AIM:To study the effect of Sanhuang Gel on the expression of TLRs/NLRP3 signal path-way in auricle acne model rats,and to explore its mechanism in treating acne inflammatory injury.METHODS:A rat model of auricular acne was in-duced by applying 100％oleic acid to the opening of the right ear catheter and injecting Propionibac-terium acnes.Rats were divided into normal group,model group,positive control group(clindamycin hydrochloride gel 10 mg/g)and Sanhuang Gel high,medium and low dose groups(280,140 and 70 mg/g).Each drug group was given drug intervention for 28 days.The changes of auricle skin lesions in each group were observed;Hematoxylin-eosin(HE)staining was used to observe the pathological changes of auricle acne.The ultrastructural chang-es of auricle tissue cells were observed by transmis-sion electron microscope(TEM).The distribution and expression changes of TLR2 and TLR4 in rat au-ricle tissue were detected by immunofluorescence.The expressions of TLR2,TLR4,NLRP3,ASC and Cas-pase-1 mRNA in rat auricle were detected by Real-time PCR.The expressions of TLR2,TLR4,NLRP3,ASC and Caspase-1 in rat auricle were detected by Western blot.RESULTS:Compared with the normal group,papules,pustules,inflammatory cell infiltra-tion and obvious edema of mitochondria can be seen in the auricle tissue of the model group.The mRNA and protein expression levels of TLR2,TLR4,NLRP3,ASC andCaspase-1 increased significantly(P＜0.01).Compared with the model group,the ap-pearance and pathological damage of auricle in each treatment group were obviously alleviated,and the morphology and structure of mitochondria returned to normal.The mRNA expression levels of TLR2,TLR4,NLRP3,ASC and Caspase-1 decreased significantly(P＜0.01).The expression levels of TLR2,TLR4,NLRP3,ASC and Caspase-1 in positive control group and high and middle dose groups de-creased(P＜0.01,P＜0.05).The expression levels of ASC and Caspase-1 protein in low dose group were significantly decreased(P＜0.01),but there was no significant difference in the expression levels of TLR2,TLR4 and NLRP3 protein(P＞0.05).CONCLU-SION:Sanhuang Gel can improve the pathological damage of auricle tissue and reduce immune in-flammatory reaction in acne rats,and its mecha-nism may be related to regulating TLRs/NLRP3 sig-naling pathway.

Objective To investigate the efficacy and safety of Linaclotide combined with Simethicone oil and compound polyethylene glycol electrolyte(PEG)for cleansing effect of bowel in patients with constipation.Methods A prospective randomized controlled trial was designed and implemented by single blind method.383 patients with constipation who underwent colonoscopy from April 2023 to August 2024 were enrolled and randomly divided into routine group(128 cases),experimental group A(128 cases)and experimental group B(127 cases).Routine group treated with 3 L PEG,experimental group A treated with 290 μg Linaclotide+2 L PEG and experimental group B treated with 290 μg Linaclotide+30 mL Simethicone+2 L PEG.Bowel preparation effect[Boston bowel preparation scale(BBPS)scores and foaming removal effect],lesion detection rate,first defecation interval,frequency of defecation,the success rate of cecal intubation,the insertion time of colonoscopy,the withdrawal time of colonoscopy,incidence of adverse reactions and willingness to repeat examination of the three groups were compared.Results No statistically significant differences were observed in the BBPS scores among the three groups(P>0.05);The foaming removal effect score in experimental group B was significantly lower than that in routine group and experimental group A,the difference was statistically significant(P<0.05);The total lesion detection rate and polyps detection rate of experimental group B were significantly higher than those of routine group and experimental group A,the differences were statistically significant(P<0.05).The first defecation interval of the routine group was significantly longer than that of experimental group A and experimental group B,the difference was statistically significant(P<0.05);The frequency of defecation was compared among the three groups,and the difference was no statistically significant(P>0.05).The success rate of cecal intubation in the three groups was 100.0%,and the insertion time of colonoscopy was similar,the differences were not statistically significant(P>0.05);The withdrawal time of colonoscopy in experimental group B was significantly shorter than that in routine group and experimental group A,the difference was statistically significant(P<0.05).The incidence of abdominal distension and total adverse reactions in the routine group were higher than those in experimental group A and experimental group B,the differences were statistically significant(P<0.05);The willingness to repeat examination rate of the routine group was significantly lower than that of experimental group A and experimental group B,the differences were statistically significant(P<0.05).Conclusion 290 μg Linaclotide combined with 30 mL Simethicone and 2 L PEG solution regimen has advantages in intestinal preparation for patients with constipation,and can achieve better intestinal cleaning effect than 3 L PEG solution and 290 μg linalopeptide+2 L PEG solution regimen,with higher safety and willingness to repeat examination.It can be recommended for bowel preparation for patients with constipation.

