Objective:To evaluate the efficacy and safety of upadacitinib in the real-world treatment of difficult-to-treat Crohn's disease (DTT-CD) .Methods:This multicenter, retrospective cohort study included patients diagnosed with DTT-CD according to the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) criteria, and treated at eight Chinese inflammatory bowel disease centers between January 2023 and March 2025. Clinical outcomes were assessed after 12 weeks of induction therapy with upadacitinib (45 mg qd), including clinical remission rate, clinical response rate, and incidence of adverse events.Results:Among 151 enrolled DTT-CD patients, the clinical remission rate was 47.0%, and the clinical response rate was 90.7% after 12 weeks of treatment. Adverse events occurred in 42 cases (27.8%) .Conclusion:Upadacitinib demonstrated favorable efficacy in inducing clinical remission in DTT-CD patients, with a good safety profile at the induction dose (45 mg qd) .

[Objective]To investigate the regulatory effect and potential mechanisms of isocitrate dehydrogenase 3A(IDH3A)on cardiomyocyte hypertrophy.[Methods]The expression of IDH3A in the myocardium of healthy volunteers(n=10)and patients with heart failure(HF)(n=10),and in the myocardium of mice subjected to transverse aortic constriction(TAC)surgery and sham operation,as well as in phenylephrine(PE)-induced neonatal rat ventricular cardiomyocytes(NRVCs),was assessed by real-time quantitative polymerase chain reaction(RT-qPCR)and Western blot assay.The effect of adenovirus-mediated overexpression of IDH3A on the expression of hypertrophy-related genes in PE-induced NRVCs was also evaluated.The effect of IDH3A on NRVCs area was examined by phalloidin staining assay.A mutant of IDH3A with abolished enzymatic activity,IDH3A_D208A,was generated through site-directed mutagenesis.The impact of this IDH3A mutant on the hypertrophic phenotype,ATP and ROS levels in NRVCs was evaluated to investigate whether the regulatory role of IDH3A in cardiomyocyte hypertrophy was dependent on its enzymatic activity.The effect of exogenous α-ketoglutaric acid(AKG)on cardiomyocyte hypertrophy was also detected by Western blot and phalloidin staining assay,respectively.[Results]IDH3A was significantly decreased in the myocardium of HF patients,in the myocardium of TAC-operated mice,and in PE-induced NRVCs(P=0.005 2,P=0.026 6,P=0.041 3 and P=0.006 6,respectively).Overexpression of IDH3A markedly suppressed the expression of hypertrophy-related genes and the increase of cell size of PE-induced NRVCs(P<0.000 1,P=0.000 1 and P=0.000 2,respectively).The ATP and ROS analysis indicated that IDH3A inhibited the increases of ATP and ROS levels in PE-induced NRVCs(P=0.001 2 and P<0.000 1,respectively),whereas the enzymatically inactive IDH3A mutant lacked this effect.Exogenous AKG provision could,but overexpression of IDH3A mutant failed to suppress PE-induced NRVCs hypertrophy.[Conclusion]IDH3A inhibits cardiomyocyte hypertrophy via elevating AKG level,providing scientific evidence for study on IDH3A-based treatment of cardiac hypertrophy.

Objective:To evaluate the efficacy and safety of upadacitinib in the real-world treatment of difficult-to-treat Crohn's disease (DTT-CD) .Methods:This multicenter, retrospective cohort study included patients diagnosed with DTT-CD according to the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) criteria, and treated at eight Chinese inflammatory bowel disease centers between January 2023 and March 2025. Clinical outcomes were assessed after 12 weeks of induction therapy with upadacitinib (45 mg qd), including clinical remission rate, clinical response rate, and incidence of adverse events.Results:Among 151 enrolled DTT-CD patients, the clinical remission rate was 47.0%, and the clinical response rate was 90.7% after 12 weeks of treatment. Adverse events occurred in 42 cases (27.8%) .Conclusion:Upadacitinib demonstrated favorable efficacy in inducing clinical remission in DTT-CD patients, with a good safety profile at the induction dose (45 mg qd) .

