ObjectiveTo investigate the role of 4-week high-intensity interval training (HIIT) in modulating the metabolic homeostasis of the pyruvate-lactate axis in the hippocampus of rats with chronic unpredictable mild stress (CUMS) to improve their depressive-like behavior. MethodsForty-eight SPF-grade 8-week-old male SD rats were randomly divided into 4 groups: the normal quiet group (C), the CUMS quiet group (M), the normal exercise group (HC), and the CUMS exercise group (HM). The M and HM groups received 8 weeks of CUMS modeling, while the HC and HM groups were exposed to 4 weeks of HIIT starting from the 5th week (3 min (85%-90%) S_max+1 min (50%-55%) S_max, 3-5 cycles, S_max is the maximum movement speed). A lactate analyzer was used to detect the blood lactate concentration in the quiet state of rats in the HC and HM groups at week 4 and in the 0, 2, 4, 8, 12, and 24 h after exercise, as well as in the quiet state of rats in each group at week 8. Behavioral indexes such as sucrose preference rate, number of times of uprightness and number of traversing frames in the absenteeism experiment, and other behavioral indexes were used to assess the depressive-like behavior of the rats at week 4 and week 8. The rats were anesthetized on the next day after the behavioral test in week 8, and hippocampal tissues were taken for assay. LC-MS non-targeted metabolomics, target quantification, ELISA and Western blot were used to detect the changes in metabolite content, lactate and pyruvate concentration, the content of key metabolic enzymes in the pyruvate-lactate axis, and the protein expression levels of monocarboxylate transporters (MCTs). Results4-week HIIT intervention significantly increased the sucrose preference rate, the number of uprights and the number of traversed frames in the absent field experiment in CUMS rats; non-targeted metabolomics assay found that 21 metabolites were significantly changed in group M compared to group C, and 14 and 11 differential metabolites were significantly dialed back in the HC and HM groups, respectively, after the 4-week HIIT intervention; the quantitative results of the targeting showed that, compared to group C, lactate concentration in the hippocampal tissues of M group, compared with group C, lactate concentration in hippocampal tissue was significantly reduced and pyruvate concentration was significantly increased, and 4-week HIIT intervention significantly increased the concentration of lactate and pyruvate in hippocampal tissue of HM group; the trend of changes in blood lactate concentration was consistent with the change in lactate concentration in hippocampal tissue; compared with group C, the LDHB content of group M was significantly increased, the content of PKM2 and PDH, as well as the protein expression level of MCT2 and MCT4 were significantly reduced. The 4-week HIIT intervention upregulated the PKM2 and PDH content as well as the protein expression levels of MCT2 and MCT4 in the HM group. ConclusionThe 4-week HIIT intervention upregulated blood lactate concentration and PKM2 and PDH metabolizing enzymes in hippocampal tissues of CUMS rats, and upregulated the expression of MCT2 and MCT4 transport carrier proteins to promote central lactate uptake and utilization, which regulated metabolic homeostasis of the pyruvate-lactate axis and improved depressive-like behaviors.

ObjectiveThis study aimed to investigate the effects of 4-week high-intensity interval training (HIIT) on synaptic plasticity in the prefrontal cortex (PFC) of rats exposed to chronic unpredictable mild stress (CUMS), and to explore its potential mechanisms. MethodsA total of 48 male Sprague-Dawley rats were randomly divided into 4 groups: control (C), model (M), control plus HIIT (HC), and model plus HIIT (HM). Rats in groups M and HM underwent 8 weeks of CUMS to establish depression-like behaviors, while groups HC and HM received HIIT intervention beginning from the 5th week for 4 consecutive weeks. The HIIT protocol consisted of repeated intervals of 3 min at high speed (85%-90% maximal training speed, S_max) alternated with one minute at low speed (50%-55% S_max), with 3 to 5 sets per session, conducted 5 d per week. Behavioral assessments and tail-vein blood lactate levels were measured at the end of the 4th and 8th weeks. After the intervention, rat PFC tissues were collected for Golgi staining to analyze synaptic morphology. Enzyme-linked immunosorbent assays (ELISA) were employed to detect brain-derived neurotrophic factor (BDNF), monocarboxylate transporter 1 (MCT1), lactate, and glutamate levels in the PFC, as well as serotonin (5-HT) levels in serum. Additionally, Western blot analysis was conducted to quantify the expression of synaptic plasticity-related proteins, including c-Fos, activity-regulated cytoskeleton-associated protein (Arc), and N-methyl-D-aspartate receptor 1 (NMDAR1). ResultsCompared to the control group (C), the CUMS-exposed rats (group M) exhibited significant reductions in sucrose preference rates, number of grid crossings, frequency of upright postures, and entries into and duration spent in open arms of the elevated plus maze, indicating marked depressive-like behaviors. Additionally, the group M showed significantly reduced dendritic spine density in the PFC, along with elevated levels of c-Fos, Arc, NMDAR1 protein expression, and increased concentrations of lactate and glutamate. Conversely, BDNF and MCT1 contents in the PFC and 5-HT levels in serum were significantly decreased. Following HIIT intervention, rats in the group HM displayed considerable improvement in behavioral indicators compared with the group M, accompanied by significant elevations in PFC MCT1 and lactate concentrations. Furthermore, HIIT notably normalized the expression levels of c-Fos, Arc, NMDAR1, as well as glutamate and BDNF contents in the PFC. Synaptic spine density also exhibited significant recovery. ConclusionFour weeks of HIIT intervention may alleviate depressive-like behaviors in CUMS rats by increasing lactate levels and reducing glutamate concentration in the PFC, thereby downregulating the overexpression of NMDAR, attenuating excitotoxicity, and enhancing synaptic plasticity.

