1.Exploring Biological Characteristics of Rat Model of Atrial Fibrillation with Phlegm-heat and Blood Stasis Pattern Based on Metabolomics
Ailin HOU ; Yuxuan LIU ; Wenxi YU ; Xing JI ; Chan WU ; Dazhuo SHI ; Ying ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):245-255
ObjectiveTo establish an animal model of atrial fibrillation(AF) that accurately reflects the phlegm-heat and blood stasis(TRYZ) pathogenesis in traditional Chinese medicine. MethodsForty SPF-grade SD rats were randomly assigned using a random number table to the following groups:the control group, the TRYZ+AF group,the AF group and the TRYZ group, with ten rats in each group. The TRYZ+AF and TRYZ groups underwent a high-fat diet combined with intraperitoneal lipopolysaccharide(LPS) injection to simulate the pathological alterations of TRYZ syndrome. Groups TRYZ+AF and AF were induced with acetylcholine-calcium chloride(Ach-CaCl2) via caudal vein injection to induce AF. The control group received no intervention and was maintained under normal conditions. The modeling period lasted 3 weeks. Electrocardiography was used to assess AF episodes and duration, echocardiography evaluated left atrial dimensions and cardiac function, fully automated biochemical analyzer measured the levels of total cholesterol(TC), triglycerides(TG), high-density lipoprotein cholesterol(HDL-C) and low-density lipoprotein cholesterol(LDL-C), hemoreometer analyzed the whole blood viscosity, plasma viscosity, and whole blood reduced viscosity, a coagulation analyzer assessed prothrombin time(PT), activated partial thromboplastin time(APTT), thrombin time(TT), and fibrinogen(FIB), enzyme-linked immunosorbent assay(ELISA) was used to determine the levels of C-reactive protein(CRP), interleukin(IL)-1β, IL-6, IL-17, tumour necrosis factor(TNF)-α, matrix metalloproteinase-9(MMP-9), galectin-3(Gal-3), Collagen Ⅰ, and α-smooth muscle actin(α-SMA). Hematoxylin-eosin(HE) staining and Masson's trichrome staining were used to analyze pathological changes in atrial myocardium, Western blot was employed to detect MMP-9, Collagen Ⅰ and α-SMA protein expression in myocardial tissue, real-time quantitative polymerase chain reaction(Real-time PCR) evaluated fibrous factor gene expression levels. Changes in the TRYZ syndrome were assessed via body weight, tongue color[red(R), green(G), and blue(B)], and rectal temperature. Ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was employed to detect differential metabolites between the control group and the TRYZ+AF group. ResultsFollowing three weeks of sustained modeling, compared with the control group, rats in the TRYZ+AF and the TRYZ groups exhibited reduced body weight, dry faeces, elevated rectal temperature, dark red tongue, decreased RGB values on the tongue surface, and markedly elevated TC and LDL-C levels(P<0.05, P<0.01). The TRYZ+AF, TRYZ, and AF groups exhibited significantly decreased TT, APTT and PT, along with markedly elevated whole blood viscosity and FIB(P<0.05, P<0.01). Rats in the TRYZ+AF and AF groups exhibited AF rhythm, markedly decreased heart rate, prolonged RR intervals, enlarged left atrium, and significantly reduced ejection fraction and shortening fraction(P<0.05, P<0.01). Serum levels of CRP, IL-1β, IL-6, IL-17, TNF-α, MMP-9, Gal-3, Collagen Ⅰ, and α-SMA were elevated in rats from the TRYZ+AF, TRYZ, and AF groups compared to the control group, with the most pronounced increase observed in the TRYZ+AF group(P<0.05, P<0.01). Histopathology revealed that the collagen fiber deposition in the atrial of rats in the TRYZ+AF, TRYZ and AF groups was higher than that in the control group(P<0.05, P<0.01). Western blot and Real-time PCR results further demonstrated that the protein and mRNA expression levels of MMP-9, Collagen Ⅰ and α-SMA in the myocardial tissue of the TRYZ+AF group were higher than those in the other three groups(P<0.05, P<0.01). Metabolomic analysis revealed 173 differentially expressed metabolites in the TRYZ+AF group and the control group, primarily enriched in pathways such as glycerophospholipid metabolism and glycolysis/gluconeogenesis. ConclusionThis study successfully establishes a rat model of AF integrated with the TRYZ syndrome, demonstrating the pathological process where the interactions of phlegm, heat and stasis jointly trigger tremor, this provides a reliable experimental tool for in-depth research into the biological basis of this disease syndrome.
