Objective:To explore the diagnostic value of contrast-enhanced ultrasound (CEUS) combined with vimentin (VIM) and carbohydrate antigen 19-9 (CA19-9) for hilar cholangiocarcinoma (HCCA).Methods:A retrospective analysis was conducted on the case data of patients with HCCA and inflammatory pseudotumor of the liver admitted to Liaocheng People′s Hospital from June 2019 to June 2022. Among them, 68 patients with HCCA who underwent radical surgical resection were the observation group, and 60 patients with inflammatory pseudotumor of the liver were the control group. All patients underwent CEUS examination before the operation. The results of ultrasound manifestations were analyzed, and the levels of tissue VIM and serum CA19-9 in the two groups were compared. The relationship between tissue VIM, serum CA19-9 levels and the clinicopathological characteristics of patients with HCCA was analyzed. The receiver operating characteristic (ROC) curve was used to evaluate the value of CEUS parameters, tissue VIM and serum CA19-9 levels in the diagnosis of HCCA.Results:Among the 68 patients with HCCA, " fast in and fast out" was presented in CEUS. The numbers of cases with high enhancement, equal enhancement and low enhancement in the arterial phase were 47(69.12%), 16(23.53%) and 5(7.35%), respectively. The numbers of cases with low enhancement and equal enhancement in the portal vein stage were 53 cases (77.94%) and 15 cases (22.06%), respectively. All 68 cases (100%) in the delay period were of low enhancement. The proportions of patients with peripheral annular enhancement, overall heterogeneous enhancement and overall uniform enhancement in 60 cases of liver inflammatory pseudotumor were 20.00%(12/60), 40.00%(24/60) and 40.00%(24/60), respectively. There was no statistically significant difference in the time of initial enhancement between the two groups ( P>0.05). The peak time, isoenhancement time and the time of initial regression in the observation group were all longer than those in the control group (all P<0.05). The positive rate of VIM and the level of serum CA19-9 in the observation group were both higher than those in the control group (all P<0.05). The expression of VIM in the tissues of HCCA patients was related to tumor size, degree of differentiation, vascular invasion, lymph node metastasis and tumor node metastasis (TNM) stage (all P<0.05), but not related to nerve invasion ( P>0.05). The level of serum CA19-9 was related to tumor size, degree of differentiation, vascular invasion, nerve invasion, lymph node metastasis and TNM stage (all P<0.05). The results of the ROC curve showed that the combined detection of each parameter of CEUS (time to peak, time to start fading, time to equal enhancement) with VIM expression and serum CA19-9 level had a higher diagnostic efficacy for HCCA than the individual detection of each index. Conclusions:CEUS parameters, tissue VIM expression and serum CA19-9 all have certain diagnostic values for HCCA, and the combined detection has higher diagnostic efficacy.

Objective:To explore the diagnostic value of contrast-enhanced ultrasound (CEUS) combined with vimentin (VIM) and carbohydrate antigen 19-9 (CA19-9) for hilar cholangiocarcinoma (HCCA).Methods:A retrospective analysis was conducted on the case data of patients with HCCA and inflammatory pseudotumor of the liver admitted to Liaocheng People′s Hospital from June 2019 to June 2022. Among them, 68 patients with HCCA who underwent radical surgical resection were the observation group, and 60 patients with inflammatory pseudotumor of the liver were the control group. All patients underwent CEUS examination before the operation. The results of ultrasound manifestations were analyzed, and the levels of tissue VIM and serum CA19-9 in the two groups were compared. The relationship between tissue VIM, serum CA19-9 levels and the clinicopathological characteristics of patients with HCCA was analyzed. The receiver operating characteristic (ROC) curve was used to evaluate the value of CEUS parameters, tissue VIM and serum CA19-9 levels in the diagnosis of HCCA.Results:Among the 68 patients with HCCA, " fast in and fast out" was presented in CEUS. The numbers of cases with high enhancement, equal enhancement and low enhancement in the arterial phase were 47(69.12%), 16(23.53%) and 5(7.35%), respectively. The numbers of cases with low enhancement and equal enhancement in the portal vein stage were 53 cases (77.94%) and 15 cases (22.06%), respectively. All 68 cases (100%) in the delay period were of low enhancement. The proportions of patients with peripheral annular enhancement, overall heterogeneous enhancement and overall uniform enhancement in 60 cases of liver inflammatory pseudotumor were 20.00%(12/60), 40.00%(24/60) and 40.00%(24/60), respectively. There was no statistically significant difference in the time of initial enhancement between the two groups ( P>0.05). The peak time, isoenhancement time and the time of initial regression in the observation group were all longer than those in the control group (all P<0.05). The positive rate of VIM and the level of serum CA19-9 in the observation group were both higher than those in the control group (all P<0.05). The expression of VIM in the tissues of HCCA patients was related to tumor size, degree of differentiation, vascular invasion, lymph node metastasis and tumor node metastasis (TNM) stage (all P<0.05), but not related to nerve invasion ( P>0.05). The level of serum CA19-9 was related to tumor size, degree of differentiation, vascular invasion, nerve invasion, lymph node metastasis and TNM stage (all P<0.05). The results of the ROC curve showed that the combined detection of each parameter of CEUS (time to peak, time to start fading, time to equal enhancement) with VIM expression and serum CA19-9 level had a higher diagnostic efficacy for HCCA than the individual detection of each index. Conclusions:CEUS parameters, tissue VIM expression and serum CA19-9 all have certain diagnostic values for HCCA, and the combined detection has higher diagnostic efficacy.

