This study investigated the effects and underlying mechanisms of vanillic acid(VA) against cardiac fibrosis(CF) induced by isoproterenol(ISO) in mice. Male C57BL/6J mice were randomly divided into control group, VA group(100 mg·kg~(-1), ig), ISO group(10 mg·kg~(-1), sc), ISO + VA group(10 mg·kg~(-1), sc + 100 mg·kg~(-1), ig), ISO + dynamin-related protein 1(Drp1) inhibitor(Mdivi-1) group(10 mg·kg~(-1), sc + 50 mg·kg~(-1), ip), and ISO + VA + Mdivi-1 group(10 mg·kg~(-1), sc + 100 mg·kg~(-1), ig + 50 mg·kg~(-1), ip). The treatment groups received the corresponding medications once daily for 14 consecutive days. On the day after the last administration, cardiac functions were evaluated, and serum and cardiac tissue samples were collected. These samples were analyzed for serum aspartate aminotransferase(AST), lactate dehydrogenase(LDH), creatine kinase-MB(CK-MB), cardiac troponin I(cTnI), reactive oxygen species(ROS), interleukin(IL)-1β, IL-4, IL-6, IL-10, IL-18, and tumor necrosis factor-α(TNF-α) levels, as well as cardiac tissue catalase(CAT), glutathione(GSH), malondialdehyde(MDA), myeloperoxidase(MPO), superoxide dismutase(SOD), total antioxidant capacity(T-AOC) activities, and cytochrome C levels in mitochondria and cytoplasm. Hematoxylin-eosin, Masson, uranium acetate and lead citrate staining were used to observe morphological and mitochondrial ultrastructural changes in the cardiac tissues, and myocardial injury area and collagen volume fraction were calculated. Flow cytometry was applied to detect the relative content and M1/M2 polarization of cardiac macrophages. The mRNA expression levels of macrophage polarization markers [CD86, CD206, arginase 1(Arg-1), inducible nitric oxide synthase(iNOS)], CF markers [type Ⅰ collagen(Coll Ⅰ), Coll Ⅲ, α-smooth muscle actin(α-SMA)], and cytokines(IL-1β, IL-4, IL-6, IL-10, IL-18, TNF-α) in cardiac tissues were determined by quantitative real-time PCR. Western blot was used to detect the protein expression levels of Coll Ⅰ, Coll Ⅲ, α-SMA, Drp1, p-Drp1, voltage-dependent anion channel(VDAC), hexokinase 1(HK1), NOD-like receptor protein 3(NLRP3), apoptosis-associated speck-like protein(ASC), caspase-1, cleaved-caspase-1, gasdermin D(GSDMD), cleaved N-terminal gasdermin D(GSDMD-N), IL-1β, IL-18, B-cell lymphoma-2(Bcl-2), B-cell lymphoma-xl(Bcl-xl), Bcl-2-associated death promoter(Bad), Bcl-2-associated X protein(Bax), apoptotic protease activating factor-1(Apaf-1), pro-caspase-3, cleaved-caspase-3, pro-caspase-9, cleaved-caspase-9, poly(ADP-ribose) polymerase-1(PARP-1), and cleaved-PARP-1 in cardiac tissues. The results showed that VA significantly improved cardiac function in mice with CF, reduced myocardial injury area and cardiac index, and decreased serum levels of AST, CK-MB, cTnI, LDH, ROS, IL-1β, IL-6, IL-18, and TNF-α. VA also lowered MDA and MPO levels, mRNA expressions of IL-1β, IL-6, IL-18, and TNF-α, and mRNA and protein expressions of Coll Ⅰ, Coll Ⅲ, and α-SMA in cardiac tissues, and increased serum levels of IL-4 and IL-10, cardiac tissue levels of CAT, GSH, SOD, and T-AOC, and mRNA expressions of IL-4 and IL-10. Additionally, VA ameliorated cardiac pathological damage, inhibited myocardial cell apoptosis, inflammatory infiltration, and collagen fiber deposition, reduced collagen volume fraction, and alleviated mitochondrial damage. VA decreased the ratio of F4/80~+CD86~+ M1 cells and the mRNA expressions of CD86 and iNOS in cardiac tissue, and increased the ratio of F4/80~+CD206~+ M2 cells and the mRNA expressions of CD206 and Arg-1. VA also reduced protein expressions of p-Drp1, VDAC, NLRP3, ASC, caspase-1, cleaved-caspase-1, GSDMD, GSDMD-N, IL-1β, IL-18, Bad, Bax, Apaf-1, cleaved-caspase-3, cleaved-caspase-9, cleaved-PARP-1, and