ObjectiveTo investigate the effect of solute carrier family 7 member 5 (SLC7A5) inhibitor JPH203 on renal fibrosis induced by unilateral ureteral obstruction in mice. MethodsSixteen SPF male C57BL/6 mice were randomly divided into the control group and the experimental group, with 8 mice in each group. The mouse model of renal fibrosis was established by unilateral ureteral obstruction. From the third day after surgery, the mice in the control group were intraperitoneally injected with phosphate-buffered saline (PBS) for 11 consecutive days, and the injection dose was 200 μL/d. Mice in the experimental group received intraperitoneal injection of JPH203 (50 mg/kg) every day for 11 days. On day 14, the mice were euthanized, then the kidney tissues were obtained. Hematoxylin and eosin (HE) staining was used to assess renal tissue damage, Masson staining was used to evaluate collagen fiber deposition in the extracellular matrix, and immunohistochemistry was used to detect the levels of fibroblast activation markers α-smooth muscle actin (α-SMA) and collagen type Ⅰ (COL-Ⅰ) in kidney tissues. Western blotting was further performed to measure the expression levels of SLC7A5 and transforming growth factor-β1 (TGF-β1), as well as the phosphorylation levels of mammalian target of rapamycin complex 1 (mTORC1) signaling pathway-related molecules. Real-time quantitative PCR was used to verify changes in the mRNA levels of SLC7A5, α-SMA, and COL-Ⅰ in kidney tissues. ResultsCompared with the control group, the experimental group showed reduced destruction of renal tissue structure and a significantly lower pathological injury score (P<0.05). Additionally, collagen deposition in the extracellular matrix was decreased, and the percentage of collagen fiber area was significantly reduced (P<0.001) in the experimental group. The levels of fibroblast activation markers α-SMA and COL-Ⅰ were significantly lower in the experimental group (both P<0.001). The expression levels of SLC7A5 and TGF-β1 were also significantly decreased (P<0.001), and the phosphorylation levels of mTORC1 signaling pathway-related proteins 4E-BP1 and mTORC1 were significantly reduced (P<0.001). Real-time quantitative PCR confirmed that the mRNA levels of SLC7A5, α- SMA, and COL-Ⅰ in kidney tissues were significantly lower in the experimental group (P<0.001). ConclusionJPH203 may inhibit the progression of renal fibrosis in mice by suppressing SLC7A5 expression, regulating the mTORC1 signaling pathway, and altering fibroblast activation status.

Objective:To investigate the mechanism of ursolic acid (UA) in inhibiting the growth and metastasis of breast cancer MDA-MB-231 (“231”) cells by downregulating ANXA6.Methods:This study conducted relevant in vitro cytology and molecular biology experiments in the Department of Clinical Laboratory and Central Laboratory of Putuo Hospital, Shanghai University of Traditional Chinese Medicine from February 2023 to August 2024. Human breast cancer 231 cells were cultured in vitro, and the effects of different concentrations of UA on the proliferation and invasion and metastasis of 231 cells were detected by CCK-8 and Transwell assays. Western Blot was used to detect the effect of UA on the expression of ANXA6 and invasion and metastasis-related proteins MMP9, β-catenin and N-cadherin in 231 cells. The 231 cells that interfered with and overexpressed ANXA6 were constructed by