Objective To investigate the expression of SORT1 in the gastric cancer tissue and analyze its relationship with clinical prognosis of patients as well as the pathways and mechanisms involved in gastric cancer progression.Methods The Gene Expression Profiling Interaction Analysis database,Western blot,and immunohistochemistry were employed to predict and analyze the expression of SORT1 in the gastric cancer and the adjacent tissue.The clinical case information of 109 patients who underwent radical surgery for gastric cancer in the First Affiliated Hospital of Bengbu Medical University from April 2015 to April 2017 was collected to analyze the relationship of SORT1 with the clinicopathological parameters and prognosis of the patients.Cell proliferation was detected by the CCK-8 assay and colony formation assay,while cell migration and invasion were assessed by the scratch assay and Transwell assay,respectively.Western blot was employed to determine the expression of proteins related to epithelial-mesenchymal transition(EMT)in gastric cancer cells,followed by further analysis on molecular mechanism through which SORT1 regulates EMT in gastric cancer cells.Results Western blot and immunocytochemistry results showed that SORT1 was highly expressed in the gastric cancer tissue(P=0.003,P<0.001),which was positively correlated with malignant progression of tumors(all P<0.05).The Kaplan-Meier survival analysis revealed shortened postoperative survival periods for the patients with high expression of SORT1(P<0.001).The Cox regression model indicated that SORT1 expression was an independent risk factor affecting the 5-year survival rate after surgery for gastric cancer patients(P<0.001).Up-regulation of SORT1 expression promoted the proliferation,migration,invasion,and EMT of gastric cancer cells(all P<0.05),while down-regulation of SORT1 showed the opposite effects(all P<0.05).Western blot results showed that high expression of SORT1 promoted the expression of β-catenin,cyclin D1,and c-Myc(all P<0.05).Moreover,in vitro use of the Wnt/β-catenin pathway inhibitor(XAV939)effectively suppressed the EMT enhancement caused by high expression of SORT1 in gastric cancer cells(all P<0.05).Conclusions SORT1 is highly expressed in gastric cancer and affects patients' postoperative survival periods.It is involved in the proliferation,migration,and invasion of gastric cancer cells and may promote the EMT of gastric cancer cells by activating the Wnt/β-catenin pathway.
Humans ; Stomach Neoplasms/pathology* ; Cell Proliferation ; Epithelial-Mesenchymal Transition ; Cell Movement ; Prognosis ; Cell Line, Tumor ; Adaptor Proteins, Vesicular Transport/metabolism* ; Male ; Female ; Middle Aged

This study was analyzed the spatial-temporal distribution and aggregation characteristics of Yersinia pestispositive host animals and vector pathogens in marmot natural foci in the Qilian-Altun mountains,Gansu Province,to provide a scientific basis for precise plague prevention and control.Y.pestissurveillance data for marmot natural foci in Qilian-Altun Mountains of Gansu Province from 2014 to 2023 were obtained from the Disease Control and Prevention Center of Gansu Province.Origin 2024 software was used for data visualization and presentation.Global and local spatial autocorrelation analyses and trend analyses were conducted in ArcGIS 10.8 software,with townships as the spatial scale.Cumulatively,440 strains of Y.pestis were isolated from the natural marmot foci in the Qilian-Altun mountainsof Gansu Province from 2014 to 2023.Most strains was isolated from marmots(345 strains,78.41%),and the remainder were isolated from vectors.Temporal distribution analysis indicated that the highest number of detected bacteria was reported in July and August(both 121 strains,27.50%).Regional distribution analysis revealed that Aksai County reported the highest number of detected bacteria(255 strains,57.95%).Global spatial autocorrelation analysis showed a spatially clustered distribution of the number of bacteria detected annually in the townships containing natural foci,except in2014,2016,and 2021-2023.The strongest spatial clustering was observed in 2020(Moran's I=0.521 2,Z=14.397 0,P<0.001).Local spatial autocorrelation analysis indicated a"high-high"aggregation area in the natural foci every year from 2014 to 2023,primarily in Hongliuwan Town of Aksai County and Dangchengwan Town of Subei County.The distribution of the"low-low"aggregation area was essentially consistent with the low activity area of the Yersinia pestisepidemic.The trend in annual total bacterial count gradually increased from east to west,and peaked in the western part of the epidemic focus.Clear spatial aggregation characteristics of the number of Y.pestis were detected in the marmot natural foci in the Qilian-Altun mountains at the townshiplevel as a whole in Gansu Province from 2014 to 2023.The aggregation area was mainly in the western section of Qilian Mountain to the Altun mountain section of the epidemic source area.Monitoring and prevention and control efforts should be focused in this key area,with prevention and control measures tailored to the local conditions,and classified guidance to decrease the risk of plague occurrence and spread.

