The elevated polyamines, amine-rich molecules with diverse functions in pathophysiology processes, are implicated in contributing to tumorigenesis and progression. Whether and how they affect the efficacy of chemotherapy is incompletely understood. Our screening assays reveal that the supplement with a low dose of spermidine (Spd), one of the polyamines, enhances ferroptosis in prostate cancer cells as evidenced by increased lipid peroxidation and intracellular Fe²⁺ levels in vitro. Combination treatment with Spd and a low dose of ferroptosis inducer erastin synergistically augments anti-tumor efficacy with undetectable toxicity in mice. Analysis of RNA-seq data indicates that heme oxygenase 1 (HMOX1), an enzyme that catalyzes the cleavage of heme to release Fe²⁺, is significantly upregulated in response to Spd and erastin cotreatment. Spd mediated the hypusine modification of the eukaryotic initiation factor 5A (EIF5A) promotes the translation of the nuclear factor erythroid 2-related factor 2 (NRF2), subsequently leading to elevation of HMOX1. Moreover, Spd and erastin significantly inhibit proteasome activity which results in a decrease in proteasomal degradation of NRF2, although many proteasome-related genes are induced either by Spd or Spd plus erastin. Thus, in addition to its pro-oncogenic activity, the supplement of Spd improves antitumor activity in combination with ferroptosis inducers and offers an optional approach to cancer treatment.

Objective:To assess the clinical efficacy and infection control outcomes of two-stage revision in managing periprosthetic joint infection (PJI) following primary total knee arthroplasty (TKA) utilizing either a low or high constrained prosthesis.Methods:A retrospective analysis was performed on 40 patients who underwent revision TKA in the Sixth People's Hospital Affiliated to Shanghai Jiao Tong University from February 2019 to February 2022. According to the type of prosthesis selected in primary TKA, they were divided into low constrained prosthesis group and high constrained prosthesis group. There were 28 patients (28 knees) in the low constrained group, including 12 males and 16 females, aged 69.0(63.0, 74.0) years, with a body mass index of 25.18±0.55 kg/m 2. And there were 12 patients (12 knees) in the high-constrained group, including 5 males and 7 females, aged 66.5(65.0, 71.5) years, with a body mass index of 23.94±0.51 kg/m 2. All patients underwent two-stage revision surgery, with RHK used in 1 case and LCCK in 27 cases in the low-constrained prosthesis group. In the high-constrained prosthesis group, 3 patients were treated with RHK, 1 patient with PFC Sigma MBT, and 8 patients with LCCK. The preoperative and postoperative range of motion (ROM), Knee Society score (KSS), and postoperative infection control rate were compared between the two groups. Results:All patients were followed up. The follow-up time was 22.79±8.02 months in the low-constrained prosthesis group and 23.92±7.04 months in the high-constrained prosthesis group, with no significant difference between the two groups ( t=0.426, P=0.680). At the last follow-up, the KSS and ROM in the low-constrained prosthesis group were 77.96±9.74 and 93.48°±7.45°, respectively, significantly higher than 38.93±8.01 and 68.89°±9.44° before the operation ( P<0.05). The KSS score and ROM in the high-constrained prosthesis group were 67.83±8.31 and 80.08°±5.89° at the last follow-up, which were also significantly higher than those before operation (34.25±6.31 and 66.50°±10.48°, P<0.05). There was no significant difference in KSS and ROM between the two groups before operation ( P>0.05), but the KSS score and ROM in the low-constrained prosthesis group were significantly higher than those in the high-constrained prosthesis group at the last follow-up ( P<0.05). Bacterial culture results revealed that the primary infectious agents were coagulase-negative Staphylococcus and Staphylococcus aureus, with an overall infection control rate of 80% (32/40). The infection control rate was 89% (25/28) in the low-constrained prosthesis group and 58% (7/12) in the high-constrained prosthesis group, but the difference between the two groups was not statistically significant (χ 2=3.283, P=0.070). Conclusion:Two-stage revision effectively controls PJI, and the clinical outcomes of two-stage revision for PJI after primary TKA with a high-constrained prosthesis are inferior to those with a low-constrained prosthesis. Further exploration is needed to enhance efficacy.