lentivirus transfection to generate stable ANXA6 interfering and overexpressing 231 cells, which were divided into 231/KD-ANXA6 group, 231/KD-NC group, 231/OE-ANXA6 group, and 231/OE-NC group. CCK-8 assay and Transwell assay were used to detect the proliferation activity, invasion and metastasis ability of 231 cells after interference and overexpression of ANXA6 and the effect of UA on the proliferation ability of 231 cells after interference and overexpression of ANXA6. Western Blot and RT-PCR assays were used to detect the expression of invasion and migration biomarkers such as MMP9, β-catenin, and N-cadherin in 231 cells after interference and overexpression of ANXA6. Immunohistochemistry was used to detect the expression level of ANXA6 in breast cancer tissues, and the relationship between ANXA6 expression and clinicopathological features and prognosis of breast cancer was analyzed.Results:The CCK-8 assay results showed that compared with the control group (0 μmol/L UA, 100.00%±7.37%), the proliferative activity of 231 cells at UA concentrations of 2.5, 5, 10, 20 and 40 μmol/L (90.23%±1.76%, t=2.24, P<0.05; 85.19%±4.23%, t=3.02, P<0.05; 65.45%±0.35%, t=8.11, P<0.01; 37.79%±0.98%, t=14.50, P<0.001; 18.18%±0.15%, t=19.23, P<0.001) were significantly decreased. Furthermore, UA (10, 15, 20 μmol/L) inhibited the invasion and metastasis ability of 231 cells; Western Blot assay showed that compared with the control group (0 μmol/L UA), the protein expressions of MMP9 (1.07±0.03 vs 0.99±0.11, t=1.27, P>0.05), β-catenin (1.21±0.01 vs 0.99±0.07, t=5.47, P<0.05), N-cadherin (1.05±0.09 vs 0.90±0.03, t=2.65, P>0.05) at UA of 10 μmol/L; MMP9 (1.07±0.03 vs 0.79±0.09, t=5.26, P<0.001), β-catenin (1.21±0.01 vs 0.89±0.05, t=10.55, P<0.001), and N-cadherin (1.04±0.09 vs 0.68±0.10, t=4.59, P<0.05) at UA of 15 μmol/L; MMP9 (1.07±0.03 vs 0.52±0.07, t=12.50, P<0.001), β-catenin (1.21±0.01 vs 0.83±0.02, t=24.01, P<0.000 1) and N-cadherin (1.04±0.09 vs 0.49±0.11, t=6.70, P<0.01) at UA of 20 μmol/L. Interfering with ANXA6 inhibits the proliferation, invasion and migration of 231 cells, and overexpression of ANXA6 promotes the proliferation, invasion and migration of 231 cells. Western Blot assay showed that compared with the control group (KD-NC group), the protein expressions of MMP9 (1.07±0.01 vs 0.62±0.16, t=4.86, P<0.01), β-catenin (1.02±0.14 vs 0.64±0.15, t=3.20, P<0.05), N-cadherin (0.98±0.14 vs 0.67±0.12, t=2.85, P<0.05) were decreased expression; Compared with the control group (OE-NC group), the protein expressions of MMP9 (0.54±0.22 vs 1.06±0.08, t=3.90, P<0.05), β-catenin (0.92±0.07 vs 1.06±0.04, t=3.06, P<0.05) and N-cadherin (0.90±0.07 vs 1.06±0.01, t=3.75, P<0.05) were significantly increased. Interference with ANXA6 promoted the inhibitory effect of UA on the proliferation ability of 231 cells ( P<0.05). Overexpression of ANXA6 weakened the inhibitory effect of UA on the proliferation of 231 cells ( P<0.05).The results of immunohistochemistry assay showed that the expression level of ANXA6 in breast cancer tissue was significantly increased, and the expression of ANXA6 was related to tumor size ( P<0.05), but not to age, T stage, N stage, pathological grade, AJCC stage, ER, PR and E-cad. Conclusion:The expression level of ANXA6 in breast cancer tissues is increased, and UA can inhibit the growth, invasion and metastasis of 231 cells by down-regulating the expression of ANXA6.

