1.Metabolomics Reveals Mechanism of Abelmoschi Corolla Total Flavonoids in Regulating Endoplasmic Reticulum Stress in IgA Nephropathy
Shuying SONG ; Changqing WEN ; Luwan XING ; Yan ZHANG ; Haitao GE ; Fujiang WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(11):153-161
ObjectiveTo elucidate the mechanism by which total flavonoids of Abelmoschi Corolla (TFA) treat immunoglobulin A (IgA) nephropathy (IgAN) through serum metabolomics analysis. MethodsSPF-grade male SD rats were randomly assigned into six groups (n=10): blank, model, low-dose TFA (TFA-L, 27 mg·kg-1), medium-dose TFA (TFA-M, 54 mg·kg-1), high-dose TFA (TFA-H, 108 mg·kg-1), and losartan potassium (LST, 4.5 mg·kg-1) groups. The remaining five groups, excluding the blank group, were modeled with bovine serum albumin (BSA), lipopolysaccharide (LPS), and carbon tetrachloride (CCl4). Specifically, from weeks 1 to 10, BSA was administered via gavage every other day, and a mixture of castor oil and CCl4 was injected subcutaneously once a week, with LPS injected into the tail vein at weeks 6 and 8. After successful modeling, each intervention group was administrated with the medication prepared with distilled water once daily by gavage for a continuous period of 4 weeks. The levels of 24-hour urinary total protein (24 h UP) and serum creatinine (SCr) were quantified by kits, and the serum IgA level was determined by enzyme-linked immunosorbent assay (ELISA). Renal pathological changes were observed by hematoxylin-eosin (HE) staining and periodic acid-Schiff (PAS) staining. Renal IgA deposition was assessed by immunofluorescence (IF). Endoplasmic reticulum (ER) stress was observed by transmission electron microscopy. Western blot and immunohistochemistry (IHC) were employed to detect the expression of ER stress-related factors. Non-targeted metabolomics was used to screen differential metabolites for analysis, and key metabolites arachidonic acid (AA), prostaglandin E2 (PGE2), and cyclooxygenase-2 (COX-2) were validated. ResultsCompared with the blank group, the model group showed increased 24-hour urine protein (24 h UP) and serum creatinine (SCr) levels (P<0.01), obvious renal pathological damage, elevated serum IgA level (P<0.01), increased renal AA and PGE2 levels (P<0.01), and up-regulated protein levels of COX-2, glucose-regulated protein 78 (GRP78), phosphorylated eukaryotic initiation factor 2α (P-EIF2α), activating transcription factor 4 (ATF4), inositol-requiring enzyme 1α (IRE1α), and spliced X-box binding protein 1 (XBP1s) in the renal tissue (P<0.05, P<0.01). Compared with the model group, the intervention groups showed reductions in 24 h UP and SCr levels (P<0.05, P<0.01), alleviated renal pathological injury, decreased serum IgA level (P<0.05, P<0.01), and reduced renal AA and PGE2 levels (P<0.01). Western blot and IHC results showed that TFA reduced the levels of COX-2, GRP78, P-EIF2α, ATF4, IRE1α, and XBP1s in the renal tissue (P<0.05, P<0.01). Metabolomics results indicated that 51 commonly differential metabolites were found among the normal, model, and TFA-M groups. TFA ameliorated IgAN by affecting metabolic pathways related to the biosynthesis of arachidonic acid and arginine through L-aspartic acid, prostaglandin 2α, leukotriene B4, leukotriene D4, among others. ConclusionTFA can regulate the arachidonic acid metabolism pathway, thereby modulating ER stress, reducing renal damage, and ameliorating IgA nephropathy.
