Neuroscience is a significant frontier discipline within the natural sciences and has become an important interdisciplinary frontier scientific field. Brain is one of the most complex organs in the human body, and its structural and functional analysis is considered the “ultimate frontier” of human self-awareness and exploration of nature. Driven by the strategic layout of “China Brain Project”, Chinese scientists have conducted systematic research focusing on “understanding the brain, simulating the brain, and protecting the brain”. They have made breakthrough progress in areas such as the principles of brain cognition, mechanisms and interventions for brain diseases, brain-like computation, and applications of brain-machine intelligence technology, aiming to enhance brain health through biomedical technology and improve the quality of human life. Due to limited understanding and comprehension of neuroscience, there are still many important unresolved issues in the field of neuroscience, resulting in a lack of effective measures to prevent and protect brain health. Therefore, in addition to actively developing new generation drugs, exploring non pharmacological treatment strategies with better health benefits and higher safety is particularly important. Epidemiological data shows that, exercise is not only an indispensable part of daily life but also an important non-pharmacological approach for protecting brain health and preventing neurodegenerative diseases, forming an emerging research field known as motor neuroscience. Basic research in motor neuroscience primarily focuses on analyzing the dynamic coding mechanisms of neural circuits involved in motor control, breakthroughs in motor neuroscience research depend on the construction of dynamic monitoring systems across temporal and spatial scales. Therefore, high spatiotemporal resolution detection of movement processes and movement-induced changes in brain structure and neural activity signals is an important technical foundation for conducting motor neuroscience research and has developed a set of tools based on traditional neuroscience methods combined with novel motor behavior decoding technologies, providing an innovative technical platform for motor neuroscience research. The protective effect of exercise in neurodegenerative diseases provides broad application prospects for its clinical translation. Applied research in motor neuroscience centers on deciphering the regulatory networks of neuroprotective molecules mediated by exercise. From the perspectives of exercise promoting neurogenesis and regeneration, enhancing synaptic plasticity, modulating neuronal functional activity, and remodeling the molecular homeostasis of the neuronal microenvironment, it aims to improve cognitive function and reduce the incidence of Parkinson’s disease and Alzheimer’s disease. This has also advanced research into the molecular regulatory networks mediating exercise-induced neuroprotection and facilitated the clinical application and promotion of exercise rehabilitation strategies. Multidimensional analysis of exercise-regulated neural plasticity is the theoretical basis for elucidating the brain-protective mechanisms mediated by exercise and developing intervention strategies for neurological diseases. Thus,real-time analysis of different neural signals during active exercise is needed to study the health effects of exercise throughout the entire life cycle and enhance lifelong sports awareness. Therefore, this article will systematically summarize the innovative technological developments in motor neuroscience research, review the mechanisms of neural plasticity that exercise utilizes to protect the brain, and explore the role of exercise in the prevention and treatment of major neurodegenerative diseases. This aims to provide new ideas for future theoretical innovations and clinical applications in the field of exercise-induced brain protection.

Piper nigrum L. is an evergreen climbing vine, which belongs to the genus Piperia in the Piperaceae family. Piper nigrum L., which known as the “king of spices”, is used as both food and medicine. The main active substances in Piper nigrum L. are alkaloids mainly composed of amides, and essential oil, as well as phenolic compounds. In this paper, the chemical compositions, especially amide alkaloids, and their biological activities of Piper nigrum L. were summarized. These studies showed that Piper nigrum L., as a medicinal and food plant, had a wide range of biological activities and was deserved further research and in-depth utilization.

Traditional Chinese Medicine (TCM), as a treasure of the Chinese nation, plays a significant role in maintaining public health. In 2019, the Central Committee of the Communist Party of China and the State Council proposed for the first time the establishment of a TCM registration and evaluation evidence system that integrates TCM theory, "personal experience" and clinical trials (referred to as the "Three-in-One" System) to promote the inheritance and innovation of TCM. Subsequently, the National Medical Products Administration issued several guiding principles to advance the improvement and implementation of this system. Owing to the complexity of its implementation, there are still differing understandings within the TCM industry regarding the positioning of the "Three-in-One" Registration and Evaluation Evidence System, as well as the connotation and value orientation of the "personal experience." To address this, Academician WANG Qi, President of the TCM Association, China International Exchange and Promotion Association for Medical and Healthcare and TCM master, led a group of academicians, TCM masters, TCM pharmacology experts and clinical TCM experts to convene a "Seminar on Promoting the Implementation of the ′Three-in-One′ Registration and Evaluation Evidence System for Chinese Medicinals." Through extensive discussions, an expert consensus was formed, clarifying the different roles of the TCM theory, "personal experience" and clinical trials within the system. It was further emphasized that the "personal experience" is the core of this system, and its data should be derived from clinical practice scenarios. In the future, the improvement of this system will require collaborative efforts across multiple fields to promote the high-quality development of the Chinese medicinal industry.

