Objective:To investigate the effect of chlorogenic acid on atherosclerosis (AS) in a mouse model.Methods:Twenty-four specific pathogen-free male ApoE-/- mice were adaptively fed for 1 week and then randomly divided into three groups ( n=8 per group): The model group, the atorvastatin group, and the chlorogenic acid group. All three groups were fed with a high-fat diet. Eight male C57BL/6N wild-type mice served as the control group and were fed with a standard diet. After 8 weeks, the atorvastatin group received intragastric administration of a solution containing 0.9% sodium chloride +2.6 mg/kg atorvastatin at 10 mL/kg, while the chlorogenic acid group received 0.9% sodium chloride +200 mg/kg chlorogenic acid at 10 mL/kg. The control and model groups were given an equal volume of 0.9% sodium chloride once a day. After 9 weeks of continuous treatment, the mice were anesthetized, and the aortas were collected for Oil Red O staining. Image J was used to measure plaque area and total vascular area, and the percentage was calculated. Liver tissues were subjected to hematoxylin-eosin (H&E) staining to observe pathological changes. Blood samples from the abdominal aorta were collected to measure lipid profiles [total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)], liver function markers [aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP)], and inflammatory cytokines [interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α)]. Non-HDL-C levels were calculated as TC minus HDL-C. Results:Aortic lipid plaque area: The model group exhibited a significantly higher plaque area than the control group [(44.91±1.91)% vs. (0.21±0.11)%]. Both the atorvastatin group [(15.00±1.29)%] and the chlorogenic acid group [(26.13±2.16)%] showed reduced plaque areas compared to the model group ( P<0.05). Liver pathology: The control group displayed intact hepatocyte structure with regular morphology, whereas the model group exhibited significant steatosis. Both the atorvastatin and chlorogenic acid groups showed alleviated liver damage compared to the model group. Blood lipid levels: The model group had higher TC, TG, HDL-C, LDL-C, and non-HDL-C levels than the control group [(30.3±4.0) mmol/L vs. (2.8±0.3) mmol/L, (1.26±0.32) mmol/L vs. (0.52±0.12) mmol/L, (3.02±0.39) mmol/L vs. (2.00±0.17) mmol/L, (14.87±5.23) mmol/L vs. (0.39±0.09) mmol/L, (27.3±4.0) mmol/L vs. (0.8±0.3) mmol/L, respectively]. Both the atorvastatin group [(24.0±3.1), (0.64±0.08), (2.04±0.41), (8.55±1.15), (22.0±3.2) mmol/L] and the chlorogenic acid group [(23.3±2.5), (0.88±0.14), (2.28±0.18), (8.90±0.29), (21.0±2.5) mmol/L] showed lower levels than the model group ( P<0.05). The model group had higher ALT, AST, and ALP levels than the control group [(274±43) U/L vs. (99±14) U/L, (130±66) U/L vs. (38±4) U/L, (86±15) U/L vs. (60±5) U/L, respectively]. Both the atorvastatin group [(139±12), (58±16), (69±5) U/L] and the chlorogenic acid group [(138±11), (55±16), (54±5) U/L] exhibited lower levels than the model group ( P<0.05). Inflammatory cytokines: The model group had higher IL-6, IL-1β, and TNF-α levels than the control group [(238±15) ng/L vs. (202±7) ng/L, (211±6) ng/L vs. (174±6) ng/L, (1 325±75) ng/L vs. (1 036±75) ng/L, respectively]. Both the atorvastatin group [(215±9), (191±4), (1 163±78) ng/L] and the chlorogenic acid group [(220±13), (195±7), (1 197±53) ng/L] showed reduced levels compared to the model group (all P<0.05). Conclusion:Chlorogenic acid may inhibit aortic lipid plaque deposition and ameliorate AS in mice by improving lipid metabolism and suppressing inflammatory responses.

