Objective: To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer. Materials and Methods: A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs. Results: All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027). Conclusion The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.

Objective To find out whether photobiomodulation(PBM)can mitigate cognitive dysfunction caused by chronic stress by affecting levels of adenosine triphosphate(ATP)and adenosine receptors.Methods Twenty-four C57BL/6J mice were randomly divided into a control group,a stress group,and a treatment group.Chronic unpredictable mild stress was used to establish a mouse model of stress.Six weeks into modeling,the treatment group was subjected to one week of PBM interventions.Behavioral tests were conducted to observe behavioral changes in the mice.Western blotting(WB)was used to detect the expressions of A1,A2B,and A3 adenosine receptors in the hippocampus and prefrontal cortex of mice in the three groups.Twelve C57BL/6J mice were randomly divided into a control group and an intervention group.The intervention group received a week of PBM interventions and underwent behavioral testing.WB was used to detect the expression changes of A1,A2B,and A3 adenosine receptors in the hippocampus and prefrontal cortex in both groups.Immunofluorescence assay was adopted to detect the expression of c-Fos in the hippocampus of mice in the two groups.The ATP assay kit made by Beyotime Biotechnology Co.,Ltd.was used to measure changes in ATP contents in the hippocampus and prefrontal cortex tissues of mice.Cell experiments were conducted to verify the effect of PBM on intracellular ATP contents.Results Mice in the stress group covered a similar distance to the control group,but finished far fewer platform crossings.There was no significant difference between the treatment group and the control group in the number of times of platform crossings,but compared favorably with the stress group where the levels of adenosine receptors in the hippocampus and prefrontal cortex were lower,but were increased by PBM.After PBM interventions in normal mice,platform crossings were increased significantly compared to the control group.PBM also raised adenosine receptor levels and ATP contents in the hippocampus and prefrontal cortex,and increased hippocampal c-Fos expressions.In vitro,PBM elevated intracellular ATP levels.Conclusion PBM may improve chronic stress-induced cognitive dysfunction by regulating ATP levels and adenosine receptor expressions,thereby modulating neuronal responsiveness in the hippocampus.

CD20 is a surface marker protein of B-cell lymphoma, and its extracellular region is the target of specific antibodies and drugs. To obtain a cheap and easily modified specific preparation targeting CD20, we optimized the gene of CD20 extracellular region according to codon degeneracy to facilitate its expression in Escherichia coli. The optimized gene was cloned into pGEX-4T-1 vector, and the recombinant vector was transformed into E. coli BL21(DE3) for expression. The purified protein was identified by SDS-PAGE and Western blotting. Systematic evolution of ligands by exponential enrichment (SELEX) was employed to screen the ssDNA aptamer that specifically binds to the fusion protein, and the affinity of the aptamer to CD20 was detected by flow cytometry. Then, the cytotoxicity test was carried out to examine the inhibitory effect of the aptamer on B lymphoma cells. In this study, we established the prokaryotic expression method of CD20 and obtained the aptamer specifically binding to the extracellular region of CD20, which laid a foundation for the development of therapeutic drugs targeting CD20.
Humans ; Escherichia coli/metabolism* ; SELEX Aptamer Technique/methods* ; Aptamers, Nucleotide/genetics* ; Antigens, CD20/metabolism* ; Ligands

Objective To investigate the effects of exposure to various concentrations of cigar smoke on gut microbiota in mice.Methods A total of 40 C57BL/6 mice were randomly divided into the control group,the low-dose cigar exposure group,the medium-dose group and the high-dose group,with 10 mice in each group.After 4 weeks of feeding,fecal samples were collected for gene sequencing of 16S ribosomal RNA and analysis of differences in gut microbiota.Results Compared to the control group,gut microbiota richness was signifi-cantly reduced in the cigar-exposed groups(P<0.05).Compared with thecontrol group,the Shannon index of mice in the high-dose group was significantly increased(P<0.05).In multi-group comparisons,ten bacterial genera with high abundance-such as Akkermansia,Allobaculum,and Alloprevotella-were identified.Pairwise comparison results indicated that compared to the control group,abundances of Akkermansia,Candidatus_Sac-charimonas,and Lactobacillus decreased while those of Allobaculum,Alloprevotella,Muribaculaceae,and Pre-votellaceae_UCG001 increased(P<0.05).Alistipes and Faecalibaculum showed significant increases in low-dose and medium-dose groups respectively,Blautia and Lachnospiraceae_NK4A136 group exhibited notable in-creases in the high-dose group(P<0.05).Linear discriminant analysis effect size revealed that six phyla and forty-four species displayed significant differences across all groups at both phylum and species levels,distinct dose-specific were observed among different cigar exposure groups.Conclusion Cigar smoke exposure and different exposure concentrations can both cause changes in the gut microbiota.The effects of different con-centrations of cigars on the gut microbiota of mice are specific.