2.The crosstalk mechanism of intestinal barrier dysfunction in the pathogenesis of hepatorenal syndrome-acute kidney injury
Wen SUN ; Xiao CHEN ; Xin ZHANG ; Borui YU ; Bo YANG ; Haitao XING
Journal of Clinical Hepatology 2025;41(8):1685-1692
In 2015,the International Ascites Club proposed a new definition of hepatorenal syndrome-acute kidney injury based on the progression of hepatorenal syndrome,and studies are still being conducted to explore the exact pathogenesis of hepatorenal syndrome-acute kidney injury.Intestinal barrier plays an important bridging role in liver-kidney connection,and intestinal flora disturbance,bacterial translocation,and endotoxins entering the blood cause damage to the kidneys by releasing proinflammatory cytokines and activating immune-related cells.The entrance of bile acid into the circulation system also directly or indirectly lead to the development and progression of hepatorenal syndrome-acute kidney injury.This article reviews the crosstalk mechanism of hepatorenal syndrome-acute kidney injury from the perspective of the intestinal barrier and further clarifies the key role of the liver-gut-kidney axis in the pathogenesis of this disease,in order to provide new treatment ideas.
3.Impact of neurovascular coupling changes on cognitive function in patients with white matter hyperintensities
Xin WANG ; Xin CHEN ; Haitao WANG ; Han WEI ; Xueping LI ; Wei XING
International Journal of Cerebrovascular Diseases 2025;33(4):252-259
Objective:To investigate the function changes in neurovascular coupling (NVC) in patients with white matter hyperintensities (WMHs) and its correlation with cognitive impairment.Methods:Thirty patients with moderate to severe WMHs admitted to the First People's Hospital of Changzhou from April 2023 to June 2024 (as case group), and 30 subjects with no or mild WMH matched by age, gender and educational level (as the control group) were included prospectively. The general clinical information was collected and cognitive assessment was conducted. Three-dimensional pseudo-continuous arterial spin labeling (3D-pCASL) and resting state functional magnetic resonance imaging (rs-fMRI) data were collected to quantify cerebral blood flow (CBF) and functional connectivity strength (FCS). NVC function was evaluated through voxel-wise CBF-FCS correlation analysis. The CBF-FCS coefficients between groups were compared, the correlation between NVC and cognitive function was explored using partial correlation analysis, controlling for the false discovery rate (FDR).Results:The prevalence of hypertension and diabetes in moderate to severe WMHs group was significantly higher than that in the no or mild WMH group (all P<0.05), while the overall cognitive function, executive function and episodic memory function were significantly lower than those in the no or mild WMH group (all P<0.05). There was no significant difference in the CBF-FCS coefficients of the whole brain gray matter between the moderate to severe WMHs group and the no or mild WMHs group. The CBF-FCS coefficients of the bilateral orbital frontal gyrus, right anterior cingulate gyrus, and bilateral hippocampus in the moderate to severe WMHs group were significantly lower than those in the no or mild WMHs group, while the CBF-FCS coefficients of the bilateral parietal gyrus and caudate nucleus were significantly higher than those in the no or mild WMHs group (all q<0.05 after FDR adjustment). Partial correlation analysis showed that after adjusting for age, gender, and education level, the CBF-FCS coefficients of the right anterior and lateral cingulate gyrus were negatively correlated with the executive function completion time in the moderate to severe WMHs group ( r=-0.55, q=0.04 after FDR adjustment), and the CBF-FCS coefficients of the right hippocampus were significantly positively correlated with the episodic memory scores ( r=0.59, q=0.03 after FDR adjustment). These correlations were not statistically significant in the no or mild WMHs group. Conclusion:Patients with moderate to severe WMHs exhibit NVC abnormalities in specific brain regions, which are closely associated with executive function and episodic memory impairment, suggesting that NVC dysfunction may be an important mechanism for WMHs-related cognitive impairment.