BACKGROUND: The clinical impact of post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) in patients treated with PCI for chronic total occlusion (CTO) was still undetermined. METHODS: All CTO vessels treated with successful anatomical PCI in patients from PANDA III trial were retrospectively measured for post-PCI QFR. The primary outcome was 2-year vessel-oriented composite endpoints (VOCEs, composite of target vessel-related cardiac death, target vessel-related myocardial infarction, and ischemia-driven target vessel revascularization). Receiver operator characteristic curve analysis was conducted to identify optimal cutoff value of post-PCI QFR for predicting the 2-year VOCEs, and all vessels were stratified by this optimal cutoff value. Cox proportional hazards models were employed to calculate the hazard ratio (HR) with 95% CI. RESULTS: Among 428 CTO vessels treated with PCI, 353 vessels (82.5%) were analyzable for post-PCI QFR. 31 VOCEs (8.7%) occurred at 2 years. Mean value of post-PCI QFR was 0.92 ± 0.13. Receiver operator characteristic curve analysis shown the optimal cutoff value of post-PCI QFR for predicting 2-year VOCEs was 0.91. The incidence of 2-year VOCEs in the vessel with post-PCI QFR < 0.91 (n = 91) was significantly higher compared with the vessels with post-PCI QFR ≥ 0.91 (n = 262) (22.0% vs. 4.2%, HR = 4.98, 95% CI: 2.32-10.70). CONCLUSIONS Higher post-PCI QFR values were associated with improved prognosis in the PCI practice for coronary CTO. Achieving functionally optimal PCI results (post-PCI QFR value ≥ 0.91) tends to get better prognosis for patients with CTO lesions.

OBJECTIVE: To investigate the therapeutic efficacy of cinnamaldehyde (CA) on systemic Candida albicans infection in mice and to provide supportive data for the development of novel antifungal drugs. METHODS: Ninety BALB/c mice were randomly divided into 3 groups according to a random number table: CA treatment group, fluconazole (positive control) group, and Tween saline (negative control) group, with 30 mice in each group. Initially, all groups of mice received consecutive intraperitoneal injections of cyclophosphamide at 200 mg/kg for 2 days, followed by intraperitoneal injection of 0.25 mL C. albicans fungal suspension (concentration of 1.0 × 10⁷ CFU/mL) on the 4th day, to establish an immunosuppressed systemic Candida albicans infection animal model. Subsequently, the mice were orally administered CA, fluconazole and Tween saline, at 240, 240 mg/kg and 0.25 mL/kg respectively for 14 days. After a 48-h discontinuation of treatment, the liver, small intestine, and kidney tissues of mice were collected for fungal direct microscopic examination, culture, and histopathological examination. Additionally, renal tissues from each group of mice were collected for (1,3)- β -D-glucan detection. The survival status of mice in all groups was monitored for 14 days of drug administration. RESULTS: The CA group exhibited a fungal clearance rate of C. albicans above 86.7% (26/30), significantly higher than the fluconazole group (60.0%, 18/30, P<0.01) and the Tween saline group (30.0%, 9/30, P<0.01). Furthermore, histopathological examination in the CA group revealed the disappearance of inflammatory cells and near-normal restoration of tissue structure. The (1,3)-β-D-glucan detection value in the CA group (860.55 ± 126.73 pg/mL) was significantly lower than that in the fluconazole group (1985.13 ± 203.56 pg/mL, P<0.01) and the Tween saline group (5910.20 ± 320.56 pg/mL, P<0.01). The mouse survival rate reached 90.0% (27/30), higher than the fluconazole group (60.0%, 18/30) and the Tween saline group (30.0%, 9/30), with a significant difference between the two groups (both P<0.01). CONCLUSIONS CA treatment exhibited significant therapeutic efficacy in mice with systemic C. albicans infection. Therefore, CA holds potential as a novel antifungal agent for targeted treatment of C. albicans infection.
Animals ; Acrolein/pharmacology* ; Candida albicans/physiology* ; Mice, Inbred BALB C ; Candidiasis/pathology* ; Antifungal Agents/therapeutic use* ; Mice ; Fluconazole/therapeutic use* ; Kidney/drug effects* ; Female

