Objective: The purpose of this study was to explore the capacity for energy production under conditions of increased energy demand in schizophrenia (SCZ) subjects compared to healthy controls. Methods: Twelve healthy controls (33.00±6.07 years) and 12 subjects diagnosed with SCZ or schizoaffective disorder (36.00±8.33 years) matched for age and sex, were recruited for this study. Hypoxic stress was induced during MR scans to elevate the energy demand on the subjects’ bioenergetic systems. Participants breathed air with a lower oxygen concentration (FiO2=13%), maintaining their SpO2 levels (86%) during the initial phase of the scan. 31Phosphorus MR spectroscopy was employed to examine metabolite levels, including phosphocreatine (PCr), β-adenosine triphosphate (ATP), and inorganic phosphate (Pi), as well as the ratios of PCr/Pi and PCr/β-ATP, in regions such as the prefrontal cortex (PFC), anterior cingulate cortex (ACC), and posterior cortex (POC), as well as across the entire brain, during both hypoxia and hyperoxia scans. Results: Subjects with SCZ had significantly lower levels of Pi across the brain and particularly, in the PFC, POC, and ACC during the hypoxia scan. Moreover, levels of PCr/Pi, indicative of mitochondrial energy production, were found to be higher in the same brain regions in the SCZ group. No significant differences were found in hyperoxia scan phase. Conclusion These findings suggest a deficit in the bioenergetic systems of individuals with SCZ under conditions of heightened energy demand. Further studies are warranted.

A growing body of research points out that gut microbiota plays a key role in tumor immunotherapy. By optimizing the composition of intestinal microbiota, it is possible to effectively improve immunotherapy resistance and enhance its therapeutic effect. This article comprehensively analyzes the mechanism of intestinal microbiota influencing tumor immunotherapy resistance, expounds the current strategies for targeted regulation of intestinal microbiota, such as traditional Chinese medicine and plant components, fecal microbiota transplantation, probiotics, prebiotics and dietary therapy, and explores the potential mechanisms of these strategies to improve patients' resistance to tumor immunotherapy. At the same time, the article also briefly discusses the prospects and challenges of targeting intestinal microbiota to improve tumor immunotherapy resistance, which provides a reference for related research to help the strategy research of reversing tumor immunotherapy resistance.

ObjectiveBased on the TCM theory of "Yang transforms materials to Qi while Yin constitutes material form"， this paper explored the effects of Zuogui Wan and Yougui Wan on the molecular mechanism of mitochondrial biogenesis during the adipogenic differentiation process of rat bone marrow mesenchymal stem cells （BMSCs） by mediating peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α） and peroxisome proliferators-activated receptor γ （PPARγ）， providing theoretical support for the prevention and treatment of postmenopausal osteoporosis （PMOP） using Zuogui Wan and Yougui Wan. MethodsBMSCs were divided into a blank group， Zuogui Wan （ZGW） group， Yougui Wan （YGW） group， and Progynova group. Cell identification was performed using flow cytometry. The growth curves of BMSCs were plotted using the methylthiazolyldiphenyl-tetrazolium bromide （MTT） method， and the effects of Zuogui Wan and Yougui Wan on the proliferation of BMSCs were detected. The Oil red O staining method was used to detect lipid droplet formation. The Western blot method was used to detect the expression of adipogenesis-related factors PPARγ， CCAAT/enharcer-binding protein （C/EBP）α， C/EBPβ， lipoprotein lipase （LPL） protein， brown adipose tissue-related （BAT） proteins PGC-1α， uncoupcing protein 1 （UCP1）， PR domdin-containing protein 16 （PRDM16）， mitochondrial biogenesis-related PGC-1α， nuclear respiratory factor 1 （Nrf1）， nuclear factor E₂-related factor 2 （Nrf2）， and mitochondrial transcription factor A （TFAM）. The expression of adipogenesis-related factors PPARγ， C/EBPα， C/EBPβ， LPL genes， and the copy number of cytochrome B （CytoB mtDNA） gene was detected using real-time polymerase chain reaction （Real-time PCR）. Mitochondrial ultrastructure was detected using transmission electron microscopy. ResultsCompared with that in the blank group， the proliferation ability of BMSCs in each treatment group increased continuously as the intervention progressed， and lipid droplets significantly decreased after the drug intervention. The mRNA and protein expression levels of adipogenesis-related factors PPARγ， C/EBPα， C/EBPβ， and LPL were significantly downregulated （P<0.01）， while those of the BAT-related factors PGC-1α， UCP1， PRDM16 were significantly upregulated （P<0.01）. The number of mitochondria increased， accompanied by reduced swelling. The double membrane and cristae structure were clear， and the internal cristae rupture was reduced. The copy number of CytoB mtDNA in each treatment group was significantly increased （P<0.01）. The protein expression levels of mitochondrial biogenesis-related PGC-1α， Nrf1， Nrf2， and TFAM in each treatment group were significantly increased （P<0.01）. ConclusionBoth Zuogui Wan and Yougui Wan can prevent and treat PMOP by intervening in mitochondrial biogenesis in BMSCs through PGC-1α/PPARγ.

