1.Aerobic Exercise Improves Cognitive Function of Aging Mice by Regulating Intestinal Flora-metabolite Network
An-Feng WANG ; Tong WU ; Hu ZHANG ; Ji-Ling LIANG ; Ning CHEN
Progress in Biochemistry and Biophysics 2025;52(6):1484-1498
ObjectiveThis study aimed to explore the effects of aerobic exercise on cognitive function in aging mice and to elucidate the underlying molecular mechanisms by which aerobic exercise ameliorates cognitive decline through the regulation of gut microbiota-metabolite network. By providing novel insights into the interplay between exercise, gut microbiota, and cognitive health, this research seeks to offer a robust theoretical foundation for developing anti-aging strategies and personalized exercise interventions targeting aging-related cognitive dysfunction. MethodsUsing naturally aged C57BL/6 mice as the experimental model, this study employed a multi-omics approach combining 16S rRNA sequencing and wide-targeted metabolomics analysis. A total of 18 mice were divided into 3 groups: young control (YC, 4-month-old), old control (OC, 21-month-old), and old+exercise (OE, 21-month-old with 12 weeks of moderate-intensity treadmill training) groups. Behavioral assessments, including the Morris water maze (MWM) test, were conducted to evaluate cognitive function. Histopathological examinations of brain tissue sections provided morphological evidence of neuronal changes. Fecal samples were collected for gut microbiota and metabolite profiling via 16S rRNA sequencing and ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-QTOF-MS). Data were analyzed using a combination of statistical and bioinformatics tools to identify differentially abundant microbial taxa and metabolites and to construct interaction networks between them. ResultsBehavioral tests revealed that 12 weeks of aerobic exercise significantly improved spatial learning and memory capacity of aged mice, as evidenced by reduced escape latency and increased target area exploration and platform crossings in the MWM. Histopathological analysis demonstrated that exercise mitigated aging-related neuronal damage in the hippocampus, enhancing neuronal density and morphology. 16S rRNA sequencing indicated that exercise increased gut microbiota α‑diversity and enriched beneficial bacterial genera, including Bifidobacterium, Parabacteroides, and Rikenella. Metabolomics analysis identified 32 differentially regulated metabolites between OC and OE groups, with 94 up-regulated and 30 down-regulated in the OE group when compared with OC group. These metabolites were primarily involved in energy metabolism reprogramming (e.g., L-homocitrulline), antioxidant defense (e.g., L-carnosine), neuroprotection (e.g., lithocholic acid), and DNA repair (e.g., ADP-ribose). Network analysis further revealed strong positive correlations between specific bacteria and metabolites, such as Parabacteroides with ADP-ribose and Bifidobacterium with lithocholic acid, suggesting potential neuroprotective pathways mediated by the gut microbiota-metabolite axis. ConclusionThis study provides comprehensive evidence that aerobic exercise elicits cognitive benefits in aging mice by modulating the gut microbiota-metabolite network. These findings highlight three key mechanisms: (1) the proliferation of beneficial gut bacteria enhances metabolic reprogramming to boost DNA repair pathways; (2) elevated neuroinflammation-inhibiting factors reduce neurodegenerative changes; and (3) enhanced antioxidant defenses maintain neuronal homeostasis. These results underscore the critical role of the “microbiota-metabolite-brain” axis in mediating the cognitive benefits of aerobic exercise. This study not only advances our understanding of the gut-brain axis in aging but also offers a scientific basis for developing personalized exercise and probiotic-based interventions targeting aging-related cognitive decline. Future research should further validate these mechanisms in non-human primates and human clinical trials to establish the translational potential of exercise-induced gut microbiota-metabolite modulation for combating neurodegenerative diseases.
2.Development of an Analytical Software for Forensic Proteomic SAP Typing
Feng HU ; Meng-Jiao WANG ; Jia-Lei WU ; Dong-Sheng DING ; Zhi-Yuan YANG ; An-Quan JI ; Lei FENG ; Jian YE
Progress in Biochemistry and Biophysics 2025;52(9):2406-2416
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.
