The ventral anterior (VA) nucleus of the thalamus is a major target of the basal ganglia and is closely associated with the pathogenesis of Parkinson's disease (PD). Notably, the VA receives direct innervation from the hypothalamic histaminergic system. However, its role in PD remains unknown. Here, we assessed the contribution of histamine to VA neuronal activity and PD motor deficits. Functional magnetic resonance imaging showed reduced VA activity in PD patients. Optogenetic activation of VA neurons or histaminergic afferents significantly alleviated motor deficits in 6-OHDA-induced PD rats. Furthermore, histamine excited VA neurons via H1 and H2 receptors and their coupled hyperpolarization-activated cyclic nucleotide-gated channels, inward-rectifier K⁺ channels, or Ca²⁺-activated K⁺ channels. These results demonstrate that histaminergic afferents actively compensate for Parkinsonian motor deficits by biasing VA activity. These findings suggest that targeting VA histamine receptors and downstream ion channels may be a potential therapeutic strategy for PD motor dysfunction.
Animals ; Histamine/metabolism* ; Male ; Oxidopamine/toxicity* ; Rats ; Ventral Thalamic Nuclei/physiopathology* ; Rats, Sprague-Dawley ; Disease Models, Animal ; Parkinson Disease/metabolism* ; Neurons/physiology* ; Humans ; Optogenetics

Objective:To investigate the value of systemic inflammatory response syndrome (SIRS), pediatric sequential organ failure assessment (pSOFA) and pediatric critical illness score (PCIS) in predicting mortality of pediatric sepsis in pediatric intensive care units (PICU) from Southwest China.Methods:This was a prospective multicenter observational study. A total of 447 children with sepsis admitted to 12 PICU in Southwest China from April 2022 to March 2023 were enrolled. Based on the prognosis, the patients were divided into survival group and non-survival group. The physiological parameters of SIRS, pSOFA and PCIS were recorded and scored within 24 h after PICU admission. The general clinical data and some laboratory results were recorded. The area under the curve (AUC) of the receiver operating characteristic curve was used to compare the predictive value of SIRS, pSOFA and PCIS in mortality of pediatric sepsis.Results:Amongst 447 children with sepsis, 260 patients were male and 187 patients were female, aged 2.5 (0.8, 7.0) years, 405 patients were in the survival group and 42 patients were in the non-survival group. 418 patients (93.5%) met the criteria of SIRS, and 440 patients (98.4%) met the criteria of pSOFA≥2. There was no significant difference in the number of items meeting the SIRS criteria between the survival group and the non-survival group (3(2, 4) vs. 3(3, 4) points, Z=1.30, P=0.192). The pSOFA score of the non-survival group was significantly higher than that of the survival group (9(6, 12) vs. 4(3, 7) points, Z=6.56, P<0.001), and the PCIS score was significantly lower than that of the survival group (72(68, 81) vs. 82(76, 88) points, Z=5.90, P<0.001). The predictive value of pSOFA (AUC=0.82) and PCIS (AUC=0.78) for sepsis mortality was significantly higher than that of SIRS (AUC=0.56) ( Z=6.59, 4.23, both P<0.001). There was no significant difference between pSOFA and PCIS ( Z=1.35, P=0.176). Platelet count, procalcitonin, lactic acid, albumin, creatinine, total bilirubin, activated partial thromboplastin time, prothrombin time and international normalized ratio were all able to predict mortality of sepsis to a certain degree (AUC=0.64, 0.68, 0.80, 0.64, 0.68, 0.60, 0.77, 0.75, 0.76, all P<0.05). Conclusion:Compared with SIRS, both pSOFA and PCIS had better predictive value in the mortality of pediatric sepsis in PICU.

Near infrared spectroscopy(NIRS)technology combined with chemometrics algorithms has been widely used in quantitative and qualitative analysis of food and medicine.However,traditional chemometrics methods,especially linear classification methods,often yield unsatisfactory results when addressing multi-class classification problems.Convolutional neural network(CNN)is adept at extracting deep-level features from data and suitable for handling non-linear relationships.The modeling performance of CNN depends on the size and diversity of sample,while the collection and preprocessing of NIRS sample data is often time-consuming and labor-intensive.This study proposed a NIRS qualitative analysis method based on data augmentation strategies and CNN.The data augmentation strategy included two steps.Firstly,applying Bootstrap resampling and generative adversarial network(GAN)methods to augment three NIRS datasets(Medicine,coffee and grape).Secondly,combining the original samples(Y)with the Bootstrap augmented samples(B)and GAN augmented samples(G)to obtain three augmented datasets(Y-B,Y-G and Y-B-G).Based on this,a CNN model structure suitable for these datasets was designed,consisting of 2 one-dimensional convolutional layers,1 max-pooling layer,and 1 fully connected layer.The results showed that compared to the optimal models of partial least squares discriminant analysis(PLS-DA),support vector machine(SVM),and back propagation neural network(BP),the CNN model based on Y-B dataset achieved average accuracy improvements of 3.998%,9.364%,and 4.689%for medicine(Binary classification);the CNN model based on the Y-B-G dataset achieved average accuracy improvements of 6.001%,2.004%,and 7.523%for coffee(7-class classification);and the CNN model based on the Y-B dataset achieved average accuracy improvements of 33.408%,51.994%,and 34.378%for grapes(20-class classification).It was evident that the models established based on data augmentation strategies and CNN demonstrated better classification accuracy and generalization performance with different datasets and classification categories.

