OBJECTIVE: To determine whether the glutamatergic neurons in the paraventricular nucleus of the thalamus (PVT) is involved in the change of consciousness induced by propofol through a combination of behavioral and electroencephalography (EEG) recordings. METHODS: Healthy male VGluT2-IRES-Cre mice aged 8-12 weeks were used in this experiment. (1) The glutamatergic neurons in the PVT was selectively damaged, and its effect on propofol anesthesia induction and recovery times as well as the energy of EEG in different frequency bands were observed. (2) Optogenetics was utilized to selectively activate or inhibit glutamatergic neurons in the PVT to assess their influence on anesthesia induction and recovery times under propofol as well as the energy of EEG in different frequency bands. RESULTS: (1) Selective ablation of glutamatergic neurons in the PVT significantly delayed recovery from propofol anesthesia with statistical difference as compared with the control group (s: 409.43±117.49 vs. 273.71±51.52, P < 0.05), but had no significant effect on anesthesia induction time. During the recovery phase of propofol, selective ablation of glutamatergic neurons in the PVT exhibited higher α-wave (1-4 Hz) power and reduced β-wave (12-15 Hz) power as compared with the control group. (2) Optogenetic activation of glutamatergic neurons in the PVT significantly prolonged anesthesia induction time under propofol (s: 161.67±29.09 vs. 119.33±18.98, P < 0.05) while significantly shortening the recovery time from propofol anesthesia (s: 208.67±57.19 vs. 288.83±34.52, P < 0.05). During the induction phase of propofol, activation of glutamatergic neurons in PVT reduced α-wave and α-wave (8-12 Hz) power, while during the recovery phase, α-wave power significantly increased as compared with the control group. (3) Optogenetic inhibition of glutamatergic neurons in the PVT delayed recovery from propofol anesthesia (s: 403.50±129.06 vs. 252.83±45.31, P < 0.05), but had no significant effect on induction time. During both the induction phase and recovery phase of propofol, the optogenetic inhibition of glutamatergic neurons in the PVT exhibited increased α-wave power. CONCLUSION Glutamatergic neurons in the PVT are involved in the regulation of propofol anesthesia recovery process.
Animals ; Propofol/pharmacology* ; Mice ; Neurons/physiology* ; Male ; Electroencephalography ; Wakefulness ; Midline Thalamic Nuclei ; Optogenetics

Objective: To explore the influencing factors and pathways of suicidal ideation among children and adolescents with severe autism spectrum disorder (ASD), so as to provide references for clarifying the impact intensity and pathways of various factors on suicidal ideation in the population. Methods: A cross sectional study was conducted from June 17, 2024, to January 12, 2025, involving 96 severely affected ASD children and adolescents aged 8-18 years from Tianjin. Participants were assessed using the Puberty Development Scale (PDS), Children s Alexithymia Measure (CAM), Strengths and Difficulties Questionnaire (SDQ), and Positive and Negative Suicide Ideation (PANSI). The random forest Boruta algorithm was employed to screen core variables, and a Bayesian network model was constructed to analyze the influencing factors of suicidal ideation in children and adolescents with severe ASD. Results: Through the screening using the Boruta algorithm, the SDQ scale score, conduct problems, hyperactivity, peer relationship problems and prosocial behavior were identified as the key predictors of suicidal ideation. A Bayesian network model was established with hyperactivity as the central mediating node. The impact of hyperactivity on suicidal ideation exhibited a non linear relationship: compared to the normal state (31.6%, 68.4%), the borderline state of hyperactivity was associated with a higher probability of low risk suicidal ideation (47.1%) and a lower probability of high risk suicidal ideation (52.9%). Suicidal ideation among children and adolescents with severe ASD was closely related to hyperactivity. In the state of hyperactivity, the abnormal peer relationship (95.2%) and the abnormal prosocial behavior (77.0%) were aggravated. Conclusions Suicide ideation among children and adolescents with severe ASD is strongly associated with hyperactivity traits. It is necessary to establish a prevention and control system centered on hyperactivity intervention to reduce this risk.