cytoplasmic cytochrome C, and increased the expressions of HK1, Bcl-2, Bcl-xl, pro-caspase-3, pro-caspase-9 proteins, as well as the Bcl-2/Bax and Bcl-xl/Bad ratios and mitochondrial cytochrome C content. These results indicate that VA has a significant ameliorative effect on ISO-induced CF in mice, alleviates ISO-induced oxidative damage and inflammatory response, and its mechanism may be closely related to the inhibition of Drp1/HK1/NLRP3 and mitochondrial apoptosis signaling pathways, suppression of myocardial cell inflammatory infiltration and collagen fiber deposition, reduction of collagen volume fraction and CollⅠ, Coll Ⅲ, and α-SMA expressions, thus mitigating CF.
Animals ; Isoproterenol/adverse effects* ; Male ; Mice ; Signal Transduction/drug effects* ; Vanillic Acid/administration & dosage* ; Dynamins/genetics* ; Mice, Inbred C57BL ; Fibrosis/genetics* ; Apoptosis/drug effects* ; Mitochondria/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Myocardium/metabolism* ; Humans

Objective:To investigate the inhibitory effect of Xiaojianzhong Granule(XJZG)on food allergy(FA)and related mecha-nisms in terms of gut microbiota,zonula occluden-1(ZO-1),and Occludin.Methods:A total of 24 specific pathogen-free female BALB/c mice were randomly divided into normal group,model group,prevention group,and treatment group,with 6 mice in each group.The mice in the prevention group were given XJZG by gavage at a standard dose of 5.85 g/kg/day from 3 days before the first challenge till 4 hours before the last challenge;the mice in the treatment group were given XJZG at the double dose for 3 days based on the allergy score;the mice in the other groups were given an equal volume of distilled water by gavage.At the end of the experiment,al-lergy score and anal temperature were measured;flow cytometry was used to measure eosinophils and mast cells in mesenteric lymph nodes(MLNs);toluidine blue staining was performed for mast cells in jejunal tissue;immunohistochemistry was used to measure the expression of ZO-1 and Occludin;16S rRNA sequencing was per-formed to analyze the microbiota in the intestinal content;high-performance liquid chromatography-mass spectrometry was used to measure the content of short-chain fatty acids(SCFAs)in jejunal lavage fluid.Results:Compared with the model group,the prevention group and the treatment group had significant reductions in al-lergy score(P=0.000,P=0.000),anal temperature(P=0.002,P=0.000),the proportion of eosinophils and mast cells in MLNs(P<0.05),and mast cell infiltration in jejunal tissue(P=0.000,P=0.000).Compared with the normal group,the model group had signifi-cant increases in the relative abundances of Erysipelaceae and Turicibacter,while the prevention group and the treatment group had disappearance of Erysipelaceae and Turicibacter and an increase in the relative abundance of Porphyromonadaceae.Compared with the normal group,the model group had a significant reduction in the content of propionate in jejunal lavage fluid(P=0.014),and compared with the model group,the prevention group had a significant increase in the content of propionate in jejunal lavage fluid(P=0.024),as well as a significant increase in the treatment group(P=0.008).In the model group,the expression of ZO-1 was downregulated(P=0.010),and the expression of Occludin was significantly downregulated(P=0.002),while the expression of ZO-1 and Occludin re-turned to normal levels in the prevention group and the treatment group(P=0.001,P=0.013;P=0.025,P=0.015).Conclusion:XJZG can change the composition and abundance of gut microbiota,increase the concentration of SCFAs,upregulate the expression of ZO-1 and Occludin,promote the repair of intestinal barrier,and inhibit food allergy.