4.Comparison of efficacy and safety of crisaborole ointment 2% versus pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children: a multicenter, randomized, controlled clinical trial
Xing XIAO ; Shan WANG ; Huan YANG ; Hong SHU ; Yanping GUO ; Jinping CHEN ; Yao LU ; Qinfeng LI ; Yuan LIANG ; Mutong ZHAO ; Xiaoyan LUO ; Limin MIAO ; Rui XU ; Xuemei LI ; Sha LAI ; Jianhong LI ; Zhen LUO ; Lu YU ; Lu XING ; Meitan WANG ; Xiaoli LI ; Haitao XU ; Ping LI ; Hua WANG ; Lin MA
Chinese Journal of Dermatology 2025;58(5):425-430
Objective:To compare the efficacy and safety of crisaborole ointment 2% versus pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged 2 years or older.Methods:A multicenter, randomized, open-label, controlled clinical trial was conducted. A total of 120 pediatric patients aged 2 - 17 years with mild to moderate atopic dermatitis were enrolled from departments of dermatology of 8 hospitals in China between March 2022 and February 2023. The participants were randomly assigned in a 1∶1 ratio to the crisaborole group and the pimecrolimus group, and received the treatment with crisaborole ointment 2% and pimecrolimus cream 1% respectively, twice a day for 4 weeks. Visits were scheduled at baseline/on day 1, as well as on days 8, 15, and 29. The primary efficacy outcome was the percentage of patients achieving the Investigator's Static Global Assessment (ISGA) success (defined as clear [0] or almost clear [1] on the ISGA scale, combined with ≥ 2‐grade improvement from baseline) on day 29. The secondary efficacy outcomes included changes in the Eczema Area and Severity Index (EASI) total scores from baseline to day 29, percentages of patients achieving ISGA improvement (defined as clear [0] or almost clear [1] on the ISGA scale), as well as changes in the Peak Pruritus Numerical Rating Scale (NRS) scores, Dermatology Life Quality Index (DLQI) /Infants' Dermatology Life Quality Index (IDLQI) /Children's Dermatology Life Quality Index (CDLQI) scores, and in the Dermatitis Family Impact (DFI) scores. Drug safety was evaluated according to the incidence of adverse events. Categorical data were compared using the chi-square test. Since measurement data did not follow a normal distribution, the rank sum test was used for comparisons of measurement data between groups.Results:A total of 106 children with mild to moderate atopic dermatitis were included in the per-protocol analysis set, with 52 in the crisaborole group (26 males and 26 females) and 54 in the pimecrolimus group (27 males and 27 females). There were no significant differences in age, disease duration, ISGA and EASI scores at baseline between the two groups (all P > 0.05). On day 29, 22 patients (42.31%) in the crisaborole group and 25 (46.30%) in the pimecrolimus group achieved ISGA success, with no significant difference between the two groups ( χ2 = 0.17, P = 0.68) ; 35 patients (67.31%) in the crisaborole group and 45 (83.33%) in the pimecrolimus group achieved ISGA improvement, also with no significant difference between the two groups ( χ2 = 3.68, P = 0.06) ; additionally, there were no significant differences in the EASI, pruritus NRS, DLQI/IDLQI/CDLQI, or DFI scores between the two groups (all P > 0.05). Adverse reactions to the two topical agents were mainly local reactions such as mild to moderate pain, itching, or worsening of itching, and no obvious systemic adverse reactions occurred. The incidence of drug-related adverse reactions was 46.15% (24 cases) in the crisaborole group and 37.04% (20 cases) in the pimecrolimus group, with no significant difference between the two groups ( χ2 = 0.91, P = 0.34) . Conclusion:The efficacy of crisaborole ointment 2% was comparable to that of pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged ≥ 2 years, and it yielded early and rapid improvement in the quality of life of patients and their families, with good safety and tolerability profiles.