3. Mechanism of Wen Shen Xuan Bi Tang in treatment of osteoporosis based on network pharmacology and animal experimental verification
Hai-Ping WANG ; Zhao-Feng YUAN ; Tian-Wei XIA ; Chao ZHANG ; Ji-Rong SHEN ; Hai-Ping WANG
Chinese Pharmacological Bulletin 2024;40(2):344-351
Aim To predict and validate the mechanism of wenshen xuanbi tang(WSXBT) in treatment of osteoporosis (OP) based on network pharmacology, molecular docking techniques and in vivo experimental techniques. Methods Network pharmacology was used to screen the key ingredients and core targets of WSXBT for the treatment of osteoporosis. Metascape database was used for gene ontology (GO) biological process enrichment analysis and kyoto encyclopedia of genes and genomes (KEGG) signaling pathway enrichment analysis of core targets. AutoDockTools 1. 5. 7 software was applied in molecular docking to simulate the binding activity of key active ingredients to core targets. To study the efficacy of WSXBT on rats with osteoporosis and to verify the related targets and pathways, rat models of osteoporosis were established by excising the bilateral ovaries of rats. Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum OPG, PINP and RANKL content. Biomechanical tester was applied to test the biomechanics of rat femurs. Micro-CT was applied to detect the femoral bone density. Then, Western blot was employed to measure the protein expression levels of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt). Results A total of 156 active ingredients of WSXBT were screened, involving 229 potential targets, 23 core targets and 145 signaling pathways. The molecular docking results showed that five key ingredients, including quercetin, kaempferol, naringenin, isobavachin and licochalcone a, possessed good binding ability to the core targets of PIK3R1 and AKT1. The results of in vivo experiments showed that WSXBT could significantly increase bone density, improve bone tissue microstructure, enhance femur biomechanics and increase PINP expression and OPG/RANKL ratio in rats with osteoporosis. Results of WB showed that WSXBT significantly increased p-PI3K/PI3K and p-Akt/Akt ratios. Conclusions WSXBT could improve bone mineral density in postmenopausal osteoporotic rats through PI3K/ Akt signaling pathway and increasing OPG/RANKL ratio.
4.Exploration of Thoughts and Possible Therapeutic Mechanism of Treating Male Infertility from the Perspective of Spleen and Kidney by Regulating Intestinal Flora
Nian-Wen HUANG ; Bin WANG ; Ji-Sheng WANG ; Huan-Zhou BI ; Juan-Long FENG ; Long-Ji SUN ; Hai-Song LI
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(3):776-781
Based on the literature study,the thoughts and possible therapeutic mechanism in treating male infertility from the perspective of spleen and kidney by regulating intestinal flora were explored.Disturbance of intestinal flora is one of the important factors leading to the development of male infertility,and the spleen and kidney have certain similarities to intestinal flora in the physiological function and pathological changes.Moreover,tonifying the kidney and strengthening the spleen can regulate the intestinal flora by fostering the growth of beneficial bacteria,inhibiting the reproduction of pathogenic bacteria,and protecting the barrier of the intestinal mucosa.Therefore,the possible therapeutic mechanisms in treating male infertility with the prescriptions for tonifying the kidney and strengthening the spleen to regulate intestinal flora are as follows:inhibiting the expression of inflammatory factors to reduce the inflammatory reaction of testicular tissues;improving the antioxidant capacity to alleviate the damage of spermatozoa caused by oxidative stress,and improving the bad mood to alleviate the impact of psychological stress on the reproductive system.The exploration of the thoughts for treating male infertility from the perspective of spleen and kidney by regulating intestinal flora may provide a new entry point for modern Chinese medicine clinical treatment of male infertility.