Objective:To explore the clinical features and molecular etiology of a patient with Dent disease due to variant of CLCN5 gene. Methods:A male patient with Dent disease diagnosed at the First Affiliated Hospital of Zhengzhou University in September 2023 was selected as the study subject. Clinical data of the patient were collected. Whole exome sequencing (WES) was carried out for the patient and his family members. Pathogenicity of candidate variant was verified by Sanger sequencing and bioinformatic analysis. This study has been approved by the Medical Ethics Committee of the Hospital (Ethics No. KS-2018-KY-36).Results:The patient, a 15-year-old male, was admitted due to proteinuria and hematuria. Ultrasonography showed diffuse echogenic changes in both kidneys. Renal biopsy revealed structural dysfunction of renal tubules. Electron microscopy revealed minor tubular and glomerular lesions. The patient was found to harbor a hemizygous c. 701dupA (p.Y234Ter) variant of the CLCN5 gene, which was derived from his mother. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic (PVS1+ PM2_Supporting). Bioinformatic analysis using multiple software predicted the deleterious effect of the variant. Conclusion:The hemizygous c.701dupA (p.Y234Ter) variant of the CLCN5 gene probably underlay the pathogenesis of Dent disease in this patient. Above finding has enriched the mutational spectrum of the CLCN5 gene.

Objective To explore the risk factors of early hypocalcemia after endoscopic thyroidectomy by breast approach(ETBA)and establish a predictive model to evaluate its occurrence risk.Methods A total of 155 patients with thyroid nodules who underwent ETBA were selected.Patients were divided into the low calcium group(＜2 mmol/L,n=41)and the normal group(≥2 mmol/L,n=114)according to the serum calcium level 24 hours after the operation.Before the operation,thyroid function and parathyroid hormone(PTH)were detected,and ultrasound was performed to evaluate cervical lymph node enlargement.Meanwhile,nodule location,maximum tumor diameter,nodule adhesion to the capsule,calcification and the edge of the nodule were also detected.The surgical conditions such as gland resection(unilateral or bilateral),operation time and misresection of parathyroid glands were recorded.PTH and serum calcium were detected 24 hours after the operation.Pathological assessment was used to evaluate benign and malignant conditions,Hashimoto's thyroiditis,multifocal lesions,thyroid capsule invasion and lymph node metastasis.Results Compared with the normal group,the cervical lymph node metastasis,malignant nodules,multifocal lesions,cervical lymph node enlargement,bilateral gland resection,parathyroid gland resection by mistake,combined Hashimoto's thyroiditis,maximum tumor diameter and operation time were increased in the hypocalcemia group,but PTH at 24 hours after the operation was decreased(P＜0.05).Multivariate Logistic regression analysis showed that cervical lymph node metastasis,long operation time,parathyroid resection by mistake,combined Hashimoto's thyroiditis and maximum tumor diameter were independent risk factors for early hypocalcemia in ETBA.Based on this,a visual nomogram model was constructed,with excellent discrimination[the area under the receiver operating characteristic(ROC)curve was 0.920(95%CI:0.834-0.971)],and the calibration curve showed that the predicted values were highly consistent with the measured values(Hosmer-Lemeshow χ2=0.007,P=0.087).Conclusion The nomogram model constructed based on multivariate Logistic regression can effectively predict the risk of early hypocalcemia after ETBA.

OBJECTIVE: To explore the clinical features and molecular etiology of a patient with Dent disease due to variant of CLCN5 gene. METHODS: A male patient with Dent disease diagnosed at the First Affiliated Hospital of Zhengzhou University in September 2023 was selected as the study subject. Clinical data of the patient were collected. Whole exome sequencing (WES) was carried out for the patient and his family members. Pathogenicity of candidate variant was verified by Sanger sequencing and bioinformatic analysis. This study has been approved by the Medical Ethics Committee of the Hospital (Ethics No. KS-2018-KY-36). RESULTS: The patient, a 15-year-old male, was admitted due to proteinuria and hematuria. Ultrasonography showed diffuse echogenic changes in both kidneys. Renal biopsy revealed structural dysfunction of renal tubules. Electron microscopy revealed minor tubular and glomerular lesions. The patient was found to harbor a hemizygous c.701dupA (p.Y234Ter) variant of the CLCN5 gene, which was derived from his mother. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic (PVS1+PM2). Bioinformatic analysis using multiple software predicted the deleterious effect of the variant. CONCLUSION The hemizygous c.701dupA (p.Y234Ter) variant of the CLCN5 gene probably underlay the pathogenesis of Dent disease in this patient. Above finding has enriched the mutational spectrum of the CLCN5 gene.
Adolescent ; Female ; Humans ; Male ; Chloride Channels/genetics* ; Dent Disease/genetics* ; Exome Sequencing ; Mutation ; Pedigree