Drug toxicity is closely related to both clinical drug safety and new drug development. Therefore, it is vital to understand the mechanisms of drug toxicity fully and to use appropriate research models with advanced technologies. Zebrafish has become an important vertebrate animal model for high-throughput drug screening and toxicity assessment. At the same time, zebrafish has an intact biological complexity, reflecting the whole organism's toxicity, which gives it an advantage over other high-throughput models in toxicity studies. Despite the gradual increase in toxicity studies utilizing zebrafish, a comprehensive and systematic review of the underlying mechanisms and new techniques is still lacking. This review aims to analyze common toxicity mechanisms in zebrafish models, such as oxidative stress, endoplasmic reticulum stress, inflammation, and apoptosis, and macroscopic changes in biological processes like lipid metabolism disorders and neurotransmitter expression abnormalities. It also introduces new technologies applied in toxicity assessment, such as gene editing, novel fluorescence imaging technology, 3D imaging technology, and novel automated technology for high-throughput screening, such as fish capsules. In addition, it also summarizes the advantages and disadvantages of the model. By doing so, it will provide new suggestions for the development and improvement of the model, make it better serve the toxicity study of clinical drugs and provide a more comprehensive perspective for drug toxicity study, thus promoting the development of the field of drug toxicity study.

OBJECTIVE: To explore and quantify the association of hot night exposure during the sperm development period (0-90 lag days) with semen quality. METHODS: A total of 6,640 male sperm donors from 6 human sperm banks in China during 2014-2020 were recruited in this multicenter study. Two indices (i.e., hot night excess [HNE] and hot night duration [HND]) were used to estimate the heat intensity and duration during nighttime. Linear mixed models were used to examine the association between hot nights and semen quality parameters. RESULTS: The exposure-response relationship revealed that HNE and HND during 0-90 days before semen collection had a significantly inverse association with sperm motility. Specifically, a 1 °C increase in HNE was associated with decreased sperm progressive motility of 0.0090 (95% confidence interval [ CI]: -0.0147, -0.0033) and decreased total motility of 0.0094 (95% CI: -0.0160, -0.0029). HND was significantly associated with reduced sperm progressive motility and total motility of 0.0021 (95% CI: -0.0040, -0.0003) and 0.0023 (95% CI: -0.0043, -0.0002), respectively. Consistent results were observed at different temperature thresholds on hot nights. CONCLUSION Our findings highlight the need to mitigate nocturnal heat exposure during spermatogenesis to maintain optimal semen quality.
Humans ; Male ; Semen Analysis ; Adult ; Sperm Motility ; Hot Temperature/adverse effects* ; China ; Middle Aged ; Spermatozoa/physiology* ; Young Adult

Objective To investigate the effect and mechanism of curculigoside(CUR)on hippocampal neuron injury in epileptic rats.Methods Forty-eight rats were selected,and the epileptic rat models were established by induction with 35 mg/kg pentylenetetrazol.The epileptic rats were randomly divided into the epilepsy group,the epilepsy+low-dose CUR group(the epilepsy+CUR-L group),the epilepsy+high-dose CUR group(the epilepsy+CUR-H group),and the epilepsy+CUR-H+PI3K activator 740Y-P group(the epilepsy+CUR-H+740Y-P group),with 12 rats in each group.Another 12 rats that were intraperitoneally injected with the same amount of normal saline were taken as the control group.Four weeks after administration,the behavioral changes of rats in each group were observed.Nissl staining was applied to determine the neuronal changes in hippocampal tissue.Immunohistochemistry was applied to detect the number of microglia in hippocampal tissue.ELISA was applied to detect the levels of interleukin-6(IL-6),IL-1β,and gamma-aminobutyric acid(GABA)in hippocampal tissue.TUNEL staining was applied to analyze the level of neuronal apoptosis in hippocampal tissue.Western blot was applied to detect the phosphorylation levels of PI3K,Akt and mTOR in hippocampal tissue.Results Compared with the control group,the Racine score and the frequency of epileptic seizures in rats,and the number of microglia,level of IL-6,level of IL-1β,the apoptosis rate of neurons,and levels of p-PI3K/PI3K,p-Akt/Akt,p-mTOR/mTOR in hippocampal tissue in the epilepsy group were obviously increased(P<0.05),while the level of GABA in hippocampal tissue was obviously reduced(P<0.05),and the arrangement of neurons in hippocampal tissue was disordered,with neuronal loss.Compared with the epilepsy group,the Racine score,and the frequency of epileptic seizures in rats,and the number of microglia,levels of IL-6,levels of IL-1β,the apoptosis rates of neurons,and levels of p-PI3K/PI3K,p-Akt/Akt,p-mTOR/mTOR in hippocampal tissue in the epilepsy+CUR-L group and the epilepsy+CUR-H group were significantly decreased(P<0.05),while the levels of GABA in hippocampus tissue were significantly increased(P<0.05),the loss and necrosis of neurons in hippocampus tissue were decreased,and the disorder of cell arrangement was improved.Compared with the epilepsy+CUR-H group,the Racine score and the frequency of epileptic seizures in rats,and the number of microglia,level of IL-6,level of IL-1β,the apoptosis rate of neurons,and levels of p-PI3K/PI3K,p-Akt/Akt,p-mTOR/mTOR in hippocampal tissue in the epilepsy+CUR-H+740Y-P group were significantly increased(P<0.05),while the level of GABA in hippocampus tissue was significantly decreased(P<0.05),the loss and necrosis of hippocampal neurons increased,and the cell arrangement was disordered.Conclusion CUR may reduce hippocampal neuron damage in epileptic rats by downregulating the PI3K/Akt/mTOR signaling pathway.