2.Research progress on the mechanisms of traditional Chinese medicine in treating functional constipation based on the gut microbiota-bile acid axis
Xiangrui KONG ; Qimeng ZHANG ; Yue ZOU ; Yong LIANG ; Yu SHI ; Yang ZHANG ; Hongxi ZHANG
China Pharmacy 2026;37(2):244-249
Functional constipation (FC) is a common functional disorder of the intestines, mainly characterized by reduced bowel movement frequency, difficulty in defecation, a sensation of incomplete evacuation, and hard stools, which severely affect patients’ quality of life. Research indicates that the pathogenesis of FC is closely related to gut microbiota dysbiosis and abnormal bile acid secretion. Bile acids, as endogenous natural laxatives, promote bowel movements by enhancing colonic secretion and regulating intestinal motility; meanwhile, gut microbiota influence colonic transit function by regulating the enteric nervous system, immune system, and their metabolic products. Based on an overview of the relationship between gut microbiota and bile acid metabolism, this article systematically reviews the current research status on the mechanisms of traditional Chinese medicine (TCM) in treating FC by regulating the balance of the gut microbiota-bile acid axis. It is found that single Chinese medicinal herbs (such as Atractylodes macrocephala), isolated compounds (such as Platycodon grandiflorum polysaccharides), herbal formulas (such as Shanger huang pill), acupuncture, and moxibustion can up-regulate the abundance of beneficial bacteria, reshape the microbial structure, correct bile acid metabolism, and activate the Takeda G-protein receptor 5/farnesoid X receptor pathway to treat FC.
3.Mechanisms of Dihuang Yinzi in Treating Advanced Parkinson's Disease Based on Gut Microbiota-SCFAs-inflammation Axis
Renzhi MA ; Yasi LIN ; Tingyue JIANG ; Hongmei ZHU ; Jiayuan LI ; Yu WANG ; Ge ZHANG ; Wenxin FAN ; Jinli SHI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):11-21
ObjectiveTo observe the effects of Dihuang Yinzi (DY) on motor dysfunction in rats with advanced Parkinson's disease (PD) and to investigate the mechanisms by which DY improves advanced PD symptoms through the "gut microbiota-short-chain fatty acids (SCFAs)-inflammation-neuroprotection pathway". MethodsAn advanced PD rat model was induced by rotenone. Rats were divided into a normal group, model group, positive drug group (levodopa, 50 mg·kg-1), and DY low-, medium-, and high-dose groups (5.2, 10.4, 20.8 g·kg-1). After 7 days of administration, motor function was evaluated using the open-field, pole-climbing, and inclined plate tests. Hematoxylin-eosin (HE) staining was used to observe pathological changes in the substantia nigra and colon, and immunohistochemistry was performed to detect α-Synuclein (α-Syn) and tyrosine hydroxylase (TH) expression in the substantia nigra. Enzyme-linked immunosorbent assay (ELISA) was used to measure levels of dopamine (DA), 5-hydroxytryptamine (5-HT), 3,4-dihydroxyphenylacetic acid (DOPAC), Levodopa, homovanillic acid (HVA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β). Western blot analysis was used to detect the expression of zonula occludens-1 (ZO-1) and occludin. Gut microbiota diversity was analyzed by 16S rRNA sequencing, and gas chromatography (GC) was used to determine the content of SCFAs in colonic contents. ResultsCompared with the normal group, the model group showed significantly decreased movement speed and distance in the open-field test, prolonged pole-climbing time, and reduced retention angle on the inclined plate (P<0.01), accompanied by increased α-Syn expression (P<0.01) and decreased TH expression (P<0.01) in the brain. Compared with the model group, all DY dose groups improved motor dysfunction in advanced PD rats to varying degrees (P<0.05, P<0.01) and alleviated pathological damage in the brain and colon. High-dose DY significantly reduced α-Syn aggregation in the substantia nigra (P<0.01) and increased TH expression (P<0.01). ELISA and Western blot results showed that, compared with the normal group, the model group exhibited decreased levels of DA, 5-HT, DOPAC, Levodopa, and HVA in the striatum (P<0.01), increased levels of TNF-α, IL-6, and IL-1β in the colon and striatum (P<0.01), and significantly reduced expression of ZO-1 (P<0.05) and occludin in the colon (P<0.01). Compared with the model group, all DY dose groups increased the levels of DA, 5-HT, DOPAC, Levodopa, and HVA in the striatum to varying degrees (P<0.05, P<0.01). In the high-dose DY group, the levels of TNF-α, IL-6, and IL-1β in the colon and striatum were reduced (P<0.01), while the expression of ZO-1 (P<0.05) and occludin in the intestine was increased. The 16S rRNA sequencing results indicated that the relative abundances of Actinobacteriota, Enterobacteriaceae, and Erysipelotrichaceae were increased in the model group, whereas the relative abundances of Bacteroidota, class Clostridia, Lachnospiraceae, and Akkermansia muciniphila were decreased. These changes were effectively reversed after high-dose DY intervention. GC analysis showed that the content of SCFAs in the colonic contents of rats in the model group was decreased (P<0.05, P<0.01), while after high-dose DY intervention, the levels of acetate, propionate, isobutyrate, and butyrate were significantly increased (P<0.05, P<0.01). ConclusionDY may exert therapeutic effects in advanced PD by regulating the gut microbiota-SCFAs-inflammation pathway.