Objective:To investigate gut microbiota differences between individuals with and without colorectal adenoma(CRA)and to identify gut microbes associated with CRA.Methods:This cross-sectional study analyzed the gut microbiota of 100 patients with CRA and 68 individuals without CRA(aged 40-75 years)who underwent colonoscopies between March 2021 and March 2022 at Tianjin Nankai Hospital.Fecal samples were sequenced for the V3-V4 region of the bacterial 16S rRNA gene using the Illumina NovaSeq platform.Results:Compared to the non-CRA group,the CRA group exhibited reduced relative abundances of identified and unidentified Lachnospiraceae,with increased Faecalibacterium and Streptococcus.In the non-CRA group,the relative abundances of Coprococcus,unidentified Clostridiaceae,and Clostridium were higher.LEfSe analysis revealed significant enrichment of Gammaproteobacteria,Proteobacteria,Enterobacteriales,and Faecalibacterium in the CRA group,while the non-CRA group was enriched for Moraxellaceae,Acinetobacter,and Anaerostipes.Conclusions:These findings suggest a discernible disparity in the gut microbiota structure between CRA patients and individuals without adenoma.The enrichment of potential pathogenic taxa,such as Faecalibacterium and Streptococcus,in the CRA group suggests a possible association with adenoma development.

Objective To investigate the efficacy and safety of Linaclotide combined with Simethicone oil and compound polyethylene glycol electrolyte(PEG)for cleansing effect of bowel in patients with constipation.Methods A prospective randomized controlled trial was designed and implemented by single blind method.383 patients with constipation who underwent colonoscopy from April 2023 to August 2024 were enrolled and randomly divided into routine group(128 cases),experimental group A(128 cases)and experimental group B(127 cases).Routine group treated with 3 L PEG,experimental group A treated with 290 μg Linaclotide+2 L PEG and experimental group B treated with 290 μg Linaclotide+30 mL Simethicone+2 L PEG.Bowel preparation effect[Boston bowel preparation scale(BBPS)scores and foaming removal effect],lesion detection rate,first defecation interval,frequency of defecation,the success rate of cecal intubation,the insertion time of colonoscopy,the withdrawal time of colonoscopy,incidence of adverse reactions and willingness to repeat examination of the three groups were compared.Results No statistically significant differences were observed in the BBPS scores among the three groups(P>0.05);The foaming removal effect score in experimental group B was significantly lower than that in routine group and experimental group A,the difference was statistically significant(P<0.05);The total lesion detection rate and polyps detection rate of experimental group B were significantly higher than those of routine group and experimental group A,the differences were statistically significant(P<0.05).The first defecation interval of the routine group was significantly longer than that of experimental group A and experimental group B,the difference was statistically significant(P<0.05);The frequency of defecation was compared among the three groups,and the difference was no statistically significant(P>0.05).The success rate of cecal intubation in the three groups was 100.0%,and the insertion time of colonoscopy was similar,the differences were not statistically significant(P>0.05);The withdrawal time of colonoscopy in experimental group B was significantly shorter than that in routine group and experimental group A,the difference was statistically significant(P<0.05).The incidence of abdominal distension and total adverse reactions in the routine group were higher than those in experimental group A and experimental group B,the differences were statistically significant(P<0.05);The willingness to repeat examination rate of the routine group was significantly lower than that of experimental group A and experimental group B,the differences were statistically significant(P<0.05).Conclusion 290 μg Linaclotide combined with 30 mL Simethicone and 2 L PEG solution regimen has advantages in intestinal preparation for patients with constipation,and can achieve better intestinal cleaning effect than 3 L PEG solution and 290 μg linalopeptide+2 L PEG solution regimen,with higher safety and willingness to repeat examination.It can be recommended for bowel preparation for patients with constipation.