Aim To explore the mechanism of Jiawei Shaofu Zhuyu decoction in antagonizing endometriosis fibrosis by regulating mitophagy.Methods After the animal model was constructed,the syndrome was evalu-ated by general condition,organ water content and ther-mal imaging.The curative effect was evaluated by the weight of ectopic focus and the degree of adhesion.The pathological changes were compared using HE stai-ning,transmission electron microscopy,Masson and Sir-ius red staining.The expression of PINK1 and Parkin was detected by immunohistochemistry.The expression of mRNA and protein was determined by qPCR and Western blot,and the level of serum ROS was detected by ELISA.Results The autonomic activity of model mice was weakened,the water content of organs rose,and the temperature of limbs and lower abdomen was reduced by thermal imaging.HE staining showed obvi-ous hyperplasia of ectopic epithelium and glands.Transmission electron microscopy showed mitochondrial and endoplasmic reticulum structure damage,and nor-mal autophagy structure disappeared.Masson and Siri-us red staining showed increased collagen deposition;immunohistochemistry showed decreased expression of PINK1 and Parkin in ectopic foci.qPCR and Western blot showed that the expression of PINK1,Parkin,Bec-lin1,LC3 mRNA and protein in ectopic foci of model mice decreased,the expression of p62 mRNA and pro-tein increased,and serum ROS increased.The syn-drome performance of model mice was improved after the intervention of Jiawei Shaofu Zhuyu decoction;the inflammatory infiltration of ectopic foci was relieved,the morphology of mitochondria and endoplasmic retic-ulum was restored,and normal autophagy structure ap-peared.The degree of collagen deposition and fibrosis was reduced;the mRNA and protein expression of PINK1,Parkin,Beclin1 and LC3 increased.The ex-pression of p62 mRNA and protein decreased,and the level of ROS decreased.Conclusions Jiawei Shaofu Zhuyu decoction can improve the fibrosis of ectopic le-sions in mice with endometriosis of cold-dampness sta-sis syndrome,which may be related to the regulation of mitophagy.

Aim To investigate the intervention effect of Rehmannia radix water extract on bleomycin(BLM)-induced pulmonary fibrosis in mice combined with metabolomics and to reveal the potential mechanism,in order to provide new ideas for clinical treatment of pul-monary fibrosis.Methods Male C57BL/6N mice were randomly divided into the control group,model group,pirfenidone group(positive control,PFD,270 mg·kg-1),and low dose(DH-L,4.55 g·kg-1)group,medium dose(DH-M,9.1 g·kg-1)group and high dose(DH-H,18.2 g·kg-1)group of Rehman-nia.Except for the control group,BLM(5 mg·kg-1)was instilled into the trachea to establish the model of pulmonary fibrosis in the other groups.The survival rate,lung index and blood oxygen saturation of mice in each group were evaluated.HE and Masson staining were used to observe the pathological changes of lung tissue.WBP was used to detect lung function.Flow cytometry was used to detect the apoptosis of primary lung cells,ROS and immune cells.ELISA was used to detect the levels of fibrosis markers and inflammatory factors(α-SMA,collagen Ⅰ,collagen Ⅲ,TGF-β1,TNF-α,IL-1 β,and IL-6).Biochemical method was employed to detect the contents of GSH-Px,T-SOD and MDA.Liquid chromatograph mass spectrometer(LC-MS)metabolomics was used to analyze the changes of serum metabolic profile.Results Water extract of Re-hmannia significantly increased the survival rate,oxy-gen saturation and lung function of mice with pulmona-ry fibrosis,reduced the lung coefficient,ameliorated pathological damage and collagen deposition in lung tissue,reduced the levels of apoptosis and oxidative stress,and down-regulated the levels of inflammatory factors in lung tissue.It regulated the levels of metabo-lites such as bile acid metabolism,sphingolipid metabo-lism,and unsaturated fatty acid metabolism.Conclu-sions Water extract of Rehmannia inhibits lung injury and collagen deposition in mice with pulmonary fibrosis by inhibiting inflammatory response,which may be a-chieved by regulating the levels of inflammatory factors through the metabolic pathways of bile acid and sphin-golipid.