This study investigated the effects of total flavonoids of Dracocephalum moldavica(TFDM) on apoptosis in rat H9c2 cells induced by endoplasmic reticulum stress(ERS) established by oxygen-glucose deprivation and reoxygenation(OGD/R) injury and tunicamycin(TM), and explored the potential mechanisms. After successful modeling, the following groups were set in this experiment: control group, model(OGD/R or TM) group, and TFDM low-, medium-, and high-dose groups(12.5, 25, and 50 μg·mL~(-1)). The OGD/R injury model was constructed in vitro. Cell proliferation was assessed using the cell counting kit-8(CCK-8) method. The levels of lactate dehydrogenase(LDH) and creatine kinase MB isoenzyme(CKMB) in the cell supernatant were detected. Western blot was used to assess the expression of ERS-related proteins, including glucose regulatory protein 78(GRP78), C/EBP homologous protein(CHOP), activating transcription factor 6(ATF6), and apoptotic proteins B-cell lymphoma 2(Bcl-2) and Bcl-2-associated X protein(Bax). Apoptosis was detected using the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL) method. In the TM-induced ERS model, Western blot was used to measure the expression of ERS pathway-related proteins GRP78, CHOP, inositol-requiring enzyme 1(IRE1), X-box binding protein 1(XBP1), protein kinase RNA-like endoplasmic reticulum kinase(PERK), eukaryotic initiation factor 2α(eIF2α), ATF6, p-ATF6, and apoptotic proteins Bcl-2, Bax, cysteinyl aspartate specific proteinase-12(caspase-12), and cleaved caspase-12. Gene expression of GRP78, CHOP, PERK, and ATF6 was detected by real-time fluorescence quantitative PCR(RT-qPCR). Apoptosis was again detected using the TUNEL method. The results showed that in the OGD/R model, compared with the control group, the levels of LDH and CKMB in the cell supernatant were significantly increased in the OGD/R group. Compared with the OGD/R group, the levels of LDH and CKMB in the TFDM group were significantly reduced. Western blot results revealed that compared with the control group, the expression of ERS-related proteins and Bax in the OGD/R group was significantly increased, while the expression of Bcl-2 was significantly decreased. Compared with the OGD/R group, the expression of ERS-related proteins and Bax in the TFDM groups was significantly reduced, and the expression of Bcl-2 was significantly increased. TUNEL assay showed that apoptosis was significantly decreased after TFDM treatment. In the TM-induced ERS experiment, compared with the control group, the expression of ERS-related genes, ERS-related proteins, and apoptotic proteins in the TM group was significantly increased, while the expression of Bcl-2 was significantly decreased. Compared with the TM group, the expression of ERS-related genes, ERS-related proteins, and apoptotic proteins in the TFDM group was significantly reduced, and the expression of Bcl-2 was significantly increased. These results suggest that ERS exists in the OGD/R-injured H9c2 cell model, and TFDM can effectively inhibit ERS-induced apoptosis. The mechanism may be related to the downregulation of ERS pathway-related proteins and apoptotic proteins.
Animals ; Endoplasmic Reticulum Stress/drug effects* ; Apoptosis/drug effects* ; Rats ; Flavonoids/pharmacology* ; Glucose/metabolism* ; Cell Line ; Lamiaceae/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Oxygen/metabolism* ; Reperfusion Injury/physiopathology* ; Myocytes, Cardiac/cytology*

Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

OBJECTIVE: To analyze the positive rate and distribution of anti-M unexpected antibody in pediatric inpatients aged 0 to 14 years in central China. METHODS: A total of 30 049 pediatric inpatients admitted to the Second Xiangya Hospital of Central South University, Wuhan Children's Hospital and Children's Hospital Affiliated of Zhengzhou University from May 2020 to August 2022 were enrolled in this study, and relevant clinical data were collected. Blood samples from the patients were tested for blood typing and screened for unexpected antibodies. For samples that screened positive for unexpected antibodies, identification was conducted using the identification panel to determine the specificity of the antibodies. The distribution and differences of anti-M antibodies in pediatric patients of different sexes, ages, blood groups, disease types, with or without a history of blood transfusion, and across different regions were analyzed. RESULTS: Among 30 049 inpatients, the positive rate of unexpected antibodies was 0.91% (273/30 049), of which the positive rate of anti-M antibodies was 0.44% (131/30 049). The positive rate of anti-M antibodies in the neonates aged 0 to < 1 month was 0.10% (5/4 881), and all of them were IgG antibodies from their mothers; The positive rate of anti-M antibodies for the group aged from 1 month to < 1 year old was 0.23% (7/3 108), with no anti-M antibodies detected in patients aged 1-6 months; The positive rates of anti-M antibodies in the 1-4 years old group, 5-9 years old group, and 10-14 years old group were 0.87% (88/10 064), 0.38% (27/7 190), and 0.08% (4/4 806), respectively. The positive rate of anti-M antibodies in the 1-4 years old group was significantly higher than that of the other groups ( P <0.001), and there were also statistical differences in the positive rate between the 5-9 years old group and the 0-< 1 month and 10-14 years old groups ( P <0.001). The prevalences of anti-M antibodies in ABO blood group A, B, O and AB were 0.32% (30/9 482), 0.70% (58/8 293), 0.32% (31/9 595) and 0.45% (12/2 679), respectively. The prevalence of anti-M antibodies in patients with blood group B was significantly higher than that in patients with blood groups A and O ( P <0.05). The prevalences of anti-M antibodies in Hunan, Hubei and Henan was 0.18%, 0.32% and 0.71%, respectively. The prevalence of anti-M antibodies in Henan was significantly higher than that in Hunan and Hubei ( P <0.05), and the distribution showed obvious regional differences between the north and the south. There were no significant differences in the positive rate of anti-M antibodies between the children with different sexes, disease types, and with or without a history of blood transfusion (P >0.05). CONCLUSION This study reveals the distribution pattern of anti-M antibodies in pediatric inpatients aged 0-14 years in central China, which has reference value for the research on unexpected red blood cell antibodies in Chinese children.
Humans ; Child ; China ; Infant ; Child, Preschool ; Adolescent ; Female ; Male ; Inpatients ; Infant, Newborn ; Blood Grouping and Crossmatching ; Antibodies/blood*

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth＞3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.

Objective To establish a high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)for the simultaneous determination of gefitinib,erlotinib,nillotinib and imatinib plasma concentrations and analyze the results.Methods The plasma samples were treated with acetonitrile precipitation and separated by Diamonsil C18 column(150 mm ×4.6 mm,3.5 μm)with mobile phase of 0.1％formic acid water(A)-0.1％formic acid acetonitrile(B).The flow rate of gradient elution was 0.7 mL·min-1,and the column temperature was 40 ℃ and the injection volume was 3 μL.Using arotinib as the internal standard,the scanning was carried out by using electrospray ionization source in positive ionization mode with multi-reaction monitoring.The specificity,standard curve,lower limit of quantitation,precision,accuracy,recovery rate,matrix effect and stability of the method were investigated.The concentrations of imatinib and erlotinib in 20 patients with chronic myelogenous leukemia(CML)and gefitinib and erlotinib in 3 patients with non-small cell lung cancer were measured.Results The standard curves of the four drugs were as follows,gefitinib:y=2.536 × 10-3x+9.362 × 10-3(linear range 20-2 000 ng·mL-1,R2=0.996 6);erlotinib:y=3.575× 10-3x+7.406 × 10-3(linear range 50-5 000 ng·mL-1,R2=0.994 9);nilotinib:y=1.945 x 10-3x+0.015 643(linear range 50-5 000 ng·mL-1,R2=0.990 6);imatinib:y=4.56 x 10-3x+0.010 451(linear range 100～104 ng·mL-1,R2=0.9963).RSD of intra-day and inter-day were less than 10％,and the accuracy ranged from 90％to 110％,and the recovery rates were 91.35％to 98.93％(RSD＜10％);the matrix effect ranged from 91.64％to 107.50％(RSD＜10％).Determination of 23 patients showed that the blood concentration of nilotinib ranged from 623.76 to 2 934.13 ng·mL-1,and the blood concentration of imatinib ranged from 757.77 to 2 637.71 ng·mL-1,and the blood concentration of gefitinib ranged from 214.76 to 387.40 ng·mL-1.The serum concentration of erlotinib was 569.57 ng·mL-1.Conclusion The method of this research is simple,fast,sensitive and dedicated,which can be monitored by the concentration of clinical blood.