Objective:To investigate the correlation of intracranial arterial calcification (IAC) and its different subtypes with the severity of white matter hyperintensities (WMHs) in patients with cerebral small vessel disease (CSVD).Methods:Consecutive CSVD patients admitted to the Department of Neurology, the First Affiliated Hospital of Zhengzhou University from March 2018 to March 2022 were enrolled. Baseline demographic, laboratory, and imaging data were collected. Based on a developed and validated IAC grading scale using head CT, IAC was classified into intimal and medial types, and further categorized as focal or diffuse based on the extent of involvement. The severity of WMHs on magnetic resonance imaging was assessed using the Fazekas Scale, with patients divided into those with moderate-to-severe (total score>2) and non-moderate-to-severe WMHs (total score≤2). Subgroups were stratified based on baseline characteristics (patients′ sex, age, hypertension history, stroke history, diabetes, coronary heart disease, hyperlipidemia, smoking, and alcohol consumption). Multivariate Logistic regression was used to analyze the correlation between IAC′s subtypes and the severity of WMHs, with forest plots illustrating the interaction between medial IAC and subgroup variables.Results:A total of 490 patients with CSVD who met the inclusion and exclusion criteria were ultimately included, with a age of (60.88±10.99) years, including 162 females (33.1%). Moderate-to-severe WMHs were present in 245 patients (50.0%). Among the 490 CSVD patients, 395 (80.6%) had IAC, including 335 (68.4%) with intimal IAC and 207 (42.2%) with medial IAC. Diffuse IAC was observed in 126 patients (25.7%), all of whom had medial IAC. Intracranial arterial stenosis was present in 271 patients (55.3%). Multivariate Logistic regression showed that IAC ( OR=2.073, 95% CI 1.142-3.761, P=0.016) was significantly associated with moderate-to-severe WMHs and medial IAC ( OR=3.230, 95% CI 1.800-5.797, P<0.001) and advanced age ( OR=1.046, 95% CI 1.019-1.074, P=0.001) were significantly associated with moderate-to-severe WMHs. Subgroup analysis revealed medial IAC had no significant interaction with patients′ gender, age, hypertension, diabetes, coronary heart disease, hyperlipidemia, alcohol or smoking consumption except for stroke history. Conclusion:In the CSVD patients, IAC, especially medial IAC, is significantly associated with the severity of WMHs.

Objective:To explore the correlation between the lesion imaging characteristics and the parent artery plaques detected by high-resolution magnetic resonance imaging (HR-MRI) in patients with recent small subcortical infarction (RSSI) in the lenticulostriate artery territory with mild stenosis of the parent artery.Methods:Consecutive patients with RSSI in the lenticulostriate artery territory admitted to Department of Neurology, the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2022 were prospectively enrolled. Patients with stenosis of <50% in the ipsilateral middle cerebral artery (MCA) who had completed HR-MRI were included. The RSSI lesion characteristics, such as the lowest slice involved (LS), total number of slices involved (TNS) were evaluated based on serialized axial levels of diffusion weighted imaging. HR-MRI was utilized to assess the presence of dorsal superior plaques in the M1 segment of the responsible MCA. Patients were divided into plaque group and non-plaque group based on the presence or absence of plaque. Logistic regression analysis was carried out to identify the lesion characteristics associated with the presence of dorsal superior plaques in the MCA. A receiver operating characteristic (ROC) curve was employed to estimate the predictive efficacy of these parameters for MCA plaques using the area under the curve (AUC) and the optimal cut-off point.Results:A total of 112 patients were incorporated into the final analysis. The age of these patients was (57.08±11.90) years, and 78 patients (69.64%) were male. Plaques were detected on the dorsal superior wall of the MCA in 57 cases (50.89%) as the plaque group, and the other 55 cases (49.11%) were regarded as the non-plaque group. Multivariate Logistic regression revealed that LS was significantly associated with MCA plaques ( OR=0.674, 95% CI 0.485-0.937, P=0.019). The optimal cut-off point (LS≤1) was determined by ROC curve analysis (AUC=0.640, P=0.007). Conclusion:The findings suggest that in RSSI patients with mild stenosis of the parent artery, an LS≤1 is notably associated with the presence of dorsal superior plaques on MCA as detected by HR-MRI.

This review systematically describes the application of artificial intelligence in the comprehensive management of patients with valvular heart disease(VHD).In population screening,technologies such as artificial intelligence(AI)electrocardiogram(AI-ECG),AI auscultation,and new imaging modalities play important roles,help early detection of VHD.In imaging assessment and diagnosis,AI can add automatic morphological and functional evaluations,assisting in precise typing and risk prediction to accurately determine the timing of VHD intervention.For treatment,especially transcatheter aortic valve replacement(TAVR),AI can assist in image analysis and strategy formulation in a variety of ways throughout the process,improving procedure success rates and avoiding complications.Although the application of AI is limited by factors such as data quality and computational capacity,in the future,multi-center cooperation can be adopted to expand data samples and enhance computational capabilities to improve AI performance,thus further optimizing VHD management.