To address the key challenges in multivariate statistical modeling,a higher-order derivative approach combined with vector space angle multiplicative error correction was proposed for establishing an acid value prediction ordinary least squares(OLS)regression model based on attenuated total reflectance-Fourier transform infrared(ATR-FTIR)spectroscopy.By using acid values measured by potentiometric titration as reference,ATR-FTIR spectroscopy was utilized for direct calibration and prediction of acid values on 96 kinds of lubricating oil samples from a wind turbine.Firstly,the simulated hyperbolic(SH)method was employed to obtain accurate fourth derivative spectrum,resolving overlapping bands and enhancing spectral selectivity.Then,from the calibration set(48 samples),informative spectral regions were identified based on correlation coefficients.Next,the sample with the highest acid value was selected as the reference and1/(1+tan(θ/2))was used as the metric relation of the spectrum to suppress the multiplicity error caused by factors such as the change of effective optical path in ATR-FTIR spectroscopy.After pretreatment of the spectrum by the method of fourth-order derivative combined with angular quantity,the number of variables decreased from 1737 to 8,and the matrix condition number decreased from 1.85×1015 to 56.34,which effectively eliminated the collinearity issue for OLS regression.Direct OLS modeling on spectral preprocessed data achieved a determination coefficient of 0.981 for 47 validation samples,with a relative error range of-8.38%-8.22%,outperforming the commonly used partial least squares(PLS)method(Determination coefficient of 0.865,relative error of-27.82%-22.38%).It was proved that effective data preprocessing significantly improved the prediction accuracy of the model.Furthermore,when the number of calibration set was compressed to 25 and the number of validation set was expanded to 70,the model retained 8 variables with a condition number of 42.60,the determination coefficient of validation set was 0.972,and the relative error ranged from-10.80%to 12.31%.Comparing with the PLS method(Determination coefficient of 0.724,relative error of-34.26%-53.84%),the improvement was more obvious,which showed that the method could still have high prediction accuracy even with fewer modeling samples as well as robustness against multiplicative error interference.

Objective To assess the effectiveness and safety of prone positioning in the treatment of neonatal respiratory distress syndrome(NRDS)using invasive respiratory support.Methods A prospective study was conducted from June 2020 to September 2023 at Suining County People's Hospital,involving 77 preterm infants with gestational ages less than 35 weeks requiring invasive respiratory support for NRDS.The infants were randomly divided into a supine group(37 infants)and a prone group(40 infants).Infants in the prone group were ventilated in the prone position for 6 hours followed by 2 hours in the supine position,continuing in this cycle until weaning from the ventilator.The effectiveness and safety of the two approaches were compared.Results At 6 hours after enrollment,the prone group showed lower arterial blood carbon dioxide levels,inspired oxygen concentration,oxygenation index,rates of tracheal intubation bacterial colonization,and Neonatal Pain,Agitation and Sedation Scale scores compared to the supine group(P<0.05).There were no significant differences between the groups in terms of pH,arterial oxygen pressure,positive end-expiratory pressure,duration of mechanical ventilation,accidental extubation,ventilator-associated pneumonia,air leak syndrome,skin pressure sores,feeding intolerance,and grades II-IV intraventricular hemorrhage(P>0.05).Conclusions Compared to supine positioning,prone ventilation effectively improves oxygenation,increases comfort,and reduces tracheal intubation bacterial colonization in neonates requiring mechanical ventilation for NRDS,without significantly increasing adverse reactions.