Purpose To evaluate the differential diagnostic value of 5.0T MRI susceptibility-weighted imaging(SWI)in hepatocellular carcinoma(HCC)and mass-forming intrahepatic cholangiocarcinoma(MICC).Materials and Methods A total of 56 patients with HCC and 36 patients with MICC confirmed by pathology from March 2023 to November 2024 in Anhui Provincial Hospital were retrospectively enrolled.Two radiologists independently analyzed three features of the lesions,including the low-signal rims around the lesion,hemorrhage within the lesion,and the relationship between lesions and adjacent vessels,on the SWI sequence between the two groups,respectively,via inter-rater consistency analysis.These above features between the two groups were compared and contrasted them with those obtained from conventional MR plain and enhanced scans,respectively.For intralesional hemorrhages,the diagnostic value was quantified by calculating the internal tissue susceptibility signal.Results The radiologists showed good consistency in the low-signal rims,intratumoral hemorrhage as well as the relationship between the lesion and the blood vessel on the SWI in the HCC group and the MICC group(Kappa=0.802-0.929,all P<0.001).Compared with conventional MR plain,SWI significantly enhanced the detection rates of perilesional low-signal rims and intratumoral hemorrhage(χ2=89.409,46.210,both P<0.001).These findings were more prevalent in HCC patients.The internal tissue susceptibility signal grading showed that HCC predominantly exhibited grade 3,whereas MICC predominantly exhibited grade 1,with statistically significant differences(Z=-4.059,P<0.05).Additionally,compared with enhanced MRI,SWI demonstrated higher accuracy in diagnosing the relationship between lesions and blood vessels in both groups;however,these differences were not statistically significant(χ2=0.275,0.247,P=0.871,0.619).In the HCC group,the relationship between tumors and blood vessels was primarily characterized by compression and tumor thrombus formation,while in the MICC group,it was predominantly marked by invasive changes,including vessel encasement,stenosis or occlusion,with a statistically significant difference between the two groups(Z=-6.809,P<0.001).Conclusion SWI sequence of 5.0T MRI provides clear visualization of the internal and peripheral structures of HCC and MICC.It can accurately delineate the relationship between lesions and blood vessels without the need for contrast agents,offering significant clinical utility in differentiating these two conditions.

Purpose To evaluate the differential diagnostic value of 5.0T MRI susceptibility-weighted imaging(SWI)in hepatocellular carcinoma(HCC)and mass-forming intrahepatic cholangiocarcinoma(MICC).Materials and Methods A total of 56 patients with HCC and 36 patients with MICC confirmed by pathology from March 2023 to November 2024 in Anhui Provincial Hospital were retrospectively enrolled.Two radiologists independently analyzed three features of the lesions,including the low-signal rims around the lesion,hemorrhage within the lesion,and the relationship between lesions and adjacent vessels,on the SWI sequence between the two groups,respectively,via inter-rater consistency analysis.These above features between the two groups were compared and contrasted them with those obtained from conventional MR plain and enhanced scans,respectively.For intralesional hemorrhages,the diagnostic value was quantified by calculating the internal tissue susceptibility signal.Results The radiologists showed good consistency in the low-signal rims,intratumoral hemorrhage as well as the relationship between the lesion and the blood vessel on the SWI in the HCC group and the MICC group(Kappa=0.802-0.929,all P<0.001).Compared with conventional MR plain,SWI significantly enhanced the detection rates of perilesional low-signal rims and intratumoral hemorrhage(χ2=89.409,46.210,both P<0.001).These findings were more prevalent in HCC patients.The internal tissue susceptibility signal grading showed that HCC predominantly exhibited grade 3,whereas MICC predominantly exhibited grade 1,with statistically significant differences(Z=-4.059,P<0.05).Additionally,compared with enhanced MRI,SWI demonstrated higher accuracy in diagnosing the relationship between lesions and blood vessels in both groups;however,these differences were not statistically significant(χ2=0.275,0.247,P=0.871,0.619).In the HCC group,the relationship between tumors and blood vessels was primarily characterized by compression and tumor thrombus formation,while in the MICC group,it was predominantly marked by invasive changes,including vessel encasement,stenosis or occlusion,with a statistically significant difference between the two groups(Z=-6.809,P<0.001).Conclusion SWI sequence of 5.0T MRI provides clear visualization of the internal and peripheral structures of HCC and MICC.It can accurately delineate the relationship between lesions and blood vessels without the need for contrast agents,offering significant clinical utility in differentiating these two conditions.