5.Longitudinal extrauterine growth restriction in extremely preterm infants: current status and prediction model
Xiaofang HUANG ; Qi FENG ; Shuaijun LI ; Xiuying TIAN ; Yong JI ; Ying ZHOU ; Bo TIAN ; Yuemei LI ; Wei GUO ; Shufen ZHAI ; Haiying HE ; Xia LIU ; Rongxiu ZHENG ; Shasha FAN ; Li MA ; Hongyun WANG ; Xiaoying WANG ; Shanyamei HUANG ; Jinyu LI ; Hua XIE ; Xiaoxiang LI ; Pingping ZHANG ; Hua MEI ; Yanju HU ; Ming YANG ; Lu CHEN ; Yajing LI ; Xiaohong GU ; Shengshun QUE ; Xiaoxian YAN ; Haijuan WANG ; Lixia SUN ; Liang ZHANG ; Jiuye GUO
Chinese Journal of Neonatology 2024;39(3):136-144
Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.
6.Application of contrast-enhanced ultrasound in differential diagnosis of ≤ 3 cm hepatocellular carcinoma and focal nodular hyperplasia of the liver
Kai YUAN ; Zhengbiao JI ; Feng MAO ; Weibin ZHANG ; Haixia YUAN ; Wenping WANG
Chinese Journal of Clinical Medicine 2024;31(6):945-950
Objective To investigate the diagnosis value of contrast-enhanced ultrasound (CEUS) in the differentiation of hepatocellular carcinoma (HCC) and focal nodular hyperplasia (FNH) of the liver with ≤3 cm of maximum diameter. Methods The image characteristics in 48 lesions of HCC with maximum diameter≤3 cm and 48 lesions of FNH with maximum diameter≤3 cm confirmed by pathology were retrospectively analyzed. The phase changes, enhancement patterns and enhancement characteristics of the lesions in the two groups were compared. Results All lesions in the two groups showed high-echo in the arterial phase. The contrast arrival time in HCC group and FNH group was 17(15, 19) s and 15(12, 18.75) s (P=0.017); the peak time in the two groups was 21(17, 25) s and 22(19, 26) s (P>0.05). The main enhancement patterns of HCC group and FNH group in arterial phase were homogeneous enhancement and centrifugal enhancement, respectively. All HCC lesions showed homogeneous enhancement, which was significantly higher than FNH (2.08%, P<0.05); 97.91% of FHN lesions showed centrifugal enhancement, which was higher that of HCC lesions (0, P<0.05). During the CEUS process, 87.5% of HCC lesions showed “rapid fill-in and rapid wash-out”, which was significantly higher than that of FNH lesions(8.33%,P<0.05); 91.67% of FNH lesions showed “rapid fill-in” and “synchronous/slow wash-out” which was significantly higher than that of HCC lesions (12.50%,P<0.05). Conclusion CEUS is helpful in the differential diagnosis of FNH and HCC with maximum diameter≤3 cm.
7.Nephrolithotomy in patients with complex kidney calculi
Feng WEI ; Guangjun ZHOU ; Shuanghui LI ; Yanyan WANG ; Zhijie JI
Journal of Modern Urology 2024;29(4):342-346
【Objective】 To analyze the predictive value of serum β-defensin-3 (HBD-3) and decoy receptor 3 (DCR3) for urinary tract infection after percutaneous nephrolithotomy (PCNL) in patients with complex kidney calculi. 【Methods】 A prospective study was conducted on 112 patients treated with PCNL at our hospital during Jan.2020 and Dec.2022.The patients were divided into the non-infection group (52 cases) and infection group (60 cases).The general data, HBD-3 and DCR3 levels of the two groups were compared.Receiver operating characteristic (ROC) curve was drawn to analyze the predictive value of C reactive protein (CRP), procalcitonin (PCT), HBD-3 and DCR3 levels for postoperative urinary tract infection. 【Results】 Compared with the non-infection group, the infection group had higher levels of HBD-3 [(0.77±0.08) ng/mL vs. (1.36±0.25) ng/mL, P=0.001] and DCR3 [(4.68±0.53) ng/mL vs.(13.21±0.28) ng/mL, P=0.001].Multivariate logistic regression showed that a history of urinary tract surgery, preoperative urinary tract infection, operation time, catheterization time, stone load, type of antibiotics, concomitant renal dysfunction, intraoperative channel type, CRP, PCT, HBD-3 and DCR3 were risk factors of postoperative urinary tract infection (P<0.05).The ROC curve showed that the accuracy of CRP, PCT, and CRP plus PCT were 70.54%, 72.32%, and 78.57%, respectively; the accuracy of HBD-3, DCR3, and HBD-3 plus DCR3 were 69.64%, 75.89%, and 86.61%, respectively. 【Conclusion】 Postoperative urinary tract infection in patients with complex kidney calculi is associated with multiple factors, especially high expression levels of HBD-3 and DCR3.Combined detection has high predictive value.