5.A method for determination of urinary iodine by a pure water direct dilution-ICP-MS
Haitao XING ; Jianbin FAN ; Dingguo JIANG ; Shuguang HU ; Ming CHEN ; Wenhua CAI ; Xiaowen LIAN ; Zujian SU
Chinese Journal of Endemiology 2025;44(8):679-683
Objective:To establish a pure water direct dilution-inductively coupled plasma mass spectrometry (ICP-MS) detection method for rapid determination of urinary iodine.Methods:Pure water was used to directly dilute the urine samples. The washing solution was 5.0 g/L ascorbic acid, the internal standard solution was 5.0 g/L ascorbic acid and 100 μg/L 128Te, the standard solution was prepared with the solution of lyophilized urine iodine biological component analysis reference material. The method was evaluated in terms of linear range, detection limit, quantification limit, precision and method comparision experiment. Results:The linear correlation coefficient of the standard curve for iodine concentration range from 0 to 50.0 μg/L was 0.999 7, with a detection limit of 0.2 μg/L and a quantification limit of 0.6 μg/L. The spiked recovery rates of low, medium, and high concentration iodine standard solutions added to actual urine samples were 100.8%, 99.1% and 99.7%, respectively, with relative standard deviations of 0.8%, 1.3% and 1.6%, respectively. There was no statistically significant difference ( t = - 0.14, P = 0.890) between the results of measuring actual urine and assessment urine using this method and "Determination of Iodine in Urine-Part 2: Inductively Coupled Plasma Mass Spectrometry (WS/T 107.2-2016)". Conclusions:We have successfully established a pure water direct dilution-ICP-MS method for determining urinary iodine. This method provides accurate and highly sensitive results, making it suitable for sudden public health emergencies and large-scale clinical measurement of urinary iodine.
6.Comparison of efficacy and safety of crisaborole ointment 2% versus pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children: a multicenter, randomized, controlled clinical trial
Xing XIAO ; Shan WANG ; Huan YANG ; Hong SHU ; Yanping GUO ; Jinping CHEN ; Yao LU ; Qinfeng LI ; Yuan LIANG ; Mutong ZHAO ; Xiaoyan LUO ; Limin MIAO ; Rui XU ; Xuemei LI ; Sha LAI ; Jianhong LI ; Zhen LUO ; Lu YU ; Lu XING ; Meitan WANG ; Xiaoli LI ; Haitao XU ; Ping LI ; Hua WANG ; Lin MA
Chinese Journal of Dermatology 2025;58(5):425-430
Objective:To compare the efficacy and safety of crisaborole ointment 2% versus pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged 2 years or older.Methods:A multicenter, randomized, open-label, controlled clinical trial was conducted. A total of 120 pediatric patients aged 2 - 17 years with mild to moderate atopic dermatitis were enrolled from departments of dermatology of 8 hospitals in China between March 2022 and February 2023. The participants were randomly assigned in a 1∶1 ratio to the crisaborole group and the pimecrolimus group, and received the treatment with crisaborole ointment 2% and pimecrolimus cream 1% respectively, twice a day for 4 weeks. Visits were scheduled at baseline/on day 1, as well as on days 8, 15, and 29. The primary efficacy outcome was the percentage of patients achieving the Investigator's Static Global Assessment (ISGA) success (defined as clear [0] or almost clear [1] on the ISGA scale, combined with ≥ 2‐grade improvement from baseline) on day 29. The secondary efficacy outcomes included changes in the Eczema Area and Severity Index (EASI) total scores from baseline to day 29, percentages of patients achieving ISGA improvement (defined as clear [0] or almost clear [1] on the ISGA scale), as well as changes in the Peak Pruritus Numerical Rating Scale (NRS) scores, Dermatology Life Quality Index (DLQI) /Infants' Dermatology Life Quality Index (IDLQI) /Children's Dermatology Life Quality Index (CDLQI) scores, and in the Dermatitis Family Impact (DFI) scores. Drug safety was evaluated according to the incidence of adverse events. Categorical data were compared using the chi-square test. Since measurement data did not follow a normal distribution, the rank sum test was used for comparisons of measurement data between groups.Results:A total of 106 children with mild to moderate atopic dermatitis were included in the per-protocol analysis set, with 52 in the crisaborole group (26 males and 26 females) and 54 in the pimecrolimus group (27 males and 27 females). There were no significant differences in age, disease duration, ISGA and EASI scores at baseline between the two groups (all P > 0.05). On day 29, 22 patients (42.31%) in the crisaborole group and 25 (46.30%) in the pimecrolimus group achieved ISGA success, with no significant difference between the two groups ( χ2 = 0.17, P = 0.68) ; 35 patients (67.31%) in the crisaborole group and 45 (83.33%) in the pimecrolimus group achieved ISGA improvement, also with no significant difference between the two groups ( χ2 = 3.68, P = 0.06) ; additionally, there were no significant differences in the EASI, pruritus NRS, DLQI/IDLQI/CDLQI, or DFI scores between the two groups (all P > 0.05). Adverse reactions to the two topical agents were mainly local reactions such as mild to moderate pain, itching, or worsening of itching, and no obvious systemic adverse reactions occurred. The incidence of drug-related adverse reactions was 46.15% (24 cases) in the crisaborole group and 37.04% (20 cases) in the pimecrolimus group, with no significant difference between the two groups ( χ2 = 0.91, P = 0.34) . Conclusion:The efficacy of crisaborole ointment 2% was comparable to that of pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged ≥ 2 years, and it yielded early and rapid improvement in the quality of life of patients and their families, with good safety and tolerability profiles.