This review has introduced the Coronary Artery Tree description and Lesion EvaluaTion(CatLet or Hexu)angiographic scoring system,which,based solely on coronary angiography results,has characterized 6 types of right coronary artery,3 types of left descending artery,and 3 types of diagonal size,together resulting in 54 types of coronary circulation pattern.This novel angiographic scoring system can be utilized to account for coronary anatomy in its diversity,severity and complexity of diseased coronary arteries,and their subtended myocardial territories in jeopardy.The CatLet angiographic scoring system is unique in that the importance of a coronary artery is weighted according to its subtended myocardial segments,by which the variability of coronary artery has been accounted for and measured.Researchers at home and abroad have increasingly paid attention to its clinical utilities,which warrant further validation in the context of large sample size,prospective,and randomized controlled trials.The CatLet angiographic scoring system is accessible at www.catletscore.com.

Aim To investigate the therapeutic effects of a newly developed Tadalafil tablets on pathological myocardial hypertrophy induced by abdominal aortic constriction(AAC)in rats,as well as its influence on the activation of the NF-κB signaling pathway in myo-cardial cells.Methods SD rats were randomly divid-ed into 4 groups:the sham operation group(Sham),the model group(AAC),the tadalafil new tablet treat-ment group(N-Tad,5 mg·kg-1),and the positive control drug treatment group(Cialis,10 mg·kg-1g).The AAC model group and treatment group rats under-went blunt dissection and constrictive ligation of the abdominal aorta at the left renal artery branch point during surgery,while the Sham group rats only had their arteries separated without any constrictive liga-tion.Rats in the treatment groups received either N-Tad or Cialis via gavage three days after modeling,while rats in the sham group and the model group re-ceived physiological saline daily for 8 weeks.Small an-imal ultra-high-resolution echocardiography and hemo-dynamic assessment were applied to evaluate left ven-tricular function in each group of rats,and the calcula-tion of the left ventricular mass index was conducted.By employing Western blot and RT-PCR.we assessed the impact of this treatment on the expression of the hy-pertrophy factor atrial natriuretic peptide(ANP),phosphorylated NF-κB p65 protein(p-NF-κB p65),and phosphorylated IκB-α in the left heart tissue of rats and in H9c2 cardiomyocytes.Results Compared to the Sham group,the AAC rats exhibited a significant decrease in left heart function,an increase in left ven-tricular mass index,and a notable increase in ANP and p-p65 expression in the left heart tissue(P＜0.05).Both N-Tad and Cialis treatments could significantly enhance left ventricular function,decrease left ventric-ular mass index,and inhibit the expression of ANP and phosphorylated NF-κB p65 in rats with myocardial hy-pertrophy(P＜0.05).Notably,the therapeutic effect of low-dose N-Tad was comparable to that of high-dose Cialis.At the cellular level,Tadalafil significantly in-hibited the activation of the NF-κB signaling pathway and reduced the expression of associated proteins in H9c2 cardiomyocytes.Conclusions N-Tad can sig-nificantly inhibit p65 and IκB-α phosphorylation,and the activation of the NF-κB signaling pathway,reduce ANP expression,and improve pathological myocardial hypertrophy,as well as mitigate left heart function damage caused by abdominal aortic constriction.

OBJECTIVE: To investigate the relationship between serum levels of fibroblast growth factor-23 (FGF-23), heparanase (HPSE) and early renal impairment (RI) in patients with multiple myeloma (MM). METHODS: A retrospective analysis was conducted on the clinical data of 125 MM patients who were initially diagnosed in the Department of Hematology of the First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology from June 2020 to June 2023. The patients were divided into RI group (>176.80 μmol/L) and non-RI group (≤176.80 μmol/L) based on their serum creatinine levels when diagnosed. The baseline data and laboratory indexes of the two groups were compared. The relationship between serum FGF-23, HPSE and early RI in MM patients was analyzed. RESULTS: Among 125 newly diagnosed MM patients, 33 cases developed early RI, accounting for 26.40%. The proportion of light chain type, blood urea nitrogen (BUN), blood uric acid, lactate dehydrogenase, FGF-23, and HPSE levels in RI group were higher than those in non-RI group (all P <0.05). There was no statistical significant difference in other data between the two groups (P >0.05). Multivariate logistic regression analysis showed that BUN, FGF-23 and HPSE were associated with early RI in MM patients (all P <0.05). The serum FGF-23 level was divided into Q1-Q4 groups by quartile, and the serum HPSE level was divided into q1-q4 groups. The correlation analysis showed that with the increase of serum FGF-23 and HPSE levels, the incidence of early RI increased (r =0.668, 0.592). Furthermore, logistic regression analysis showed that after controlling for confounding factors, elevated levels of serum FGF-23 and HPSE were still influencing factors for early RI in MM patients (OR>1, P <0.05). According to Pearson's linear correlation test, there was a positive correlation between serum FGF-23 level and HPSE level (r =0.373). CONCLUSION There is a certain correlation between serum levels of FGF-23, HPSE and early RI in MM patients, and the incidence of early RI is higher in patients with abnormally high levels of both.
Humans ; Multiple Myeloma/complications* ; Fibroblast Growth Factor-23 ; Retrospective Studies ; Fibroblast Growth Factors/blood* ; Glucuronidase/blood* ; Male ; Female ; Middle Aged ; Renal Insufficiency/blood* ; Aged