4.Herbal Textual Research on Bambusae Succus in Famous Classical Formulas
Yu SHI ; Feng ZHOU ; Yihan WANG ; Yanmeng LIU ; Ming YANG ; Zhiping CHEN ; Jiangshan ZHANG ; Conglong XU ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(9):231-239
This article systematically reviews and examines the historical evolution of Bambusae Succus as a medicinal material, covering aspects such as nomenclature, origin, geographical distribution, harvesting and processing methods, quality assessment, therapeutic effects and indications, by consulting ancient herbal texts, medical compendia, and modern literature. The aim is to provide a reference for the development and utilization of famous classical formulas containing this herb. Research indicated that Bambusae Succus was first documented in the Shennong Bencaojing during the Han dynasty, with Zhuli being the standard name used throughout history, alongside aliases like Zhuzhi, Zhuyou and Huoquan. Historically, the primary source of Bambusae Succus has been Phyllostachys nigra var. henonis(Danzhu), although other species such as Pleioblastus amarus and Bambusa emeiensis have also been used medicinally. Ancient records predominantly noted its origin in Yizhou(present-day Chengdu and surrounding areas in Sichuan) and the Wuling region(between present-day Hunan, Guangdong, Guangxi and Jiangxi provinces), while contemporary sources are mainly from regions south of the Yangtze River and southwestern China. Traditionally, Bambusae Succus was harvested from bamboo that had grown for exactly one year, today, it can be collected year-round without strict age requirements. Ancient preparation methods included direct fire roasting or dry distillation, whereas modern industrial production employs dry distillation, reflux extraction, and percolation. In terms of quality evaluation, ancient texts considered a sweet taste to be superior, while today, clarity and transparency are prioritized. Historically, Bambusae Succus was characterized as sweet and cold nature, targeting the lung and stomach meridians, with uses evolving from clearing heat and resolving phlegm to nourishing Yin, moistening dryness, and relaxing tendons and unblocking meridians. Modern descriptions classify it as sweet, bitter, and cold in nature, affecting the heart, liver, and lung meridians, with functions including clearing heat, resolving phlegm, and facilitating orifices. It is indicated for conditions such as stroke with phlegm confusion, lung heat with phlegm congestion, convulsions, epilepsy, excessive phlegm in febrile diseases, high fever with thirst, irritability during pregnancy, and tetanus, with more clearly defined applications. Based on the results of the research, it is recommended that when developing and utilizing famous classical formulas containing Bambusae Succus, the one-year-old Phyllostachys nigra var. Henonis, which has been highly praised throughout history, should be selected as the source material. Industrial production should adopt the dry distillation method. Furthermore, in-depth research should be conducted on the modern technological characterization of the traditional quality control indicator of sweet taste, and reasonable modern quality control standards should be established.
