Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.

Objective:To investigate the characteristics of resting-state mirror homotopic connectivity and the gray matter volume of brain in patients with neuropsychiatric systemic lupus erythematosus (NPSLE).Methods:From June 2020 to March 2023, a total of 35 NPSLE patients (NPSLE group) and 30 non-NPSLE patients (non-NPSLE group) were selected from Taizhou People's Hospital Affiliated to Nanjing Medical University, another 31 healthy volunteers were recruited as the healthy controls(HC group). All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) and mini-mental state examination (MMSE) assessments. The patients in NPSLE and non-NPSLE groups were additionally assessed using the fatigue scale for motor and cognitive functions (FSMC) and the hospital anxiety and depression scale (HADS).The DPABI V7.0 toolkit based on the MATLAB platform was used to preprocess the rs-fMRI data and calculate the voxel-mirrored homotopic connectivity(VMHC) indexes, and the differences in VMHC between groups were evaluated by covariance analysis in SPM12.0 software, and the VMHC values of brain regions with significant differences were extracted for further comparison between the two groups.Partial correlation analysis was performed to investigate the association between VMHC values and clinical parameters in NPSLE patients.The brain regions with significant differences between NPSLE patients and non-NPSLE patients were used as region of interest (ROI), and gray matter volumes within these ROIs were then calculated by VBM8 toolbox.Results:(1)There were statistically significant differences in the VMHC values of bilateral precentral gyrus, bilateral dorsolateral superior frontal gyrus, bilateral medial and paracingulate gyrus, bilateral parahippocampal gyrus, bilateral middle occipital gyrus, bilateral postcentral gyrus, and bilateral superior temporal gyrus among the 3 groups( F=11.246-14.102, all P<0.05). The NPSLE group exhibited significantly lower VMHC values in these regions compared to both the non-NPSLE group and HC group (all P<0.05), but there were no significant differences in these regions between the non-NPSLE group and HC group (all P>0.05).(2) The gray matter volumes of bilateral dorsolateral superior frontal gyrus(right: (0.57±0.11)mm 3, (0.65±0.08)mm 3, t=-3.409, P=0.001; left: (0.53±0.10)mm 3, (0.60±0.07)mm 3, t=-3.082, P=0.003), bilateral precentral gyrus(right: (0.32±0.06)mm 3, (0.35±0.04)mm 3, t=-2.044, P=0.045; left: (0.39±0.06)mm 3, (0.42±0.04)mm 3, t=-2.505, P=0.015), right medial and paracingulate gyrus((0.66±0.08)mm 3, (0.70±0.07)mm 3, t=-2.491, P=0.015) and left superior temporal gyrus((0.57±0.09)mm 3, (0.61±0.06)mm 3, t=- 2.344, P=0.022) in the NPSLE group were smaller than those of non-NPSLE group.(3)Correlation analysis showed that the VMHC value of dorsolateral superior frontal gyrus was positively correlated with IgA level in NPSLE patients ( r=0.353, P=0.047). Conclusion:Patients with NPSLE generally have decreased mirror homotopy functional connectivity in the cerebral hemispheres, accompanied by a decrease in gray matter volume in some brain regions, which can provide a certain neuroimaging basis for the pathogenesis of brain injury.