Objective To explore the roles of the mechanoreceptor Yes-associated protein 1(YAP1)and piezo type mechanosensitive ion channel component 2(PIEZO2)in mechanotransduction in mouse bladder urothelial cells.Methods Mouse bladder urothelial cells were subjected to mechanical stretching using the FX-6000T cell stretching system and treated with the YAP1-specific inhibitor verteporfin(VP).The expressions of PIEZO2,YAP1 and connective tissue growth factor(CTGF)at the mRNA and protein levels,as well as changes in cellular adenosine triphosphatase(ATP)concentration,were detected using reverse transcription quantitative PCR(RT-qPCR)and Western blotting(WB).Results After stretching stimulation,under the fluorescence microscope,it was observed that the diameter length of the stretched cells were longer than that before stretching,and the difference was statistically significant(P＜0.05).The expressions of YAP1,PIEZO2 and CTGF at the mRNA and protein levels were increased in the stretched group compared to those of the non-stretched group(P＜0.05).VP effectively reduced the expressions of YAP1,PIEZO2 and CTGF at the mRNA and protein levels after stretching stimulation(P＜0.05).Stretching stimulation significantly increased the intracellular ATP concentration,while VP was able to inhibit the increase in ATP concentration,with a statistically significant difference(P＜0.000 1).Conclusion Stretching stimulation increased the expressions of YAP1 and PIEZO2 in bladder urothelial cells and promoted the release of ATP;verteporfin inhibited the increase in YAP1 activity and the overexpression of PIEZO2 caused by stretching,thereby reducing the release of ATP.It is suggested that mouse bladder urothelial cells may primarily sense mechanical signals through the YAP1-PIEZO2-ATP pathway.

Neurological dysfunction and genetic alterations are important factors to hyperhidrosis. In recent years, numerous clinical trials have confirmed the effectiveness and safety of botulinum toxin type A as both a neurotoxin and cytotoxin in the treatment of axillary hyperhidrosis. This article describes the pathogenesis of hyperhidrosis, the therapeutic applications and mechanistic advances of botulinum toxin type A for axillary hyperhidrosis, aiming to provide insights for future basic research and clinical practice.

Objective To explore the roles of the mechanoreceptor Yes-associated protein 1(YAP1)and piezo type mechanosensitive ion channel component 2(PIEZO2)in mechanotransduction in mouse bladder urothelial cells.Methods Mouse bladder urothelial cells were subjected to mechanical stretching using the FX-6000T cell stretching system and treated with the YAP1-specific inhibitor verteporfin(VP).The expressions of PIEZO2,YAP1 and connective tissue growth factor(CTGF)at the mRNA and protein levels,as well as changes in cellular adenosine triphosphatase(ATP)concentration,were detected using reverse transcription quantitative PCR(RT-qPCR)and Western blotting(WB).Results After stretching stimulation,under the fluorescence microscope,it was observed that the diameter length of the stretched cells were longer than that before stretching,and the difference was statistically significant(P＜0.05).The expressions of YAP1,PIEZO2 and CTGF at the mRNA and protein levels were increased in the stretched group compared to those of the non-stretched group(P＜0.05).VP effectively reduced the expressions of YAP1,PIEZO2 and CTGF at the mRNA and protein levels after stretching stimulation(P＜0.05).Stretching stimulation significantly increased the intracellular ATP concentration,while VP was able to inhibit the increase in ATP concentration,with a statistically significant difference(P＜0.000 1).Conclusion Stretching stimulation increased the expressions of YAP1 and PIEZO2 in bladder urothelial cells and promoted the release of ATP;verteporfin inhibited the increase in YAP1 activity and the overexpression of PIEZO2 caused by stretching,thereby reducing the release of ATP.It is suggested that mouse bladder urothelial cells may primarily sense mechanical signals through the YAP1-PIEZO2-ATP pathway.

