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%) S_max+1 min (50%-55%) S_max, 3-5 cycles, S_max 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.

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, S_max) alternated with one minute at low speed (50%-55% S_max), 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.

OBJECTIVE: To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective. METHODS: Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ₊TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction. RESULTS: TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45⁺ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01). CONCLUSIONS TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.
Male ; Animals ; Mice ; Tripterygium ; Psoriasis/drug therapy* ; Keratinocytes ; Skin Diseases/metabolism* ; Cytokines/metabolism* ; Imiquimod/metabolism* ; Dermatitis/pathology* ; Disease Models, Animal ; Mice, Inbred BALB C ; Skin/metabolism*

Objective: To investigate the efficacy and safety of Liqingtong (LQT) granules in patients with dampness-heat hyperuricemia. Methods: A randomized, double-blind, placebo-controlled pilot trial was conducted at the 983rd Hospital of the Joint Logistic Support Force of the People's Liberation Army from March 15, 2023, to August 10, 2023. In total, 119 participants were enrolled in this trial, and participants were given either LQT granules or placebo for 60 days based on a health education. The primary outcome was serum uric acid (SUA) level, and the secondary outcome was the traditional Chinese medicine (TCM) symptom score, measured on days 0, 30, and 60. Safety indicators, including liver function, kidney function, blood routine, glucose, blood lipid, blood pressure, and heart rate were tested on days 0 and 60 of the trial. The data were analyzed using Prism 9 software, and the significance level was set at P < .05. Results: Among 119 participants, six in the LQT granule group and seven in the placebo group dropped out, and 106 participants completed clinical observation. Baseline information, including SUA levels, TCM symptom scores, and other clinical characteristics, did not differ between the groups. At the end of the trial, compared with baseline values, the SUA levels in the LQT granule group decreased (P < .001), and no significant change was observed in the placebo group (P = .422); compared with the placebo group, the SUA levels decreased in the LQT granule group (P = .001). Compared with baseline values, the total TCM symptom scores in the LQT granule group decreased (P < .001), with no change in the placebo group (P = .136). Safety indicators did not differ significantly between the two groups. Conclusion The pilot trial demonstrated the potential of LQT granules to lower SUA levels and improve symptoms of dampness and heat.

Objective:To investigate the association between hyperuricemia and the risk for stroke occurrence, as well as the mediating effect of hypertension on this association.Methods:In this study, the China Chronic Diseases and Nutrition Surveillance system in 2015 was used as baseline data. We identified hospital admissions for stroke using the electronic homepage of inpatient medical records from 2013-2020, and death data were obtained from the 2015-2020 National Mortality Surveillance System. A retrospective cohort was established after matching and linking the database. The Cox proportional hazard regression model was used to analyze the relationship between hyperuricemia and the risk of stroke and its subtypes. Restricted cubic spline analysis was conducted to examine the dose-response relationship between serum uric acid levels and the risk for stroke. Mediation analysis was performed to investigate the mediating effect of hypertension on the association between hyperuricemia and the risk for stroke and its subtypes. Subgroup analyses were conducted based on gender and age groups.Results:A total of 124 352 study subjects were included, with an accumulative follow-up time of 612 911.36 person-years. During the follow-up period, 4 638 cases of stroke were found, including 3 919 cases of ischemic stroke and 689 cases of hemorrhagic stroke. The incidence density of stroke was 756.72 per 100 000 person-years, 641.37 per 100 000 person-years for ischemic stroke, and 114.60 per 100 000 person-years for hemorrhagic stroke. Multivariable Cox proportional hazards regression models showed that after adjusting for covariates, compared to those without hyperuricemia, individuals with hyperuricemia had a 16% higher risk for stroke [hazard ratio ( HR)=1.16, 95% CI: 1.06-1.27], a 12% higher risk of ischemic stroke ( HR=1.12, 95% CI: 1.01-1.24), and a 39% higher risk of hemorrhagic stroke ( HR=1.39, 95% CI: 1.11-1.75). Mediation analysis showed that hypertension partially mediated the associations between hyperuricemia and the risk for stroke, ischemic stroke, and hemorrhagic stroke, with mediation proportions of 36.07%, 39.98%, and 25.34%, respectively. The mediating effect is pronounced in the male population and individuals below 65. Conclusion:Hyperuricemia is a risk factor for stroke, and hypertension partially mediates the effect of hyperuricemia on stroke.