Objective:To explore the differences in distribution of colorectal cancer-related risk factors between patients with early-onset colorectal cancer (EOCRC) and those with late-onset colorectal cancer (LOCRC) in a Chinese cohort, and to provide reference and guidance for the prevention, diagnosis, and treatment of EOCRC.Methods:Using data from the National Colorectal Cancer Cohort study cohort, 5377 patients with newly diagnosed colorectal cancer (CRC) attending the Department of Colorectal Surgery and Oncology of the Second Affiliated Hospital, Zhejiang University School of Medicine from June 2018 to February 2023 were included in the study cohort. Questionnaires capturing epidemiological features, including lifestyle and dietary habits, were administered. The patients were divided into two groups, the cut-off age being 50 years. Those aged ≥50 years were defined as having LOCRC and those aged <50 years as having EOCRC. Wilcoxon (continuous variates) or χ 2 tests (categorical variates) were performed to compare differences in epidemiological features. Results:A total of 3799 people who had completed the questionnaire were included in this study, 491 of whom had EOCRC and 3308 LOCRC. The response rate to the questionnaire was 70.7%. The median ages of patients in the EOCRC and LOCRC groups were 43 and 66 years, respectively. There was a higher proportion of female patients (48.5% [253/491] vs. 35.8% [1184/3308], χ 2=28.8, P<0.001) in the EOCRC than the LOCRC group. Patients with EOCRC and lower body mass index (medium 22.1 kg/m 2 vs. 22.9 kg/m 2, W=744 793, P=0.005) and lower proportion of abdominal obesity (87.2% [428/491] vs. 93.8% [3103/3308], χ 2=38.3, P<0.001). Patients with EORC significantly less commonly reported a history of hypertension (5.9% [29/491] vs. 41.6% [1375/3308], χ 2=231.8, P<0.001), diabetes (1.4% [7/491] vs. 14.4% [476/3308], χ 2=63.6, P<0.001) and cardiovascular and cerebrovascular diseases (0.8% [4/491] vs. 7.3% [241/3308], χ 2=28.6, P<0.001). However, the proportion of patients with a family history of CRC was significantly higher ( P<0.05) in the EOCRC group (10.2% [50/491] vs. 6.9% [227/3 308], χ 2=6.5, P=0.010]. In terms of lifestyle, patients with EOCRC had shorter sleep duration (median: 8.0 hours vs. 8.5 hours, W=578 989, P<0.001), and were less likely to participate in physical exercise (29.5% [145/491] vs. 38.7% [1281/3308] χ 2=15.0, P<0.001) or engage in physical work (65.2% [320/491] vs. 74.1% [2450/3308], χ 2=16.7, P<0.001). Meanwhile, in the EOCRC group a lower percentage of patients were smokers (29.3% [144/491] vs. 42.7% [1411/3308], χ 2=46.9, P<0.001) and they smoked less (median 17.6 pack/year vs. 30.0 pack/year,W=55 850, P<0.001). Fewer patients in the EOCRC group habitually drank alcohol (21.0% [103/491] vs. 38.0% [1257/3308], χ 2=57.5, P<0.001) or tea (17.5% [86/491] vs. 28.7% [948/3308], χ 2=26.2, P<0.001) than in the LOCRC group. Compared with the LOCRC group, patients with EOCRC had a higher frequency of intake of fresh meat, fresh fruit, eggs, and dairy products and a lower frequency of intake of preserved meat and pickled vegetables; these differences are statistically significant (all P<0.05). There was no statistically significant difference in consumption of fresh vegetables or a high-sugar diet between the two groups (both P>0.05). Conclusions:This study highlights disparities in adverse lifestyle and dietary habits between patients in China with EOCRC versus LOCRC.