7.The crosstalk mechanism of intestinal barrier dysfunction in the pathogenesis of hepatorenal syndrome-acute kidney injury
Wen SUN ; Xiao CHEN ; Xin ZHANG ; Borui YU ; Bo YANG ; Haitao XING
Journal of Clinical Hepatology 2025;41(8):1685-1692
In 2015,the International Ascites Club proposed a new definition of hepatorenal syndrome-acute kidney injury based on the progression of hepatorenal syndrome,and studies are still being conducted to explore the exact pathogenesis of hepatorenal syndrome-acute kidney injury.Intestinal barrier plays an important bridging role in liver-kidney connection,and intestinal flora disturbance,bacterial translocation,and endotoxins entering the blood cause damage to the kidneys by releasing proinflammatory cytokines and activating immune-related cells.The entrance of bile acid into the circulation system also directly or indirectly lead to the development and progression of hepatorenal syndrome-acute kidney injury.This article reviews the crosstalk mechanism of hepatorenal syndrome-acute kidney injury from the perspective of the intestinal barrier and further clarifies the key role of the liver-gut-kidney axis in the pathogenesis of this disease,in order to provide new treatment ideas.
8.A method for determination of urinary iodine by a pure water direct dilution-ICP-MS
Haitao XING ; Jianbin FAN ; Dingguo JIANG ; Shuguang HU ; Ming CHEN ; Wenhua CAI ; Xiaowen LIAN ; Zujian SU
Chinese Journal of Endemiology 2025;44(8):679-683
Objective:To establish a pure water direct dilution-inductively coupled plasma mass spectrometry (ICP-MS) detection method for rapid determination of urinary iodine.Methods:Pure water was used to directly dilute the urine samples. The washing solution was 5.0 g/L ascorbic acid, the internal standard solution was 5.0 g/L ascorbic acid and 100 μg/L 128Te, the standard solution was prepared with the solution of lyophilized urine iodine biological component analysis reference material. The method was evaluated in terms of linear range, detection limit, quantification limit, precision and method comparision experiment. Results:The linear correlation coefficient of the standard curve for iodine concentration range from 0 to 50.0 μg/L was 0.999 7, with a detection limit of 0.2 μg/L and a quantification limit of 0.6 μg/L. The spiked recovery rates of low, medium, and high concentration iodine standard solutions added to actual urine samples were 100.8%, 99.1% and 99.7%, respectively, with relative standard deviations of 0.8%, 1.3% and 1.6%, respectively. There was no statistically significant difference ( t = - 0.14, P = 0.890) between the results of measuring actual urine and assessment urine using this method and "Determination of Iodine in Urine-Part 2: Inductively Coupled Plasma Mass Spectrometry (WS/T 107.2-2016)". Conclusions:We have successfully established a pure water direct dilution-ICP-MS method for determining urinary iodine. This method provides accurate and highly sensitive results, making it suitable for sudden public health emergencies and large-scale clinical measurement of urinary iodine.