Objective To investigate and analyze the distribution of serum cytokeratin 19 fragment antigen 21-1(CYFRA21-1)and squamous cell carcinoma-associated antigen(SCCA)levels in healthy pregnant women during pregnancy and to assess their diagnostic value for cervical cancer in pregnancy.Methods A total of 441 healthy pregnant women and 69 patients with cervical cancer in pregnancy who attended the Obstetrics and Gynecology Hospital of Fudan University from Jan 2021 to May 2024 were selected,and 165 healthy women in the Physical Examination Center of the Obstetrics and Gynecology Hospital of Fudan University were included in the same period as the control group.The healthy pregnant women were divided into 143 in early pregnancy(T1 group),147 in middle pregnancy(T2)and 151 in late pregnancy(T3).Serum CYFRA21-1 and SCCA values were detected and analyzed in all groups.One-way ANOVA,independent samples t-test,Mann-Whitney U-test,Kruskal-Wallis H-test,logistic analysis,and ROC curves were used for comparative analysis.Results The CYFRA21-1 and SCCA values were 1.66(1.19-2.17)ng/mL and 0.8(0.6-1.0)ng/mL in the control group,3.07(2.11-4.14)ng/mL and 0.9(0.7-1.3)ng/mL in the healthy pregnant women group,and were 4.33(2.99-7.60)ng/mL and 1.8(0.9-8.5)ng/mL in the patients with cervical cancer in pregnancy group,respectively.There was a statistically significant difference in the two serum values between every two groups(P<0.05).CYFRA21-1 levels were 3.13(2.46-4.05)ng/mL,1.89(1.50-2.53)ng/mL and 4.19(3.48-5.43)ng/mL in the T1,T2,and T3 groups,respectively;and SCCA levels were 0.9(0.7-1.1)ng/mL,0.7(0.6-1.0)ng/mL and 1.2(0.8-1.7)ng/mL,respectively.The results of T1 and T3 groups were higher than those of the control group(P<0.05);however,there was no statistically significant difference between the results of the T2 group and those of the control group(P>0.05).The areas under the ROC curves for the diagnosis of cervical cancer in pregnancy for CYFRA21-1,SCCA,human epididymis protein 4(HE4),anti-carcinoembryonic antigen(CEA)and joint indicators were 0.684,0.724,0.612,0.791 and 0.913,with sensitivities of 36%,48%,38%,57%and 73%,specificities of 96%,97%,89%,86%and 99%,respectively.The cut-off values of each indicator were 6.05 ng/mL,2.60 ng/mL,51.45 pg/mL and 1.75 ng/mL,respectively.Conclusion Serum CYFRA21-1 and SCCA levels were higher in pregnant women during early and late pregnancy compared with non-pregnant individuals,while they were not statistically different from non-pregnant women during mid-trimester.CYFRA21-1 and SCCA have diagnostic value for patients with cervical cancer during pregnancy.

Objective To evaluate the clinical efficacy of Xiaojianzhong Decoction plus Dachaihu Decoction in the treatment of chronic atrophic gastritis(CAG),and to provide scientific evidence for the clinical application of the formula.Methods The clinical observation was carried out in 80 CAG patients with spleen deficiency and stasis-heat syndrome of normal-people pulse type(the ratio of patients'pulse to the number of respirations within one minute being 4-5 evaluated by Changsangjun pulse-taking method)who attended the clinic of the Department of Gastroenterology of Shunde Hospital,Guangzhou University of Chinese Medicine,from January 2020 to December 2023.According to the treatment method,the patients were divided into the treatment group and the control group,with 40 cases in each group.The control group was given conventional western medicine treatment,and the treatment group was given Xiaojianzhong Decoction plus Dachaihu Decoction.Seven days constituted one course of treatment,and the treatment covered 6 months.The changes of traditional Chinese medicine(TCM)syndrome score,gastroscopy score,pathological score and gastric function indicators in the two groups were observed before and after the treatment.After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)After 6 months of treatment,the total effective rate of the treatment group was 90.00%(36/40),and that of the control group was 60.00%(24/40).The intergroup comparison(tested by chi-square test)showed that the efficacy of the treatment group was significantly superior to that of the control group(P＜0.05).(2)After treatment,the scores of TCM syndromes in the two groups were significantly lower than those before treatment(P＜0.05),and the decrease of the scores in the treatment group was superior to that in the control group(P＜0.05).(3)After treatment,the gastroscopy scores of the two groups were significantly lower than those before treatment(P＜0.05),but there was no significant difference between the two groups after treatment(P＞0.05).(4)After treatment,the total pathological scores of the two groups and the scores of the gastric mucosal atrophy and intestinal metaplasia of the gastric antrum,gastric angle and gastric body in the treatment group were significantly improved compared with those before treatment(P＜0.05),and the improvement of the gastroscopy scores in the treatment group was significantly superior to that in the control group(P＜0.05).No statistically significant differences were presented in the scores of the gastric mucosal dysplasia and chronic inflammation of gastric antrum,gastric angle and gastric body in the two groups and in the scores of the gastric mucosal atrophy and intestinal metaplasia of gastric antrum,gastric angle and gastric body in the control group when compared with those before treatment(P＞0.05).(5)After treatment,the serum levels of gastric function indicators of pepsinogen Ⅰ(PGⅠ),pepsinogen Ⅱ(PGⅡ)and gastrin 17(G-17)in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease in the treatment group was significantly superior to that in the control group(P＜0.05).(6)There were no obvious adverse reactions occurring in the two groups during the treatment,with high safety.Conclusion Xiaojianzhong Decoction plus Dachaihu Decoction can significantly enhance the clinical efficacy of CAG patients with spleen deficiency and stasis-heat syndrome of normal-people pulse type,significantly improve the gastrointestinal function and pathological scores of the patients,and has high safety.