Objective:To analyze the genetic characteristics of the complete genome of a strain of human respiratory syncytial virus (HRSV) in Qinghai province in 2024.Methods:A total of 300 samples were collected during 2024 influenza surveillance in Qinghai province sentinel hospitals from patients with fever accompanied by severe respiratory infection symptoms. We used real-time fluorescent quantitative reverse transcription polymerase chain reaction RT-PCR) method to screen out HRSV subtype B (HRSVB) positive specimens, whole genome sequencing was performed on positivespecimens meeting the requirements for the sequencing. After downloading the global representative HRSVB genotypes at GenBank database, sequence alignment was performed, related evolutionary tree was built and the calculation and analyses of genetic distance were done, analyses of HRSVB sequencing of sequence homology of nucleotides, amino acids and amino acid mutation were performed.Results:The first strain in Qinghai, China/qinghai/2024-03 had a complete sequence of 15 140 bp nucleotides, with HRSV′s all structural characteristics, and subtype HRSVA prototype strain Long strains of nucleotide the lowest homology was 80.0%, and subtype HRSVB prototype strain nucleotide homology was above 94.7%. The result indicated that the first strain in Qinghai belonged to HRSVB subtype. Genetic evolution shows China/qinghai/2024-03 and USA/WA-S23450/2021 (OR326803.1) and Germany/2021 (OR795235.1) all belong to a branch, they have the closest relationship. Phylogenetic analysis of G gene showed that the strain belonged to BA9 genotype of HRSVB subtype, and the hypervariable regions of the genome were SH and G genes.Conclusions:In this study, the complete genome sequence of HRSV China/qinghai/2024-03 was obtained for the first time, and the basic molecular structural characteristics were elucidated, which filled the gaps in the gene and amino acid data of HRSV in our province, and also provided a basis for HRSV epidemiology.

AIM:To investigate the anti-fibrotic effect of Panax notoginseng saponins(PNS)in arecoline(ANE)-induced oral submucous fibrosis,and to analyze the effect of PNS on nuclear factor E2-related factor 2(Nrf2)/glu-tamate-cysteine ligase catalytic subunit(GCLC)signaling pathway.METHODS:CCK-8 assay was used to evaluate the effects of different concentrations of PNS and arecoline on the survival rate of human immortalized keratinocyte cell line Ha-CaT.The results of CCK-8 were used to select 75 mg/L arecoline,and 25,50 and 100 mg/L PNS as subsequent experi-mental concentrations.The cells were set as blank control group,model group,and low,medium and high doses(25,50 and 100 mg/L)of PNS groups.The protein and mRNA expressions of collagen type I(COL-I),E-cadherin,Nrf2,GCLC and glutathione reductase(GR)in each group were detected by Western blot and RT-qPCR.Immunofluorescence method was used to detect the entry of Nrf2 into the nucleus.Biochemical kits were used to detect the content of glutathione(GSH),nicotinamide adenine dinucleotide phosphate(NADPH)and malondialdehyde(MDA),and superoxide dis-mutase(SOD)activity in each group of cells.DCFH-DA fluorescent probe was used to detect the content of intracellular reactive oxygen species(ROS).RESULTS:Compared with the blank control group,the protein and mRNA expression of COL-I in the model group was up-regulated,and the protein and mRNA levels of E-cadherin,Nrf2,GCLC,nuclear Nrf2 and GR were down-regulated.The content of NADPH,MDA and ROS in the cells increased,and the content of GSH and the activity of SOD was significantly reduced.Compared with the model group,the protein and mRNA expression of COL-I was down-regulated,and the protein and mRNA expression of E-cadherin,Nrf2,GCLC,nuclear Nrf2 and GR were up-regulated in PNS 50 and 100 mg/L groups.Compared with the model group,the content of NADPH,MDA and ROS in cells decreased,and the content of GSH and the activity of SOD was significantly enhanced(P<0.05 or P<0.01).CON-CLUSION:Panax notoginseng saponins have anti-fibrosis effects in HaCaT cells,and their mechanism may be related to the activation of Nrf2/GCLC signaling pathway,thereby resisting oxidative stress and improving oral submucosal fibrosis.

Breast cancer, as a malignant tumor with a high incidence rate in women, seriously endangers the life health and safety of women. Its pathogenesis and treatment strategies are still the hot and difficult points in current research. More and more studies have shown that the occurrence and development of breast cancer is closely related to the microbial community in intestinal tissue and breast tissue, and the microbial community in human tissue may promote or inhibit the occurrence of breast cancer through various ways and mechanisms. Defining the relationship between microbial communities and breast cancer will provide new directions for the prevention and comprehensive treatment of breast cancer.

