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.

Objective To compare screw versus Kirschner wire fixation in the treatment of lateral humeral condyle frac-tures in children.Methods A systematic search was conducted in PubMed,Embase,the Cochrane library,Web of Science,China National Knowledge Internet(CNKI),Wanfang Datebase from in ception to February 2022.Studies comparing screws and Kirschner wire fixation in the treatment of lateral humeral condyle fractures in children were included.Outcome measures included and excluded by a set of inclusion and exclusion criteria and evaluated for their quality,their excellent and good rate of fracture healing,malunion,delayed union or nonunion,infection,limitation of elbow flexion or extension(＞10°)were ex-tracted and analyzed using software Rev Man 5.3.Results A total of 9 retrospective studies involving 647 patients were includ-ed,with 255 patients in the screw fixation group(including screw combined with Kirschner wire)and 392 patients in the Kirschner wire fixation group.Meta analysis showed the following:infection rate in the screw group was significantly lower than that in the Kirschner wire group[OR=0.22,95％CI(0.09,0.56),P=0.001].There were no significant differences between the 2 groups in excellent and good rate of fracture healing,malunion rate(P＞0.05).Subgroup analysis showed that infection rate in the screw-only group was significantly lower than that in the Kirschner wire group[OR=0.18,95％CI(0.05,0.65),P=0.009].Conclusion For lateral humeral condyle fractures,Screw fixation alone had a lower infection rate than kirschner wire fixation and screw combined with Kirschner wire fixation.There were no significant differences in the excellent and good rate of fracture healing,malunion.In terms of postoperative efficacy and safety of internal fixation,orthopaedic surgeons are more like-ly to recommend screws for fixation of lateral humeral condyle fractures in children.

This study was aimed at examining the influence of meteorological factors on scrub typhus in Xiamen.Scrub ty-phus monitoring data and meteorological factors were collected in Xiamen from 2005 to 2023.Spearman correlation analysis and nonlinear regression were used to analyze the correlation between scrub typhus incidence and meteorological factors.The inci-dence of scrub typhus first increased and subsequently decreased in Xiamen from 2005 to 2023.The highest incidence was be-tween 2014 and 2016,and the peak incidence was from June to October.The monthly incidence of scrub typhus positively cor-related with daily minimum temperature(r=0.637,P＜0.001,daily average temperature(r=0.627,P＜0.001),daily maxi-mum temperature(r=0.612,P＜0.001),sunshine duration(r=0.405,P＜0.001),average relative humidity(r=0.346,P＜0.001),and daily rainfall(r=0.207,P=0.002),and negatively correlated with average atmospheric pressure(r=-0.549,P＜0.001),whereas no correlation was observed with the average wind speed in Xiamen.The regression equation of scrub ty-phus monthly incidence and meteorological parameters was y=-433.869-11.503x1+0.381x1 2+9.150x2-0.197x2 2+3.936 x3-0.132x3 2+0.881x4+0.035x4 2-1.048x5+0.009x5 2+0.186x6-0.023x6 2+0.421x7+6.210×10-5x8-1.051 × 10-10x8 2 in Xiamen,and the R2 was 0.473,thus indicating good model fit.Scrub typhus incidence correlated with the daily minimum av-erage temperature,average temperature,daily maximum tem-perature,sunshine duration,daily rainfall,relative humidity,and average atmospheric pressure in Xiamen.Various meteoro-logical factors had differing effects on scrub typhus.