This study was aimed at examining the influence of meteorological factors on scrub typhus in Xiamen.Scrub ty-phus monitoring data and meteorological factors were collected in Xiamen from 2005 to 2023.Spearman correlation analysis and nonlinear regression were used to analyze the correlation between scrub typhus incidence and meteorological factors.The inci-dence of scrub typhus first increased and subsequently decreased in Xiamen from 2005 to 2023.The highest incidence was be-tween 2014 and 2016,and the peak incidence was from June to October.The monthly incidence of scrub typhus positively cor-related with daily minimum temperature(r=0.637,P＜0.001,daily average temperature(r=0.627,P＜0.001),daily maxi-mum temperature(r=0.612,P＜0.001),sunshine duration(r=0.405,P＜0.001),average relative humidity(r=0.346,P＜0.001),and daily rainfall(r=0.207,P=0.002),and negatively correlated with average atmospheric pressure(r=-0.549,P＜0.001),whereas no correlation was observed with the average wind speed in Xiamen.The regression equation of scrub ty-phus monthly incidence and meteorological parameters was y=-433.869-11.503x1+0.381x1 2+9.150x2-0.197x2 2+3.936 x3-0.132x3 2+0.881x4+0.035x4 2-1.048x5+0.009x5 2+0.186x6-0.023x6 2+0.421x7+6.210×10-5x8-1.051 × 10-10x8 2 in Xiamen,and the R2 was 0.473,thus indicating good model fit.Scrub typhus incidence correlated with the daily minimum av-erage temperature,average temperature,daily maximum tem-perature,sunshine duration,daily rainfall,relative humidity,and average atmospheric pressure in Xiamen.Various meteoro-logical factors had differing effects on scrub typhus.

Methamphetamine abuse is a major public health problem in the world,and in recent years,methamphetamine is also the most abused synthetic drug in China.The neurotoxic or addiction mechanism of methamphetamine has not been fully clarified,and there is still a lack of specific withdrawal methods and drugs for methamphetamine abuse.Mitochondria are not on-ly the organelles to which methamphetamine directly produces toxic effects,but also participate in regulating the neurotoxic damage process of methamphetamine.Mitochondrial quality is the regulatory basis for maintaining mitochondrial homeostasis and is regulated by three main mechanisms,which are mitochon-drial biogenesis,mitochondrial dynamic,and mitophagy.This review summarizes the research progress of mitochondrial quality control in methamphetamine-induced neurotoxicity,which may provide theoretical support for further research on the mechanism of methamphetamine neurotoxicity and development the mito-chondria-targeting drugs.

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

OBJECTIVE: To detect the gene mutations in patients with myeloid malignancies by high-throughput sequencing and explore the correlation between gene mutations and prognosis. METHODS: A retrospective analysis was performed on 56 patients with myeloid malignancies who were hospitalized in the department of hematology, Peking University International Hospital from January 2020 to May 2021. The genetic mutations of the patients were detected by next-generation sequencing technology, and the correlation between the genetic mutations and prognosis of myeloid malignancies was analyzed. RESULTS: In 56 patients, the number of mutated genes detected in a single patient is 0-9, with a median of 3. Sequencing results showed that the most common mutated genes were RUNX1(21.4%), TET2(17.9%), DNMT3A(17.9%), TP53(14.3%) and ASXL1(14.3%), among which the most common mutations occurred in the signaling pathway-related genes (23.3%) and the transcription factor genes (18.3%). 84% of the patients carried multiple mutated genes (≥2), and correlation analysis showed there were obvious co-occurring mutations between WT1 and FLT3, NPM1 and FLT3-ITD, and MYC and FLT3. TP53 mutation was more common in MDS patients.The overall survival time of patients with NRAS mutation was significantly shortened (P =0.049). The prognosis of patients with TP53 mutation was poor compared with those without TP53 mutation, but the difference wasn't statistically significant (P =0.08). CONCLUSION The application of next-generation sequencing technology is of great significance in myeloid malignancies, which is helpful to better understand the pathogenesis of the disease, to judge the prognosis and to find possible therapeutic targets.
Humans ; Leukemia, Myeloid, Acute/genetics* ; Nucleophosmin ; Prognosis ; Retrospective Studies ; High-Throughput Nucleotide Sequencing ; Myeloproliferative Disorders ; Mutation