Objective:To explore the real experiences of patients during the preoperative decision-making process for metabolic-bariatric surgery, providing a reference for developing targeted decision-support interventions.Methods:This descriptive phenomenological study used purposive sampling to select 21 patients who underwent metabolic-bariatric surgery at Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine, from September 2022 to February 2023. Interviews were conducted, and the data were analyzed using Colaizzi's seven-step method.Results:Four themes and 14 sub-themes were extracted: decision-making motivation (health threats, pursuit of higher quality of life, diminished self-esteem, family responsibility drive) ; pre-decision assessment (failure of other weight-loss methods, surgery as a last resort) ; decision-making dilemmas (low quality of accessible information, low social acceptance of surgery, lack of medical insurance coverage, concerns about surgical outcomes) ; and decision-making support (professional medical support, family support, peer support, self-support) .Conclusions:Patients considering metabolic-bariatric surgery have diverse decision-making motivations and face significant dilemmas. It is recommended that relevant authorities, healthcare providers, and family members work together to create a comprehensive decision-supportive environment from the patients' perspective.

ObjectiveTo investigate the regulatory effect of circular RNA circ_0120051 on the fibrotic phenotype of cardiac fibroblasts and the potential mechanism involved. MethodsThe expression of circ_0120051 and its host gene of solute carrier family 8 member A1（SLC8A1） mRNA in the myocardium of healthy organ donors （n=24） and heart failure （HF） patients （n=21） were assessed by real-time quantitative polymerase chain reaction （RT-qPCR） assay. RNA stability of circ_0120051 was identified by RNase R exonuclease digestion assay. The cytoplasmic and nuclear distribution of circ_0120051 in human cardiomyocyte AC16 was detected by RT-qPCR assay. The expression of fibrosis-related genes in mouse cardiac fibroblasts （mCFs） with adenovirus-mediated overexpression of circ_0120051 was detected by RT-qPCR and Western blot assay， respectively. The effect of overexpression of circ_0120051 on the migration activity of mCFs was evaluated by wound-healing assay. RNA co-immunoprecipitation （RIP） was conducted to detect the interaction between circ_0120051 and miR-144-3p. The binding site of miR-144-3p in the 3'-UTR of isocitrate dehydrogenase 2 （Idh2） mRNA was identified by the dual luciferase reporter gene assay. ResultsCirc_0120051 was significantly up-regulated in the myocardium of HF patients， while the mRNA expression of its host gene SLC8A1 was not changed. Circ_0120051 was mainly located in the cytoplasm of human AC16 cells. Results of RNase R exonuclease digestion revealed that circ_0120051 possesses the characteristic stability of circular RNA compared to the linear SLC8A1 mRNA. Overexpression of circ_0120051 could inhibit the expression of fibrosis-related gene in mCFs and mCFs migration. RIP assay confirmed the specific interaction between circ_0120051 and miR-144-3p. Transfection of miR-144-3p mimic could efficiently promote the expression of fibrosis-related genes in mCFs and reverse the inhibitory effect of circ_0120051 on the fibrotic phenotype of mCFs. Results of the dual luciferase reporter gene assay confirmed the interaction between miR-144-3p and the 3'-UTR of Idh2. Transfection of miR-144-3p transcriptionally inhibited Idh2 expression， and overexpression of circ_0120051 enhanced IDH2 expression in mCFs. MiR-144-3p mimic and Idh2 small interfering RNA （siRNA） could consistently reverse the inhibitory effects of circ_0120051 on fibrosis-related genes expression in mCFs and mCFs migration. ConclusionsCirc_0120051 inhibits the fibrotic phenotype of cardiac fibroblasts via sponging miR-144-3p to enhance the target gene of IDH2 expression.

Objective:To explore the real experiences of patients during the preoperative decision-making process for metabolic-bariatric surgery, providing a reference for developing targeted decision-support interventions.Methods:This descriptive phenomenological study used purposive sampling to select 21 patients who underwent metabolic-bariatric surgery at Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine, from September 2022 to February 2023. Interviews were conducted, and the data were analyzed using Colaizzi's seven-step method.Results:Four themes and 14 sub-themes were extracted: decision-making motivation (health threats, pursuit of higher quality of life, diminished self-esteem, family responsibility drive) ; pre-decision assessment (failure of other weight-loss methods, surgery as a last resort) ; decision-making dilemmas (low quality of accessible information, low social acceptance of surgery, lack of medical insurance coverage, concerns about surgical outcomes) ; and decision-making support (professional medical support, family support, peer support, self-support) .Conclusions:Patients considering metabolic-bariatric surgery have diverse decision-making motivations and face significant dilemmas. It is recommended that relevant authorities, healthcare providers, and family members work together to create a comprehensive decision-supportive environment from the patients' perspective.