Aim To investigate the mechanism of py-roptosis mediated by the NLRP3/caspase-1/GSDMD signaling pathway and the intervention effect of Radix Angelica Sinensis and Radix Astragalus ultrafiltration extract(RAS-RA)in radiation-induced pulmonary fi-brosis.Methods Fifty Wistar rats were randomly di-vided into five groups,with ten rats in each group.Ex-cept for the blank control group,all other groups of rats were anesthetized and received a single dose of 40 Gy X-ray local chest radiation to establish a radiation-in-duced pulmonary fibrosis rat model.After radiation,the rats in the RAS-RA intervention groups were orally administered doses of 0.12,0.24 and 0.48 g·kg-1 once a day for 30 days.The average weight and lung index of the rats were observed after 30 days of contin-uous administration.Hydroxyproline(HYP)content in lung tissue was determined by hydrolysis method.The levels of IL-18 and IL-1 β in serum were detected by ELISA.Lung tissue pathological changes were ob-served by HE and Masson staining.Ultrastructural changes in lung tissue were observed by transmission e-lectron microscopy.The expression levels of NLRP3/caspase-1/GSDMD pyroptosis pathway-related proteins and fibrosis-related proteins in lung tissue were detec-ted by Western blot.Results Compared with the blank group,the HYP content in lung tissue and the levels of IL-18 and IL-1 β in serum significantly in-creased in the model group(P＜0.01).HE and Mas-son staining showed inflammatory cell infiltration and collagen fiber deposition.Transmission electron mi-croscopy revealed increased damaged mitochondria,disordered arrangement,irregular morphology,shallow matrix,outer membrane rupture,mostly fractured and shortened cristae,mild expansion,increased electron density of individual mitochondrial matrix,mild sparse structure of lamellar bodies,partial disorder,unclear organelles,and characteristic changes of pyroptosis.Western blot analysis showed increased expression of caspase-1,GSDMD,NLRP3,CoL-Ⅰ,α-SMA,and CoL-Ⅲ proteins(P＜0.01).Compared with the model group,the RAS-RA intervention group showed signifi-cant improvement in body mass index and lung index of rats,decreased levels of IL-18 and IL-1 β inflammatory factors(P＜0.01),improved mitochondrial structure,reduced degree of fibrosis,and decreased expression of caspase-1,GSDMD,NLRP3,COL-Ⅰ,COL-Ⅲ,and α-SMA proteins in lung tissue(P＜0.01).Conclusion RAS-RA has an inhibitory effect on radiation-in-duced pulmonary fibrosis,and its mechanism may be related to the inhibition of pyroptosis through the regu-lation of the NLRP3/caspase-1/GSDMD signaling pathway.

Objective:To investigate the prognostic value of serum adenosylhomocysteinase (AHCY) in patients with hepatitis E virus acute liver failure (HEV-ALF).Methods:From 1 January 2017 to 31 December 2022, 100 patients each with HEV-ALF and acute hepatitis E (AHE) from the First Affiliated Hospital of Medical School of Zhejiang University and Affiliated Suzhou Hospital of Nanjing Medical University were included in this case-control study. The HEV-ALF group was 58.56±11.16 years old, including 71 men. The AHE group was 56.04±14.30 years old, including 61 men. All serum samples were obtained before the patient had an acute onset and were obtained without treatment. Firstly, the serum AHCY levels in patients with HEV-ALF and AHE were analyzed by ELISA. Secondly, the serum AHCY levels in HEV-ALF patients with different organ failure and disease condition were compared. According to the number of organ failure, 100 HEV-ALF patients were divided into organ failure number=2 group ( n=58), number=3 group ( n=24) and number>3 groups ( n=18). According to the disease condition, 100 patients were divided into improvement group ( n=49), disease fluctuation group ( n=37), and deterioration group ( n=14). Thirdly, the survival times between the high serum AHCY level group ( n=50) and the low serum AHCY level group ( n=50) were compared. Finally, the independent risk factors to predict mortality using the multivariate Logistic regression analysis, and evaluated the predictive and decision-making abilities of serum AHCY levels were explored using the receiver operating characteristic (ROC) curve and decision curve analysis (DCA). Results:Serum AHCY levels in HEV-ALF patients were significantly higher than those in AHE patients [326.92 (295.37-385.84) pg/ml vs. 222.88 (188.04-246.78) pg/ml, Z=-12.217, P<0.001]. Serum AHCY levels in group 2 were significantly lower than those in group 3 [303.44 (284.40-330.15) pg/ml vs. 335.36 (306.30-385.84) pg/ml, Z=-3.353, P=0.001]. Serum AHCY level in group 3 were significantly lowerthan those in group>3 [335.36 (306.30-385.84) pg/ml vs. 549.89 (423.35-660.22) pg/ml, P<0.001]. The serum AHCY levels in the fluctuation group were lower than those in the deterioration group [322.17 (283.92-423.74) pg/ml vs. 458.26 (374.66, 593.89) pg/ml, Z=-4.016, P=0.009]. The survival time of high serum AHCY level group was significantly lower than that of low serum AHCY level group [23.11 (20.25-25.96) days vs. 29.49 (28.79-30.20) days, Z=-2.596, P<0.001]. The multivariate Logistic regression analysis showed that the levels of serum AHCY and total bilirubin were independent risk factors to predict mortality in HEV-ALF patients [AHCY, OR (95% CI): 1.008 (1.002-1.015), P=0.008; total bilirubin, OR (95% CI): 1.011 (1.005-1.018), P=0.001]. Serum AHCY level predicting the area under the curve (AUC) of 30-day mortality in HEV-ALF patients was 0.912, with a sensitivity of 90.00% and a specificity of 93.75%. DCA results demonstrated that serum AHCY level had good decision-making power for predicting 30-day mortality in HEV-ALF patients. Conclusion:Serum AHCY has an important prognostic value for HEV-ALF patients. Higher serum AHCY levels indicate the worse prognosis of HEV-ALF patients.