8.A national questionnaire survey on endoscopic treatment for gastroesophageal varices in portal hypertension in China
Xing WANG ; Bing HU ; Yiling LI ; Zhijie FENG ; Yanjing GAO ; Zhining FAN ; Feng JI ; Bingrong LIU ; Jinhai WANG ; Wenhui ZHANG ; Tong DANG ; Hong XU ; Derun KONG ; Lili YUAN ; Liangbi XU ; Shengjuan HU ; Liangzhi WEN ; Ping YAO ; Yunxiao LIANG ; Xiaodong ZHOU ; Huiling XIANG ; Xiaowei LIU ; Xiaoquan HUANG ; Yinglei MIAO ; Xiaoliang ZHU ; De'an TIAN ; Feihu BAI ; Jitao SONG ; Ligang CHEN ; Yingcai MA ; Yifei HUANG ; Bin WU ; Xiaolong QI
Chinese Journal of Digestive Endoscopy 2024;41(1):43-51
Objective:To investigate the current status of endoscopic treatment for gastroesophageal varices in portal hypertension in China, and to provide supporting data and reference for the development of endoscopic treatment.Methods:In this study, initiated by the Liver Health Consortium in China (CHESS), a questionnaire was designed and distributed online to investigate the basic condition of endoscopic treatment for gastroesophageal varices in portal hypertension in 2022 in China. Questions included annual number and indication of endoscopic procedures, adherence to guideline for preventing esophagogastric variceal bleeding (EGVB), management and timing of emergent EGVB, management of gastric and isolated varices, and improvement of endoscopic treatment. Proportions of hospitals concerning therapeutic choices to all participant hospitals were calculated. Guideline adherence between secondary and tertiary hospitals were compared by using Chi-square test.Results:A total of 836 hospitals from 31 provinces (anotomous regions and municipalities) participated in the survey. According to the survey, the control of acute EGVB (49.3%, 412/836) and the prevention of recurrent bleeding (38.3%, 320/836) were major indications of endoscopic treatment. For primary [non-selective β-blocker (NSBB) or endoscopic therapies] and secondary prophylaxis (NSBB and endoscopic therapies) of EGVB, adherence to domestic guideline was 72.5% (606/836) and 39.2% (328/836), respectively. There were significant differences in the adherence between secondary and tertiary hospitals in primary prophylaxis of EGVB [71.0% (495/697) VS 79.9% (111/139), χ2=4.11, P=0.033] and secondary prophylaxis of EGVB [41.6% (290/697) VS 27.3% (38/139), χ2=9.31, P=0.002]. A total of 78.2% (654/836) hospitals preferred endoscopic therapies treating acute EGVB, and endoscopic therapy was more likely to be the first choice for treating acute EGVB in tertiary hospitals (82.6%, 576/697) than secondary hospitals [56.1% (78/139), χ2=46.33, P<0.001]. The optimal timing was usually within 12 hours (48.5%, 317/654) and 12-24 hours (36.9%, 241/654) after the bleeding. Regarding the management of gastroesophageal varices type 2 and isolated gastric varices type 1, most hospitals used cyanoacrylate injection in combination with sclerotherapy [48.2% (403/836) and 29.9% (250/836), respectively], but substantial proportions of hospitals preferred clip-assisted therapies [12.4% (104/836) and 26.4% (221/836), respectively]. Improving the skills of endoscopic doctors (84.2%, 704/836), and enhancing the precision of pre-procedure evaluation and quality of multidisciplinary team (78.9%, 660/836) were considered urgent needs in the development of endoscopic treatment. Conclusion:A variety of endoscopic treatments for gastroesophageal varices in portal hypertension are implemented nationwide. Participant hospitals are active to perform emergent endoscopy for acute EGVB, but are inadequate in following recommendations regarding primary and secondary prophylaxis of EGVB. Moreover, the selection of endoscopic procedures for gastric varices differs greatly among hospitals.
