers and students training, etc. The results show that the establishment of the first two dental schools have laid important foundation for the establishment and development of Shanghai Dental College by the reserve of trained professional teachers and accumulated valuable experience in running schools. The systematic review of this history will help us better understand the establishment and development of Shanghai Dental College and the efforts in dentistry education made by dentists growed up in modern China, as well as the early development process of stomatology.

METTL3 and METTL14 are two components that form the core heterodimer of the main RNA m6A methyltransferase complex (MTC) that installs m6A. Surprisingly, depletion of METTL3 or METTL14 displayed distinct effects on stemness maintenance of mouse embryonic stem cell (mESC). While comparable global hypo-methylation in RNA m6A was observed in Mettl3 or Mettl14 knockout mESCs, respectively. Mettl14 knockout led to a globally decreased nascent RNA synthesis, whereas Mettl3 depletion resulted in transcription upregulation, suggesting that METTL14 might possess an m6A-independent role in gene regulation. We found that METTL14 colocalizes with the repressive H3K27me3 modification. Mechanistically, METTL14, but not METTL3, binds H3K27me3 and recruits KDM6B to induce H3K27me3 demethylation independent of METTL3. Depletion of METTL14 thus led to a global increase in H3K27me3 level along with a global gene suppression. The effects of METTL14 on regulation of H3K27me3 is essential for the transition from self-renewal to differentiation of mESCs. This work reveals a regulatory mechanism on heterochromatin by METTL14 in a manner distinct from METTL3 and independently of m6A, and critically impacts transcriptional regulation, stemness maintenance, and differentiation of mESCs.
Animals ; Mice ; Methylation ; Chromatin ; Histones/metabolism* ; RNA, Messenger/genetics* ; Methyltransferases/metabolism* ; RNA/metabolism*

Aim To investigate the inhibition effect of 2-dodecyl-6-methoxycyclohexa-2, 5-diene-l, 4-dione ( DMDD) on renal tubular epithelial cell HK-2 endo¬plasmic reticulum stress and inflammatory responses induced by high glucose. Methods HK-2 cells were cultured in vitro and divided into normal group, high glucose group, endoplasmic reticulum stress inhibitor 4-PBA group (5 mmoL • L ) , DMDD high, medium and low dose groups (8,4,2 μmol • L

OBJECTIVES: To investigate the reliability and accuracy of deep learning technology in automatic sex estimation using the 3D reconstructed images of the computed tomography (CT) from the Chinese Han population. METHODS: The pelvic CT images of 700 individuals (350 males and 350 females) of the Chinese Han population aged 20 to 85 years were collected and reconstructed into 3D virtual skeletal models. The feature region images of the medial aspect of the ischiopubic ramus (MIPR) were intercepted. The Inception v4 was adopted as the image recognition model, and two methods of initial learning and transfer learning were used for training. Eighty percent of the individuals' images were randomly selected as the training and validation dataset, and the remaining were used as the test dataset. The left and right sides of the MIPR images were trained separately and combinedly. Subsequently, the models' performance was evaluated by overall accuracy, female accuracy, male accuracy, etc. RESULTS: When both sides of the MIPR images were trained separately with initial learning, the overall accuracy of the right model was 95.7%, the female accuracy and male accuracy were both 95.7%; the overall accuracy of the left model was 92.1%, the female accuracy was 88.6% and the male accuracy was 95.7%. When the left and right MIPR images were combined to train with initial learning, the overall accuracy of the model was 94.6%, the female accuracy was 92.1% and the male accuracy was 97.1%. When the left and right MIPR images were combined to train with transfer learning, the model achieved an overall accuracy of 95.7%, and the female and male accuracies were both 95.7%. CONCLUSIONS The use of deep learning model of Inception v4 and transfer learning algorithm to construct a sex estimation model for pelvic MIPR images of Chinese Han population has high accuracy and well generalizability in human remains, which can effectively estimate the sex in adults.
Adult ; Female ; Humans ; Male ; Deep Learning ; Imaging, Three-Dimensional ; Pelvis ; Reproducibility of Results ; Tomography, X-Ray Computed ; Young Adult ; Middle Aged ; Aged ; Aged, 80 and over

Morphine is a frequently used analgesic that activates the mu-opioid receptor(MOR),which has prominent side effects of tolerance.Although the inefficiency of morphine in inducing the endocytosis of MOR underlies the development of morphine tolerance,currently,there is no effective therapy to treat morphine tolerance.In the current study,we aimed to develop a monoclonal antibody(mAb)precisely targeting MOR and to determine its therapeutic efficacy on morphine tolerance and the underlying molecular mechanisms.We successfully prepared a mAb targeting MOR,named 3A5C7,by hybridoma technique using a strategy of deoxyribonucleic acid immunization combined with cell immunization,and identified it as an immunoglobulin G mAb with high specificity and affinity for MOR and binding ability to antigens with spatial conformation.Treatment of two cell lines,HEK293T and SH-SY5Y,with 3A5C7 enhanced morphine-induced MOR endocytosis via a G protein-coupled receptor kinase 2(GRK2)/β-arrestin2-dependent mechanism,as demonstrated by immunofluorescence staining,flow cytometry,Western blotting,coimmunoprecipitation,and small interfering ribonucleic acid(siRNA)-based knock-down.This mAb also allowed MOR recycling from cytoplasm to plasma membrane and attenuated morphine-induced phosphorylation of MOR.We established an in vitro morphine tolerance model using differentiated SH-SY5Y cells induced by retinoic acid.Western blot,enzyme-linked immunosorbent assays,and siRNA-based knockdown revealed that 3A5C7 mAb diminished hyperactivation of adenylate cyclase,the in vitro biomarker of morphine tolerance,via the GRK2/β-arrestin2 pathway.Furthermore,in vivo hotplate test demonstrated that chronic intrathecal administration of 3A5C7 significantly alle-viated morphine tolerance in mice,and withdrawal jumping test revealed that both chronic and acute 3A5C7 intrathecal administration attenuated morphine dependence.Finally,intrathecal electroporation of silencing short hairpin RNA illustrated that the in vivo anti-tolerance and anti-dependence efficacy of 3A5C7 was mediated by enhanced morphine-induced MOR endocytosis via GRK2/β-arrestin2 pathway.Collectively,our study provided a therapeutic mAb,3A5C7,targeting MOR to treat morphine tolerance,mediated by enhancing morphine-induced MOR endocytosis.The mAb 3A5C7 demonstrates promising translational value to treat clinical morphine tolerance.