This study aimed to explore the potentiating effect and mechanism of the extract of Jingfang Granules(JFG) on the activation of macrophages. The RAW264.7 cells were treated with JFG extract and then stimulated by multiple agents. Subsequently, mRNA was extracted, and reverse transcription-polymerase chain reaction(RT-PCR) was used to measure the mRNA transcription of multiple cytokines in RAW264.7 cells. The levels of cytokines in the cell supernatant were detected by enzyme-linked immunosorbent assay(ELISA). In addition, the intracellular proteins were extracted and the activation of signaling pathways was determined by Western blot. The results showed that JFG extract alone could not promote or slightly promote the mRNA transcription of TNF-α, IL-6, IL-1β, MIP-1α, MCP-1, CCL5, IP-10, and IFN-β, and significantly enhance the mRNA transcription of these cytokines in RAW264.7 cells induced by R848 and CpG in a dose-dependent manner. Furthermore, JFG extract also potentiated the secretion of TNF-α, IL-6, MCP-1, and IFN-β by RAW264.7 cells stimulated with R848 and CpG. As revealed by mechanism analysis, JFG extract enhanced the phosphorylation of p38, ERK1/2, IRF3, STAT1, and STAT3 in RAW264.7 cells induced by CpG. The findings of this study indicate that JFG extract can selectively potentiate the activation of macrophages induced by R848 and CpG, which may be attributed to the promotion of the activation of MAPKs, IRF3, and STAT1/3 signaling pathways.
Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6/metabolism* ; Plant Extracts/metabolism* ; Lipopolysaccharides/pharmacology* ; Macrophages ; Cytokines/metabolism* ; RNA, Messenger/metabolism*

