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.

Processing for deodorization is widely used in the production of animal-derived Chinese medicinal materials. In this study, Heracles Neo ultra-fast gas-phase electronic nose combined with chemometrics was employed to analyze the overall odor difference of Cervi Cornu Pantotrichum(focusing on that derived from Cervus nippon Temminck in this study) before and after processing. The results showed that the electronic nose effectively distinguished between the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum. HS-GC-MS was used to identify and quantify the volatile components in the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum, and 35 and 37 volatile components were detected in the medicinal materials and decoction pieces, respectively. The medicinal materials and decoction pieces contained 28 common volatile components contributing to the odor of Cervi Cornu Pantotrichum. The odor activity value(OAV) of each volatile component was calculated based on the olfactory threshold and relative content. The results showed that there were 17 key odor substances such as isovaleraldehyde, 2-methylbutanal, isobutyraldehyde, hexanal, and methanethiol in the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum. All of them had bad odor and were the main source of the odor of Cervi Cornu Pantotrichum. The results of principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) showed that there were significant differences in volatile components between the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum. Based on the thresholds of P<0.05 and Variable Importance in Projection(VIP)>1, 21 differential volatile odor components were screened out. Among them, isopentanol, isovaleraldehyde, 2-methylbutanal, n-nonanal, and dimethylamine were the key differential odor compounds between the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum. The odor compounds and their relative content reduced, and some flavor substances such as esters were produced after processing with wine, which was the main reason for the reduction of the odor after processing of Cervi Cornu Pantotrichum.
Odorants/analysis* ; Electronic Nose ; Gas Chromatography-Mass Spectrometry/methods* ; Animals ; Volatile Organic Compounds/analysis* ; Deer ; Drugs, Chinese Herbal/chemistry*

Resveratrol(Res) is a kind of polyphenolic compound, possessing multiple biological activities such as antioxidant, anti-inflammatory, cardioprotective, and anticancer effects. In recent years, the cardiovascular protective mechanism of Res has become a research hotspot. Studies have shown that Res has a protective effect on the cardiovascular system through various pathways, such as inhibiting oxidative stress, regulating ferroptosis of cells, improving ischemia-reperfusion(I/R) injury, regulating lipid metabolism, suppressing inflammatory responses, and enhancing endothelial function. It can also alleviate cardiotoxicity caused by drugs and chemicals. In terms of oxidative stress, Res reduces the level of intracellular reactive oxygen species(ROS) by enhancing the expression of proteins such as silent information regulator 1(SIRT1) and regulating mitochondrial function, thereby alleviating myocardial cell damage. Regarding ferroptosis, Res inhibits the occurrence of ferroptosis by regulating the expression of proteins related to iron metabolism. Res can also improve I/R injury through mechanisms such as activating autophagy and the mitochondrial quality control network. In regard to improving endothelial function, Res protects the function of endothelial cells by regulating multiple signaling pathways, such as downregulating the PREP1-mediated pathway. Res can also regulate lipid metabolism and inhibit the progression of atherosclerosis. In terms of inflammatory responses, Res exerts anti-inflammatory effects through mechanisms such as inhibiting the nuclear factor-kappa B(NF-κB) signaling pathway. In addition, Res has an improving effect on cardiotoxicity caused by different drugs or environmental factors. However, the clinical application of Res still faces limitations such as poor pharmacokinetic properties. In the future, in-depth exploration is needed at multiple levels from basic research to clinical application to clarify the dose-response relationship and standardize the standards of medication regimens with the expectation of providing more effective strategies for the prevention and treatment of cardiovascular diseases.
Humans ; Resveratrol/pharmacology* ; Animals ; Cardiotonic Agents/pharmacology* ; Oxidative Stress/drug effects* ; Cardiovascular Diseases/genetics* ; Cardiovascular System/metabolism* ; Signal Transduction/drug effects*