Objective:To investigate the clinical characteristics and genetic etiology of Duchenne muscular dystrophy (DMD) with myogenic tumors.Methods:The clinical data of 2 children with DMD combined with myogenic tumors diagnosed in Children′s Hospital Affiliated to Zhengzhou University in July 2021 and February 2022 were collected. The relevant literature was reviewed to summarize the clinical characteristics and explore the mechanism of the dystrophin ( DMD) gene in myogenic tumors. Results:A 6-year and 10-month-old boy with DMD (deletion of exon 45) and a 12-year-old boy with DMD (deletion of exon 51) were diagnosed with tumors. They were diagnosed with DMD for delayed motor development in the Department of Neurology of Children′s Hospital Affiliated to Zhengzhou University. They presented with painless masses in the waist. Postoperative pathological diagnosis: the pathology and immunohistochemistry of case 1 showed an alveolar rhabdomyosarcoma (ARMS) and both myogenin and myogenic differentiation 1 positive; the pathology and immunohistochemistry of case 2 showed an alveolar soft part sarcoma(ASPS) and transcription factor enhancer 3 positive; both cases were myogenic tumors. Literature review (including this paper) showed that there were in total 14 cases with DMD combined with myogenic tumors including 13 cases of rhabdomyosarcoma (RMS) and 1 case of ASPS. All of them are male, and the age of onset of the tumors was 4-17 years. Pathological subtypes were described in 6 cases of ARMS and 5 cases of embryonal RMS, and were not described in 2 cases. The 9 cases described all had large deletions in the DMD gene which can change the reading frame of the DMD gene, and all gene mutations did not exceed exon 62. Conclusions:DMD gene with deletion may increase the risk of having myogenic tumors, and RMS is more common, which is manifested as painless mass in early stage. All DMD gene deletions do not exceed exon 62 and lead to change of the gene reading frame with severe clinical phenotype and degenerative changes in muscle function.

Objective: The purpose of this study was to explore the capacity for energy production under conditions of increased energy demand in schizophrenia (SCZ) subjects compared to healthy controls. Methods: Twelve healthy controls (33.00±6.07 years) and 12 subjects diagnosed with SCZ or schizoaffective disorder (36.00±8.33 years) matched for age and sex, were recruited for this study. Hypoxic stress was induced during MR scans to elevate the energy demand on the subjects’ bioenergetic systems. Participants breathed air with a lower oxygen concentration (FiO2=13%), maintaining their SpO2 levels (86%) during the initial phase of the scan. 31Phosphorus MR spectroscopy was employed to examine metabolite levels, including phosphocreatine (PCr), β-adenosine triphosphate (ATP), and inorganic phosphate (Pi), as well as the ratios of PCr/Pi and PCr/β-ATP, in regions such as the prefrontal cortex (PFC), anterior cingulate cortex (ACC), and posterior cortex (POC), as well as across the entire brain, during both hypoxia and hyperoxia scans. Results: Subjects with SCZ had significantly lower levels of Pi across the brain and particularly, in the PFC, POC, and ACC during the hypoxia scan. Moreover, levels of PCr/Pi, indicative of mitochondrial energy production, were found to be higher in the same brain regions in the SCZ group. No significant differences were found in hyperoxia scan phase. Conclusion These findings suggest a deficit in the bioenergetic systems of individuals with SCZ under conditions of heightened energy demand. Further studies are warranted.