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

This study investigated the mechanism of Danggui Shaoyao Powder(DSP) against mitophagy in rat model of Alzheimer's disease(AD) induced by streptozotocin(STZ) based on PTEN induced putative kinase 1(PINK1)-Parkin signaling pathway. The AD rat model was established by injecting STZ into the lateral ventricle, and the rats were divided into normal group, model group, DSP low-dose group(12 g·kg~(-1)·d~(-1)), DSP medium-dose group(24 g·kg~(-1)·d~(-1)), and DSP high-dose group(36 g·kg~(-1)·d~(-1)). Morris water maze test was used to detect the learning and memory function of the rats, and transmission electron microscopy and immunofluorescence were employed to detect mitophagy. The protein expression levels of PINK1, Parkin, LC3BⅠ/LC3BⅡ, and p62 were assayed by Western blot. Compared with the normal group, the model group showed a significant decrease in the learning and memory function(P<0.01), reduced protein expression of PINK1 and Parkin(P<0.05), increased protein expression of LC3BⅠ/LC3BⅡ and p62(P<0.05), and decreased occurrence of mitophagy(P<0.01). Compared with the model group, the DSP medium-and high-dose groups notably improved the learning and memory ability of AD rats, which mainly manifested as shortened escape latency, leng-thened time in target quadrants and elevated number of crossing the platform(P<0.05 or P<0.01), remarkably activated mitophagy(P<0.05), up-regulated the protein expression of PINK1 and Parkin, and down-regulated the protein expression of LC3BⅠ/LC3BⅡ and p62(P<0.05 or P<0.01). These results demonstrated that DSP might promote mitophagy mediated by PINK1-Parkin pathway to remove damaged mitochondria and improve mitochondrial function, thereby exerting a neuroprotective effect.
Rats ; Animals ; Mitophagy ; Alzheimer Disease/genetics* ; Powders ; Protein Kinases/metabolism* ; Ubiquitin-Protein Ligases/metabolism*

Aim To investigate the effect of terpinen-4-ol (T40) on inflammatory injury of vascular smooth muscle cells (VSMCs) induced by high glucose based on the improvement of autophagic flow disorder and involved molecular signals. Methods The scratch test was used to analyze the migration ability of VSMCs, the levels of IL-1β and IL-6 in cell culture supernatant were measured by ELISA, the expression levels of inflammation-related proteins NF-κb p65, p-NF-κb p65, IL-1β, IL-18 and autophagy-related proteins p62, LC3-HYLC3-I, Beclinl, p-Beclinl were de-tected by Western blot. Results T40 inhibited migration of VSMCs induced by high glucose, reduced the secretion and release of pro-inflammatory factors IL-1β and IL-6, inhibited the expression of p-NF-κb p65/ NF-κb p65, IL-1β, IL-18, downregulated the expression of p62, LC3-TJ/LC3- I and p-Beclinl at same time. After interfering the autophagic flux of VSMCs with autophagy inhibitor chloroquine (CQ) , T40 pre-treatment significantly inhibited the protein expression levels of the above inflammatory factors and autophagy-related signals which mediated by CQ. Conclusion T40 inhibits the inflammatory injury of VSMCs induced by high glucose through improving the autophagic flow disorder.

Aim To investigate the effect of luteolin on M1 macrophages polarization through HIF-1α-mediated glycolytic pathway. Methods RAW264.7 cells were divided into control groups(M0)and LPS+IFN-γ groups(M1). M1 groups were further divided into luteolin group, 2-DG(glycolysis inhibitor)group, luteolin+2-DG group,luteolin+DMOG(HIF-1α agonist)group. The protein expression levels of iNOS, Arg-1 and HIF-1α were detected by Western blot. Macrophage phenotype was detected by flow cytometry. In addition, the expression levels of IL-6 and IL-10 were measured by ELISA. The gene expression levels of GLUT1, HK2, PFK1, PK and HIF-1α were quantified by quantitative real-time PCR. Results Compared with M1 groups, luteolin and luteolin+2-DG treatment groups decreased the expression levels of GLUT1, HK2, PFK1, PK and HIF-1α related to glycolysis. In addition, luteolin and luteolin+2-DG treatment group significantly inhibited the expression of M1 macrophage markers such as iNOS, CD86 and IL-6, whereas up-regulated M2 macrophage markers Arg-1, CD206 and IL-10. Notably, the inhibitory effects of luteolin on M1 macrophages were restored by DMOG. Conclusion Luteolin regulates M1 macrophage polarization by inhibiting the glycolytic pathway induced by HIF-1α.