5.Optimized monovision Q-value-customized FS-LASIK for myopia, astigmatism, and presbyopia
Linjuan YANG ; Qiang SHI ; Zhao LIU ; Yu ZHANG ; Shengjian MI
International Eye Science 2026;26(5):772-779
AIM: To evaluate safety, efficacy, visual quality, and patient satisfaction after optimized monovision Q-value-customized femtosecond laser-assisted in situ keratomileusis(FS-LASIK)for myopia, astigmatism, and presbyopia. METHODS: This prospective study enrolled patients suffering myopia, astigmatism, and presbyopia. At 1 y post operation, uncorrected distance, intermediate and near visual acuity(UDVA, UIVA, UNVA), refraction, corneal higher order aberrations(HOAs), Q value, objective visual quality, and near stereoacuity were evaluated. The impact of surgery on patients' living quality and their satisfaction were evaluated based on National Eye Institute Refractive Error Quality of Life Instrument(NEI RQL)scores at 1-year follow-up.RESULTS:The study enrolled 36 patients(72 eyes)including 12 males(33%)and 24 females(67%)with an average age of 46.03±3.60(range 40-53)y. One year postoperatively, 97% of patients achieved binocular UDVA of 1.0 or better, 89% achieved UIVA of 0.63 or better, and 97% achieved UNVA of 1.0 or better. The spherical equivalent refraction(SE)in dominant eye within ±1.00 D was 100%. SE in non-dominant eyes was uncorrected compared with the preoperative target correction, with a mean difference of -0.27±0.34 D before and after surgery(P<0.001). while in the non-dominant eyes, the anterior corneal Q-value within the 5 mm zone increased negatively compared with the preoperative value(-0.33±0.24 vs -0.21±0.09, P<0.001). In the non-dominant eye, spherical aberration and longitudinal spherical aberration were lower than preoperative values(both P<0.001). Besides, there were no significant changes in objective scatter index(OSI), modulation transfer function cutoff frequency(MTF cut off)and Strehl ratio(SR)in both dominant and non-dominant eyes(all P>0.05), and the near stereoacuity was better after surgery(P=0.007). Additionally, the patient satisfaction rate with the surgery was 94%, the satisfaction rates for UDVA and UNVA were both 98%. The 11% of patients required to wear low-diopter glasses when driving at night.CONCLUSION:Optimized monovision Q-value-customised FS-LASIK is a safe and effective procedure for correcting myopia, astigmatism, and presbyopia. It provides favorable subjective and objective visual quality and high patient satisfaction. The under correction in non-dominant eyes is observed, indicating the further optimization of nomogram is needed.
6.Establishment and validation of a model for femoral head necrosis after internal fixation of femoral neck fracture using logistic regression and SHAP analysis
Long LIAO ; Zepeng ZHAO ; Zongyuan LI ; Qinglong YU ; Tao ZHANG ; Jinyuan TANG ; Nan YE ; Han XU ; Bo SHI
Chinese Journal of Tissue Engineering Research 2026;30(3):626-633
BACKGROUND:The most common complication of traumatic femoral neck fractures after internal fixation is femoral head necrosis.Currently,many studies have reported on the risk factors that affect the occurrence and development of postoperative femoral head necrosis,but there is still a lack of tools to predict the risk of femoral head necrosis after internal fixation of femoral neck fractures.OBJECTIVE:To develop a predictive model that estimates the risk of femoral head necrosis shortly after patients with femoral neck fractures receive cannulated screw internal fixation.METHODS:A retrospective analysis reviewed clinical records of 172 patients who underwent cannulated screw internal fixation for femoral neck fractures at Department of Orthopedics of Mianyang Central Hospital from January 2013 to June 2023.Patients were categorized into two groups based on the presence or absence of femoral head necrosis within one year post-operation:the necrosis group and the non-necrosis group.Univariate analysis,Lasso regression,and multivariate Logistic regression techniques were employed to identify the determinants of femoral head necrosis.A nomogram prediction model was constructed using R language's"rms"package,version 4.0.The receiver operating characteristic curve was used to evaluate the discriminatory ability of the model.The Hosmer-Lemeshow test was used to evaluate the goodness of fit of the model,and the decision curve analysis was used to determine its clinical application benefits.Internal validation of the study was conducted using the Bootstrap method,involving 1 000 repeated samplings.To delve deeper into the primary factors influencing femoral head necrosis post-internal fixation of the femoral neck,this paper employed the SHAP method for data set analysis.RESULTS AND CONCLUSION:(1)The risk factors leading to femoral head necrosis in the short term after cannulated screw fixation of femoral neck fractures include:smoking,diabetes,Garden classification,fracture line location,reduction quality,age,and operation time.(2)The prediction model demonstrated robust performance,evidenced by an area under the curve of 0.940(95%Confidence Interval:0.903 to 0.977),indicating a high level of prediction accuracy.The model achieved a sensitivity of 90.2%and a specificity of 87.6%,indicating that its diagnostic performance was stable.The Hosmer-Lemeshow goodness-of-fit test yielded a chi-square value of 6.593 with a P-value of 0.581,confirming that the model's predictions closely align with the observed outcomes.