Objective To explore the risk factors of early hypocalcemia after endoscopic thyroidectomy by breast approach(ETBA)and establish a predictive model to evaluate its occurrence risk.Methods A total of 155 patients with thyroid nodules who underwent ETBA were selected.Patients were divided into the low calcium group(＜2 mmol/L,n=41)and the normal group(≥2 mmol/L,n=114)according to the serum calcium level 24 hours after the operation.Before the operation,thyroid function and parathyroid hormone(PTH)were detected,and ultrasound was performed to evaluate cervical lymph node enlargement.Meanwhile,nodule location,maximum tumor diameter,nodule adhesion to the capsule,calcification and the edge of the nodule were also detected.The surgical conditions such as gland resection(unilateral or bilateral),operation time and misresection of parathyroid glands were recorded.PTH and serum calcium were detected 24 hours after the operation.Pathological assessment was used to evaluate benign and malignant conditions,Hashimoto's thyroiditis,multifocal lesions,thyroid capsule invasion and lymph node metastasis.Results Compared with the normal group,the cervical lymph node metastasis,malignant nodules,multifocal lesions,cervical lymph node enlargement,bilateral gland resection,parathyroid gland resection by mistake,combined Hashimoto's thyroiditis,maximum tumor diameter and operation time were increased in the hypocalcemia group,but PTH at 24 hours after the operation was decreased(P＜0.05).Multivariate Logistic regression analysis showed that cervical lymph node metastasis,long operation time,parathyroid resection by mistake,combined Hashimoto's thyroiditis and maximum tumor diameter were independent risk factors for early hypocalcemia in ETBA.Based on this,a visual nomogram model was constructed,with excellent discrimination[the area under the receiver operating characteristic(ROC)curve was 0.920(95%CI:0.834-0.971)],and the calibration curve showed that the predicted values were highly consistent with the measured values(Hosmer-Lemeshow χ2=0.007,P=0.087).Conclusion The nomogram model constructed based on multivariate Logistic regression can effectively predict the risk of early hypocalcemia after ETBA.

Objective:To investigate the effect of chlorogenic acid on atherosclerosis (AS) in a mouse model.Methods:Twenty-four specific pathogen-free male ApoE-/- mice were adaptively fed for 1 week and then randomly divided into three groups ( n=8 per group): The model group, the atorvastatin group, and the chlorogenic acid group. All three groups were fed with a high-fat diet. Eight male C57BL/6N wild-type mice served as the control group and were fed with a standard diet. After 8 weeks, the atorvastatin group received intragastric administration of a solution containing 0.9% sodium chloride +2.6 mg/kg atorvastatin at 10 mL/kg, while the chlorogenic acid group received 0.9% sodium chloride +200 mg/kg chlorogenic acid at 10 mL/kg. The control and model groups were given an equal volume of 0.9% sodium chloride once a day. After 9 weeks of continuous treatment, the mice were anesthetized, and the aortas were collected for Oil Red O staining. Image J was used to measure plaque area and total vascular area, and the percentage was calculated. Liver tissues were subjected to hematoxylin-eosin (H&E) staining to observe pathological changes. Blood samples from the abdominal aorta were collected to measure lipid profiles [total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)], liver function markers [aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP)], and inflammatory cytokines [interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α)]. Non-HDL-C levels were calculated as TC minus HDL-C. Results:Aortic lipid plaque area: The model group exhibited a significantly higher plaque area than the control group [(44.91±1.91)% vs. (0.21±0.11)%]. Both the atorvastatin group [(15.00±1.29)%] and the chlorogenic acid group [(26.13±2.16)%] showed reduced plaque areas compared to the model group ( P<0.05). Liver pathology: The control group displayed intact hepatocyte structure with regular morphology, whereas the model group exhibited significant steatosis. Both the atorvastatin and chlorogenic acid groups showed alleviated liver damage compared to the model group. Blood lipid levels: The model group had higher TC, TG, HDL-C, LDL-C, and non-HDL-C levels than the control group [(30.3±4.0) mmol/L vs. (2.8±0.3) mmol/L, (1.26±0.32) mmol/L vs. (0.52±0.12) mmol/L, (3.02±0.39) mmol/L vs. (2.00±0.17) mmol/L, (14.87±5.23) mmol/L vs. (0.39±0.09) mmol/L, (27.3±4.0) mmol/L vs. (0.8±0.3) mmol/L, respectively]. Both the atorvastatin group [(24.0±3.1), (0.64±0.08), (2.04±0.41), (8.55±1.15), (22.0±3.2) mmol/L] and the chlorogenic acid group [(23.3±2.5), (0.88±0.14), (2.28±0.18), (8.90±0.29), (21.0±2.5) mmol/L] showed lower levels than the model group ( P<0.05). The model group had higher ALT, AST, and ALP levels than the control group [(274±43) U/L vs. (99±14) U/L, (130±66) U/L vs. (38±4) U/L, (86±15) U/L vs. (60±5) U/L, respectively]. Both the atorvastatin group [(139±12), (58±16), (69±5) U/L] and the chlorogenic acid group [(138±11), (55±16), (54±5) U/L] exhibited lower levels than the model group ( P<0.05). Inflammatory cytokines: The model group had higher IL-6, IL-1β, and TNF-α levels than the control group [(238±15) ng/L vs. (202±7) ng/L, (211±6) ng/L vs. (174±6) ng/L, (1 325±75) ng/L vs. (1 036±75) ng/L, respectively]. Both the atorvastatin group [(215±9), (191±4), (1 163±78) ng/L] and the chlorogenic acid group [(220±13), (195±7), (1 197±53) ng/L] showed reduced levels compared to the model group (all P<0.05). Conclusion:Chlorogenic acid may inhibit aortic lipid plaque deposition and ameliorate AS in mice by improving lipid metabolism and suppressing inflammatory responses.

