ObjectiveThe proteome of biological evidence contains rich genetic information, namely single amino acid polymorphisms (SAPs) in protein sequences. However, due to the lack of efficient and convenient analysis tools, the application of SAP in public security still faces many challenges. This paper aims to meet the application requirements of SAP analysis for forensic biological evidence’s proteome data. MethodsThe software is divided into three modules. First, based on a built-in database of common non-synonymous single nucleotide polymorphisms (nsSNPs) and SAPs in East Asian populations, the software integrates and annotates newly identified exonic nsSNPs as SAPs, thereby constructing a customized SAP protein sequence database. It then utilizes a pre-installed search engine—either pFind or MaxQuant—to perform analysis and output SAP typing results, identifying both reference and variant types, along with their corresponding imputed nsSNPs. Finally, SAPTyper compares the proteome-based typing results with the individual’s exome-derived nsSNP profile and outputs the comparison report. ResultsSAPTyper accepts proteomic DDA mass spectrometry raw data (DDA acquisition mode) and exome sequencing results of nsSNPs as input and outputs the report of SAPs result. The pFind and Maxquant search engines were used to test the proteome data of 2 hair shafts of2 individuals, and both obtained SAP results. It was found that the results of the Maxquant search engine were slightly less than those of pFind. This result shows that SAPTyper can achieve SAP fingding function. Moreover, the pFind search engine was used to test the proteome data of 3 hair shafts from 1 European person and 1 African person in the literature. Among the sites fully matched by the literature method, sites detected by SAPTyper are also included; for semi-matching sites, that is, nsSNPs are heterozygous, both literature method and SAPTyper method had the risk of missing detection for one type of the allele. Comparing the analysis results of SAPTyper with the SAP test results reported in the literature, it was found that some imputed nsSNP sites identified by the literature method but not detected by SAPTyper had a MAF of less than 0.1% in East Asian populations, and therefore they were not included in the common nsSNP database of East Asian populations constructed by this software. Since the database construction of this software is based on the genetic variation information of East Asian populations, it is currently unable to effectively identify representative unique common variation sites in European or African populations, but it can still identify SAP sites shared by these populations and East Asian populations. ConclusionAn automated SAP analysis algorithm was developed for East Asian populations, and the software named SAPTyper was developed. This software provides a convenient and efficient analysis tool for the research and application of forensic proteomic SAP and has important application prospects in individual identification and phenotypic inference based on SAP.

The neurophysiological mechanisms by which exercise improves cognitive function have not been fully elucidated. A comprehensive and systematic review of current domestic and international neurophysiological evidence on exercise improving cognitive function was conducted from multiple perspectives. At the molecular level, exercise promotes nerve cell regeneration and synaptogenesis and maintains cellular development and homeostasis through the modulation of a variety of neurotrophic factors, receptor activity, neuropeptides, and monoamine neurotransmitters, and by decreasing the levels of inflammatory factors and other modulators of neuroplasticity. At the cellular level, exercise enhances neural activation and control and improves brain structure through nerve regeneration, synaptogenesis, improved glial cell function and angiogenesis. At the structural level of the brain, exercise promotes cognitive function by affecting white and gray matter volumes, neural activation and brain region connectivity, as well as increasing cerebral blood flow. This review elucidates how exercise improves the internal environment at the molecular level, promotes cell regeneration and functional differentiation, and enhances the brain structure and neural efficiency. It provides a comprehensive, multi-dimensional explanation of the neurophysiological mechanisms through which exercise promotes cognitive function.
Animals ; Humans ; Brain/physiology* ; Cognition/physiology* ; Exercise/physiology* ; Nerve Regeneration/physiology* ; Neuronal Plasticity/physiology*