Objective:To investigate the characteristics of resting-state mirror homotopic connectivity and the gray matter volume of brain in patients with neuropsychiatric systemic lupus erythematosus (NPSLE).Methods:From June 2020 to March 2023, a total of 35 NPSLE patients (NPSLE group) and 30 non-NPSLE patients (non-NPSLE group) were selected from Taizhou People's Hospital Affiliated to Nanjing Medical University, another 31 healthy volunteers were recruited as the healthy controls(HC group). All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) and mini-mental state examination (MMSE) assessments. The patients in NPSLE and non-NPSLE groups were additionally assessed using the fatigue scale for motor and cognitive functions (FSMC) and the hospital anxiety and depression scale (HADS).The DPABI V7.0 toolkit based on the MATLAB platform was used to preprocess the rs-fMRI data and calculate the voxel-mirrored homotopic connectivity(VMHC) indexes, and the differences in VMHC between groups were evaluated by covariance analysis in SPM12.0 software, and the VMHC values of brain regions with significant differences were extracted for further comparison between the two groups.Partial correlation analysis was performed to investigate the association between VMHC values and clinical parameters in NPSLE patients.The brain regions with significant differences between NPSLE patients and non-NPSLE patients were used as region of interest (ROI), and gray matter volumes within these ROIs were then calculated by VBM8 toolbox.Results:(1)There were statistically significant differences in the VMHC values of bilateral precentral gyrus, bilateral dorsolateral superior frontal gyrus, bilateral medial and paracingulate gyrus, bilateral parahippocampal gyrus, bilateral middle occipital gyrus, bilateral postcentral gyrus, and bilateral superior temporal gyrus among the 3 groups( F=11.246-14.102, all P<0.05). The NPSLE group exhibited significantly lower VMHC values in these regions compared to both the non-NPSLE group and HC group (all P<0.05), but there were no significant differences in these regions between the non-NPSLE group and HC group (all P>0.05).(2) The gray matter volumes of bilateral dorsolateral superior frontal gyrus(right: (0.57±0.11)mm 3, (0.65±0.08)mm 3, t=-3.409, P=0.001; left: (0.53±0.10)mm 3, (0.60±0.07)mm 3, t=-3.082, P=0.003), bilateral precentral gyrus(right: (0.32±0.06)mm 3, (0.35±0.04)mm 3, t=-2.044, P=0.045; left: (0.39±0.06)mm 3, (0.42±0.04)mm 3, t=-2.505, P=0.015), right medial and paracingulate gyrus((0.66±0.08)mm 3, (0.70±0.07)mm 3, t=-2.491, P=0.015) and left superior temporal gyrus((0.57±0.09)mm 3, (0.61±0.06)mm 3, t=- 2.344, P=0.022) in the NPSLE group were smaller than those of non-NPSLE group.(3)Correlation analysis showed that the VMHC value of dorsolateral superior frontal gyrus was positively correlated with IgA level in NPSLE patients ( r=0.353, P=0.047). Conclusion:Patients with NPSLE generally have decreased mirror homotopy functional connectivity in the cerebral hemispheres, accompanied by a decrease in gray matter volume in some brain regions, which can provide a certain neuroimaging basis for the pathogenesis of brain injury.

The incidence of depression is increasing year by year,seriously affecting people's work and life.With the continuous in-depth study of its pathogenesis,it is found that depression is closely related to intestinal flora.The imbalance of intestinal flora can cause central nervous system diseases through the microbial-brain-gut axis,which involves neurotransmitters,neuroendocrine,neurotrophic factors,inflammatory response and other mechanisms.This paper introduced intestinal flora and relevant regulatory factors related to various mechanisms of depression,listed experimental examples of intestinal flora imbalance leading to depression,and then summarized relevant studies on the anti-depression mechanism of traditional Chinese medicine through regulation of intestinal flora according to the mechanism of action,among which the regulation of microbial metabolism,inflammatory factors and neurotransmitters was mainly studied.The conclusion is expected to provide some reference for the study of anti-depression effect of Chinese medicine.

The incidence of depression is increasing year by year,seriously affecting people's work and life.With the continuous in-depth study of its pathogenesis,it is found that depression is closely related to intestinal flora.The imbalance of intestinal flora can cause central nervous system diseases through the microbial-brain-gut axis,which involves neurotransmitters,neuroendocrine,neurotrophic factors,inflammatory response and other mechanisms.This paper introduced intestinal flora and relevant regulatory factors related to various mechanisms of depression,listed experimental examples of intestinal flora imbalance leading to depression,and then summarized relevant studies on the anti-depression mechanism of traditional Chinese medicine through regulation of intestinal flora according to the mechanism of action,among which the regulation of microbial metabolism,inflammatory factors and neurotransmitters was mainly studied.The conclusion is expected to provide some reference for the study of anti-depression effect of Chinese medicine.