OBJECTIVE: To investigate the molecular mechanism underlying the inhibitory effect of aloin on the proliferation and migration of gastric cancer cells. METHODS: Human gastric cancer MGC-803 cells treated with 100, 200 and 300 μg/mL aloin were examined for changes in cell viability, proliferation and migration abilities using CCK-8, EdU and Transwell assays. HMGB1 mRNA level in the cells was detected with RT-qPCR, and the protein expressions of HMGB1, cyclin B1, cyclin E1, E-cadherin, MMP-2, MMP-9 and p-STAT3 were determined using Western blotting. JASPAR database was used to predict the binding of STAT3 to HMGB1 promoter. In a BALB/c-Nu mouse model bearing subcutaneous MGC-803 cell xenograft, the effect of intraperitoneal injection of aloin (50 mg/kg) on tumor growth was observed. The protein expressions of HMGB1, cyclin B1, cyclin E1, E-cadherin, MMP-2, MMP-9 and p-STAT3 in the tumor tissue was examined using Western blotting, and tumor metastasis in the liver and lung tissues was detected using HE staining. RESULTS: Treatment with aloin concentration-dependently inhibited the viability of MGC-803 cells (P < 0.05), significantly reduced the number of EdU-positive cells (P < 0.01), and attenuated the migration ability of the cells (P < 0.01). Aloin treatment dose-dependently down-regulated HMGB1 mRNA expression (P < 0.01), lowered the protein expressions of HMGB1, cyclin B1, cyclin E1, MMP-2, MMP-9 and p-STAT3, and up-regulated E-cadherin expression in MGC-803 cells. Prediction based on JASPAR database suggested that STAT3 could bind to the promoter region of HMGB1. In the tumor-bearing mice, aloin treatment significantly reduced the tumor size and weight (P < 0.01), lowered the protein expressions of cyclin B1, cyclin E1, MMP-2, MMP-9, HMGB1 and p-STAT3 and increased the expression of E-cadherin in the tumor tissue (P < 0.01). CONCLUSION Aloin attenuates the proliferation and migration of gastric cancer cells by inhibiting the STAT3/HMGB1 signaling pathway.
Humans ; Animals ; Mice ; Stomach Neoplasms ; Cyclin B1 ; Matrix Metalloproteinase 2 ; Matrix Metalloproteinase 9 ; HMGB1 Protein ; Signal Transduction ; Cell Proliferation ; STAT3 Transcription Factor

Objective:To propose a model using the maximum intensity projection (MIP) of lung field computed tomography (CT) images and deep convolution neural network (CNN) and explore its value in identifying chronic obstructive pulmonary disease (COPD).Methods:A total of 201 subjects were selected from the Second Hospital of Dalian Medical University from January 2010 to May 2021. All subjects were included according to the inclusion criteria and were divided into COPD group (101 cases) and healthy controls group (100 cases). Each patient underwent a high-resolution CT scan of the chest and pulmonary function test. First, the lung field was extracted from CT images and the intrapulmonary MIP images were acquired. Second, with these MIP images as input, the model for identifying COPD was constructed based on a modified residual network (ResNet). Finally, the influence of the number of residual blocks on the performance of the models was investigated. Accuracy, sensitivity, specificity, positive predictive value, negative predictive value, receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the identification efficiency.Results:The accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) of ResNet26 was 76.1%, 76.2%, 76.0%, 76.2%, and 76.0%, respectively; and the AUC of the test was 0.855 (95% CI: 0.799-0.901). The accuracy, sensitivity, specificity, PPV, NPV of ResNet50 was 77.6%, 76.2%, 79.0%, 78.6%, and 76.7%, respectively; and the AUC of the test was 0.854 (95% CI: 0.797-0.900). The accuracy, sensitivity, specificity, PPV, NPV of ResNet26d was 82.1%, 83.2%, 81.0%, 81.6%, and 82.7%, respectively; and the AUC of the test was 0.885 (95% CI: 0.830-0.926). Conclusions:The COPD identification model via MIP images from CT images within the lung and deep CNN is successfully constructed and achieves accurate COPD identification. And it can provide an effective tool for COPD screening.