Objective:To explore the clinical characteristics and treatment methods of patients with small bowel obstruction secondary to mesenteric ischemia (MI).Methods:The clinical data of 24 patients with small intestinal obstruction secondary to MI from December 2021 to December 2024 in the Fourth Affiliated Hospital of Nanjing Medical University were retrospectively analyzed, including the clinical characteristics and surgical treatment.Results:Among the 24 patients with small intestinal obstruction secondary to MI, 19 were male and 5 were female, with ages ranging from 21 to 65 years old, and the disease course was 0.5 (1.0, 5.5) months. There were 8 cases of deep vein thrombosis, 6 cases of hypertension, 6 cases of atrial fibrillation, 5 cases of short bowel syndrome, 4 cases of abdominal trauma and 23 cases with a history of abdominal surgery. There were 4 cases of acute onset, presenting with full abdominal pain, elevated D-dimer and hematogenous intestinal obstruction. There were 20 cases of chronic onset, presenting with recurrent abdominal pain, weight loss and mechanical intestinal obstruction. The pathogenic factors were superior mesenteric vein thrombosis in 7 cases, superior mesenteric arteriosclerosis in 6 cases, mesenteric injury repair in 4 cases, superior mesenteric artery embolism in 3 cases, superior mesenteric aneurysm in 2 cases, superior mesenteric artery dissection in 1 case, and ileocolic aneurysm in 1 case. Three patients underwent surgical operations after the failure of interventional surgeries, and 20 patients were directly treated with surgery. The small intestinal obstruction was completely relieved in all cases. Another case was treated conservatively, but the small intestinal obstruction was not completely relieved.Conclusions:Small bowel obstruction secondary to MI is often atypical. CT angiography should be performed to identify the cause of obstruction due to deep vein thrombosis, atrial fibrillation, abdominal trauma or abdominal surgery. Surgery is the preferred treatment.

Objective:To explore the clinical characteristics and treatment methods of patients with small bowel obstruction secondary to mesenteric ischemia (MI).Methods:The clinical data of 24 patients with small intestinal obstruction secondary to MI from December 2021 to December 2024 in the Fourth Affiliated Hospital of Nanjing Medical University were retrospectively analyzed, including the clinical characteristics and surgical treatment.Results:Among the 24 patients with small intestinal obstruction secondary to MI, 19 were male and 5 were female, with ages ranging from 21 to 65 years old, and the disease course was 0.5 (1.0, 5.5) months. There were 8 cases of deep vein thrombosis, 6 cases of hypertension, 6 cases of atrial fibrillation, 5 cases of short bowel syndrome, 4 cases of abdominal trauma and 23 cases with a history of abdominal surgery. There were 4 cases of acute onset, presenting with full abdominal pain, elevated D-dimer and hematogenous intestinal obstruction. There were 20 cases of chronic onset, presenting with recurrent abdominal pain, weight loss and mechanical intestinal obstruction. The pathogenic factors were superior mesenteric vein thrombosis in 7 cases, superior mesenteric arteriosclerosis in 6 cases, mesenteric injury repair in 4 cases, superior mesenteric artery embolism in 3 cases, superior mesenteric aneurysm in 2 cases, superior mesenteric artery dissection in 1 case, and ileocolic aneurysm in 1 case. Three patients underwent surgical operations after the failure of interventional surgeries, and 20 patients were directly treated with surgery. The small intestinal obstruction was completely relieved in all cases. Another case was treated conservatively, but the small intestinal obstruction was not completely relieved.Conclusions:Small bowel obstruction secondary to MI is often atypical. CT angiography should be performed to identify the cause of obstruction due to deep vein thrombosis, atrial fibrillation, abdominal trauma or abdominal surgery. Surgery is the preferred treatment.