Background:Ideal bowel preparation is the prerequisite for the successful diagnostic and therapeutic colonoscopy.The retention of intestinal bubbles can seriously affect the clarity of the intestinal mucosa and subsequently decrease the detection rate of colonoscopy.Aims:To investigate the application value of dyclonine hydrochloride mucilage in bowel preparation for colonoscopy.Methods:This study was a randomized double-blinded placebo-controlled trial.Patients who underwent colonoscopy from October 2020 to October 2023 at Hainan West Central Hospital were enrolled and randomly allocated into the dyclonine hydrochloride mucilage group and the control group.3 L polyethylene glycol(PEG)+dyclonine hydrochloride mucilage and 3 L PEG+placebo were given for bowel preparation,respectively.The quality of bowel preparation was evaluated by Boston bowel preparation scale(BBPS)score and bubble score.Furthermore,a questionnaire was conducted.The cecal intubation time,withdrawal time,adenoma detection rate and adverse reaction were compared between the two groups.Results:A total of 482 patients who underwent colonoscopy were included.No significant differences in clinical characteristics such as gender,age,body mass index(BMI)and main reasons for colonoscopy were found between the dyclonine hydrochloride mucilage group and the control group(all P>0.05).Compared with the control group,no significant differences existed in total BBPS score and segment scores for right,transverse,and left colon in the dyclonine hydrochloride mucilage group(all P>0.05),but the total bubble score and segment scores for right,transverse,and left colon were significantly decreased(all P<0.001).The withdrawal time in the dyclonine hydrochloride mucilage group was significantly decreased compared to the control group(P<0.001),and the adenoma detection rate was significantly increased(P=0.001).However,no significant differences in cecal intubation time and incidence of adverse reaction were found between the two groups(all P>0.05).Conclusions:Administration of dyclonine hydrochloride mucilage during bowel preparation for colonoscopy can reduce the formation of intestinal bubbles,shorten the withdrawal time and increase the adenoma detection rate.

Objective:To investigate the mechanism of ursolic acid (UA) in inhibiting the growth and metastasis of breast cancer MDA-MB-231 (“231”) cells by downregulating ANXA6.Methods:This study conducted relevant in vitro cytology and molecular biology experiments in the Department of Clinical Laboratory and Central Laboratory of Putuo Hospital, Shanghai University of Traditional Chinese Medicine from February 2023 to August 2024. Human breast cancer 231 cells were cultured in vitro, and the effects of different concentrations of UA on the proliferation and invasion and metastasis of 231 cells were detected by CCK-8 and Transwell assays. Western Blot was used to detect the effect of UA on the expression of ANXA6 and invasion and metastasis-related proteins MMP9, β-catenin and N-cadherin in 231 cells. The 231 cells that interfered with and overexpressed ANXA6 were constructed by lentivirus transfection to generate stable ANXA6 interfering and overexpressing 231 cells, which were divided into 231/KD-ANXA6 group, 231/KD-NC group, 231/OE-ANXA6 group, and 231/OE-NC group. CCK-8 assay and Transwell assay were used to detect the proliferation activity, invasion and metastasis ability of 231 cells after interference and overexpression of ANXA6 and the effect of UA on the proliferation ability of 231 cells after interference and overexpression of ANXA6. Western Blot and RT-PCR assays were used to detect the expression of invasion and migration biomarkers such as MMP9, β-catenin, and N-cadherin in 231 cells after interference and overexpression of