Objective:To explore the clinical features and molecular etiology of a patient with Dent disease due to variant of CLCN5 gene. Methods:A male patient with Dent disease diagnosed at the First Affiliated Hospital of Zhengzhou University in September 2023 was selected as the study subject. Clinical data of the patient were collected. Whole exome sequencing (WES) was carried out for the patient and his family members. Pathogenicity of candidate variant was verified by Sanger sequencing and bioinformatic analysis. This study has been approved by the Medical Ethics Committee of the Hospital (Ethics No. KS-2018-KY-36).Results:The patient, a 15-year-old male, was admitted due to proteinuria and hematuria. Ultrasonography showed diffuse echogenic changes in both kidneys. Renal biopsy revealed structural dysfunction of renal tubules. Electron microscopy revealed minor tubular and glomerular lesions. The patient was found to harbor a hemizygous c. 701dupA (p.Y234Ter) variant of the CLCN5 gene, which was derived from his mother. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic (PVS1+ PM2_Supporting). Bioinformatic analysis using multiple software predicted the deleterious effect of the variant. Conclusion:The hemizygous c.701dupA (p.Y234Ter) variant of the CLCN5 gene probably underlay the pathogenesis of Dent disease in this patient. Above finding has enriched the mutational spectrum of the CLCN5 gene.

Objective To investigate the safety of rigid scleral contact lenses in correcting ametropia.Methods A total of 96 patients(192 eyes)with myopia between-20.00 and 0 D and astigmatism between 0 and 3.5 D were included in this perspective study.They were divided into an experimental group(wearing rigid scleral contact lenses)and a control group[wearing rigid corneal contact lenses(RGP)],with 48 patients in each group.Eye indicators including best correc-ted visual acuity(BCVA),corneal endothelial cell density,hexagonal cell ratio,tear film break-up time(BUT),intraocu-lar pressure(IOP),corneal fluorescence staining score,conjunctival congestion score,and ciliary congestion score were measured and compared between the two groups before wearing,on the day of wearing,and 1 week,1 month,and 3 months after wearing lenses,and eye changes were observed.Results The BCVA of patients in the two groups was grea-ter than or equal to 1.00 before wearing lenses and within 3 months after wearing lenses.Compared with before wearing lenses,the corneal endothelial cell density in the experimental group slightly decreased,and the hexagonal cell ratio slightly increased at 3 months after wearing lenses,but the differences were not statistically significant(both P＞0.05).Before wearing lenses and at 3 months after wearing lenses,the corneal endothelial cell density and the hexagonal cell ratio in the experimental group were slightly higher than those in the control group,but the differences were not statistically significant(both P＞0.05).There were no significant differences in BUT and IOP between the experimental group and the control group before wearing,on the day of wearing,and 1 week,1 month,and 3 months after wearing lenses(all P＞0.05).There were no significant differences in corneal fluorescence staining score and conjunctival and ciliary congestion ratings between the experimental group and the control group before wearing lenses and at 3 months after wearing lenses(all P＞0.05).At 3 months after wearing lenses,no conjunctival or corneal edema was observed in the experimental group.Con-clusion Rigid scleral contact lenses and RGP are safe and effective in correcting ametropia;thus,they can be applied widely.

