Objective To investigate the expression characteristics of RAB1A in the breast tumor microenvironment (TME) and its mechanism of promoting tumor metastasis, with the aim of identifying potential targets for TME-targeted antimetastatic therapy. Methods Proteomic sequencing was performed on tumor and adjacent tissues from 16 patients with triple-negative breast cancer (TNBC) or HER2-overexpressing breast cancer. Single-cell RNA sequencing was conducted on biopsy samples from four patients with TNBC or HER2-overexpressing breast cancer. TME cell heterogeneity and RAB1A expression patterns were analyzed at the proteomic and single-cell transcriptomic levels. ELISA and wound healing assays were utilized to verify the mechanism by which RAB1A regulates the function of cancer-associated fibroblasts (CAFs), thereby promoting the metastasis of TNBC cells. Results RAB1A was specifically highly expressed in CAFs. Functional module analysis indicated an association with the prometastatic secretion pathway and matrix remodeling modules. Human mammary fibroblasts (HMFs), CAFs, and RAB1A-overexpressing CAFs (CAF-OE-RAB1A) were cocultured with MDA-MB-231 cells for 24 h. The wound healing assay revealed that after 24 h of coculture with MDA-MB-231 cells, the CAF coculture group exhibited a significantly higher migration rate (38.86%) than the negative control (25.07%, P<0.01) and HMF coculture groups (30.56%, P<0.05). Notably, the migration rate in the CAF-OE-RAB1A coculture group further enhanced to 47.21% relative to that in the CAF coculture group (P<0.05). Additionally, TGF-β1 secretion in the CAF-OE-RAB1A coculture group (1030.56 pg/ml) was markedly elevated relative to that in the CAF (417.62 pg/ml, P<0.001) and HMF coculture groups (29.52 pg/ml, P<0.0001). Conclusion RAB1A is specifically highly expressed in CAFs within the breast cancer TME. It may be involved in the metastatic process of breast cancer. Furthermore, RAB1A can promote TNBC cell migration by regulating the secretory function of CAFs.

Background/Aims: Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population. Methods: This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019). Results: Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg. Conclusions In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.

Background/Aims: Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population. Methods: This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019). Results: Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg. Conclusions In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.

Background/Aims: Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population. Methods: This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019). Results: Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg. Conclusions In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.

Purpose: Administering early parenteral amino acids to very low birth weight (VLBW) premature infants (birth body weight [BBW]<1,500 g) is challenging due to factors such as holidays, cost, and access to sterile compounding facilities. Using advance-prepared parenteral nutrition (PN) may address this issue and should be evaluated for its safety and potential benefits. Methods: We extracted data from medical records collected between July 2015 and August 2019. VLBW infants received PN for at least seven days and were split into two groups:the traditional group (n=30), which initially received a glucose solution and then PN on workdays, and the pre-preparation group (n=16), which received advance-prepared PN immediately upon admission to the neonatal intensive care unit. Results: The median BBWs of the traditional and pre-preparation groups were 1,180.0 vs. 1,210.0 g. In the initial two days, the pre-preparation group had a significantly higher amino acid intake (2.23 and 2.24 g/kg/d) than the traditional group (0 and 1.78 g/kg/d). The pre-preparation group exhibited greater head circumference growth ratio relative to birth (7th day: 1.21% vs. −3.57%, p=0.014; 21st day: 7.71% vs. 3.31%, p=0.017). No significant differences in metabolic tolerance were observed. Conclusion Advanced preparation of PN can be safely implemented in VLBW preterm infants, offering advantages such as early, higher amino acid intake and improved head circumference growth within the first 21 days post-birth. This strategy may serve as a viable alternative in settings where immediate provision of sterile compounding facilities is challenging.

Purpose: Some patients with respiratory failure fail initial weaning attempts and need prolonged mechanical ventilation (MV). Prolonged MV is associated with many complications and consumption of heathcare resources. Objective weaning indices help staffs to identify high-potential patients for weaning from the MV. Traditional weaning indices are not reliable in clinical practice. Transitional percentage of minute volume (TMV%) is a new index of the work of breathing. This study aimed to investigate the utility of TMV% in the prediction of weaning potential. Methods: This study was prospectively performed including all patients with prolonged MV. Researchers recorded their demographics, TMV%, respiratory parameters, Acute Physiology and Chronic Health Evaluation II score, and laboratory data upon arrival at the respiratory care center. The factors associated with successful weaning were analyzed. Results: Out of the 120 patients included, 84 (70.0%) were successfully weaned from MV. Traditional weaning indices such as rapid shallow breathing index could not predict the weaning outcome. TMV% was a valuable parameter as patients with a lower TMV%, higher tidal volume, higher hemoglobin, lower blood urea nitrogen, and lower Acute Physiology and Chronic Health Evaluation II scores had a higher rate of successful weaning. TMV%, tidal volume, and HCO3- levels were independent predictors of successful weaning, and the area under the curve was .79 in the logistic regression model. Conclusion TMV% is a novel and effective predictor of successful weaning. Patients with lower TMV% had a higher MV weaning outcome. Once patients with a high potential for successful weaning are identified, they should be aggressively weaned from MV as soon as possible.