ANXA6. Immunohistochemistry was used to detect the expression level of ANXA6 in breast cancer tissues, and the relationship between ANXA6 expression and clinicopathological features and prognosis of breast cancer was analyzed.Results:The CCK-8 assay results showed that compared with the control group (0 μmol/L UA, 100.00%±7.37%), the proliferative activity of 231 cells at UA concentrations of 2.5, 5, 10, 20 and 40 μmol/L (90.23%±1.76%, t=2.24, P<0.05; 85.19%±4.23%, t=3.02, P<0.05; 65.45%±0.35%, t=8.11, P<0.01; 37.79%±0.98%, t=14.50, P<0.001; 18.18%±0.15%, t=19.23, P<0.001) were significantly decreased. Furthermore, UA (10, 15, 20 μmol/L) inhibited the invasion and metastasis ability of 231 cells; Western Blot assay showed that compared with the control group (0 μmol/L UA), the protein expressions of MMP9 (1.07±0.03 vs 0.99±0.11, t=1.27, P>0.05), β-catenin (1.21±0.01 vs 0.99±0.07, t=5.47, P<0.05), N-cadherin (1.05±0.09 vs 0.90±0.03, t=2.65, P>0.05) at UA of 10 μmol/L; MMP9 (1.07±0.03 vs 0.79±0.09, t=5.26, P<0.001), β-catenin (1.21±0.01 vs 0.89±0.05, t=10.55, P<0.001), and N-cadherin (1.04±0.09 vs 0.68±0.10, t=4.59, P<0.05) at UA of 15 μmol/L; MMP9 (1.07±0.03 vs 0.52±0.07, t=12.50, P<0.001), β-catenin (1.21±0.01 vs 0.83±0.02, t=24.01, P<0.000 1) and N-cadherin (1.04±0.09 vs 0.49±0.11, t=6.70, P<0.01) at UA of 20 μmol/L. Interfering with ANXA6 inhibits the proliferation, invasion and migration of 231 cells, and overexpression of ANXA6 promotes the proliferation, invasion and migration of 231 cells. Western Blot assay showed that compared with the control group (KD-NC group), the protein expressions of MMP9 (1.07±0.01 vs 0.62±0.16, t=4.86, P<0.01), β-catenin (1.02±0.14 vs 0.64±0.15, t=3.20, P<0.05), N-cadherin (0.98±0.14 vs 0.67±0.12, t=2.85, P<0.05) were decreased expression; Compared with the control group (OE-NC group), the protein expressions of MMP9 (0.54±0.22 vs 1.06±0.08, t=3.90, P<0.05), β-catenin (0.92±0.07 vs 1.06±0.04, t=3.06, P<0.05) and N-cadherin (0.90±0.07 vs 1.06±0.01, t=3.75, P<0.05) were significantly increased. Interference with ANXA6 promoted the inhibitory effect of UA on the proliferation ability of 231 cells ( P<0.05). Overexpression of ANXA6 weakened the inhibitory effect of UA on the proliferation of 231 cells ( P<0.05).The results of immunohistochemistry assay showed that the expression level of ANXA6 in breast cancer tissue was significantly increased, and the expression of ANXA6 was related to tumor size ( P<0.05), but not to age, T stage, N stage, pathological grade, AJCC stage, ER, PR and E-cad. Conclusion:The expression level of ANXA6 in breast cancer tissues is increased, and UA can inhibit the growth, invasion and metastasis of 231 cells by down-regulating the expression of ANXA6.

This review systematically describes the application of artificial intelligence in the comprehensive management of patients with valvular heart disease(VHD).In population screening,technologies such as artificial intelligence(AI)electrocardiogram(AI-ECG),AI auscultation,and new imaging modalities play important roles,help early detection of VHD.In imaging assessment and diagnosis,AI can add automatic morphological and functional evaluations,assisting in precise typing and risk prediction to accurately determine the timing of VHD intervention.For treatment,especially transcatheter aortic valve replacement(TAVR),AI can assist in image analysis and strategy formulation in a variety of ways throughout the process,improving procedure success rates and avoiding complications.Although the application of AI is limited by factors such as data quality and computational capacity,in the future,multi-center cooperation can be adopted to expand data samples and enhance computational capabilities to improve AI performance,thus further optimizing VHD management.