Objective:To investigate the clinical value of magnetic resonance imaging (MRI) plain scan and diffusion weighted imaging (DWI) in the diagnosis of brain metastases.Methods:The MRI plain imaging findings of 105 cases with brain metastases and 103 cases without brain metastases confirmed by enhanced MRI examination and clinical diagnosis were retrospectively analyzed. The comparisons of plain MRI findings including T1 weighted image (T1WI), T2WI, T2/fluid attenuated inversion recovery (T2/FLAIR), DWI and apparent diffusion coefficient (ADC) values were made between brain metastases and non-brain metastases.Results:The numbers of hypo-intensity, iso-intensity, hyper-intensity and heterogeneous signal intensity of T1WI in the brain metastatic group were 54, 23, 9 and 19, respectively, while the numbers of hypo-intensity and iso-intensity in the non-brain metastatic group were 52 and 51, respectively, with statistically significant difference ( P<0.001). The numbers of hypo-intensity, iso-intensity, hyper-intensity and heterogeneous signal intensity of T2WI in the brain metastatic group were 1, 9, 72 and 23, respectively, while the numbers of iso-intensity and hyper-intensity in the non-brain metastatic group were 11 and 92, respectively, with statistically significant difference ( P<0.001). The numbers of hypo-intensity, hyper-intensity and heterogeneous signal intensity of DWI in the brain metastatic group were 4, 31 and 65, respectively, while the number of hyper-intensity in the non-brain metastatic group was 4 and others were iso-intensity, respectively, with statistically significant difference ( P<0.001). The numbers of hypo-intensity, iso-intensity, hyper-intensity and heterogeneous signal intensity of T2WI/FLAIR in the brain metastatic group were 4, 5, 60 and 36, respectively, while all cases in the non-brain metastatic group were hyper-intensity, with statistically significant difference ( P<0.001). The number of lesion accompanied with peripheral edema in the brain metastatic group were 69 cases, significantly higher than 0 cases in the non-brain metastatic group ( P<0.001). The mean ADC value in the brain metastatic group were (0.919±0.019)×10 -3 mm 2/s, significantly lower than (1.098±0.012)×10 -3 mm 2/s of non-brain metastatic group ( P<0.05). Conclusions:For patients with a history of primary malignancy, the MRI plain scan signals of T1WI, T2WI, T2WI/FLAIR and DWI are significantly different between brain metastatic tumor and non-metastatic tumor. The mixed signal, peripheral edema and the restriction of DWI diffusion indicate brain metastases. The combined application of the above parameters can improve the diagnostic efficacy of predicting brain metastases, and contrast enhancement MRI examination should be performed for the confirmation of diagnosis.

Objective:To investigate the clinical value of magnetic resonance imaging (MRI) plain scan and diffusion weighted imaging (DWI) in the diagnosis of brain metastases.Methods:The MRI plain imaging findings of 105 cases with brain metastases and 103 cases without brain metastases confirmed by enhanced MRI examination and clinical diagnosis were retrospectively analyzed. The comparisons of plain MRI findings including T1 weighted image (T1WI), T2WI, T2/fluid attenuated inversion recovery (T2/FLAIR), DWI and apparent diffusion coefficient (ADC) values were made between brain metastases and non-brain metastases.Results:The numbers of hypo-intensity, iso-intensity, hyper-intensity and heterogeneous signal intensity of T1WI in the brain metastatic group were 54, 23, 9 and 19, respectively, while the numbers of hypo-intensity and iso-intensity in the non-brain metastatic group were 52 and 51, respectively, with statistically significant difference ( P<0.001). The numbers of hypo-intensity, iso-intensity, hyper-intensity and heterogeneous signal intensity of T2WI in the brain metastatic group were 1, 9, 72 and 23, respectively, while the numbers of iso-intensity and hyper-intensity in the non-brain metastatic group were 11 and 92, respectively, with statistically significant difference ( P<0.001). The numbers of hypo-intensity, hyper-intensity and heterogeneous signal intensity of DWI in the brain metastatic group were 4, 31 and 65, respectively, while the number of hyper-intensity in the non-brain metastatic group was 4 and others were iso-intensity, respectively, with statistically significant difference ( P<0.001). The numbers of hypo-intensity, iso-intensity, hyper-intensity and heterogeneous signal intensity of T2WI/FLAIR in the brain metastatic group were 4, 5, 60 and 36, respectively, while all cases in the non-brain metastatic group were hyper-intensity, with statistically significant difference ( P<0.001). The number of lesion accompanied with peripheral edema in the brain metastatic group were 69 cases, significantly higher than 0 cases in the non-brain metastatic group ( P<0.001). The mean ADC value in the brain metastatic group were (0.919±0.019)×10 -3 mm 2/s, significantly lower than (1.098±0.012)×10 -3 mm 2/s of non-brain metastatic group ( P<0.05). Conclusions:For patients with a history of primary malignancy, the MRI plain scan signals of T1WI, T2WI, T2WI/FLAIR and DWI are significantly different between brain metastatic tumor and non-metastatic tumor. The mixed signal, peripheral edema and the restriction of DWI diffusion indicate brain metastases. The combined application of the above parameters can improve the diagnostic efficacy of predicting brain metastases, and contrast enhancement MRI examination should be performed for the confirmation of diagnosis.