OBJECTIVE: To investigate platelet count trajectories after induction therapy with venetoclax combined with azacitidine (VA regimen) in newly diagnosed AML patients and further analyze its clinical significance. METHODS: Clinical date of 50 newly diagnosed AML patients who received VA treatment from March 2020 to July 2023 in Department of Hematology of the First Hospital of Lanzhou University were retrospectively collected. The platelet trajectories after induction chemotherapy were constructed by using group-based trajectory modeling. To study the association between diverse trajectories of platelet counts and compound complete remission (cCR) rate, overall response rate (ORR), minimal residual disease (MRD) negative rate and overall survival (OS) rate. The Cox proportional hazard model was used to evaluate the relationship between platelet trajectory and OS. The logistic regression was used to analyze the influence of individual characteristics on platelet trajectory. RESULTS: Two platelet trajectories were identified based on the model, including platelet slowly increased group (n=31, 62.0%) and platelet rapidly increased group (n=19, 38.0%). There were statistically significant differences in cCR rate, ORR and OS rate between platelet slowly increased group and platelet rapidly increased group (all P < 0.05). The Cox regression analysis showed that platelet rapidly increased group was associated with a decreased risk of mortality compared with platelet slowly increased group (HR=0.153, 95%CI : 0.045-0.527, P =0.003). Logistic regression analysis showed that IDH1/2 mutation (OR =3.908, 95%CI : 1.023-14.923, P =0.046) and platelet transfusion (OR =0.771, 95%CI : 0.620-0.959, P =0.020) were independent influencing factors of platelet trajectory. CONCLUSION The dynamic trajectory of platelet counts in newly diagnosed AML patients who received VA treatment can serve as a significant indicator to observe the efficacy and prognosis. The platelet rapidly increased is an independent protective factor for good prognosis. TheIDH1 /2 mutation and platelet transfusion are independent influencing factors of platelet trajectory.
Humans ; Leukemia, Myeloid, Acute/blood* ; Sulfonamides/administration & dosage* ; Azacitidine/therapeutic use* ; Platelet Count ; Retrospective Studies ; Bridged Bicyclo Compounds, Heterocyclic/administration & dosage* ; Male ; Female ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Induction Chemotherapy ; Survival Rate

OBJECTIVE: By analyzing the differential miRNA in seminal plasma between individuals with normal and abnormal sperm DNA fragmentation index（DFI）, we aim to identify miRNA that may impact sperm DNA integrity and target genes, and attempt to analyze their potential mechanisms of action. METHODS: A total of 161 study subjects were collected and divided into normal control group, DFI-medium group and DFI-abnormal group based on the DFI detection values. Differential miRNA were identified through miRNA chip analysis. Through bioinformatics analysis and target gene prediction, miRNA related to DFI and specific target genes were identified. The relative expression levels of differential miRNA and target genes in each group were compared to explore the impact of their differential expression on DFI. RESULTS: Through miRNA chip analysis, a total of 11 differential miRNA were detected. Bioinformatics analysis suggested that miR-26a-5p may be associated with reduced sperm DNA integrity. And gene prediction indicated that PTEN was a specific target gene of miR-26a-5p. Compared to the normal control group, the relative expression levels of miR-26a-5p in both the DFI-medium group and the DFI-abnormal group showed a decrease, while the relative expression levels of PTEN showed an increase. The relative expression levels of miR-26a-5p in all groups were negatively correlated with DFI values, while the relative expression levels of PTEN showed a positive correlation with DFI values in the DFI-medium group and the DFI-abnormal group. The AUC of miR-26a-5p in the DFI-medium group was 0.740 (P<0.05), with a sensitivity of 73.6% and a specificity of 71.5%; the AUC of PTEN was 0.797 (P<0.05), with a sensitivity of 76.5% and a specificity of 78.4%. In the DFI-abnormal group, the AUC of miR-26a-5p was 0.848 (P<0.05), with a sensitivity of 81.3% and a specificity of 78.1%. While the AUC of PTEN was 0.763 (P<0.05), with a sensitivity of 77.2% and a specificity of 80.2%. CONCLUSION miR-26a-5p affects the integrity of sperm DNA by regulating the expression of PTEN negatively. The relative expression levels of seminal plasma miR-26a-5p and PTEN have good diagnostic value for sperm DNA integrity damage, which can help in the etiological diagnosis and prognosis analysis of abnormal DFI. This provides a diagnostic and treatment approach for the study and diagnosis of DFI abnormalities without clear etiology.
Male ; Humans ; MicroRNAs/genetics* ; PTEN Phosphohydrolase/genetics* ; Spermatozoa ; Semen/metabolism* ; DNA Fragmentation