OBJECTIVE: To investigate the characteristics of gut microbiota changes in patients with acute myeloid leukemia (AML) undergoing induction chemotherapy and to explore the relationship between infectious complications and gut microbiota. METHODS: Fecal samples were collected from 37 newly diagnosed AML patients at four time points: before induction chemotherapy, during chemotherapy, during the neutropenic phase, and during the recovery phase. Metagenomic sequencing was used to analyze the dynamic changes in gut microbiota. Correlation analyses were conducted to assess the relationship between changes in gut microbiota and the occurrence of infectious complications. RESULTS: During chemotherapy, the gut microbiota α-diversity (Shannon index) of AML patients exhibited significant fluctuations. Specifically, the diversity decreased significantly during induction chemotherapy, further declined during the neutropenic phase (P < 0.05, compared to baseline), and gradually recovered during the recovery phase, though not fully returning to baseline levels.The abundances of beneficial bacteria, such as Firmicutes and Bacteroidetes, gradually decreased during chemotherapy, whereas the abundances of opportunistic pathogens, including Enterococcus, Klebsiella, and Escherichia coli, progressively increased.Analysis of the dynamic changes in gut microbiota of seven patients with bloodstream infections revealed that the bloodstream infection pathogens could be detected in the gut microbiota of the corresponding patients, with their abundance gradually increasing during the course of infection. This finding suggests that bloodstream infections may be associated with opportunistic pathogens originating from the gut microbiota.Compared to non-infected patients, the baseline samples of infected patients showed a significantly lower relative abundance of Bacteroidetes (P < 0.05). Regression analysis indicated that Bacteroidetes abundance is an independent predictive factor for infectious complications (P < 0.05, OR =13.143). CONCLUSION During induction chemotherapy in AML patients, gut microbiota α-diversity fluctuates significantly, and the abundance of opportunistic pathogens increase, which may be associated with bloodstream infections. Patients with lower baseline Bacteroidetes abundance are more prone to infections, and its abundance can serve as an independent predictor of infectious complications.
Humans ; Gastrointestinal Microbiome ; Leukemia, Myeloid, Acute/microbiology* ; Induction Chemotherapy ; Feces/microbiology* ; Male ; Female ; Middle Aged

OBJECTIVE: To elucidate the modulation mechanism of Suanzaoren Decoction (SZRD) on basolateral amygdala (BLA) neuronal activity to alleviate chronic restraint stress (CRS)-related behavioral deficits. METHODS: The male C57BL/6J mice were assigned to 4 groups using the complete randomization method, including control (CON, n=19), CRS (n=19), SZRD (n=21), and fluoxetine (Flu, n=22) groups. Mice were restrained for 6 h per day, over a 21-d period to establish CRS models. The CON group remained in their cages without food or water during the 6-h matching period. SZRD and Flu groups received intragastric administration of SZRD (4.68 g/kg) and Flu (20 mg/kg) daily, respectively, 30 min before restraint for 21 consecutive days. The therapeutic effects of SZRD were evaluated using behavioral tests including the tail suspension test, elevated plus maze test, and forced swimming test. The cellular Fletcher B. Judson murine osteosarcoma proto-oncogene (c-Fos) expression in the BLA was measured using immunofluorescence, while action potential (AP) firing and synaptic transmission in BLA pyramidal neurons were evaluated using whole-cell patch-clamp recordings. RESULTS: SZRD administration significantly increased time spent in the open arms and open-arm entries while reducing immobility time (P<0.05 or P<0.01). It downregulated CRS-induced c-Fos expression and AP firing of pyramidal neurons in the BLA (P<0.01). Additionally, SZRD selectively attenuated excitatory (P<0.01), but not inhibitory, synaptic transmission onto BLA pyramidal neurons. CONCLUSION SZRD alleviated CRS-induced anxiety- and depression-like behaviors in mice by modulating the excitability and synaptic transmission of BLA pyramidal neurons.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Depression/complications* ; Pyramidal Cells/pathology* ; Male ; Mice, Inbred C57BL ; Basolateral Nuclear Complex/pathology* ; Restraint, Physical ; Anxiety/complications* ; Behavior, Animal/drug effects* ; Stress, Psychological/physiopathology* ; Mice ; Proto-Oncogene Proteins c-fos/metabolism* ; Action Potentials/drug effects* ; Synaptic Transmission/drug effects*