Objective To construct a nomogram model for predicting pulmonary hemorrhage associated with the positioning of pulmonary nodules with the new four-hook positioning needle based on clinical-CT imaging features and evaluate its predictive efficacy.Methods We made a retrospective analysis of the clinical,imaging and pathological data of 449 patients with pulmonary nodules positioned by the new four-hook positioning needle.According to the random number table method(7∶3),they were divided into a training set of 314 cases and a validation set of 135 cases.Each data set was further divided into positive group and negative group for pulmonary hemorrhage according to the presence or absence of pulmonary hemorrhage.We evaluated the CT imaging features of pulmonary nodules,including nodule nature(pure ground-glass density,mixed ground-glass density,solid nodule),nodule diameter,distance from the nodule to the pleural surface(hereinafter referred to as length),nodule positioning time,and association with pulmonary hemorrhage.Independent sample t-test,Mann-Whitney U test and x2 test were used to compare the correlations of clinical and CT features of pulmonary nodules with pulmonary hemorrhage.LASSO regression and multivariate Logistic regression were employed to screen the independent risk factors related to pulmonary hemorrhage and construct a nomogram model.The receiver operating characteristic(ROC)curve was used to evaluate the predictive efficacy of the model,and the calibration curve and decision curve were respectively used for the verification of the nomogram model and evaluation of the clinical net benefit.Results The results of LASSO regression showed that the nature of pulmonary nodules,underlying diseases,smoking and length were the characteristic variables related to pulmonary hemorrhage.Based on the minimum akaike information criterion(AIC),the screened characteristic variables were included in the multivariate Logistic backward stepwise regression analysis.The results showed that the nature of pulmonary nodules,underlying diseases,smoking and length were all independent risk factors related to pulmonary hemorrhage.A nomogram was established according to the above independent risk factors and the ROC curve was drawn.The AUC of the training set was 0.86(95％CI:0.80-0.91),and the AUC of the validation set was 0.88(95％CI:0.80-0.96),with no statistically significant difference(P＞0.05).The calibration curve suggested that the predicted values of the nomogram were close to the actual values,and the decision curve analysis showed that the net benefit of the model was good.Conclusion The nomogram model established by combining clinical-CT features such as the nature of pulmonary nodules,underlying diseases,smoking and length can effectively predict pulmonary hemorrhage associated with the positioning of pulmonary nodules with the new four-hook positioning needle.

To target the pivotal BCR/ABL oncoprotein in chronic myeloid leukemia (CML) cells, tyrosine kinase inhibitors (TKIs) are utilized as landmark achievements in CML therapy. However, TKI resistance and intolerance remain principal obstacles in the treatment of CML patients. In recent years, drug repositioning provided alternative and promising perspectives apart from the classical cancer therapies, and promoted anthelmintic mebendazole (MBZ) as an effective anti-cancer drug in various cancers. Here, we investigated the role of MBZ in CML treatment including imatinib-resistant CML cells. Our results proved that MBZ inhibited the proliferation and induced apoptosis in CML cells. We found that MBZ effectively suppressed BCR/ABL kinase activity and MEK/ERK signaling pathway by reducing p-BCR/ABL and p-ERK levels with ABL1 targeting ability. Meanwhile, MBZ directly targeted the colchicine-binding site of β-tubulin protein, hampered microtubule polymerization and induced mitosis arrest and mitotic catastrophe. In addition, MBZ increased DNA damage levels and hampered the accumulation of ataxia-telangiectasia mutated and DNA-dependent protein kinase into the nucleus. This work discovered that anthelmintic MBZ exerts remarkable anticancer effects in both imatinib-sensitive and imatinib-resistant CML cells in vitro and revealed mechanisms underlying. From the perspective of drug repositioning and multi‐target therapeutic strategy, this study provides a promising option for CML treatment, especially in TKI-resistant or intolerant individuals.

To target the pivotal BCR/ABL oncoprotein in chronic myeloid leukemia (CML) cells, tyrosine kinase inhibitors (TKIs) are utilized as landmark achievements in CML therapy. However, TKI resistance and intolerance remain principal obstacles in the treatment of CML patients. In recent years, drug repositioning provided alternative and promising perspectives apart from the classical cancer therapies, and promoted anthelmintic mebendazole (MBZ) as an effective anti-cancer drug in various cancers. Here, we investigated the role of MBZ in CML treatment including imatinib-resistant CML cells. Our results proved that MBZ inhibited the proliferation and induced apoptosis in CML cells. We found that MBZ effectively suppressed BCR/ABL kinase activity and MEK/ERK signaling pathway by reducing p-BCR/ABL and p-ERK levels with ABL1 targeting ability. Meanwhile, MBZ directly targeted the colchicine-binding site of β-tubulin protein, hampered microtubule polymerization and induced mitosis arrest and mitotic catastrophe. In addition, MBZ increased DNA damage levels and hampered the accumulation of ataxia-telangiectasia mutated and DNA-dependent protein kinase into the nucleus. This work discovered that anthelmintic MBZ exerts remarkable anticancer effects in both imatinib-sensitive and imatinib-resistant CML cells in vitro and revealed mechanisms underlying. From the perspective of drug repositioning and multi‐target therapeutic strategy, this study provides a promising option for CML treatment, especially in TKI-resistant or intolerant individuals.

