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.

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 value of high resolution computed tomography（HRCT） combined with Magnetic Resonance Imaging（MRI） in the diagnosis of inner ear malformation. Methods:HRCT and MRI data of 82 patients with inner ear malformations were analyzed retrospectively. HRCT MPR and CPR reconstruction of the inner ear structure, facial nerve canal and oblique sagittal MRI reconstruction of the internal auditory canal were performed. The inner ear malformations were classified, the conditions of facial nerve canal and cochlear nerve were evaluated. The association between inner ear malformation and cochlear nerve dysplasia were analyzed by Chi-square test with continuity correction. Results:Among the 82 patients with inner ear malformations,there were 49 cases of bilateral symmetry, 11 cases of bilateral asymmetry and 22 cases of unilateral inner ear malformations. Respectively, the most prevalent types were IP-Ⅱ（42.96%）, dilatation of atrium aqueduct（18.31%） and malformations of atrium and semicircular canal 19.72%. Out of 50 cases of cochlear malformations,only 3 were isolated cochlear malformations, and the rest were accompanied by other malformations of varying degrees. In the 67 ears examined by MRI, 26（38.81%） had cochlear nerve deficiency（CND）, and the incidence of CND varied with different types of inner ear malformations. Out of 142 ears, 28（19.72%） had abnormalities of the facial nerve canal. Conclusion:HRCT combined with MRI can accurately distinguish the types of inner ear malformation and effectively evaluate the facial nerve canal and cochlear nerve, and further provides the important finger and Guide value for the clinician to formulate the reasonable treatment and the operation plan.
Humans ; Ear, Inner/diagnostic imaging* ; Magnetic Resonance Imaging/methods* ; Retrospective Studies ; Female ; Male ; Tomography, X-Ray Computed/methods* ; Child ; Adolescent ; Adult ; Child, Preschool ; Cochlear Nerve/diagnostic imaging* ; Facial Nerve/abnormalities* ; Cochlea/abnormalities* ; Infant ; Young Adult

Objective:With the aging of the population, the health of women's ovarian in China has received increasing attention.Ovarian aging not only affects reproductive health but also increases the risk of chronic diseases.This study aims to systematically explore the relationship between living habits and ovarian aging.Methods:Based on the data from the China Health and Retirement Longitudinal Study(CHARLS)from 2011 to 2018, 8 287 postmenopausal women were included.A retrospective cohort study was conducted using statistical analysis and machine learning methods to evaluate the impact of lifestyle factors such as smoking, drinking, sleep, and dietary patterns on the age of menopause.Results:It was found that adverse lifestyle factors such as reduced daily meal frequency [the early menopause group(2.85±0.38)times/day vs.the normal group(2.89±0.38)times/day, P=0.002], smoking [the smoking rate of the early menopause group(7.75%) vs.that of the normal group(6.15%), P=0.004], and high-frequency drinking [the early menopause rate of people who drink daily(19.76%(33/167)) vs.that of people who rarely or never drink(14.62%(1 162/7 949)), P=0.047]were associated with accelerated ovarian aging. Conclusions:Reasonable adjustment of living habits maybe help to delay the age of menopause and reduce related health risks.This study provides a scientific basis for optimizing women's healthy lifestyles, which is conducive to improving the quality of life and happiness of middle-aged and elderly women in China.

Under the background of climate change, the escalating air pollution and extreme weather events have been identified as risk factors for chronic respiratory diseases (CRD), causing serious public health burden worldwide. This review aims to summarize the effects of changed atmospheric environment caused by climate change on CRD. Results indicated an increased risk of CRD (mainly COPD, asthma) associated with environmental factors, such as air pollutants, adverse meteorological conditions, extreme temperatures, sandstorms, wildfire, and atmospheric allergens. Furthermore, this association can be modified by factors such as socioeconomic status, adaptability, individual behavior, medical services. Potential pathophysiological mechanisms linking climate change and increased risk of CRD involved pulmonary inflammation, immune disorders, oxidative stress. Notably, the elderly, children, impoverished groups and people in regions with limited adaptability are more sensitive to respiratory health risks caused by climate change. This review provides a reference for understanding risk factors of CRD in the context of climate change, and calls for the necessity of adaptive strategies. Further interdisciplinary research and global collaboration are needed in the future to enhance adaptability and address climate health inequality.
Climate Change ; Humans ; Air Pollution/adverse effects* ; Risk Factors ; Respiratory Tract Diseases/etiology* ; Chronic Disease ; Air Pollutants/adverse effects* ; Environmental Exposure/adverse effects*

Dent disease is a rare X-linked recessive inherited renal tubular disorder characterized by low molecular weight proteinuria (LMWP), hypercalciuria, nephrocalcinosis, and other clinical features, and can lead to progressive renal failure. It is primarily caused by mutations in the CLCN5 gene. This article reports the case of a 10-year-old male patient of Chinese descent who was incidentally found to have asymptomatic proteinuria during a routine health examination. Comprehensive biochemical testing and clinical evaluation revealed significant LMWP and hypercalciuria, while renal biopsy showed mesangial cell and matrix proliferation. Whole exome sequencing identified a novel deletion mutation in the CLCN5 gene (NM_001127899.4, c.1158delC, p.F387Lfs*42) causing a frameshift and premature termination, which is likely to disrupt its role in chloride/hydrogen ion exchange and endosomal acidification. Bioinformatic analysis indicated the variant is pathogenic. Genetic testing plays an important role in diagnosing rare kidney diseases. Early identification of pathogenic mutations is essential for facilitating timely intervention and appropriate management, potentially enhancing patient outcomes. This report expands the CLCN5 mutation spectrum and contributes to understanding the genetic and molecular mechanisms of Dent disease.
Humans ; Chloride Channels/genetics* ; Dent Disease/genetics* ; Male ; Child ; Computational Biology ; Mutation ; Proteinuria/genetics* ; Hypercalciuria/genetics*

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.

Nerve dysfunction and alterations in genetic material are important factors in hyperhidrosis. In recent years, numerous clinical trials have confirmed the effectiveness and safety of botulinum toxin type A as a neurotoxin and cytotoxin in the treatment of axillary hyperhidrosis. This article describes the pathogenesis of hyperhidrosis and the application and mechanism research progress of botulinum toxin type A in the treatment of axillary hyperhidrosis, hoping to provide a basis for basic studies and clinical treatment related to axillary hyperhidrosis and botulinum toxin type A.

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.