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

With the growing emphasis on maternal and child oral health, the significance of managing oral health across preconception, pregnancy, and infancy stages has become increasingly apparent. Oral health challenges extend beyond affecting maternal well-being, exerting profound influences on fetal and neonatal oral development as well as immune system maturation. This expert consensus paper, developed using a modified Delphi method, reviews current research and provides recommendations on maternal and child oral health management. It underscores the critical role of comprehensive oral assessments prior to conception, diligent oral health management throughout pregnancy, and meticulous oral hygiene practices during infancy. Effective strategies should be seamlessly integrated across the life course, encompassing preconception oral assessments, systematic dental care during pregnancy, and routine infant oral hygiene. Collaborative efforts among pediatric dentists, maternal and child health workers, and obstetricians are crucial to improving outcomes and fostering clinical research, contributing to evidence-based health management strategies.
Humans ; Pregnancy ; Female ; Infant ; Consensus ; Mouth Diseases/therapy* ; Pregnancy Complications/therapy* ; Oral Health ; Infant, Newborn ; Delphi Technique ; Oral Hygiene

Identifying drug-drug interactions (DDIs) is essential to prevent adverse effects from polypharmacy. Although deep learning has advanced DDI identification, the gap between powerful models and their lack of clinical application and evaluation has hindered clinical benefits. Here, we developed a Multi-Dimensional Feature Fusion model named MDFF, which integrates one-dimensional simplified molecular input line entry system sequence features, two-dimensional molecular graph features, and three-dimensional geometric features to enhance drug representations for predicting DDIs. MDFF was trained and validated on two DDI datasets, evaluated across three distinct scenarios, and compared with advanced DDI prediction models using accuracy, precision, recall, area under the curve, and F1 score metrics. MDFF achieved state-of-the-art performance across all metrics. Ablation experiments showed that integrating multi-dimensional drug features yielded the best results. More importantly, we obtained adverse drug reaction reports uploaded by Xiangya Hospital of Central South University from 2021 to 2023 and used MDFF to identify potential adverse DDIs. Among 12 real-world adverse drug reaction reports, the predictions of 9 reports were supported by relevant evidence. Additionally, MDFF demonstrated the ability to explain adverse DDI mechanisms, providing insights into the mechanisms behind one specific report and highlighting its potential to assist practitioners in improving medical practice.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To explore the clinical effects of tibial periosteal distraction combined with antibiotic bone cement in treating diabetic foot ulcer.Methods:The study was a retrospective observational study. From March 2021 to March 2024, 52 patients with diabetic foot ulcers who met the inclusion criteria were admitted to Gansu Provincial People's Hospital, including 25 males and 27 females, aged 34-77 years. According to the treatment methods used by the patients, they were divided into control group (22 cases) treated with antibiotic bone cement alone and combined group (30 cases) treated with tibial periosteal distraction combined with antibiotic bone cement. Toe amputation rate, limb amputation rate, length of hospitalization, and ulcer healing time-consuming of patients were recorded. Before the first treatment and 3 weeks after the last treatment, the ankle skin temperature and ankle-brachial index of the affected foot were measured routinely, the pain of the affected foot was evaluated by using visual analog scale (VAS), and the peripheral nerve function of the affected foot was evaluated by 10 g nylon thread examination (denoted as 10 g nylon thread test value). Three weeks after the last treatment, the clinical efficacy of patients was evaluated and the overall rate of clinical efficacy was calculated.Results:There were no statistically significant differences in the comparison of toe amputation rate and limb amputation rate of patients in the 2 groups ( P>0.05). The length of hospitalization and ulcer healing time-consuming of patients in combined group were (23±5) and (41±6) d, respectively, which were significantly shorter than (27±5) and (46±6) d in control group (with t values of 3.08 and 3.18, respectively, both P values <0.05). The ankle skin temperature of the affected foot of patients in combined group was (34.1±1.5) ℃, and the ankle-brachial index was 0.72±0.08 three weeks after the last treatment, which were significantly higher than (32.1±1.6) ℃ and 0.58±0.09 before the first treatment within the group (with t values of 5.10 and 6.37, respectively, P<0.05) and (31.8±1.1) ℃ and 0.59±0.09 three weeks after the last treatment in control group (with t values of 6.88 and 5.49, respectively, P<0.05). The pain VAS score of the affected foot of patients in combined group 3 weeks after the last treatment was significantly lower than that before the first treatment within the group and 3 weeks after the last treatment in control group (with t values of 8.16 and 6.83, respectively, both P values <0.05), and the 10 g nylon thread test value was significantly higher than that before the first treatment within the group and 3 weeks after the last treatment in control group (with t values of 6.15 and 4.23, respectively, both P values <0.05). Three weeks after the last treatment, the overall rate of clinical efficacy of patients in combined group was 96.7% (29/30), which was significantly higher than 63.6% (14/22) in control group, χ2=7.51, P<0.05. Conclusions:Tibial periosteal distraction combined with antibiotic bone cement has good clinical effects in the treatment of diabetic foot ulcers. It can shorten the length of patients' hospitalization, promote the healing of the ulcers, reduce the pain in the affected foot, and improve the blood supply and peripheral nerve function in the affected foot.