Objective To observe the clinical effect of acupuncture combined with Shenqi Huoxue Decoction in the treatment of adenomyosis of qi deficiency and blood stasis type.Methods Seventy patients with adenomyosis of qi deficiency and blood stasis type were randomly divided into observation group and control group,35 cases in each group.The control group was treated with Levonorgestrel-releasing intrauterine system,and the observation group was treated with acupuncture combined with Shenqi Huoxue Decoction on the basis of the treatment of the control group.One menstrual cycle was a course of treatment,and the treatment lasted for three courses.After 3 months of treatment,the clinical efficacy of the two groups was evaluated,and the changes of Endometriosis Health Profile-5(EHP-5)score,serum superoxide dismutase(SOD)and catalase(CAT)were observed in the two groups before and after treatment.The changes of serum carbohydrate antigen CA125,carbohydrate antigen 199(CA199)and human epididymis protein 4(HE4)levels were compared before and after treatment between the two groups.Results(1)The total effective rate was 97.14％(34/35)in the observation group and 77.14％(27/35)in the control group.The clinical efficacy of the observation group was superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,the levels of serum CA125,CA199 and HE4 in the two groups were significantly improved(P＜0.05),and the improvement of serum CA1 25,CA199 and HE4 levels in the observation group was significantly superior to that in the control group,the difference was statistically significant(P＜0.05).(3)After treatment,the levels of serum SOD and CAT in the two groups were significantly improved(P＜0.05),and the improvement of serum SOD and CAT levels in the observation group was significantly superior to that in the control group,the difference was statistically significant(P＜0.05).(4)After treatment,the EHP-5 score of quality of life in the two groups was significantly improved(P＜0.05),and the EHP-5 score of quality of life in the observation group was significantly superior to that in the control group,the difference was statistically significant(P＜0.05).Conclusion Acupuncture combined with Shenqi Huoxue Decoction in the treatment of adenomyosis of qi deficiency and blood stasis type can significantly improve the clinical symptoms of patients,regulate the levels of SOD and CAT,so as to improve the quality of life of patients,and the curative effect is significant.

Objective To explore the correlation between serum lipid levels of total cholesterol(TC)and triglyceride(TG)and the survival prognosis in postoperative patients with early lung cancer,and to observe the effect of Fuzheng Quxie Prescription on serum lipid levels in postoperative patients with early lung cancer,so as to explore the mechanism of Fuzheng Quxie Prescription in improving the survival prognosis of postoperative patients with early lung cancer.Methods The correlation of serum TC and TG levels with survival prognosis of 257 postoperative patients with early lung cancer admitted in Shanghai Municipal Hospital of Traditional Chinese Medicine from July 2010 to December 2015 was retrospectively analyzed.The changes of serum TC and TG levels in postoperative patients with early lung cancer before and after treatment with Fuzheng Quxie Prescription were statistically analyzed.From January 2017 to April 2021,a prospective analysis of the one-year,two-year,three-year and four-year disease-free survival rates and serum TC and TG levels was carried out in 281 postoperative patients with early lung cancer treated with Fuzheng Quxie Prescription orally in Shanghai Municipal Hospital of Traditional Chinese Medicine(treatment group)and in 287 postoperative patients with early lung cancer who were followed up in clinic while had no medciation in Shanghai Pulmonary Hospital(control group).Results(1)The retrospective study showed that pre-treatment TC level was correlated with progression-free survival(PFS)in postoperative patients with early lung cancer,and the patients with high TC level had longer PFS.There was no significant correlation between pre-treatment TG level and PFS in postoperative patients with early lung cancer.The patients with high TG level had higher short-term survival rate while the patients with low TG level had higher long-term survival rate.(2)The prospective study showed that there were nine cases of recurrence in the treatment group and 24 cases of recurrence in the control group till the last follow-up time on April 1,2021.The one-year,two-year,three-year and four-year disease-free survival rates in the treatment group were 99.3％,96.8％,95.7％and 95.7％,respectively,which were superior to 97.6％,92.3％,89.2％and 87.1％in the control group(P＜0.05),indicating that the recurrence and metastasis in the postoperative patients with early lung cancer treated by Fuzheng Quxie Prescription were significantly reduced when compared with the control group,and the disease-free survival rate was significantly improved.After treatment,the serum levels of TC and TG in the treatment group were increased when compared with those before treatment(P＜0.05)while the control group showed no obvious changes(P＞0.05).The intergroup comparison showed that the increase of serum TC and TG levels in the treatment group was superior to that in the control group(P＜0.05),indicating that Fuzheng Quxie Prescription had regulatory effect on the blood lipid level of patients to a certain extent.Conclusion The analysis of the correlation between pre-treatment blood lipids and PFS prognosis in postoperative patients with early lung cancer indicated that lung cancer patients with high TC level had longer PFS;Fuzheng Quxie Prescription can regulate the blood lipid level of postoperative patients with early lung adenocarcinoma.It is speculated that Fuzheng Quxie Prescription may improve the survival prognosis of postoperative patients with early lung cancer probably by regulating the blood lipid level of the patients.