Objective:To explore the effects of probiotics on non-motor symptoms in patients with Parkinson disease through Meta-analysis, so as to provide objective evidence for the clinical practice of probiotics on non-motor symptoms in patients with Parkinson disease.Methods:Randomized controlled trials on probiotics for non-motor symptoms of Parkinson disease were searched in Cochrane Library, PubMed, Embase, Web of Science, China National Knowledge Infrastructure, VIP, Wanfang Data and SinoMed. The search time limit was from the establishment of the database to September 1, 2022. Two researchers independently conducted article screening, data extraction, and quality evaluation, and used RevMan 5.4.1 for Meta-analysis.Results:A total of 543 patients were included in 8 articles. The results of Meta-analysis showed that the clinical efficacy of probiotics on constipation in patients with Parkinson disease [ OR=7.25, 95% CI (2.00, 26.23) , P=0.003], constipation symptoms [ SMD=1.21, 95% CI (0.38, 2.04) , P=0.004], constipation-associated quality of life [ SMD=0.93, 95% CI (0.60, 1.27) , P<0.001], average number of weekly spontaneous defecation [ SMD=0.80, 95% CI (0.42, 1.17) , P<0.001], anxiety [ SMD=0.54, 95% CI (0.28, 0.80) , P<0.001], depression [ SMD=0.73, 95% CI (0.48, 0.97) , P<0.001] and sleep quality [ SMD=0.53, 95% CI (0.16, 0.90) , P=0.005] were better than those in the control group, with statistically significant differences. Conclusions:Probiotics can effectively improve constipation, anxiety, depression, and sleep disorders in non-motor symptoms of Parkinson disease patients.

Purpose: Platelet-related indices, including mean platelet volume (MPV) and plateletocrit (PCT), have been reported as new prognostic factors of overall survival (OS) in many cancers, but not yet in biliary tract cancer (BTC). We intended to assess these indices in predicting OS in BTC patients with the aim to build a new prognostic model for patients with BTC after surgical resection. Materials and Methods: Survival analysis and time receiver operating characteristic analysis were applied to screen the platelet indices. Univariate and multivariate Cox analyses were used to identify independent prognostic factors and develop a new prognostic model. Harrell’s C-statistics, calibration curves, and decisive curve analysis were used to assess the model. Results: MPV and platelet distribution width (PDW)/PCT showed the best prognostic accuracy among the platelet indices. In multivariable analysis, factors predictive of poor OS were presence of nodal involvement, Non-radical surgery, poor tumor differentiation, carbohydrate antigen 19-9 > 100 U/mL, MPV > 8.1 fl, and PDW/PCT > 190. The new model was found to be superior to the TNM staging system and our new staging system showed higher discriminative power. Conclusion MPV and PDW/PCT have high prognostic value in BTC patients, and the novel staging system based on these two indices showed good discrimination and accuracy compared with the American Joint Committee on Cancer 7th TNM staging system.

Purpose: Platelet-related indices, including mean platelet volume (MPV) and plateletocrit (PCT), have been reported as new prognostic factors of overall survival (OS) in many cancers, but not yet in biliary tract cancer (BTC). We intended to assess these indices in predicting OS in BTC patients with the aim to build a new prognostic model for patients with BTC after surgical resection. Materials and Methods: Survival analysis and time receiver operating characteristic analysis were applied to screen the platelet indices. Univariate and multivariate Cox analyses were used to identify independent prognostic factors and develop a new prognostic model. Harrell’s C-statistics, calibration curves, and decisive curve analysis were used to assess the model. Results: MPV and platelet distribution width (PDW)/PCT showed the best prognostic accuracy among the platelet indices. In multivariable analysis, factors predictive of poor OS were presence of nodal involvement, Non-radical surgery, poor tumor differentiation, carbohydrate antigen 19-9 > 100 U/mL, MPV > 8.1 fl, and PDW/PCT > 190. The new model was found to be superior to the TNM staging system and our new staging system showed higher discriminative power. Conclusion MPV and PDW/PCT have high prognostic value in BTC patients, and the novel staging system based on these two indices showed good discrimination and accuracy compared with the American Joint Committee on Cancer 7th TNM staging system.