OBJECTIVE: To investigate the clinical efficacy of moxibustion (Mox) combined with low-dose tadalafil (TAD) in the treatment of diabetes mellitus-induced erectile dysfunction (DMED) with the syndrome of Qi deficiency and blood stasis. METHODS: According to the inclusion and exclusion criteria, we selected 90 patients with DMED for this trial and equally randomized them into a Mox, a TAD, and a Mox combined with TAD (Mox+TAD) group to be treated by mild Mox applied to the acupoints Zusanli, Sanyinjiao and Yinlingquan qd alt, oral medication with low-dose TAD at 5 mg per dose qd, and combination of the above two therapies, respectively, all for 4 weeks. We obtained from the patients their IIEF-5 scores, traditional Chinese medicine (TCM) symptoms scores, Erectile Hardness Scale (EHS) scores, corpus cavernosal hemodynamic indexes, and the peak systolic velocity (PSV), end diastolic velocity (EDV) and resistance index (RI) of the corpus cavernosal arteries before and after treatment, and compared them among the three groups. RESULTS: The total effectiveness rate was significantly higher in the Mox+TAD (90.0%) than in the Mox (46.7%) and TAD groups (60.0%) (P< 0.05). Compared with the baseline, the IIEF-5 and EHS scores were increased, while the TCM symptoms scores decreased in all the three groups after treatment, more significantly in the Mox+TAD group than in the other two (P< 0.05). And the PSV and RI were remarkably increased, while the EDV decreased (P< 0.05) in all the three groups (P< 0.05) after treatment, with PSV even higher in the Mox+TAD than in the Mox and TAD groups (P< 0.05). CONCLUSION Moxibustion combined with tadalafil has a definite efficacy and safety for the treatment of DMED, which can effectively improve the erectile function of the patients by increasing penile blood supply, benefiting qi and activating blood circulation.
Humans ; Male ; Tadalafil ; Erectile Dysfunction/etiology* ; Moxibustion ; Middle Aged ; Prospective Studies ; Adult ; Carbolines/administration & dosage* ; Diabetes Complications/therapy* ; Aged ; Treatment Outcome ; Combined Modality Therapy