Purpose: Some patients with respiratory failure fail initial weaning attempts and need prolonged mechanical ventilation (MV). Prolonged MV is associated with many complications and consumption of heathcare resources. Objective weaning indices help staffs to identify high-potential patients for weaning from the MV. Traditional weaning indices are not reliable in clinical practice. Transitional percentage of minute volume (TMV%) is a new index of the work of breathing. This study aimed to investigate the utility of TMV% in the prediction of weaning potential. Methods: This study was prospectively performed including all patients with prolonged MV. Researchers recorded their demographics, TMV%, respiratory parameters, Acute Physiology and Chronic Health Evaluation II score, and laboratory data upon arrival at the respiratory care center. The factors associated with successful weaning were analyzed. Results: Out of the 120 patients included, 84 (70.0%) were successfully weaned from MV. Traditional weaning indices such as rapid shallow breathing index could not predict the weaning outcome. TMV% was a valuable parameter as patients with a lower TMV%, higher tidal volume, higher hemoglobin, lower blood urea nitrogen, and lower Acute Physiology and Chronic Health Evaluation II scores had a higher rate of successful weaning. TMV%, tidal volume, and HCO3- levels were independent predictors of successful weaning, and the area under the curve was .79 in the logistic regression model. Conclusion TMV% is a novel and effective predictor of successful weaning. Patients with lower TMV% had a higher MV weaning outcome. Once patients with a high potential for successful weaning are identified, they should be aggressively weaned from MV as soon as possible.

Resveratrol, an anti-inflammatory agent, can inhibit pro-inflammatory mediators by activating Sirt1, which is a class III histone deacetylase. However, whether resveratrol can regulate inhibitory or anti-inflammatory molecules has been less studied. FcγRIIB, a receptor for IgG, is an essential inhibitory receptor of B cells for blocking B-cell receptor-mediated activation and for directly inducing apoptosis of B cells. Because mice deficient in either Sirt1 or FcγRIIB develop lupus-like diseases, we investigated whether resveratrol can alleviate lupus through FcγRIIB. We found that resveratrol enhanced the expression of FcγRIIB in B cells, resulting in a marked depletion of plasma cells in the spleen and notably in the bone marrow, thereby decreasing serum autoantibody titers in MRL/lpr mice. The upregulation of FcγRIIB by resveratrol involved an increase of Sirt1 protein and deacetylation of p65 NF-κB (K310). Moreover, increased binding of phosphor-p65 NF-κB (S536) but decreased association of acetylated p65 NF-κB (K310) and phosphor-p65 NF-κB (S468) to the −480 promoter region of Fcgr2b gene was responsible for the resveratrol-mediated enhancement of FcγRIIB gene transcription. Consequently, B cells, especially plasma cells, were considerably reduced in MRL/lpr mice, leading to improvement of nephritis and prolonged survival. Taken together, we provide evidence that pharmacological upregulation of FcγRIIB expression in B cells via resveratrol can selectively reduce B cells, decrease serum autoantibodies and ameliorate lupus nephritis. Our findings lead us to propose FcγRIIB as a new target for therapeutic exploitation, particularly for lupus patients whose FcγRIIB expression levels in B cells are downregulated.
Animals ; Apoptosis ; Autoantibodies ; B-Lymphocytes* ; Bone Marrow ; Histone Deacetylases ; Humans ; Immunoglobulin G ; Lupus Nephritis ; Mice ; Nephritis ; Plasma Cells ; Promoter Regions, Genetic ; Spleen ; Up-Regulation*

BACKGROUND: Spinocerebel ar ataxia is a common neurodegenerative disease characterized by slowly progressive movement incoordination of the limbs. It responds badly to common medication. OBJECTIVE: To observe the clinical effect of autologous bone marrow mesenchymal stem cells and al ogeneic umbilical cord mesenchymal stem cells tranfusion in the treatment of spinocerebel ar ataxia. METHODS: A total of 27 spinocerebel ar ataxia patients treated with mesenchymal stem cells treatment were included for comprehensive statistical analysis. Among these patients, six patients received autologous bone marrow mesenchymal stem cells lumbar puncture treatment and 21 patients received al ogeneic umbilical cord mesenchymal stem cells lumbar puncture treatment combined with intravenous infusion. The neurologic function of the patients in the two groups was evaluated with International Cooperative Ataxia Rating Scale before and after treatment. RESULTS AND CONCLUSION: There was no obvious adverse effect in the 27 spinocerebel ar ataxia patients during, before or after mesenchymal stem cells treatment. The effect of autologous bone marrow mesenchymal stem cells in six patents was not significant; for the other 21 patients treated with al ogeneic umbilical cord mesenchymal stem cells transfusion, the subjective symptoms of the patients were improved, and the International Cooperative Ataxia Rating Scale scores were decreased significantly at 3 months after treatment when compared with those before treatment (P < 0.05). The results suggest that umbilical cord mesenchymal stem cells treatment is safe and able to ameliorate the clinical symptoms and improve life quality of spinocerebel ar ataxia patients to some extent.

The purpose of the technical note is to introduce the complex coil assisted coil embolization method in the treatment of intracranial small aneurysm, in order to enhance the safety of the procedure. The first microcatheter was navigated into the aneurysm sac and the ultrasoft coil was used as the embolization coil. If the embolizations coil could not stay within the aneurysm sac smoothly, such as coil herniation into parent artery during the delivery process. The second microcatheter would be navigated to the aneurysm level in the parent artery. Another complex coil was delivered within the parent artery via the second microcatheter to provide the neck bridge effect in order to enhance the stability of embolization coil. Besides, the protection coil will not disturb the parent artery flow. While the embolization coil was put into the aneurysm sac smoothly under the help of complex protective coil, the protective coil was then withdrawn gently. We use the most magnified view, dual-plane approach simultaneously to observe the stability of embolization coil. The embolization coil would be detached without any evidence of coil motion or vibration. The new method could provide the physiological protective method, without leaving any protective device such as stent within the parent artery.
Aneurysm ; Arteries ; Humans ; Intracranial Aneurysm ; Neck ; Parents ; Protective Devices ; Stents ; Vibration