(3)The calibration curve of the model also performed well,and its overall trend was very close to the ideal curve,further proving the high accuracy of the model.(4)The internal validation was carried out by the Bootstrap method with 1 000 repeated samplings,and the area under the curve of the model internal validation was still as high as 0.939,proving that the model had good stability.(5)Through the decision curve,it is found that within the probability threshold range of 1%to 92%,the model can obtain the maximum net benefit value.(6)The SHAP analysis results show that among the risk factors analyzed in this study,the location of the fracture line serves as the most significant predictor of femoral head necrosis following internal fixation with cannulated screws in femoral neck fractures,and subcapital fractures are extremely prone to femoral head necrosis after surgery.(7)It is concluded that the validated prediction model demonstrates strong discriminative power and reliability,offering practical clinical utility.It serves as a useful reference tool for short-term risk assessment of femoral head necrosis following internal fixation of femoral neck fractures.
7.Establishment and validation of a model for femoral head necrosis after internal fixation of femoral neck fracture using logistic regression and SHAP analysis
Long LIAO ; Zepeng ZHAO ; Zongyuan LI ; Qinglong YU ; Tao ZHANG ; Jinyuan TANG ; Nan YE ; Han XU ; Bo SHI
Chinese Journal of Tissue Engineering Research 2026;30(3):626-633
BACKGROUND:The most common complication of traumatic femoral neck fractures after internal fixation is femoral head necrosis.Currently,many studies have reported on the risk factors that affect the occurrence and development of postoperative femoral head necrosis,but there is still a lack of tools to predict the risk of femoral head necrosis after internal fixation of femoral neck fractures.OBJECTIVE:To develop a predictive model that estimates the risk of femoral head necrosis shortly after patients with femoral neck fractures receive cannulated screw internal fixation.METHODS:A retrospective analysis reviewed clinical records of 172 patients who underwent cannulated screw internal fixation for femoral neck fractures at Department of Orthopedics of Mianyang Central Hospital from January 2013 to June 2023.Patients were categorized into two groups based on the presence or absence of femoral head necrosis within one year post-operation:the necrosis group and the non-necrosis group.Univariate analysis,Lasso regression,and multivariate Logistic regression techniques were employed to identify the determinants of femoral head necrosis.A nomogram prediction model was constructed using R language's"rms"package,version 4.0.The receiver operating characteristic curve was used to evaluate the discriminatory ability of the model.The Hosmer-Lemeshow test was used to evaluate the goodness of fit of the model,and the decision curve analysis was used to determine its clinical application benefits.Internal validation of the study was conducted using the Bootstrap method,involving 1 000 repeated samplings.To delve deeper into the primary factors influencing femoral head necrosis post-internal fixation of the femoral neck,this paper employed the SHAP method for data set analysis.RESULTS AND CONCLUSION:(1)The risk factors leading to femoral head necrosis in the short term after cannulated screw fixation of femoral neck fractures include:smoking,diabetes,Garden classification,fracture line location,reduction quality,age,and operation time.(2)The prediction model demonstrated robust performance,evidenced by an area under the curve of 0.940(95%Confidence Interval:0.903 to 0.977),indicating a high level of prediction accuracy.The model achieved a sensitivity of 90.2%and a specificity of 87.6%,indicating that its diagnostic performance was stable.The Hosmer-Lemeshow goodness-of-fit test yielded a chi-square value of 6.593 with a P-value of 0.581,confirming that the model's predictions closely align with the observed outcomes.(3)The calibration curve of the model also performed well,and its overall trend was very close to the ideal curve,further proving the high accuracy of the model.(4)The internal validation was carried out by the Bootstrap method with 1 000 repeated samplings,and the area under the curve of the model internal validation was still as high as 0.939,proving that the model had good stability.(5)Through the decision curve,it is found that within the probability threshold range of 1%to 92%,the model can obtain the maximum net benefit value.(6)The SHAP analysis results show that among the risk factors analyzed in this study,the location of the fracture line serves as the most significant predictor of femoral head necrosis following internal fixation with cannulated screws in femoral neck fractures,and subcapital fractures are extremely prone to femoral head necrosis after surgery.(7)It is concluded that the validated prediction model demonstrates strong discriminative power and reliability,offering practical clinical utility.It serves as a useful reference tool for short-term risk assessment of femoral head necrosis following internal fixation of femoral neck fractures.