Purpose: The systemic inflammation response index (SIRI) has been reported to have prognostic ability in various solid tumors but has not been studied in gallbladder cancer (GBC). We aimed to determine its prognostic value in GBC. Materials and Methods: From 2003 to 2017, patients with confirmed GBC were recruited. To determine the SIRI’s optimal cutoff value, a time-dependent receiver operating characteristic curve was applied. Univariate and multivariate Cox analyses were performed for the recognition of significant factors. Then the cohort was randomly divided into the training and the validation set. A nomogram was constructed using the SIRI and other selected indicators in the training set, and compared with the TNM staging system. C-index, calibration plots, and decision curve analysis were performed to assess the nomogram’s clinical utility. Results: One hundred twenty-four patients were included. The SIRI’s optimal cutoff value divided patients into high (≥ 0.89) and low SIRI (< 0.89) groups. Kaplan-Meier curves according to SIRI levels were significantly different (p < 0.001). The high SIRI group tended to stay longer in hospital and lost more blood during surgery. SIRI, body mass index, weight loss, carbohydrate antigen 19-9, radical surgery, and TNM stage were combined to generate a nomogram (C-index, 0.821 in the training cohort, 0.828 in the validation cohort) that was significantly superior to the TNM staging system both in the training (C-index, 0.655) and validation cohort (C-index, 0.649). Conclusion The SIRI is an independent predictor of prognosis in GBC. A nomogram based on the SIRI may help physicians to precisely stratify patients and implement individualized treatment.

Objective To explore the diagnostic value of MR elastography and diffusion?weighted imaging in patients with liver fibrosis in the context of chronic hepatitis B. Methods Twenty?four patients with chronic hepatitis B, whose course of liver disease was more than 6 months and hepatitis B surface antigen was positive, were prospectively enrolled in the First Affiliated Hospital of Soochow University from July to December 2017. All of the patients underwent abdominal transient elastography (TE), routine MRI, magnetic resonance elastography (MRE) and DWI examination, TE and MRI were performed within one week. TE liver stiffness was measured, the MRE liver stiffness and ADC value were measured on MR imagings. All patients were divided into three groups: mild and non fibrosis (F0 to 1), significant fibrosis(F2 to 3) and cirrhosis (F4), according to the recommended standard of FibroTouch. Correlation between TE liver stiffness, MRE liver stiffness and ADC values were identified by using Spearman correlation test. The difference of the MRE liver stiffness and ADC value among the three groups was tested using independent sample t test. The overall predictive ability of MRE and DWI in assessment of liver fibrosis and cirrhosis was analyzed by constructing ROC curve. Results TE and MRI were successfully performed in all subjects, and the image quality was good. The MRE liver stiffness in mild and non fibrosis, significant fibrosis and cirrhosis was (2.32±0.31),(3.43±1.05),(4.77±0.68) kPa with statistically significant difference(F=61.690, P<0.01). The ADC values in three groups were (1.31 ± 0.14)×10-3, (1.23 ± 0.15)×10-3,(1.22±0.12)×10-3mm2/s without significant difference(F=1.074,P=0.360). The TE liver stiffness in three groups was (5.61±1.05),(9.56±0.57),(17.25±3.55)kPa, respectively, there was significant correlation between the MRE liver stiffness and the TE liver stiffness(t=0.858, P<0.01), but no significant correlation between the TE liver stiffness and the ADC value was found (r=-0.326,P=0.120). The area under ROC of MRE liver stiffness in diagnosing liver fibrosis grade (≥F2 and F4) was 0.96 and 1.00 respectively, while the AUC of ADC value was less than 0.70, which were 0.67 and 0.62 respectively. Conclusion MRE is a non?invasive promising tool for assessing liver fibrosis with chronic hepatitis B, while DWI has limited role.