9.Surface morphometry analysis of cortical abnormalities in adolescents with self-injury
Haitao WANG ; Xin WANG ; Suhong WANG ; Haitao LU ; Yuting QIU ; Wei XING
Chinese Journal of Behavioral Medicine and Brain Science 2024;33(11):1001-1006
Objective:To explore the cortical abnormalities in brain regions in adolescent with self-injury and the correlation between cortical structural changes and clinical emotional manifestations.Methods:From April 2023 to June 2024, totally 38 adolescents with self-injury(self-injury group) from psychological outpatient department of First People’s Hospital of Changzhou and 41 healthy volunteers (HC group) matched with age, gender and years of education were selected.T1-weighted magnetic resonance imaging and clinical data of all participants were collected. All of them were investigated by the 17-item Hamilton depression scale (HAMD-17) and Hamilton anxiety scale (HAMA). Image preprocessing and surface-based morphometry analysis were performed by the DPABISurf software. Cortical parameters from regions showing significant differences were extracted, which were then evaluated the correlation with the emotional scores based on Spearman correlation analysis by SPSS 29.0 software.Results:Compared with HC group, self-injury group showed reduced thickness in areas primarily involving the left somatosensory and motor cortex, left paracentral lobular and mid cingulate cortex, left posterior cingulate cortex and premotor cortex(MNI: cluster 1: x=-17.73, y=-32.81, z=43.87, cluster 2: x=-35.97, y=-8.72, z=52.01, cluster 3: x=-18.94, y=-41.39, z=65.94)(all P<0.05). Lower sulcal depth in the left orbital and polar frontal cortex (MNI: x=-39.9, y=47.92, z=-5.42) ( P<0.05) and higher mean curvature in the right superior parietal cortex (MNI: x=21.89, y=-61.89, z=50.55) ( P<0.05) were found in the self-injury group. In the self-injury group, Spearman correlation analysis revealed negative correlations between cortical thickness in the regions of interest and clinical emotional scores (HAMD-17: r=-0.385, -0.332, P<0.05; HAMA: r=-0.395, -0.481, P<0.05), primarily involving the left supplementary motor area, left premotor cortex and the left somatosensory and motor cortex. Conclusion:The perception and execution cortex of adolescents with self-injury shows surface morphological abnormalities, which may be relevant to clinical emotional manifestations.
10.The clinical application value of semiconductor laser combined with flat-panel CT in guiding foramen ovale puncture
Tao ZHANG ; Yongqiang XU ; Qingbo WANG ; Haitao ZHANG ; Zefu LI ; Hailong XING
Journal of Practical Radiology 2024;40(12):2046-2049
Objective To explore the clinical application value of semiconductor laser combined with flat-panel CT guidance in foramen ovale puncture for trigeminal neuralgia(TN).Methods A total of 86 patients with primary TN were selected and randomly divided into control group(n=43)and observation group(n=43).The control group used empirical manual puncture,and the observation group used semiconductor laser combined with flat-panel CT-guided radiofrequency ablation.The first puncture success rate,puncture success time,total operation time,and intraoperative flat-panel CT scan times were carefully evaluated.Results The puncture success time,total operation time,and intraoperative flat-panel CT scan times in the observation group were significantly lower than those in the control group(P<0.05).In addition,the first puncture success rate and surgical efficiency 12 months after surgery were significantly improved(P<0.05).The incidence of facial congestion in the observation group was significantly lower than that in the control group(P<0.05),but there was no statistically significant difference in the incidence of chewing weakness,cerebrospinal fluid leakage,and intracranial infection between the two groups(P>0.05).Conclusion Minimally invasive foramen ovale puncture under the guidance of semiconductor laser combined with flat-panel CT for the treatment of TN has the advantages of simple operation,accurate positioning,low risk,and few complications,with important clinical application value.

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