Objective To analyze the diagnostic values of H2FPEF and HFA-PEFF scores for heart failure with preserved ejection fraction(HFpEF)and HFpEF complicated with atrial fibrillation(HFpEF-AF)in Chinese patients and explore the related factors.Methods A cross-sectional study was conducted.A total of 835 consecutive HFpEF patients treated in the Department of Geriatric Cardiology,the First Hospital of Lanzhou Uni-versity from 2009 to 2020 were selected and assigned to a HFpEF-AF group(n =267)and a HFpEF group(n = 568)according to the presence of AF or not.HFA-PEFF and H2FPEF scores were used for retrospective diagnosis and the diagnostic consistency of the two scores was assessed.One hundred and thirty-six healthy volunteers with age and sex matching the patients during the same period were selected as healthy controls.The receiver operating characteristic(ROC)curves were established for H2FPEF and HFA-PEFF scores in diagnosing HFpEF-AF and HFpEF,on the basis of which the diagnostic performance of the two scores was evaluated.Results There was no difference in the HFA-PEFF score between the two groups(P =0.070).However,the HFpEF-AF group had higher mean H2FPEF score and higher proportion of patients with the score no less than 6 than the HFpEF group(P<0.001).According to the ROC curves,HFA-PEFF and H2FPEF scores demonstrated high perform-ance in diagnosing all HFpEF patients,with the area under the curve(AUC)of 0.892 and 0.922 and the opti-mal cut-offs of 4 and 4,respectively.The HFA-PEFF score showed similar performance in diagnosing HFpEF and HFpEF-AF,with the AUC of 0.899 and 0.911,respectively.The H2FPEF score had higher performance in di-agnosing HFpEF-AF(AUC of approximately 1.000)and low performance in diagnosing HFpEF(AUC of 0.885).Conclusions The HFA-PEFF score is applicable in the diagnosis of both HFpEF and HFpEF-AF.The H2FPEF score may underestimate HFpEF in Chinese patients,and its applicability in the Chinese patients with HFpEF alone remains to be investigated.

Objective To investigate the hemodynamic characteristics of carotid artery models with different degrees of artificial arterial stenosis based on hemodynamic numerical simulation,and to analyze causes of internal carotid artery stenosis and the diseases due to the stenosis from the perspective of hemodynamics.Methods Two-dimensional CT data of healthy individuals were collected from Affiliated Hospital of Inner Mongolia Minzu University,and the three-dimensional model of carotid artery was reconstructed from the two-dimensional CT data using medical modeling software MIMICS20.0.Subsequently,the obtained carotid artery model was imported to 3-Matic Medical software and interfered with various degrees of artificial internal carotid artery stenosis at the same location to obtain the models with 25%,50%and 75%internal carotid artery stenosis.After format conversion,boundary condition setting and mesh generation,the models were imported to computational fluid dynamics software FLUENT14.5 for the hemodynamic numerical simulation and analysis of the carotid artery and two-phase blood flow.Results The comparison of the blood streamlines and velocity vector maps of 3 different degrees of internal carotid artery stenosis at the same location revealed that with the increase of stenosis severity,the phenomenon of blood vortex flow at the carotid sinus decreases rapidly,but obvious vortex flow appeared above and below the internal carotid artery stenosis,and the blood flow was selectively deflected.During the internal carotid artery stenosis from 25%to 50%and then to 75%,the pressure on the wall of internal carotid artery was always low,and the pressure on the wall of internal carotid artery was gradually increased,forming a high pressure area.There was high shear stress area at the stenosis,and the low shear stress ranges above and below the stenosis were obviously larger.Conclusion The technology of using computer software to obtain models with artificial stenosis is convenient and efficient.When the internal carotid artery stenosis increases from 25%to 50%and then to 75%,the blood flow of the carotid artery changes obviously,obvious vortex flow appears in the internal carotid artery,and the mechanical properties of the wall of the carotid artery also change.