Objective:To explore the prognostic value of the age-adjusted Charlson comorbidity index (ACCI) in patients with stage IIB cervical squamous cell carcinoma (CSCC) who received radical concurrent chemoradiotherapy (rCCRT).Methods:Clinical data of 115 patients with stage IIB CSCC who underwent rCCRT at the First Affiliated Hospital of Xinxiang Medical University from January 2017 to January 2023 were retrospectively analyzed. Fourteen clinical factors, including ACCI, were assessed. Univariate and multivariate Cox regression analyses were performed to identify the independent prognostic factors for progression-free survival (PFS) and overall survival (OS). The optimal cut-off value for ACCI was determined using the receiver operating characteristic (ROC) curve analysis, and patients were divided into the high ACCI (ACCI > 3) and low ACCI (ACCI ≤ 3) groups. Survival differences between two groups were evaluated using Kaplan-Meier curves and compared by log-rank tests.Results:Multivariate Cox regression analysis revealed that ACCI was an independent prognostic factor for both PFS and OS ( HR=3.405, 95% CI: 1.108-10.467, P=0.032; HR=4.732, 95% CI: 1.363-16.425, P=0.014). Significant differences were observed in PFS and OS between the high and low ACCI groups ( P=0.023 and 0.003, respectively). The median PFS was 44 months in the high ACCI group and 56 months in the low ACCI group. The 2-year and 3-year PFS rates were 81.9% and 80.1% in the high ACCI group, and 94.4% and 94.4% in the low ACCI group, respectively. The median OS was 46 months in the high ACCI group and 56 months in the low ACCI group. The 2-year and 3-year OS rates were 88.3% and 84.7% in the high ACCI group, and 94.4% and 94.4% in the low ACCI group, respectively. Conclusions:For patients with stage IIB CSCC receiving rCCRT, ACCI is an independent and significant prognostic factor, with patients in the high ACCI group exhibiting worse prognosis.

Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

Objective:To investigate the correlation between non-Hodgkin lymphoma (NHL) and chronic hepatitis B virus (HBV) infection by using the method of two-sample bidirectional Mendelian randomization (MR) analysis.Methods:Genetic variation data for NHL came from the Finnish database (FinnGen) Consortium 2021 public genome-wide association study (GWAS) dataset including 1 088 patients with NHL and 299 952 control subjects. The GWAS dataset for chronic HBV infection was derived from GWAS analysis published in 2021, including 145 NHL patients and 351 740 control subjects. NHL was used as an exposure factor, single nucleotide polymorphism (SNP) significantly associated with NHL was used as an instrumental variable (IV), chronic HBV infection was used as an outcome variable. The two-sample MR analysis was performed by using inverse-variance weighted (IVW) method. Chronic HBV infection was taken as an exposure factor, SNP significantly associated with chronic HBV infection was taken as IV, and NHL was taken as outcome variable, and then reverse two-sample MR analysis was performed. The IVW method used the inverse variance of each IV as the weight to fit, and the ratio method was used to measure SNP one by one and make weighted regression analysis, so as to obtain the overall estimate. MR-Egger regression and the weighted median (WME) method were also used to supplement the IVW method. In sensitivity analysis, leave-one-out sensitivity analysis was used to evaluate the impact of a single SNP. Cochran Q test was used to analyze the heterogeneity of the selected IV. MR-Egger regression was used to measure the average horizontal pleiotropy of IV, and the P-value of directivity was calculated. The MR-pleiotropy residual sum and outlier (MR-PRESSO) Global Test was used to exclude possible horizontal pleiotropic outliers and reduce bias. Results:In the leave-one-out sensitivity analysis, SNP with significant effects on causal associations was excluded. In forward MR analysis, IVs were 10 SNPs associated with NHL; the IVW method indicated that there was no causal association between NHL and chronic HBV infection ( OR = 0.979, 95% CI: 0.925-1.036, P = 0.465). MR-Egger regression ( OR = 0.992, 95% CI: 0.926-1.062, P = 0.825) and WME method ( OR = 0.992, 95% CI: 0.934-1.055, P = 0.805) were used as supplementary methods to obtain the consistent results. In sensitivity analysis, Cochran Q test showed no heterogeneity among IVs (IVW method: P = 0.271, MR-Egger regression: P = 0.239). Horizontal pleiotropy was not found in the MR-Egger regression (intercept was -0.01, P = 0.778) and the MR-PRESSO Global Test ( P > 0.05), suggesting robust results. In the reverse MR analysis, IVs were 8 SNPs associated with NHL; the IVW method ( OR = 1.117, 95% CI: 0.942-1.324, P = 0.202) also found no significant causal relationship between chronic HBV infection and NHL; MR-Egger regression ( OR = 0.777, 95% CI: 0.450-1.343, P = 0.401) and WME method ( OR = 1.120, 95% CI: 0.887-1.415, P = 0.351) also showed similar risk estimates. Sensitivity analysis also suggested the consistency and reliability of the results. Cochran Q test showed no heterogeneity among IVs (IVW method: P = 0.775, MR-Egger regression: P = 0.903). Horizontal pleiotropy was not found by MR-Egger regression (intercept was 0.102, P = 0.548) and MR-PRESSO Global Test ( P > 0.05). Conclusions:MR analysis suggests no causal relationship between NHL and chronic HBV infection.