Objective To focus on the imaging features of liposclerosing myxofibrous tumor(LSMFT)and diagnostic chal-lenges to enhance clinical recognition and differential diagnosis accuracy.Methods Retrospective analysis was conducted on the imaging and pathological data from 21 cases diagnosed with LSMFT between January 2014 and November 2022,including 14 males and 7 females(aged from 21 to 73 years;the course of disease ranged from 4 to 48 months).Patient demographics,clinical presentations,and imaging modalities including X-ray,CT,and MRI were reviewed.Pathological findings were corre-lated with imaging features to delineate diagnostic criteria and identify causes of misdiagnosis.Results All 21 patients repre-sented primary lesions,located in 14 bilateral femurs[9 on the right and 5 on the left;12 proximal femurs(intertrochanteric and peripheral)and 2 distal femurs],2 proximal tibia,2 proximal humerus,1 proximal radius,and 1 ilium and 1 calcaneus.On X-ray and CT,all lesions showed cartographical or quasi-circular osteolytic destruction with distinct and sclerotic margins,continuous bone cortex,absence of periosteal reaction and surrounding soft tissue mass.Calcification,bone ridge and varying degrees of fat components were observed in 16 lesions,displaying mixed density;5 lesions showed ground-glass density with minimal bone ridge.On MRI,the signal intensity of the lesion was heterogeneous.T1-weighted imaging showed iso-to slightly high signal intensity,while T2-weighted imaging demonstrated unevenly high signal intensity.Fat-suppressed sequences de-picted significantly elevated signal intensity within lesions,with post-contrast enhancement showing uneven patterns.5 Cases were initially misdiagnosed as fibrous dysplasia.Conclusion LSMFT is an uncommon benign bone tumor,typically localized in the proximal femur but occasionally found in other skeletal sites.Understanding its distinct imaging characteristics is crucial for accurate diagnosis.Typical cases exhibit identifiable imaging patterns,whereas atypical presentations may lead to misdiagnosis as fibrous dysplasia.

Purpose: This study aims to investigate the current status of affiliate stigma among parents of autistic children, analyze the influencing factors, explore the relationship among mindfulness, coping styles, and affiliate stigma, and verify the mediating role of coping styles between mindfulness and affiliate stigma in parents of children with autism in China.MethodBetween February and April 2023, the Child Development Behaviour Centre of a public hospital in China recruited 345 parents of children with autism. These parents completed the general information questionnaire, the Mindful Attention Awareness Scale, the Affiliate Stigma Scale, and the Simple Coping Style Questionnaire. We then adapted the Hayes Process Macro and Bootstrap methods to examine the mediating effects of coping styles between mindfulness and affiliate stigma. Results: (1) The total affiliate stigma score of parents of children with autism was 48.53 (standard deviation:: 10.74). Parents' age, monthly family income, duration of care, mindfulness, and coping styles were the influencing factors of parental affiliate stigma. (2) Mindfulness was positively correlated with positive coping style (r = 0.33, p < .01) and negatively correlated with negative coping style, affiliate stigma (r = −0.38, −0.39, p < .01), whereas affiliate stigma was negatively correlated with positive coping style (r = −0.34, p < .01) and positively correlated with negative coping style (r = 0.41, p < .01). (3) Positive coping style and negative coping style play a parallel mediating role between mindfulness and affiliate stigma of parents of autistic children. Conclusions Parents of children with autism experience significant levels of affiliate stigma. Mindfulness has a direct impact on associated stigma in parents of children with autism and also indirectly predicts associated stigma through the intermediary influence of positive and negative coping styles. Healthcare professionals could perform mindfulness interventions from an optimistic psychology viewpoint to boost parents' mindfulness and coping abilities, thereby accomplishing the objective of mitigating affiliate stigma.