8.4 Weeks of HIIT Modulates Metabolic Homeostasis of Hippocampal Pyruvate-lactate Axis in CUMS Rats Improving Their Depression-like Behavior
Yu-Mei HAN ; Chun-Hui BAO ; Zi-Wei ZHANG ; Jia-Ren LIANG ; Huan XIANG ; Jun-Sheng TIAN ; Shi ZHOU ; Shuang-Shuang WU
Progress in Biochemistry and Biophysics 2025;52(6):1468-1483
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%) Smax+1 min (50%-55%) Smax, 3-5 cycles, Smax 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.
9.Four Weeks of HIIT Modulates Lactate-mediated Synaptic Plasticity to Improve Depressive-like Behavior in CUMS Rats
Yu-Mei HAN ; Zi-Wei ZHANG ; Jia-Ren LIANG ; Chun-Hui BAO ; Jun-Sheng TIAN ; Shi ZHOU ; Huan XIANG ; Yong-Hong YANG
Progress in Biochemistry and Biophysics 2025;52(6):1499-1510
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, Smax) alternated with one minute at low speed (50%-55% Smax), 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.
10.Effects of Different Modes in Hypoxic Training on Metabolic Improvements in Obese Individuals: a Systematic Review With Meta-analysis on Randomized Controlled Trail
Jie-Ping WANG ; Xiao-Shi LI ; Ru-Wen WANG ; Yi-Yin ZHANG ; Feng-Zhi YU ; Ru WANG
Progress in Biochemistry and Biophysics 2025;52(6):1587-1604
This paper aimed to systematically evaluate the effects of hypoxic training at different fraction of inspired oxygen (FiO2) on body composition, glucose metabolism, and lipid metabolism in obese individuals, and to determine the optimal oxygen concentration range to provide scientific evidence for personalized and precise hypoxic exercise prescriptions. A systematic search was conducted in the Cochrane Library, PubMed, Web of Science, Embase, and CNKI databases for randomized controlled trials and pre-post intervention studies published up to March 31, 2025, involving hypoxic training interventions in obese populations. Meta-analysis was performed using RevMan 5.4 software to assess the effects of different fraction of inspired oxygen (FiO2≤14% vs. FiO2>14%) on BMI, body fat percentage, waist circumference, fasting blood glucose, insulin, HOMA-IR, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), with subgroup analyses based on oxygen concentration. A total of 22 studies involving 292 participants were included. Meta-analysis showed that hypoxic training significantly reduced BMI (mean difference (MD)=-2.29,95%CI: -3.42 to -1.17, P<0.000 1), body fat percentage (MD=-2.32, 95%CI: -3.16 to -1.47, P<0.001), waist circumference (MD=-3.79, 95%CI: -6.73 to -0.85, P=0.01), fasting blood glucose (MD=-3.58, 95%CI: -6.23 to -0.93, P=0.008), insulin (MD=-1.60, 95%CI: -2.98 to -0.22, P=0.02), TG (MD=-0.18, 95%CI: -0.25 to -0.12, P<0.001), and LDL-C (MD=-0.25, 95%CI: -0.39 to -0.11, P=0.000 3). Greater improvements were observed under moderate hypoxic conditions with FiO2>14%. Changes in HOMA-IR (MD=-0.74, 95%CI: -1.52 to 0.04,P=0.06) and HDL-C (MD=-0.09, 95%CI: -0.21 to 0.02, P=0.11) were not statistically significant. Hypoxic training can significantly improve body composition, glucose metabolism, and lipid metabolism indicators in obese individuals, with greater benefits observed under moderate hypoxia (FiO>14%). As a key parameter in hypoxic exercise interventions, the precise setting of oxygen concentration is crucial for optimizing intervention outcomes.

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