Background:Ideal bowel preparation is the prerequisite for the successful diagnostic and therapeutic colonoscopy.The retention of intestinal bubbles can seriously affect the clarity of the intestinal mucosa and subsequently decrease the detection rate of colonoscopy.Aims:To investigate the application value of dyclonine hydrochloride mucilage in bowel preparation for colonoscopy.Methods:This study was a randomized double-blinded placebo-controlled trial.Patients who underwent colonoscopy from October 2020 to October 2023 at Hainan West Central Hospital were enrolled and randomly allocated into the dyclonine hydrochloride mucilage group and the control group.3 L polyethylene glycol(PEG)+dyclonine hydrochloride mucilage and 3 L PEG+placebo were given for bowel preparation,respectively.The quality of bowel preparation was evaluated by Boston bowel preparation scale(BBPS)score and bubble score.Furthermore,a questionnaire was conducted.The cecal intubation time,withdrawal time,adenoma detection rate and adverse reaction were compared between the two groups.Results:A total of 482 patients who underwent colonoscopy were included.No significant differences in clinical characteristics such as gender,age,body mass index(BMI)and main reasons for colonoscopy were found between the dyclonine hydrochloride mucilage group and the control group(all P>0.05).Compared with the control group,no significant differences existed in total BBPS score and segment scores for right,transverse,and left colon in the dyclonine hydrochloride mucilage group(all P>0.05),but the total bubble score and segment scores for right,transverse,and left colon were significantly decreased(all P<0.001).The withdrawal time in the dyclonine hydrochloride mucilage group was significantly decreased compared to the control group(P<0.001),and the adenoma detection rate was significantly increased(P=0.001).However,no significant differences in cecal intubation time and incidence of adverse reaction were found between the two groups(all P>0.05).Conclusions:Administration of dyclonine hydrochloride mucilage during bowel preparation for colonoscopy can reduce the formation of intestinal bubbles,shorten the withdrawal time and increase the adenoma detection rate.

Objective:To investigate the correlation of intracranial arterial calcification (IAC) and its different subtypes with the severity of white matter hyperintensities (WMHs) in patients with cerebral small vessel disease (CSVD).Methods:Consecutive CSVD patients admitted to the Department of Neurology, the First Affiliated Hospital of Zhengzhou University from March 2018 to March 2022 were enrolled. Baseline demographic, laboratory, and imaging data were collected. Based on a developed and validated IAC grading scale using head CT, IAC was classified into intimal and medial types, and further categorized as focal or diffuse based on the extent of involvement. The severity of WMHs on magnetic resonance imaging was assessed using the Fazekas Scale, with patients divided into those with moderate-to-severe (total score>2) and non-moderate-to-severe WMHs (total score≤2). Subgroups were stratified based on baseline characteristics (patients′ sex, age, hypertension history, stroke history, diabetes, coronary heart disease, hyperlipidemia, smoking, and alcohol consumption). Multivariate Logistic regression was used to analyze the correlation between IAC′s subtypes and the severity of WMHs, with forest plots illustrating the interaction between medial IAC and subgroup variables.Results:A total of 490 patients with CSVD who met the inclusion and exclusion criteria were ultimately included, with a age of (60.88±10.99) years, including 162 females (33.1%). Moderate-to-severe WMHs were present in 245 patients (50.0%). Among the 490 CSVD patients, 395 (80.6%) had IAC, including 335 (68.4%) with intimal IAC and 207 (42.2%) with medial IAC. Diffuse IAC was observed in 126 patients (25.7%), all of whom had medial IAC. Intracranial arterial stenosis was present in 271 patients (55.3%). Multivariate Logistic regression showed that IAC ( OR=2.073, 95% CI 1.142-3.761, P=0.016) was significantly associated with moderate-to-severe WMHs and medial IAC ( OR=3.230, 95% CI 1.800-5.797, P<0.001) and advanced age ( OR=1.046, 95% CI 1.019-1.074, P=0.001) were significantly associated with moderate-to-severe WMHs. Subgroup analysis revealed medial IAC had no significant interaction with patients′ gender, age, hypertension, diabetes, coronary heart disease, hyperlipidemia, alcohol or smoking consumption except for stroke history. Conclusion:In the CSVD patients, IAC, especially medial IAC, is significantly associated with the severity of WMHs.