Objective: The purpose of this study was to explore the capacity for energy production under conditions of increased energy demand in schizophrenia (SCZ) subjects compared to healthy controls. Methods: Twelve healthy controls (33.00±6.07 years) and 12 subjects diagnosed with SCZ or schizoaffective disorder (36.00±8.33 years) matched for age and sex, were recruited for this study. Hypoxic stress was induced during MR scans to elevate the energy demand on the subjects’ bioenergetic systems. Participants breathed air with a lower oxygen concentration (FiO2=13%), maintaining their SpO2 levels (86%) during the initial phase of the scan. 31Phosphorus MR spectroscopy was employed to examine metabolite levels, including phosphocreatine (PCr), β-adenosine triphosphate (ATP), and inorganic phosphate (Pi), as well as the ratios of PCr/Pi and PCr/β-ATP, in regions such as the prefrontal cortex (PFC), anterior cingulate cortex (ACC), and posterior cortex (POC), as well as across the entire brain, during both hypoxia and hyperoxia scans. Results: Subjects with SCZ had significantly lower levels of Pi across the brain and particularly, in the PFC, POC, and ACC during the hypoxia scan. Moreover, levels of PCr/Pi, indicative of mitochondrial energy production, were found to be higher in the same brain regions in the SCZ group. No significant differences were found in hyperoxia scan phase. Conclusion These findings suggest a deficit in the bioenergetic systems of individuals with SCZ under conditions of heightened energy demand. Further studies are warranted.

Objective:To analyze the correlation and predictive value of obesity measurement indicators and cerebrovascular function scores in healthy physical examination population.Methods:It was a cross-sectional analysis that employed a simple random sampling method to select 3 496 individuals who underwent healthy physical examinations and cerebrovascular function tests at the Physical Examination Center of the Affiliated Hospital of Guizhou Medical University from January to December 2022. The general information, physical examination data, biochemical examination results, human component analyses, and cerebrovascular function integral data were collected. Based on cerebrovascular function scores, the participants were divided into high-risk group (0-24 points, 70 cases), medium-risk group (25-49 points, 317 cases), low-risk group (50-74 points, 787 cases), and normal group (≥75 points, 2 322 cases). Spearman correlation analysis and receiver operating characteristic (ROC) curve analyses were utilized to assess the correlation and predictive value of obesity measurement indicators and cerebrovascular function integrals.Results:Among the 3 496 subjects included in the analysis, 2 018 were male and 1 478 were female, with an average age of (46.4±7.9) years. The age, systolic blood pressure, diastolic blood pressure, body mass index, waist-to-hip ratio, body fat ratio, body fat content, visceral fat area, fasting blood glucose, total cholesterol, low-density lipoprotein, homocysteine all exhibited an increasing trend as the cerebrovascular function integral value decreased (all P<0.05). The skeletal muscle content in the low-risk group was significantly higher than those in the high-risk group, medium-risk group, and normal group [45.00 (36.80, 50.60) vs 44.10 (36.98, 50.45), 44.50 (37.80, 50.20), and 42.75 (36.30, 48.60) kg, respectively] ( P<0.05). The triglyceride level in the medium-risk group was higher when compared to those in the high-risk group, low-risk group, and normal group[1.87 (1.29, 2.70) vs 1.71 (1.24, 2.80), 1.75 (1.18, 2.70), and 1.43 (1.00, 2.14) mmol/L] ( P<0.05). The high-density lipoprotein level in the normal group was higher than the high-risk group, medium-risk group, and low-risk group[1.26 (1.05, 1.51) vs 1.16 (0.94, 1.36), 1.15 (0.99, 1.39), and 1.16 (0.97, 1.39) mmol/L, respectively] ( P<0.05). The increases in systolic blood pressure, diastolic blood pressure, body mass index, and body fat content were all moderately negatively correlated with the cerebrovascular function score ( rs=-0.347, -0.335, -0.370, and -0.340, respectively, all P<0.05). The increase in age ( OR=1.012, 95% CI: 1.002-1.022), systolic blood pressure ( OR=1.027, 95% CI: 1.017-1.036), diastolic blood pressure ( OR=1.028, 95% CI: 1.014-1.042), body mass index ( OR=1.157, 95% CI: 1.083-1.237), body fat rate ( OR=1.021, 95% CI: 1.007-1.035), and fasting blood glucose ( OR=1.072, 95% CI: 1.020-1.127) were all positively correlated with the decrease of the cerebrovascular function score; conversely, the increase in skeletal muscle content ( OR=0.967, 95% CI: 0.951-0.982) was negatively correlated with the decrease in cerebrovascular function score (all P<0.05). The area under the curve for the combined prediction of cerebrovascular function integral value by age, systolic blood pressure, diastolic blood pressure, body mass index, body fat rate, skeletal muscle content, and fasting blood glucose was 0.754. Conclusions:As the body mass index and body fat content increase and the skeletal muscle content decreases in the healthy physical examination population, the likelihood of abnormal cerebrovascular function integral values rises; the combination of age, systolic blood pressure, diastolic blood pressure, body mass index, body fat percentage, skeletal muscle content, and fasting blood glucose indicators can predict the increased risk of cerebrovascular function integral values.