The autolysis of brewer's yeast seriously affects the quality of beer and the quality of yeast is considered as one of the key factors in beer brewing. Previous studies on brewer's yeast autolysis showed that RLM1 gene, an important transcription factor in cell integrity pathway, is closely related to the autolysis of yeast. In this study, RLM1 was knocked out and overexpressed in a haploid brewer's yeast. RLM1 disruption resulted in poor anti-autolysis performance of yeast, whereas overexpression of RLM1 contributed to the anti-autolytic ability of yeast. In addition, RLM1 gene knockout affected the osmotic stress resistance, cell wall damage resistance, nitrogen starvation resistance and temperature tolerance of yeast strain. The transcriptional level of GAS1 involved in cell wall assembly and DNA damage response was regulated along with the expression of RLM1, whereas other genes in CWI pathway did not show apparent regularity. RLM1 might mainly affect the expression of GAS1 so as to improve the stress resistance of lager yeast in harsh environment. The result from this study help further understand the mechanism of yeast autolysis and lay a foundation for breeding brewer's yeast strain with better anti-autolytic ability.
Autolysis ; Beer ; Cell Wall ; Humans ; MADS Domain Proteins ; Saccharomyces cerevisiae ; Saccharomyces cerevisiae Proteins

Objective To investigate the effect of capsaicin on cognitive function and the expression of TRPV1 protein in hippocampus of rats with chronic cerebral hypoperfusion (CCH).Methods 60 SD rats were randomly divided into control group (SHAM group),chronic cerebral hypoperfusion group (CCH group),placebo control group(PC group) and capsaicin group(CAP group) with 15 in each group.The chronic cerebral hypoperfusion rat model was established by permanent bilateral common carotid artery occlusion.The rats in CAP group and PC group were given capsaicin and saline respectively by intraperitoneal injection,twice a week.The spatial learning and memory ability and emotion of rats were observed by Morris water maze test and open field test,and the expression of TRPV1 in the hippocampus of rats was detected by Western blot.Results (1) In the open field experiment,compared with the SHAM group (22.60±4.60),the standing times of the CCH group(12.10±2.80) decreased (P＜0.01),but the standing times of CAP group (19.30± 4.16) increased compared with that of h PC group(12.50 ±2.68) (P＜0.01).(2) In Morris water maze test,positioning navigation experiment showed that compared with the SHAM group,the escape latency of the CCH group and the PC group increased (P＜0.05),while the escape latency of CAP group was shorter than that of the PC group (P＜ 0.05).And in the space exploration experiment,compared with the SHAM group (1.87 ± 0.64),the times of crossing the platform in CCH group (0.75 ± 0.89) and the PC group (1.00± 0.93) decreased,while the latency of crossing the platform increased (P＜0.01).And the times of crossing the platform in CAP group((2.38±0.74) increased compared with that of PC group,and the latency of crossing the platform of CAP group decreased compared with that of PC group (P＜0.01).(3) Results of Western blot showed that compared with the SHAM group,the level of TRPV1 in rat hippocampus of CCH group was down regulated (P＜0.05),and the expression of TRPV1 in CAP group was higher than that of PC group (P＜0.05).Conclusion Capsaicin can effectively improve cognitive impairment in rats with chronic cerebral hypoperfusion,which may be related to the up-regulation of TRPV1 protein expression in hippocampal tissues.

BACKGROUND/AIMS: To investigate the role of selected serum microRNA (miRNA) levels as potential noninvasive biomarkers for differentiating S0–S2 (early fibrosis) from S3–S4 (late fibrosis) in patients with a chronic hepatitis B virus (HBV) infection. METHODS: One hundred twenty-three treatment-naive patients with a chronic HBV infection who underwent a liver biopsy were enrolled in this study. The levels of selected miRNAs were measured using a real-time quantitative polymerase chain reaction assay. A logistic regression analysis was performed to assess factors associated with fibrosis progression. Receiver operating characteristic (ROC) curve and discriminant analyses validated these the ability of these predicted variables to discriminate S0–S2 from S3–S4. RESULTS: Serum miR-29, miR-143, miR-223, miR-21, and miR-374 levels were significantly downregulated as fibrosis progressed from S0–S2 to S3–S4 (p < 0.05), but not miR-16. The multivariate logistic regression analysis identified a panel of three miRNAs and platelets that were associated with a high diagnostic accuracy in discriminating S0–S2 from S3–S4, with an area under the curve of 0.936. CONCLUSIONS: The levels of the studied miRNAs, with the exception of miR-16, varied with fibrosis progression. A panel was identified that was capable of discriminating S0–S2 from S3–S4, indicating that serum miRNA levels could serve as a potential noninvasive biomarker of fibrosis progression.
Biomarkers ; Biopsy ; Early Diagnosis* ; Fibrosis ; Hepatitis B virus ; Hepatitis B* ; Hepatitis B, Chronic ; Hepatitis* ; Humans ; Liver Cirrhosis* ; Liver* ; Logistic Models ; MicroRNAs* ; Polymerase Chain Reaction ; ROC Curve