Objective To investigate the clinical efficacy and safety of Yiqi Huatan Tongluo Prescription(mainly composed of Fici Simplicissimae Radix,Notoginseng Radix et Rhizoma,Pinelliae Rhizoma Praeparatum,Poria,Nelumbinis Folium,and Glycyrrhizae Radix et Rhizoma,etc.)combined with drug-coated balloon(DCB)in the treatment of coronary heart disease(CHD)and to observe its effect on low-shear related serological indicators.Methods A total of 106 patients with CHD of qi deficiency and phlegm stasis obstructing collateral type who were scheduled to undergo percutaneous coronary intervention were randomly divided into a treatment group and a control group,with 53 cases in each group.The control group was treated with drug-eluting stent implantation,and the treatment group was treated with DCB.After the operation,the control group was given conventional antiplatelet aggregation drugs,and the treatment group was given oral administration of Yiqi Huatan Tongluo Prescription.The medication for the two groups lasted for 12 weeks.The changes in the serum levels of monocyte chemoattractant protein 1(MCP-1),interleukin 1 β(IL-1β)and vascular endothelial growth factor(VEGF)in the two groups were observed before and after treatment.Moreover,the traditional Chinese medicine(TCM)syndrome efficacy after treatment and the incidence of adverse events one year after operation were compared between the two groups.Results(1)After 12 weeks of treatment,the total effective rate for TCM syndrome efficacy of the treatment group was 88.68％(47/53),and that of the control group was 75.47％(40/53).The intergroup comparison(tested by chi-square test)showed that the TCM syndrome efficacy in the treatment group was significantly superior to that in the control group(P＜0.05).(2)The analysis of indicators related to endothelial dysfunction in the blood flow with low shear stress showed that after treatment,the levels of serum MCP-1,IL-1βand VEGF in the control group presented no obvious changes(P＞0.05),but the serum levels of MCP-1 and IL-1β in the treatment group were significantly lowered compared with those before treatment(P＜0.05).The intergroup comparison showed that the decrease of serum MCP-1,IL-1β and VEGF levels in the treatment group was significantly superior to that in the control group(P＜0.05).(3)The one-year follow-up after the operation showed that the total incidence of adverse events in the treatment group was 18.87％(10/53),and that in the control group was 20.75％(11/53).There was no significant difference between the two groups(P＞0.05).Conclusion Yiqi Huatan Tongluo Prescription combined with DCB has definite action on the targets related to endothelial dysfunction in coronary blood flow with low shear stress,which is conducive to reducing inflammatory response,improving the symptoms of angina pectoris and enhancing clinical efficacy.The incidence of adverse events did not increase one year after operation,indicating good safety and effectiveness.

Chronic kidney disease(CKD)commonly used dietary assessments including 24-hour dietary recall(24 h DR)/3-day dietary recall(3DDR),food frequency questionnaire(FFQ),dietary records,and estimation of dietary protein intake based on nitrogen balance.Given the high prevalence of CKD patients in Asian population and the scarcity of research using FFQ method,it is crucial to develop an FFQ suitable for Chinese CKD patients.This review summarizes the advantages and disadvantages of dietary assessment methods for CKD,the current research status,and the content and steps involved in establishing an FFQ,with the aim of providing reference for the modification of FFQ for Chinese CKD patients.

Sepsis-induced coagulopathy(SIC),a critical and potentially lethal condition arising from sepsis,results in endothelial damage and significant coagulation dysregulation,making it a major factor contributing to mortality among sepsis patients.Early diagnosis and treatment of SIC are expected to improve the prognosis of sepsis patients.In 2019,the International Society on Thrombosis and Hemostasis(ISTH)issued the first guidelines for the diagnosis and treatment of SIC,but there are no corresponding protocols in China.Therefore,Chinese Society of Thrombosis,Hemostasis and Critical Care,Chinese Medicine Education Association,and Chinese People's Liberation Army Professional Committee of Critical Care Medicine jointly formulated the"Chinese Expert Consensus on the Diagnosis and Treatment of Sepsis-induced Coagulopathy(2024 edition)."This consensus includes 5 parts:pathogenesis,classification,laboratory approaches,diagnosis and treatment,with a total of 14 evidence-based recommendations to guide clinical practice.