OBJECTIVE: This study aimed to evaluate the effects of a mindfulness-based psychosomatic intervention on depression, anxiety, fear of childbirth (FOC), and life satisfaction of pregnant women in China. METHODS: Women experiencing first-time pregnancy ( n = 104) were randomly allocated to the intervention group or a parallel active control group. We collected data at baseline (T0), post-intervention (T1), 3 days after delivery (T2), and 42 days after delivery (T3). The participants completed questionnaires for the assessment of the levels of depression, anxiety, FOC, life satisfaction, and mindfulness. Differences between the two groups and changes within the same group were analyzed at four time points using repeated-measures analysis of variance. RESULTS: Compared with the active control group, the intervention group reported lower depression levels at T2 ( P = 0.038) and T3 ( P = 0.013); reduced anxiety at T1 ( P = 0.001) and T2 ( P = 0.003); reduced FOC at T1 ( P < 0.001) and T2 ( P = 0.04); increased life satisfaction at T1 ( P < 0.001) and T3 ( P = 0.015); and increased mindfulness at T1 ( P = 0.01) and T2 ( P = 0.006). CONCLUSION The mindfulness-based psychosomatic intervention effectively increased life satisfaction and reduced perinatal depression, anxiety, and FOC.
Humans ; Pregnancy ; Female ; Mental Health ; Mindfulness ; Pregnant Women/psychology* ; Anxiety/prevention & control* ; China ; Depression/prevention & control*

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R² of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.
Pregnancy ; Child ; Humans ; Female ; Glycated Hemoglobin ; Cohort Studies ; Diabetes Mellitus/diagnosis* ; Sensitivity and Specificity ; ROC Curve

OBJECTIVES: To evaluate myocardial injury in neonates born to pregnant women with pregnancy complicated by severe preeclampsia by myocardial work indices. METHODS: A prospective cohort study was performed on 25 preterm infants born to the pregnant women with severe preeclampsia from June 2020 to April 2021 (severe preeclampsia group), and 25 preterm infants born to the pregnant women without severe complications in pregnancy were enrolled as the control group. Echocardiography was performed within 24 hours and at 48-72 hours and 14-28 days after birth to measure conventional parameters. Two-dimensional speckle-tracking echocardiography was performed to construct a noninvasive left ventricular pressure-strain loop based on two-dimensional myocardial strain and left ventricular systolic pressure noninvasively measured, so as to calculate myocardial work indices. RESULTS: Compared with the control group, the severe preeclampsia group had significant reductions in left ventricular global work index and global constructive work within 24 hours after birth (P<0.05), a significant reduction in left ventricular global work efficiency and a significant increase in global waste work at 48-72 hours after birth (P<0.05), and a significant reduction in left ventricular global work efficiency at 14-28 days after birth (P<0.05). CONCLUSIONS Subclinical myocardial injury persists in the neonatal period in preterm infants born to pregnant women with severe preeclampsia.
Echocardiography/methods* ; Female ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Pre-Eclampsia ; Pregnancy ; Pregnant Women ; Prospective Studies

Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ²=4.16, P=0.041) and group C2 (χ²=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ²=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Burkitt Lymphoma/drug therapy* ; Child ; Disease-Free Survival ; Female ; Humans ; Lactate Dehydrogenases ; Lymphoma, B-Cell/drug therapy* ; Male ; Prognosis ; Retrospective Studies ; Rituximab/therapeutic use* ; Treatment Outcome

OBJECTIVE: To investigate the incidence rate and risk factors for metabolic bone disease of prematurity (MBDP) in very low birth weight/extremely low birth weight (VLBW/ELBW) infants. METHODS: The medical data of 61 786 neonates from multiple centers of China between September 1, 2013 and August 31, 2016 were retrospectively investigated, including 504 VLBW/ELBW preterm infants who met the inclusion criteria. Among the 504 infants, 108 infants diagnosed with MBDP were enrolled as the MBDP group and the remaining 396 infants were enrolled as the non-MBDP group. The two groups were compared in terms of general information of mothers and preterm infants, major diseases during hospitalization, nutritional support strategies, and other treatment conditions. The multivariate logistic regression analysis was used to investigate the risk factors for MBDP. RESULTS: The incidence rate of MBDP was 19.4% (88/452) in VLBW preterm infants and 38.5% (20/52) in ELBW preterm infants. The incidence rate of MBDP was 21.7% in preterm infants with a gestational age of < 32 weeks and 45.5% in those with a gestational age of < 28 weeks. The univariate analysis showed that compared with the non-MBDP group, the MBDP group had significantly lower gestational age and birth weight, a significantly longer length of hospital stay, and a significantly higher incidence rate of extrauterine growth retardation ( CONCLUSIONS A lower gestational age, hypocalcemia, extrauterine growth retardation at discharge, and neonatal sepsis may be associated an increased risk of MBDP in VLBW/ELBW preterm infants. It is necessary to strengthen perinatal healthcare, avoid premature delivery, improve the awareness of the prevention and treatment of MBDP among neonatal pediatricians, and adopt positive and reasonable nutrition strategies and comprehensive management measures for preterm infants.
Birth Weight ; Bone Diseases, Metabolic/etiology* ; China/epidemiology* ; Female ; Humans ; Infant ; Infant, Extremely Low Birth Weight ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Pregnancy ; Retrospective Studies ; Risk Factors