Objective:To analyze the clinical and genetic characteristics of acute myeloid leukemia,myelodysplasia-related(AML-MR)patients and evaluate their prognostic risk stratification,to guide clinical treatment decisions and improve understanding of the biological characteristics and disease progression.Methods:The study analyzed cellular and molecular genetic information of 307 AML-MR patients,diagnosed based on clinical history,bone marrow morphology,cytogenetics,and molecular genetic abnormalities.The risk stratification followed the 2022 ELN guidelines.Results:57 cases(18.6％)met the AML-MR diagnostic criteria based on morphology and clinical history,110 cases(37.2％)met the AML-MR diagnostic criteria based on cytogenetic results,and 210 cases(74.5％)met the AML-MR diagnostic criteria based on molecular testing results.Among different type of mutations,ASXL1 mutation was the most frequent,followed by SRSF2 and BCOR mutations.Except for 2 cases with incomplete data that could not be classified.263(86.2％)of the 305 patients were classified as poor prognosis,20(6.6％)were classified as good prognosis group,and 22(7.2％)were classified as intermediate prognosis group.Conclusion:Molecular genetic information plays a crucial role in diagnosing AML-MR,highlighting the importance of genetics in diagnosis and prognosis.Most AML-MR patients fall into poor prognosis categories,necessitating early intensive and targeted therapy for better survival outcomes.

Objective To observe the clinical efficacy of Yangxue Sanhan Tongmai Prescription(derived from the modification of Danggui Sini plus Wuzhuyu Shengjiang Decoction,i.e.,Danggui Sini Decoction with Euodiae Fructus and Zingiberis Rhizoma Recens added)for the treatment of endometriosis(EMS)of blood deficiency and cold coagulation type.Methods A total of 120 cases of EMS with blood deficiency and cold coagulation syndrome were randomly divided into the study group and the control group,with 60 cases in each group.The study group was treated with Yangxue Sanhan Tongmai Prescription,and the control group was treated with Shaofu Zhuyu Granules.Both groups were treated for a period of 3 months,and were followed up for one year after the completion of the treatment.The two groups were observed in the changes of the visual analogue scale(VAS)scores of menstrual abdominal pain,the grading scores of dysmenorrhea,non-menstrual pelvic pain,pain during sexual intercourse,pelvic pressure pain and sacral ligament tenderness,the size of ovarian endometriosis cysts,and the serum levels of carbohydrate antigen 125(CA125),vascular endothelial growth factor(VEGF),soluble intercellular adhesion molecule 1(SICAM-1),matrix metalloproteinase 9(MMP-9)and tissue inhibitor of metalloproteinase 2(TIMP-2).After treatment,the clinical efficacy and safety,recurrence and pregnancy in the two groups were evaluated.Results(1)In the course of the trial,3 cases fell off in the study group and 5 cases fell off in the control group,and a total of 112 patients were eventually included in the statistical analysis,including 57 cases in the study group and 55 cases in the control group.(2)After 3 months of treatment,the total effective rate in the study group was 92.98%(53/57)and that in the control group was 85.45%(47/55),and the intergroup comparison showed that the efficacy of the study group was significantly superior to that of the control group(P＜0.05).(3)After treatment,VAS scores of menstrual abdominal pain and the grading scores of dysmenorrhea,non-menstrual pelvic pain,pain during sexual intercourse,pelvic pressure pain and sacral ligament tenderness in the two groups were significantly reduced compared with those before treatment(P＜0.05),and the reduction in the study group was significantly superior to that in the control group(P＜0.05).(4)After treatment,the ovarian endometriosis cysts of the two groups were slightly reduced,but the intragroup pre-and post-treatment differences and the intergroup post-treatment differences were not statistically significant(P＞0.05).(5)After treatment,the levels of serum CA125,VEGF,SICAM-1 and MMP-9 were decreased and the serum TIMP-2 level was increased in both groups compared with those before treatment(P＜0.05).And the decrease of serum CA125,VEGF,SICAM-1 and MMP-9 as well as the increase of serum TIMP-2 in the study group were significantly superior to those in the control group(P＜0.05).(6)The results of one-year follow-up showed that the recurrence rate of the study group was 30.19%(16/53),which was significantly lower than that of the control group(68.09%,32/47),and the difference was statistically significant between the two groups(P＜0.05).In the study group,there were 21 patients having the fertility desire,and then 14 cases of them were pregnant after treatment,with a pregnancy rate of 66.67%(14/21);in the control group,there were 20 cases having fertility desire,and then 4 cases of them were pregnant after treatment,with a pregnancy rate of 20.00%(4/20).The intergroup comparison showed that the pregnancy rate of the study group was significantly higher than that of the control group,and the difference was statistically significant(P＜0.05).(7)During the treatment period,there were no obvious adverse reactions in the two groups,and there were no abnormal changes in the safety indexes of blood,urine,and stool routine test,electrocardiogram,and liver and kidney function.Conclusion Yangxue Sanhan Tongmai Prescription exerts certain effect in treating patients with endometriosis of blood deficiency and cold coagulation type,which can significantly alleviate various pain symptoms,improve pregnancy outcomes,and effectively regulate the levels of serum CA125,VEGF,SICAM-1,MMP-9 and TIMP-2 of the patients.