To target the pivotal BCR/ABL oncoprotein in chronic myeloid leukemia (CML) cells, tyrosine kinase inhibitors (TKIs) are utilized as landmark achievements in CML therapy. However, TKI resistance and intolerance remain principal obstacles in the treatment of CML patients. In recent years, drug repositioning provided alternative and promising perspectives apart from the classical cancer therapies, and promoted anthelmintic mebendazole (MBZ) as an effective anti-cancer drug in various cancers. Here, we investigated the role of MBZ in CML treatment including imatinib-resistant CML cells. Our results proved that MBZ inhibited the proliferation and induced apoptosis in CML cells. We found that MBZ effectively suppressed BCR/ABL kinase activity and MEK/ERK signaling pathway by reducing p-BCR/ABL and p-ERK levels with ABL1 targeting ability. Meanwhile, MBZ directly targeted the colchicine-binding site of β-tubulin protein, hampered microtubule polymerization and induced mitosis arrest and mitotic catastrophe. In addition, MBZ increased DNA damage levels and hampered the accumulation of ataxia-telangiectasia mutated and DNA-dependent protein kinase into the nucleus. This work discovered that anthelmintic MBZ exerts remarkable anticancer effects in both imatinib-sensitive and imatinib-resistant CML cells in vitro and revealed mechanisms underlying. From the perspective of drug repositioning and multi‐target therapeutic strategy, this study provides a promising option for CML treatment, especially in TKI-resistant or intolerant individuals.

To target the pivotal BCR/ABL oncoprotein in chronic myeloid leukemia (CML) cells, tyrosine kinase inhibitors (TKIs) are utilized as landmark achievements in CML therapy. However, TKI resistance and intolerance remain principal obstacles in the treatment of CML patients. In recent years, drug repositioning provided alternative and promising perspectives apart from the classical cancer therapies, and promoted anthelmintic mebendazole (MBZ) as an effective anti-cancer drug in various cancers. Here, we investigated the role of MBZ in CML treatment including imatinib-resistant CML cells. Our results proved that MBZ inhibited the proliferation and induced apoptosis in CML cells. We found that MBZ effectively suppressed BCR/ABL kinase activity and MEK/ERK signaling pathway by reducing p-BCR/ABL and p-ERK levels with ABL1 targeting ability. Meanwhile, MBZ directly targeted the colchicine-binding site of β-tubulin protein, hampered microtubule polymerization and induced mitosis arrest and mitotic catastrophe. In addition, MBZ increased DNA damage levels and hampered the accumulation of ataxia-telangiectasia mutated and DNA-dependent protein kinase into the nucleus. This work discovered that anthelmintic MBZ exerts remarkable anticancer effects in both imatinib-sensitive and imatinib-resistant CML cells in vitro and revealed mechanisms underlying. From the perspective of drug repositioning and multi‐target therapeutic strategy, this study provides a promising option for CML treatment, especially in TKI-resistant or intolerant individuals.

To target the pivotal BCR/ABL oncoprotein in chronic myeloid leukemia (CML) cells, tyrosine kinase inhibitors (TKIs) are utilized as landmark achievements in CML therapy. However, TKI resistance and intolerance remain principal obstacles in the treatment of CML patients. In recent years, drug repositioning provided alternative and promising perspectives apart from the classical cancer therapies, and promoted anthelmintic mebendazole (MBZ) as an effective anti-cancer drug in various cancers. Here, we investigated the role of MBZ in CML treatment including imatinib-resistant CML cells. Our results proved that MBZ inhibited the proliferation and induced apoptosis in CML cells. We found that MBZ effectively suppressed BCR/ABL kinase activity and MEK/ERK signaling pathway by reducing p-BCR/ABL and p-ERK levels with ABL1 targeting ability. Meanwhile, MBZ directly targeted the colchicine-binding site of β-tubulin protein, hampered microtubule polymerization and induced mitosis arrest and mitotic catastrophe. In addition, MBZ increased DNA damage levels and hampered the accumulation of ataxia-telangiectasia mutated and DNA-dependent protein kinase into the nucleus. This work discovered that anthelmintic MBZ exerts remarkable anticancer effects in both imatinib-sensitive and imatinib-resistant CML cells in vitro and revealed mechanisms underlying. From the perspective of drug repositioning and multi‐target therapeutic strategy, this study provides a promising option for CML treatment, especially in TKI-resistant or intolerant individuals.