OBJECTIVE To establish a method for determining the content of 11 antioxidants and their degradation products in recombinant Exendin-4-FC fusion protein injection by HPLC. METHODS The protein was precipitated with saturated ammonium sulfate. After centrifugation, the supernatant was transferred to a C18 solid phase extraction cartridge activated by methanol. Then the cartridge was eluted with 4 mL of methanol and 5 mL of ethyl acetate respectively, and the eluent was diluted with methanol-ethyl acetate(2∶3) mixed solvent and passed through a 0.22 µm PTFE hydrophobic filter. It was analyzed by HPLC and quantified by external standard method. Chromatographic conditions: Kinetex® XB-C18 100Å (100 mm×4.6 mm, 2.6 µm)column, the detection wavelength was 230 nm, the column oven was 30 ℃, the injection volume was 5 µL and the flow rate was 0.4 mL·min–1, mobile phase was 0.1% formic acid-methanol(A)-0.1% formic acid aqueous solution(B), the running time was 45 min. RESULTS The 11 target substances showed a good linear relationship in the range of 2.5−35 μg·mL–1 with R2 ≥0.99. At three different concentration(25, 10, 5 μg·mL–1) of spiked samples, the average recovery rates of 11 antioxidants ranged from 88.1% to 106.5%, with RSDs in the range of 0.10%–9.05%. The RSDs of 6 repeatable samples was 2.01%–4.77%, which of 12 intermediate precision samples was 2.58%–9.75%. The positive/inverted samples of three batches of recombinant Exendin-4-FC fusion protein injection were detected at 0 month, 3 months and 6 months(25 ℃), and the results showed that there was no antioxidant and its degradation leaching in all batches of samples at different detection points. CONCLUSION The method has good specificity, high accuracy and precision, good solution stability, high durability and can be used for the content detection of antioxidants in drugs.

Objective:To establish a prediction model for symptomatic radiation pneumonitis (SRP) after radiotherapy for thoracic cancer based on a longitudinal cohort and dose interval variations.Methods:Clinical data of 587 patients who received thoracic radiotherapy in Department of Radiotherapy of Yunnan Cancer Hospital from July 2022 to June 2023 were retrospectively analyzed. The National Cancer Institute common terminology criteria for adverse events (CTCAE) version 5.0 was used to grade radiation pneumonitis, and clinical factors, traditional independent dosimetric characteristics and dose interval variation characteristics were collected. Features used to predict the occurrence of SRP were screened using genetic algorithms and analyzed the correlation between the selected features and SRP occurrence. Predictive models for SRP occurrence were established using the selected features and evaluated, and the optimal predictive model was visualized using a column chart.Results:The incidence of SRP was 35.94%. Five clinical factors, seven independent dosimetric features and six dose interval variation features were screened out by genetic algorithms to effectively predict the occurrence of SRP. The area under ROC curve (AUC) of clinical factors combined with traditional independent dosimetric factors and dose interval variation factors was 76%. The AUC of clinical factors combined with traditional independent dosimetric factors and that of clinical factors combined with dose interval variation factors was 69% and 67%, respectively. The addition of the characteristics of dose interval variation factors significantly improved the effectiveness of the prediction model.Conclusions:The supplement of the characteristics of dose interval variation factors can significantly improve the performance of the SRP prediction model for thoracic tumors after radiotherapy. The SRP prediction model based on dose interval variations can effectively predict the occurrence of SRP.

Immunotherapy drugs are a class of medications that treat diseases by modulating the function of immune system.As frontline therapies in clinical practice,they play a particularly crucial role in alleviating disease symptoms and improving adverse prognoses caused by severe inflammation.In recent years,with the rapid development of internet technology and the continuous innova-tion in the technology industry,various national directives have been issued,urging schools to strengthen online teaching and promote the development of"Internet+education".Online teaching,unaffected by time or geographical constraints,has facilitated resource sharing and stimulated student interest.However,in practice,both singular online or offline teaching models have their drawbacks.This article takes the severe inflammation immunotherapy drugs as an example,integrating the concept of intersubjectivity in teaching to explore a"two-line"teaching mode in immunotherapy drugs.This study views students as the main body of learning,emphasizes the importance of individual learning,and solves the drawbacks of"one-line"teaching mode.Exploration and application of intersubjective"two-line"teaching mode has guiding significance for educational reform in the internet era.