Objective To investigate the influences of circular RNA(circRNA)DCUN1D4 on the proliferation,apoptosis and immune escape of lung cancer cells by regulating the microRNA(miR)-18a-5p/fructose-1,6-bisphosphatase 1(FBP1)axis.Methods The human lung cancer cell lines H1975,H1650,A549 and SPCA-1 and human normal lung epidermal cells HPL-1 were selected,qRT-PCR was used to detect the expression levels of circDCUN1D4,miR-18a-5p and FBP1 mRNA in various cells.A549 cells in logarithmic growth phase were selected and divided into the blank group,circDCUN1D4 overexpression plasmid(circDCUN1D4)group,overexpression plasmid negative control(NC)group,circDCUN1D4+miR-18a-5p mimics negative control(circDCUN1D4+mimics NC)group,and circDCUN1D4+miR-18a-5p mimics group.The cell viability of each group was detected by CCK-8 method,the cell apoptosis was detected by flow cytometry,the expression levels of circDCUN1D4,miR-18a-5p and FBP1 mRNA of cells in each group were detected by qRT-PCR,the expression levels of FBP1,caspase-3,Ki67,proliferating cell nuclear antigen(PCNA)and programmed death ligand-1(PD-L1)were detected by Western blot,the targeting relationships of miR-18a-5p with circDCUN1D4 and FBP1 were verified by dual luciferase assay.Results Compared with HPL-1 cells,the mRNA expressions of circDCUN1D4 and FBP1 were significantly decreased(P<0.05),and the expression of miR-18a-5p was significantly increased(P<0.05).miR-18a-5p had targeting relationships with circDCUN1D4 and FBP1,respectively.Compared with the blank group and NC group,the OD values at 24 hours and 48 hours,and the expressions of Ki67,PCNA,miR-18a-5p and PD-L1 of cells in the circDCUN1D4 group were significantly decreased(P<0.05),and the apoptosis rate,and the expressions of circDCUN1D4,FBP1 and caspase-3 were significantly increased(P<0.05).Overexpression of miR-18a-5p reversed the inhibitory effect of circDCUN1D4 on the malignant behavior of lung cancer cells(P<0.05).Conclusion Overexpression of circDCUN1D4 can promote lung cancer cell apoptosis,inhibit lung cancer cell proliferation and immune escape,and its mechanism may be related to the regulation of miR-18a-5p/FBP1 axis.