9.Ten kinds of antipyretic-antidotal traditional Chinese medicine extracts against extensively drug-resistant Acinetobacter baumannii infection
Yan YANG ; Jian-Wen FENG ; Bo JI ; Jin YUAN ; Yan WANG ; Jian LI ; Xue-Jiu CAI ; Zhi-Hui JIANG
Chinese Journal of Infection Control 2024;23(3):271-276
Objective To study the activity of ten kinds of antipyretic-antidotal traditional Chinese medicine(TCM),including radix tinosporae.herb of blin conyza and turmeric,against extensively drug-resistant Acineto-bacter baumannii(XDR-AB)infection,screen out the extracts of antipyretic-antidotal TCM which have in vivo anti-infection activity,provide a research basis for the discovery of novel antimicrobials against XD-RAB infection.Methods Ten antipyretic-antidotal TCM were extracted with water,50%ethanol and 95%ethanol respectively,and TCM extracts with different concentrations were prepared,which were co-incubated with the model of XDR-AB-infected Caenorhabditis elegans previously optimized by the research group.The in vivo activity of antipyretic-antidotal TCM against XDR-AB infection was judged through the survival rate of Caenorhabditis elegans.Results With the increase of concentration of turmeric and cortex pseudolaricis extracts,the survival rate of XDR-AB-infec-ted nematodes continued to improve.The water extract,50%ethanol extract,and 95%ethanol extract of turmeric at a concentration of 1 000 μg/mL could increase the survival rates of XDR-AB-infected Caenorhabditis elegans to 54.2%(compared to the negative control group,P<0.001),18.8%,and 13.3%,respectively.The water ex-tract,50%ethanol extract,and 95%ethanol extract of cortex pseudolaricis at a concentration of 1 000 μg/mL could increase the survival rates of XDR-AB-infected Caenorhabditis elegans to 47.4%(compared to the negative control group,P<0.001),23.8%,and 15.8%,respectively.Conclusion The water extracts of turmeric and cortex pseudolaricis have good activity against XDR-AB infection,and their main chemical components can be tested for in vitro antimicrobial efficacy to discover novel antimicrobial agents against XDR-AB infection.
10.The construction and its implication of the cancer life-cycle prevention and control system in Japan
Dong-Ni HONG ; Sheng WANG ; Xian-Ji WANG ; Chun-Feng WU ; Chun-Yu RONG ; Ping ZHOU
Chinese Journal of Health Policy 2024;17(2):72-78
As the country with the largest number of new cancer cases and deaths,China faces a serious situation with a large cancer population base,low relative survival rate,and low adherence to cancer screening.Neighboring Japan,which has the longest life expectancy in the world,has a much higher relative survival rate than China,despite having a similarly high cancer rate,due to its well-established system of cancer prevention and control.Being an Asian country,the major prevalent cancers in China and Japan are similar in spectrum and can be referred to more.This article introduces the construction of Japan's cancer life-cycle prevention and control system of"cancer prevention","cancer care",and"coexistence with cancer"starting from the three major goals of Japan's cancer prevention and control program,and focuses on the improvement of cancer screening in Japan and the improvement of cancer survival in China.It also highlights the means and methods used to increase the cancer screening rate in Japan,with a view to providing suggestions for cancer prevention and control in China.

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