Objective:To analyze the clinical characteristics and prognosis of acute pancreatitis (AP) in children, and provide reference for clinical prevention and treatment of AP in children.Methods:Based on the electronic medical record system of the Affiliated Hospital of Zunyi Medical University, the clinical data of children with AP in the hospital from January 2011 to December 2020 were retrospectively analyzed. According to the severity of the disease, the children were divided into mild acute pancreatitis (MAP) group and severe acute pancreatitis (SAP) group. The general data, laboratory tests and outcomes indicators of the two groups were collected and compared. The epidemiological characteristics of children with AP were analyzed. Multivariate Logistic regression was used to analyze the risk factors of SAP in children.Results:A total of 227 children with AP were enrolled, including 161 in MAP group and 66 in SAP group. The median age of children with AP was 12.00 (8.00, 16.00) years old, and 126 cases (55.51%) were male. The main initial clinical symptoms were abdominal pain, nausea, vomiting and abdominal distension (97.36%, 61.67% and 14.10%, respectively), 21 cases (9.25%) were admitted to intensive care unit (ICU), and 4 cases (1.76%) died in hospital due to sepsis, multiple organ dysfunction or traumatic shock. The epidemiological characteristics showed that the first onset age of AP was mainly 7-17 years old (85.02%); the main etiologies were biliary tract disease (29.96%), viral infection (29.07%) and idiopathic factors (19.82%). From 2011 to 2020, the number of children with AP showed a fluctuating trend, and from 2018 to 2020, the number of children with AP increased for three consecutive years. Compared with MAP group, the age of SAP group was significantly older, the proportion of female, the proportion of rural source, acute physiology and chronic health evaluationⅡ(APACHEⅡ), body mass index (BMI), and the levels of white blood cell count (WBC), C-reactive protein (CRP), hospitalization expenses, the proportion of AP caused by traumatic factors and drug factors in SAP group were significantly higher (all P < 0.05). The level of blood calcium and the proportion of AP caused by virus infection were significantly lower, and the length of hospital stay in SAP group was significantly longer (all P < 0.05). The multivariate Logistic regression analysis showed that APACHEⅡscore [odds ratio ( OR) = 1.495, 95% confidence interval (95% CI) was 1.293-1.728] and age ( OR = 1.352, 95% CI was 1.182-1.546) were closely related to SAP in children (all P < 0.001). Conclusion:Children with AP mostly occurs in preschool and adolescence, and the overall mortality is relatively low; biliary tract disease, viral infection and idiopathic factors are common causes; APACHEⅡ score and age may be risk factors for SAP in children.

AIM:To explore the effects of moderate-altitude exposure on intestinal flora in healthy individuals.METHODS:The aid-Tibet cadres,who were sent to work from Guangdong(average altitude<50 m)to Nyingchi(average altitude of 2 900 m),were recruited.A total of 76 samples were collected,including 42 samples from healthy adults with plateau living for 0 day and 34 samples from healthy adults with plateau living for 6 months.Fecal samples DNA were ex-tracted,sequenced by the 16S rDNA high-throughput sequencing technology and analyzed bioinformatically.RESULTS:Compared with the base group,α diversity was increased(P=4.00×10-4)and β diversity was decreased(P=1.00×10-3).After moderate altitude exposure,the relative abundance of phylum Proteobacteria(|LDA|>4,P<0.05),genus Escherich-ia-Shigella,species Enterococcus_faecalis,Haemophilus_influenzae and Helicobacter_sp._UNSW1.7sp decreased(adjust-ed P<0.05),wheras the relative abundance of phylum Bacteroidetes(|LDA|>4,P<0.05),genus Butyricimona,species Lactobacillus_sp._RA2113(s)and Butyricimonas_sp._Marseille-P2440(s)increased(adjusted P<0.05).The function-al prediction by PICRUSt showed a decrease in the relative abundance of pathway related to xenobiotics biodegradation and metabolism,membrane transport and amino acid metabolism(adjusted P<0.05).Conversely,the relative abundance of pathway related to biosynthesis of other secondary metabolites and nucleotide metabolism was increased(adjusted P<0.05).Finally,the results of microbiome phenotype prediction by BugBase showed that moderate altitude exposure im-proves the gut microbiota functions involving anaerobic oxygen tolerance and gram positive(adjusted P<0.05).And bacte-ria containing facultatively anaerobic oxygen tolerance,oxidative stress tolerance,gram negative and biofilm formation in the six-group decreased significantly compared with those in base group(adjusted P<0.05).CONCLUSION:Moderate altitude exposure impacts the diversity,abundance and function of intestinal flora in healthy population,suggesting that al-titude factors may have some influence on gut microbiota.