Mycobacterium intracellular CHPC 1.5701 strain was isolated from the sputum specimen of the patient.This study attempted to establish a guinea pig infection model to evaluate its virulence,so as to provide basic scientific basis for the prevention and treatment of Mycobacterium intracellular infection.Mycobacterium intracellular CHPC 1.5701 was cultured in 7H10 medium.The morphology of the colony changed from colorless to light yellow smooth colony,and the acid-fast staining was positive.Mycobacterium intracellular suspension was diluted with 0.9％sodium chloride solution to 1 × 1010 CFU/mL,1×109 CFU/mL,1 × 108 CFU/mL,1 × 107 CFU/mL and 1 × 106 CFU/mL,respectively.Healthy Hartly guinea pigs with negative skin test of pure protein derivatives of tuberculin were selected and randomly divided into 6 groups with 10 guinea pigs in each group,half male and half female.Guinea pigs in the ex-perimental group were divided into 5 groups,which were intra-peritoneally injected with 5 different concentrations of 1.0 mL suspension/guinea pig,and those in the control group were in-traperitoneally injected with 0.9％sodium chloride solution 1.0 mL suspension/guinea pig.The guinea pigs was then observed,weighed every week,dissected 5 weeks later,lung,spleen and liver tissues were taken,and the tissue lesions were analyzed by hematoxylin-eosin(HE)staining,and the bacteria load was detected by tissue homogenate culture in 7H10 medium.The results showed that Mycobacterium intracellular challenge test had no significant effect on body weight of male guinea pigs(P＞0.05),but could reduce body weight of female guinea pigs(P＜0.01).No pathological changes of organ tissues were ob-served in guinea pigs in the control group,while HE staining of lung,spleen and liver tissues of guinea pigs in challenge experi-mental groups showed alveolar wall alveolar epithelial hyperplasia,monocyte infiltration in liver and spleen,granulomatous in-flammation and other pathological changes,and the degree of pathological changes was related to the injection dose of Mycobac-terium intracellular.Mycobacteria intracellular could be isolated from tissue culture of some organs,among which the spleen had a large amount of bacteria.Intrabitoneal injection of Mycobacteria intracellular CHPC 1.5701 can affect the body weight of female guinea pigs and cause lung,liver and spleen infection of guinea pigs,but no caseous necrosis of guinea pigs was ob-served.Compared with the reported data of Mycobacterium tuberculosis virulence test,it is concluded that Mycobacterium in-tracellular has certain virulence to guinea pigs and belongs to low virulence and low pathogenicity bacteria...

Mycobacterium intracellular CHPC 1.5701 strain was isolated from the sputum specimen of the patient.This study attempted to establish a guinea pig infection model to evaluate its virulence,so as to provide basic scientific basis for the prevention and treatment of Mycobacterium intracellular infection.Mycobacterium intracellular CHPC 1.5701 was cultured in 7H10 medium.The morphology of the colony changed from colorless to light yellow smooth colony,and the acid-fast staining was positive.Mycobacterium intracellular suspension was diluted with 0.9％sodium chloride solution to 1 × 1010 CFU/mL,1×109 CFU/mL,1 × 108 CFU/mL,1 × 107 CFU/mL and 1 × 106 CFU/mL,respectively.Healthy Hartly guinea pigs with negative skin test of pure protein derivatives of tuberculin were selected and randomly divided into 6 groups with 10 guinea pigs in each group,half male and half female.Guinea pigs in the ex-perimental group were divided into 5 groups,which were intra-peritoneally injected with 5 different concentrations of 1.0 mL suspension/guinea pig,and those in the control group were in-traperitoneally injected with 0.9％sodium chloride solution 1.0 mL suspension/guinea pig.The guinea pigs was then observed,weighed every week,dissected 5 weeks later,lung,spleen and liver tissues were taken,and the tissue lesions were analyzed by hematoxylin-eosin(HE)staining,and the bacteria load was detected by tissue homogenate culture in 7H10 medium.The results showed that Mycobacterium intracellular challenge test had no significant effect on body weight of male guinea pigs(P＞0.05),but could reduce body weight of female guinea pigs(P＜0.01).No pathological changes of organ tissues were ob-served in guinea pigs in the control group,while HE staining of lung,spleen and liver tissues of guinea pigs in challenge experi-mental groups showed alveolar wall alveolar epithelial hyperplasia,monocyte infiltration in liver and spleen,granulomatous in-flammation and other pathological changes,and the degree of pathological changes was related to the injection dose of Mycobac-terium intracellular.Mycobacteria intracellular could be isolated from tissue culture of some organs,among which the spleen had a large amount of bacteria.Intrabitoneal injection of Mycobacteria intracellular CHPC 1.5701 can affect the body weight of female guinea pigs and cause lung,liver and spleen infection of guinea pigs,but no caseous necrosis of guinea pigs was ob-served.Compared with the reported data of Mycobacterium tuberculosis virulence test,it is concluded that Mycobacterium in-tracellular has certain virulence to guinea pigs and belongs to low virulence and low pathogenicity bacteria...