PURPOSE: Although the effect of lysosome-associated protein transmembrane 4 beta (LAPTM4B) on the proliferation, migration, and invasion of breast cancer (BC) cells has already been studied, its specific role in BC progression is still elusive. Here, we evaluated the effect of different levels of LAPTM4B expression on the proliferation, invasion, adhesion, and tumor formation abilities of BC cells in vitro, as well as on breast tumor progression in vivo. METHODS: We investigated the influence of LAPTM4B expression on MCF-7 cell proliferation, invasion, adhesion, and tube formation abilities in vitro through its overexpression or knockdown and on breast tumor progression in vivo. RESULTS: Cell growth curves and colony formation assays showed that LAPTM4B promoted the proliferation of breast tumor cells. Cell cycle analysis results revealed that LAPTM4B promoted the entry of cells from the G1 into the S phase. Transwell invasion and cell extracellular matrix adhesion assays showed that LAPTM4B overexpression increased the invasion and adhesion capabilities of MCF-7 cells. More branches were observed in MCF-7 cells overexpressing LAPTM4B under an electron microscope. In comparison with LAPTM4B overexpression, LAPTM4B knockdown decreased the expression of vascular endothelial growth factor-A and significantly inhibited the vasculogenic tube formation ability of tumors. These results were also verified with western blot analysis. CONCLUSION: LAPTM4B promoted the proliferation of MCF-7 cells through the downregulation of p21 (WAF1/CIP1) and caspase-3, and induced cell invasion, adhesion, and angiogenesis through the upregulation of hypoxia-inducible factor 1 alpha, matrix metalloproteinase 2 (MMP2), and MMP9 expression. This specific role deems LAPTM4B as a potential therapeutic target for BC treatment.
Blotting, Western ; Breast Neoplasms ; Breast ; Caspase 3 ; Cell Cycle ; Disease Progression ; Down-Regulation ; Extracellular Matrix ; Hypoxia-Inducible Factor 1 ; In Vitro Techniques ; Matrix Metalloproteinase 2 ; MCF-7 Cells ; S Phase ; Up-Regulation ; Vascular Endothelial Growth Factor A

Objective: To study laparoscopic ultrasound assisted hepatectomy in treatment of intrahepatic and extrahepatic bile duct stones. Methods: The data of 52 patients with hepatolithiasis who underwent laparoscopic hepatectomy from May 2014 to January 2019 at the Fuyang District First People's Hospital in Hangzhou were analyzed retrospectively. There were 28 men and 24 women. The median age was 56 years. Operative laparoscopic ultrasonography was used to detect the location, size, distribution of stones and their relations to blood vessels. A total of 43 patients underwent anatomic hepatectomy, while 38 patients underwent choledochoscopic stone extraction. A " T" tube was used according to intraoperative conditions. Results: Laparoscopic surgery was successfully carried out in 50 patients, while conversion to open surgery was required in 2 patients because of adhesions and bleeding. Laparoscopic ultrasonography revealed intrahepatic calcifications in 5 patients and choledochoscopy in 2 patients. Postoperative complications included 5 patients who devleoped abdominal abscesses. The operation time was (289.0±132.0) minutes. The intraoperative blood loss was (451.0±256.0) ml. The hospitalization after operation was (12.0±3.0) days. In 52 patients, 4 patients had residual stones and the residual rate was 7.7%. All of them were completely removed by T-tube sinus 8 weeks after operation. Conclusions Laparoscopic ultrasound helped to detect relevant bile ducts containing stones, reduced chance of bleeding in surgery, helped to clarify location and distribution of stones, improved accuracy of diagnosis, and reduced unnecessary hepatectomy by clearly defining intrahepatic bile duct stones intraoperatively. The residual intrahepatic and intrahepatic bile duct stones rates were reduced, and the safety and accuracy of the operations were improved.