OBJECTIVE: To explore the efficacy and safety of Juan Bi Pill (JBP) in treatment of active rheumatoid arthritis (RA). METHODS: From February 2017 to May 2018, 115 participants from 4 centers were randomly divided into JBP group (57 cases) and placebo group (58 cases) in a 1:1 ratio using a random number table method. Participants received a dose of JBP (4 g, twice a day, orally) combined with methotrexate (MTX, 10 mg per week) or placebo (4 g, twice a day, orally) combined with MTX for 12 weeks. Participants were required with follow-up visits at 24 and 48 weeks, attending 7 assessment visits. Participants were undergo disease activity assessment 7 times (at baseline and 2, 4, 8, 12, 24, 48 weeks) and safety assessments 6 times (at baseline and 4, 8, 12, 24, 48 weeks). The primary endpoint was 28-joint Disease Activity Score (DAS28-ESR and DAS28-CRP). The secondary endpoints included American College of Rheumatology (ACR) criteria for 20% and 50% improvement (ACR20/50), Health Assessment Questionnaire Disability Index (HAQ-DI), clinical disease activity index (CDAI), visual analog scale (VAS), Short Form-36 (SF-36) score, Medial Outcomes Study (MOS) sleep scale score, serum erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tender joint count, swollen joint count, and morning stiffness. The adverse reactions were observed during the treatment. RESULTS: After 12 weeks of treatment, DAS28-ESR and DAS28-CRP scores in both groups were lower than before treatment (both P<0.01), while the remission rate of DAS28-ESR and DAS28-CRP and low disease activity of JBP group were higher than those in the placebo group (both P<0.01). JBP demonstrated better efficacy on ACR20 and ACR50 compliance rate at 12 and 48 weeks comparing to placebo (all P<0.05). The CDAI and HAQ-DI score, pain VAS and global VAS change of RA patients and physicians, the serum ESR and CRP levels, and the number of tenderness and swelling joints were lower than before treatment at 4, 8, 12, 24, 48 weeks in both groups (P<0.05 or P<0.01), while the reduction of above indices in the JBP group was more obvious than those in the placebo group at 12 weeks (ESR and CRP, both P<0.05) or at 12 and 48 weeks (all P<0.01). There was no difference in adverse reactions between the 2 groups during treatment (P=0.75). CONCLUSION JBP combined with MTX could effectively reduce disease activity in patients with RA in active stage, reduce the symptoms of arthritis, and improve the quality of life, while ensuring safety, reliability, and fewer adverse effects. (Trial Registration: ClinicalTrials.gov, No. NCT02885597).
Humans ; Arthritis, Rheumatoid/drug therapy* ; Methotrexate/adverse effects* ; Female ; Double-Blind Method ; Male ; Middle Aged ; Treatment Outcome ; Drugs, Chinese Herbal/adverse effects* ; Drug Therapy, Combination ; Adult ; Antirheumatic Agents/adverse effects* ; Aged

OBJECTIVES: To explore the underlying pharmacological mechanisms and its potential effects of Chinese medicine herbal formula Sini Powder (SNP) on hepatocellular carcinoma (HCC). METHODS: The active components of SNP and their in vivo distribution were identified using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Construction of component-target-disease networks, protein-protein interaction network, Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and molecular docking were employed to analyze the active components and anti-HCC mechanisms of SNP. Cell viability assay and wound healing assay were utilized to confirm the effect of SNP-containing serum (2.5%, 5.0%, 10%, 20%, and 40%), isoprenaline or propranolol (both 10, 100, and 1,000 µ mol/L) on proliferation and migration of HepG 2 or Huh7 cells. Meanwhile, the effect of isoprenaline or propranolol on the β 2 adrenergic receptor (ADRB2) mRNA expression on HepG2 cells were measured by real-time quantitative reverse transcription (RT-qPCR). Mice with subcutaneous tumors were either subjected to chronic restraint stress (CRS) followed by SNP administration (364 mg/mL) or directly treated with SNP (364 mg/mL). These two parallel experiments were performed to validate the effects of SNP on stress responses. Stress-related proteins and hormones were quantified using RT-qPCR, enzyme-linked immunosorbent assay, and immunohistochemistry. Metagenomic sequencing was performed to confirm the influence of SNP on the gut microbiota in the tumor-bearing CRS mice. RESULTS: The distribution of the 12 active components of SNP was confirmed in various tissues and feces. Network pharmacology analysis confirmed the anti-HCC effects of the 5 active components. The potential anti-HCC mechanisms of SNP may involve the epidermal growth factor receptor (EGFR), proto-oncogene tyrosine-protein kinase Src (SRC) and signal transducer and activator of transcription 3 (STAT3) pathways. SNP-containing serum inhibited the proliferation of HepG2 and Huh7 cells at concentrations of 2.5% and 5.0%, respectively, after 24 h of treatment. Furthermore, SNP suppressed tumor progression in tumor-bearing mice exposed to CRS. SNP treatment also downregulated the expressions of stress-related proteins and pro-inflammatory cytokines, primarily by modulating the gut microbiota. Specifically, the abundance of Alistipes and Prevotella, which belong to the phylum Bacteroidetes, increased in the SNP-treated group, whereas Lachnospira, in the phylum Firmicutes, decreased. CONCLUSION SNP can combat HCC by alleviating stress responses through the regulation of gut microbiota.
Animals ; Gastrointestinal Microbiome/drug effects* ; Liver Neoplasms/microbiology* ; Carcinoma, Hepatocellular/microbiology* ; Humans ; Drugs, Chinese Herbal/therapeutic use* ; Powders ; Cell Proliferation/drug effects* ; Mice ; Molecular Docking Simulation ; Cell Line, Tumor ; Hep G2 Cells ; Receptors, Adrenergic, beta-2/genetics* ; Stress, Physiological/drug effects* ; Cell Movement/drug effects* ; Male ; Protein Interaction Maps/drug effects* ; Cell Survival/drug effects* ; Proto-Oncogene Mas