Objective: To delineate the epidemiologic profile of rifampicin resistant pulmonary tuberculosis (RR-PTB) among students in Chongqing, so as to provide evidence for effectively controlling RR-PTB outbreaks in schools. Methods: Individual level surveillance records of 395 student RR-PTB cases reported from 2015 to 2024 were extracted from the China Information System for Disease Control and Prevention. The Joinpoint regression analysis was employed to quantify temporal trends in the registration rate of student RR-PTB cases, and the comparison of RR-PTB registration rates with different demographic characteristics and different regions was performed using Chi-square test. Results: From 2015 to 2024, a total of 395 student RR-PTB cases were identified, with the registration rate ranged from 0.07 per 100 000 to 1.47 per 100 000, showed a fluctuating upward trend ( AAPC= 35.22%, t =4.13, P <0.01). A turning point was detected in 2017, rates rose during 2015-2017 (APC=295.23%， t =4.62， P < 0.01 ) and plateaued thereafter (APC=-0.47%， t =-0.12， P =0.91). The proportion of RR-PTB cases occurring among students increased both among all RR-PTB cases (1.54% in 2015, 7.48% in 2024) and all student pulmonary tuberculosis cases (0.20% in 2015, 7.17% in 2024), with significant linear trends ( χ 2 trend =33.55,159.98, both P <0.01). The majority of cases were enrolled in senior high school (50.38%), classified as retreatment (53.92%), of Han ethnicity (75.95%), and diagnosed with multidrug resistant tuberculosis(53.16%). There were significant differences in the composition of different ethnicity, registration category and resistance pattern between different years( χ 2=23.47, 17.23, 59.64，all P <0.05). The South-Eastern Wuling Mountainous Region exhibited the highest notification rate (3.96 per 100 000), whereas the western region had the lowest rate ( 0.47 per 100 000). County level jurisdictions reported higher rates than district level ones (2.16 per 100 000 vs 0.63 per 100 000 ). Statistically significant differences were observed in the RR-PTB reported rates among students across different districts and counties( χ 2=418.05,167.05,both P <0.01). Conclusions From 2015 to 2024, the registration rate of detected student RR-PTB cases in Chongqing showed an increasing trend. Students have become one of the key populations for drug resistant TB prevention and control. Intensified health education and active case finding should be implemented to enhance proactive surveillance capabilities.