Objective:This study aims to explore the risk factors of Multi-center Investigator-Initiated Clinical Trials (MIITs), and provide a basis for developing study management strategies.Methods:The original draft of MIIT risk evaluation factors was determined through literature analysis and internal discussions of the research group. Thirty five experts were consulted using the Delphi method, and then the MIIT risk evaluation elements were finally determined. Analytic Hierarchy Process (AHP) was used to calculate the weights of each index.Results:The recovery rates of both rounds of expert consultation were 100%, and the degree of expert authority was 0.856. The study ultimately formed an MIIT risk evaluation framework consisting of three first-class indexes, twelve second-class indexes, and thirty-eight third-class indexes. The weight values of the first-class indexes (start-up period, implementation period, and summary period) were 0.209 8, 0.710 6, and 0.079 6, respectively. Meanwhile, the weight values of the second-class indexes and third-class indexes were determined.Conclusions:Exploring the risk evaluation factors of MIIT provides valuable insights into identifying critical risk points, which, in turn, contributes to enhancing MIIT management efficiency, research progress, and quality.

Objective:This study aims to construct an evaluation index system suitable for the core competency of Clinical Research Coordinators (CRCs) in Investigator-Initiated Trials (IITs) in China.Methods:This study developed a system framework through the Onion Model, literature research, and expert interviews, utilized the Delphi method to build the index system. and analyzed the weight of each indicator through the Analytic Hierarchy Process (AHP).Results:Four first-level indicators were basic knowledge (0.143), job skills (0.300 8), professional quality (0.483 9), and personality traits (0.072 3). Besides, 18 second-level indicators and 49 third-level indicators were developed through the Delphi method. According to the third round expert′s consultation, the average scores of all indexes were >3.50, the authoritative coefficient was 0.86, the coefficient of variation of each index was <0.30, and Kendall coefficients of concordance were 0.183~0.366 ( P<0.001). The consistency ratios of single-sort were<0.1, and the overall sort of all indexes was 0.043 7, which showed good logical reliability. Conclusions:This evaluation index system for Clinical Research Coordinators is of great scientific sense. It provides IIT-conducting investigators in institutions with a proficient assessment tool to help them find qualified and reliable CRCs.

Cervi Cornu Pantotrichum is a precious animal-derived Chinese medicinal material, while there are often adulterants derived from animals not specified in the Chinese Pharmacopeia in the market, which disturbs the safety of medication. This study was conducted with the aim of strengthening the quality control of Cervi Cornu Pantotrichum and standardizing the medication. To achieve digital identification of Cervi Cornu Pantotrichum from different sources, a digital identification model was constructed based on ultra-high performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry(UHPLC-QTOF-MS~E) combined with an adaptive boosting algorithm(Adaboost). The young furred antlers of sika deer, red deer, elk, and reindeer were processed and then subjected to polypeptide analysis by UHPLC-QTOF-MS~E. Then, the mass spectral data reflecting the polypeptide information were obtained by digital quantification. Next, the key data were obtained by feature screening based on Gini index, and the digital identification model was constructed by Adaboost. The model was evaluated based on the recall rate, F_1 composite score, and accuracy. Finally, the results of identification based on the constructed digital identification model were validated. The results showed that when the Gini index was used to screen the data of top 100 characteristic polypeptides, the digital identification model based on Adaboost had the best performance, with the recall rate, F_1 composite score, and accuracy not less than 0.953. The validation analysis showed that the accuracy of the identification of the 10 batches of samples was as high as 100.0%. Therefore, based on UHPLC-QTOF-MS~E and Adaboost algorithm, the digital identification of Cervi Cornu Pantotrichum can be realized efficiently and accurately, which can provide reference for the quality control and original animal identification of Cervi Cornu Pantotrichum.
Animals ; Algorithms ; Antlers/chemistry* ; Boosting Machine Learning Algorithms ; Chromatography, High Pressure Liquid/methods* ; Deer ; Drugs, Chinese Herbal/chemistry* ; Mass Spectrometry/methods* ; Quality Control ; Reindeer ; Tandem Mass Spectrometry/methods* ; Tissue Extracts/analysis*