OBJECTIVE: This study summarizes and compares clinical and laboratory characteristics of 34 patients admitted to the intensive care unit (ICU) for complications from coronavirus disease 2019 (COVID-19) at the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China from Jan. 22 to Mar. 5, 2020. METHODS: A total of 34 patients were divided into two groups, including those who required noninvasive ventilation (NIV) and invasive mechanical ventilation (IMV) with additional extracorporeal membrane oxygenation (ECMO) in 11 patients. Clinical features of COVID-19 patients were described and the parameters of clinical characteristics between the two groups were compared. RESULTS: The rates of the acute cardiac and kidney complications were higher in IMV cases than those in NIV cases. Most patients had lymphocytopenia on admission, with lymphocyte levels dropping progressively on the following days, and the more severe lymphopenia developed in the IMV group. In both groups, T lymphocyte counts were below typical lower limit norms compared to B lymphocytes. On admission, both groups had higher than expected amounts of plasma interleukin-6 (IL-6), which over time declined more in NIV patients. The prothrombin time was increased and the levels of platelet, hemoglobin, blood urea nitrogen (BUN), D-dimer, lactate dehydrogenase (LDH), and IL-6 were higher in IMV cases compared with NIV cases during hospitalization. CONCLUSIONS Data showed that the rates of complications, dynamics of lymphocytopenia, and changes in levels of platelet, hemoglobin, BUN, D-dimer, LDH and IL-6, and prothrombin time in these ICU patients were significantly different between IMV and NIV cases.
Acute Kidney Injury ; virology ; Aged ; Aged, 80 and over ; Betacoronavirus ; Blood Urea Nitrogen ; China ; Coronavirus Infections ; complications ; therapy ; Extracorporeal Membrane Oxygenation ; Female ; Fibrin Fibrinogen Degradation Products ; analysis ; Heart Diseases ; virology ; Hemoglobins ; analysis ; Hospitalization ; Humans ; Intensive Care Units ; Interleukin-6 ; blood ; L-Lactate Dehydrogenase ; blood ; Lymphopenia ; virology ; Male ; Middle Aged ; Noninvasive Ventilation ; Pandemics ; Pneumonia, Viral ; complications ; therapy ; Positive-Pressure Respiration ; Prothrombin Time ; Retrospective Studies

Hyaluronic acid, also called hyaluronan(HA)is a biocompatible and biodegradable linear polysaccharide which is of interest for tumor targeting through cell surface CD44 receptors. It is widely applied in the field of tumor therapy as an anticancer drug delivery carrier, and has become a hot spot in the research of tumor targeted drug delivery system. In tumor drug therapy, the key to reduce toxicity is to actively target tumors by using anatomical, pathophysiological and microenvironmental differences between malignant tumors and normal tissues. Differentiation cluster 44(CD44)is a high-affinity receptor for HA, which can be marked as a tumor marker or a targeting receptor because it is overexpressed in tumor cells. The overexpression of CD44 receptors was observed in many tumors such as breast cancer, colorectal cancer, liver cancer and pancreatic cancer. The effect of hyaluronic acid drug nanocarriers on various tumors is briefly described, indicating that the overexpression of CD44 receptor is an ideal choice for the treatment of hyaluronic acid-based drug carriers. The CD44 ligand can increase the affinity of the nanocarrier for tumor cells by binding to the nano drug carrier. The HA structure is known for its potent tumor targeting effect due to the inclusion of CD44 ligand, which enhances uptake of tumor cells by the HA-CD44 receptor-mediated endocytosis pathway. The study reviewed the progression of hyaluronic acid nanomicelles in clinical tumor therapy and its release behavior. The percentage of drug release and release rate are the key factors in the overall efficacy of the treatment strategy. Therefore, a great number of studies have focused on inducing drug release in Cytosol by taking advantage of the difference between the internal and external environments of nanostructured micelles or through external stimulation post-treatment applications. The study proved that an acid environment is more favorable to achieve a greater release and drugs can be quickly and completely released in an oxygen-deficient environment. In addition, the great potential of hyaluronic acid nanomicelles in tumor therapy was also further identified in this article. In vitro and in vivo experimental studies have repeatedly shown that hyaluronic acid-based nanomicelles are a drug- and gene-specific targeting tumor delivery method, in combination with passive targeting, this active targeting strategy is a promising approach to providing chemotherapy drugs to CD44 overexpressing tumors. In conclusion, hyaluronic acid-based nanomicelles are biologically safe with great potential to drug release, blood compatibility and systemic tumor targeting which all implied it has good application prospects in clinical tumor treatment.