Long-segment lichen sclerosus (LS) urethral stricture is a challenge for urologists. Limited data are available for surgeons to make a surgical decision between Kulkarni and Asopa urethroplasty. In this retrospective study, we investigated the outcomes of these two procedures in patients with LS urethral stricture. Between January 2015 and December 2020, 77 patients with LS urethral stricture underwent Kulkarni and Asopa procedures for urethroplasty in the Department of Urology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine (Shanghai, China). Of the 77 patients, 42 (54.5%) underwent the Asopa procedure and 35 (45.5%) underwent the Kulkarni procedure. The overall complication rate was 34.2% in the Kulkarni group and 19.0% in the Asopa group, and no difference was observed ( P = 0.105). Among the complications, no statistical difference was observed in the incidence of urethral stricture recurrence ( P = 0.724) or glans dehiscence ( P = 0.246) except for postoperative meatus stenosis ( P = 0.020). However, the recurrence-free survival rate between the two procedures was significantly different ( P = 0.016). Cox survival analysis showed that antiplatelet/anticoagulant therapy use ( P = 0.020), diabetes ( P = 0.003), current/former smoking ( P = 0.019), coronary heart disease ( P < 0.001), and stricture length ( P = 0.028) may lead to a higher hazard ratio of complications. Even so, these two techniques can still provide acceptable results with their own advantages in the surgical treatment of LS urethral strictures. The surgical alternative should be considered comprehensively according to the patient characteristics and surgeon preferences. Moreover, our results showed that antiplatelet/anticoagulant therapy use, diabetes, coronary heart disease, current/former smoking, and stricture length may be contributing factors of complications. Therefore, patients with LS are advised to undergo early interventions for better therapeutic effects.
Male ; Humans ; Urethral Stricture/etiology* ; Retrospective Studies ; Constriction, Pathologic/surgery* ; Lichen Sclerosus et Atrophicus/surgery* ; Treatment Outcome ; Urologic Surgical Procedures, Male/methods* ; China ; Urethra/surgery* ; Postoperative Complications/etiology* ; Mouth Mucosa ; Diabetes Mellitus/etiology* ; Anticoagulants ; Coronary Disease

Breast cancer has become the most prevalent malignant tumor among women, putting the health of women at serious risk. Screening for lead compounds in the active ingredients of plant that are effective and less toxic continues to be an important strategy for treating breast cancer. Gerbeloid J, a coumarin isolated from Gerbera piloselloides (L.) Cass., showed significant anti-cancer activity. But there is no report on the effect and mechanism of gerbeloid J on cycle and apoptosis of breast cancer. By using the CCK-8, clone formation, and PI staining assays, the effects of gerbeloid J on the proliferation of MCF-7 and MDA-MB-231 cells were assessed in this study. The effects of gerbeloid J on the apoptosis and mitochondrial function of MCF-7 and MDA-MB-231 cells were assessed using DAPI, Annexin V/TO-PRO-3, Rhod-2 AM, TMRM, DCFDA staining assays, and Western blot. The results demonstrated that gerbeloid J regulated the P21/CDC25C/CDK-1/cyclin B1 pathway and arrested the cell cycle at G2/M phase to suppressed the proliferation of MCF-7 and MDA-MB-231 cells. Additionally, gerbeloid J induced apoptosis through the stimulation of mitochondrial calcium excess, reduction of mitochondrial membrane potential, and promotion of ROS generation, and its mechanism was related to the activation of mitochondrial apoptotic pathway. In conclusion, by regulating the P21/CDC25C/CDK-1/cyclin B1 pathway and activating the mitochondrial apoptosis pathway, gerbeloid J could cause breast cancer cell cycle arrest and apoptosis, which might offer a promising candidate for the creation of new drugs against breast cancer.