Objective:To summarize the clinical characteristics, prognostic factors and treatment outcomes of childhood aggressive mature B-cell lymphoma after liver transplantation.Methods:This retrospective study included 18 children with newly diagnosed aggressive mature B-cell lymphoma after liver transplantation and treated from June 2018 to June 2022 in the Department of Hematology and Oncology of Shanghai Children′s Medical Center, Shanghai Jiao Tong University School of Medicine. Clinical characteristics, treatment and outcomes of patients at last evaluation were analyzed. Overall survival (OS) and event free survival (EFS) rates were calculated by Kaplan-Meier method and Log-Rank analysis was performed to find factors of poor prognosis.Results:Among all 18 patients, there were 6 males and 12 females, and the age of onset was 40 (35, 54) months. The interval from transplant to tumor diagnosis was 21 (17, 35) months and 5 patients had early onset disease (<1 year since transplant). Seventeen patients had abdominal lesions. Diarrhea, vomiting and abdominal masses were the main clinical manifestations. All patients were Epstein-Barr virus (EBV) related posttransplant lymphoproliferative disorders (PTLD). One patient received individualized therapy due to critical sick at diagnosis, and the remaining 17 patients received CP (cyclophosphamide, methylprednisolone plus rituximab) and (or) modified EPOCH (prednisone, etoposide, doxorubicin, vincristine, cyclophosphamide plus rituximab) regimens. Of all 18 patients, 15 cases got complete response, 2 cases got partial response, 1 patient died of severe infection. The 2-year OS and EFS rates of 18 patients were (94±5)% and (83±8)%, respectively. None of age, gender or early onset disease had effect on OS and EFS rates in univariate analysis (all P>0.05). Conclusions:The symptoms of PTLD were atypical. Close surveillance of EBV-DNA for patients after liver transplantation was crucial to early stage PTLD diagnosis. CP or modified EPOCH regimen was efficient for pediatric patients with aggressive mature B cell lymphoma after liver transplantation.

Objective:To study the survival and prognostic factors for the recurrent extracranial malignant germ cell tumors (MGCTs) in children, and to explore feasible salvage treatment.Methods:A retrospective study.Pediatric patients with recurrent extracranial MGCTs diagnosed in Shanghai Children′s Medical Center between January 2010 and January 2020 were retrospectively recruited.Comprehensive treatment regimens included surgery, chemotherapy and radiation.Kaplan-Meier survival analysis and Cox regression model were employed to analyze the survival and prognostic factors for children with recurrent extracranial MGCTs.Results:A total of 172 children with extracranial MGCTs were treated, including 21 (12.2%) recurrent cases.The median time of MGCT recurrence after the end of the first treatment was 11 months.Finally, 19 patients were recruited after excluding 2 non-eligible cases, including 10 boys and 9 girls with the age at recurrence of 26 (8-170) months.The follow-up time was 57 (13-122) months.Salvage chemotherapy, complete resection and radiotherapy were performed in 16, 14 and 4 patients, respectively.The 4-year overall survival (4yr-OS) rate was (82.5±9.2)%(19 cases). The 4yr-OS rate was significantly higher in patients managed with surgery but without adjuvant chemotherapy at the initial treatment (13 cases) than those managed with chemotherapy at the initial treatment (6 cases)[(92.3±7.4)% vs.(60.0%±21.9)%, P=0.002]. Univariant and Cox multivariant regression analyses showed that failure to achieve the normal range of alpha fetoprotein after 3 cycles of chemotherapy significantly influenced the survival of recurrent extracranial MGCTs. Conclusions:For patients with recurrent extracranial MGCTs, comprehensive treatment approaches like complete surgical resection, chemotherapy, and radiotherapy offer a favorable survival rate.Specifically, recurrent and re-treated patients who initially received surgery alone without adjuvant chemotherapy have a higher survival rate compared to those who received chemotherapy during the initial treatment.

【Objective】 To develop a quick and accurate crossmatching test technology without the power equipment and additional reagents before blood transfusion, so as to improve the timeliness and safety of blood transfusion treatment in sudden situations as war or natural disasters. 【Methods】 The irregular antibodies quickly promote coagulants (QPC) were used as the reaction medium reagent. The 200 μL QPC were wrapped in the bursts bead and preset within different recess of the detection tubes. The bursts beads were squeezed with the reagent left in the well, then the blood samples were dropped in the main(recipient plasma: 200 μL, donor 3%—5% RBC: 100 μL) and secondary(donor plasma: 200 μL, recipient 3%—5% RBC: 100 μL)reaction grooves. The result interpretated by hand wrestling or 1 500 g centrifugation of 15 seconds. Meanwhile, the comparing experiments with the prior methods were implemented to evaluate the method’s reliability. 【Results】 The results of the bursting reagent, being stored at 37℃ for one week, were consistent with those of the freshly prepared cross-matching reagent, indicating that the bursting reagent was practical in the field and had good stability at normal temperature. No statistical difference between the sensitivity and the results of the microcolumn gel method was noticed by paired data t test (P>0.05). The parallel cross matching tests of 50 clinical samples were performed by microcolumn gel method and coagulant-bursting technique; the Kappa value was 0.973 2, and irregular antibodies were detected in 2 cases, with concordance rate at 100%, showing good consistency. 【Conclusion】 The improved method is simple and fast, and also safe and reliable for compatibility testing before blood transfusion, which is especially suitable for the field rescue of the wounded in wartime and sudden natural disasters, and is worthy of popularization.