Objective: To evaluate the association between pre-and post-diagnosis body mass index (BMI) and risk of colorectal cancer (CRC) death. Methods: The cohort consisted of 3, 057 CRC patients from Shanghai who were diagnosed from Jan. 1, 2009 to Dec. 31, 2011 and aged from 20 to 74 years. The pre- and post-diagnosis BMI and clinical and lifestyle factors were collected at baseline. Death information was collected using record linkage with the Shanghai Cancer Registry and telephone confirmation during follow-up by the end of 2019. The Cox proportional regression model was used to estimate HR with 95% CI. Results: Analysis by multivariable Cox model showed no association between pre-diagnosis BMI and death risk in both male and female patients. Male patients with a post-diagnosis underweight BMI had an elevated risk of death compared to those in normal weight (HR=1.69, 95% CI: 1.21-2.37), especially in early stage cases. Overweight patients (HR=0.74, 95% CI: 0.61-0.89) and patients with obesity class Ⅰ (HR=0.63, 95% CI: 0.45-0.89)had better survival with decreased risks of death, especially in advanced stage cases. The decreased death risk in patients with obesity class Ⅱ was not significant (HR=0.57, 95% CI: 0.24-1.39). The P(trend) value for decreased risk of death with increased BMI in female patients was statistically significant (P<0.001), and the overweight and obesity class Ⅰ categories had better survival in advanced stage(HR(overweight)=0.62, 95% CI: 0.42-0.93; HR(obesity class Ⅰ)=0.39, 95% CI: 0.16-0.98). Both male and female patients with post-diagnosis BMI loss >2.0 kg/m(2) had an increased death risk when compared with those with stable BMI (change≤1.0 kg/m(2)) between pre- and post-diagnosis. BMI gain after diagnosis did not change death risk. Conclusions: Post-diagnosis BMI in the overweight or obesity class Ⅰ groups might be conducive to prolonging male CRC patients' survival, while underweight might result in poor prognosis. Keeping weight and avoiding excessive weight loss should be suggested for all CRC patients after diagnosis.
Female ; Humans ; Male ; Body Mass Index ; China/epidemiology* ; Colorectal Neoplasms/complications* ; Obesity/complications* ; Overweight/complications* ; Proportional Hazards Models ; Prospective Studies ; Risk Factors ; Thinness/complications* ; Young Adult ; Adult ; Middle Aged ; Aged

Objective: To evaluate the association between pre-and post-diagnosis body mass index (BMI) and risk of colorectal cancer (CRC) death. Methods: The cohort consisted of 3, 057 CRC patients from Shanghai who were diagnosed from Jan. 1, 2009 to Dec. 31, 2011 and aged from 20 to 74 years. The pre- and post-diagnosis BMI and clinical and lifestyle factors were collected at baseline. Death information was collected using record linkage with the Shanghai Cancer Registry and telephone confirmation during follow-up by the end of 2019. The Cox proportional regression model was used to estimate HR with 95% CI. Results: Analysis by multivariable Cox model showed no association between pre-diagnosis BMI and death risk in both male and female patients. Male patients with a post-diagnosis underweight BMI had an elevated risk of death compared to those in normal weight (HR=1.69, 95% CI: 1.21-2.37), especially in early stage cases. Overweight patients (HR=0.74, 95% CI: 0.61-0.89) and patients with obesity class Ⅰ (HR=0.63, 95% CI: 0.45-0.89)had better survival with decreased risks of death, especially in advanced stage cases. The decreased death risk in patients with obesity class Ⅱ was not significant (HR=0.57, 95% CI: 0.24-1.39). The P(trend) value for decreased risk of death with increased BMI in female patients was statistically significant (P<0.001), and the overweight and obesity class Ⅰ categories had better survival in advanced stage(HR(overweight)=0.62, 95% CI: 0.42-0.93; HR(obesity class Ⅰ)=0.39, 95% CI: 0.16-0.98). Both male and female patients with post-diagnosis BMI loss >2.0 kg/m(2) had an increased death risk when compared with those with stable BMI (change≤1.0 kg/m(2)) between pre- and post-diagnosis. BMI gain after diagnosis did not change death risk. Conclusions: Post-diagnosis BMI in the overweight or obesity class Ⅰ groups might be conducive to prolonging male CRC patients' survival, while underweight might result in poor prognosis. Keeping weight and avoiding excessive weight loss should be suggested for all CRC patients after diagnosis.
Female ; Humans ; Male ; Body Mass Index ; China/epidemiology* ; Colorectal Neoplasms/complications* ; Obesity/complications* ; Overweight/complications* ; Proportional Hazards Models ; Prospective Studies ; Risk Factors ; Thinness/complications* ; Young Adult ; Adult ; Middle Aged ; Aged