The accumulation of uremic toxins such as urea nitrogen, blood creatinine, and uric acid of patients with renal failure in vivo would lead to aggravated kidney damage. In this study, coated aldehyde oxy-starch (CAO) was used as an adsorbent to investigate its in vitro adsorption performance on renal failure indexes for urea, indoxyl sulfate (INS), monomethylamine (MMA), dimethylamine (DMA), uric acid (UA), and creatinine (Cr). The effects of variables such as pH, temperature, concentration, dosage, and time on the adsorption capacity of CAO were systematically investigated, employing analytical techniques of high-performance liquid chromatography (HPLC) and gas chromatography (GC). The results revealed that CAO exhibited a strong adsorption capacity for urea, INS, and MMA, alongside a moderate adsorption capacity for DMA, UA, and Cr. The adsorption kinetics and thermodynamic studies indicated that the adsorption of urea and UA by CAO were fitted in pseudo-first-order kinetics, and the adsorption isotherm aligned with the Freundlich adsorption model. The enthalpy change ΔH of urea in adsorption was in the range of 40 to 60 kJ·mol^-1, which demonstrated the presence of strong adsorption force due to the interactions of coordinating groups. The ΔH of UA was greater than 80 kJ·mol^-1, indicating the generation of chemical bonds during the adsorption. Both of them, Gibbs free energy ΔG was less than 0, within the range of -20 to 0 kJ·mol^-1, suggested that the adsorption of urea and UA by CAO occurred spontaneously as physical adsorption process. The adsorption entropy ΔS of urea and UA was > 0, which indicated an increase in entropy throughout the adsorption. The infrared spectroscopygram showed the formation of a chemical bond, specifically the imine bond, following the adsorption of urea by CAO, thereby indicating a chemical reaction during the adsorption. This study elucidates the adsorption mechanism of CAO on various indexes of renal failure, providing a scientific basis for its clinical usage.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Objective: To explore the correlation between Diabetes Complication Severity Index(DCSI), C-reactive protein/albumin ratio(CAR) and death in patients with diabetic foot ulcer(DFU) and to clarify their predictive value for all-cause death in DFU patients. Methods: Retrospectively analyzed the clinical data of 354 DFU patients who were treated in the Endocrinology Department of the First Affiliated Hospital of Anhui Medical University from July 2019 to December 2022. Based on survival status during follow-up, patients were divided into a survival group(n=268) and a death group(n=86). Univariate and multivariate Cox regression analyses were used to identify risk factors for all-cause death in DFU patients. Receiver operating characteristic(ROC) curves were plotted to evaluate the predictive value of DCSI, CAR, and their combination for all-cause death in DFU patients. Kaplan-Meier curves were used to explore the impact of different DCSI and CAR levels on survival in DFU patients. Results: Univariate Cox regression analysis showed that older age, history of hypertension, higher Wagner classification levels, and elevated levels of CRP, Scr, FDP, DCSI score, and CAR were associated with a higher risk of death in DFU patients(P<0.05). Higher levels of HGB, HCT, ALB, or eGFR were associated with a lower risk of death. Patients receiving combined insulin and oral hypoglycemic medication had a lower risk of death compared to those receiving only insulin therapy(P<0.05). Multivariate Cox regression analysis indicated that older age, higher levels of Scr, DCSI, and CAR were independent risk factors for all-cause death in DFU patients, while higher levels of ALB and combined insulin and oral hypoglycemic therapy were protective factors. ROC curve analysis showed that the AUC values for DCSI, CAR, and their combination were 0.652, 0.633, and 0.686, respectively. Kaplan-Meier curve analysis revealed that patients with high DCSI scores(≥4.5) had a lower survival rate compared to those with lower DCSI scores(<4.5). Similarly, patients with high CAR levels(≥0.124) had a lower survival rate compared to those with lower CAR levels(<0.124). Conclusion High levels of DCSI and CAR are independent risk factors for all-cause death in DFU patients. DCSI, CAR, and their combination have predictive value for all-cause mortality in DFU patients.

AIM To analyze the component composition of Xeriga-4 Powder,and to determine the contents of phellodendrine,chlorogenic acid,gardenoside,berberine,rutin and curcumin.METHODS The high performance liquid chromatography-Q-exactive orbitrap mass spectrometry(HPLC-Q-Exactive-MS)qualitative analysis was performed on a 35℃thermostatic Agilent ZORBAX SB-Aq column(4.6 mm×150 mm,5 μm),with the mobile phase comprising of methanol-0.1%formic acid flowing at 0.35 mL/min in a gradient elution manner,and electron spray ionization source was adopted in positive and negative ion scanning.High performance liquid chromatography tandem mass spectrometry(HPLC-MS/MS)quantitative analysis was performed on a 35℃thermostatic Shim-pack GIST-HP C18 column(2.1 mm×100 mm,3 μm),with the mobile phase comprising of methanol-0.1%formic acid flowing at 0.25 mL/min in a gradient elution manner,and electron spray ionization source was adopted in positive and negative ion scanning with multiple reaction monitoring mode.RESULTS Total 65 constituents were identified,containing 19 alkaloids,13 organic acids,13 flavonoids,7 curcumins,6 iridoids,4 fatty acids,2 aldehydes,and 1 amino acid.Six constituents showed good linear relationships within their own ranges(r≥0.999 1),whose average recoveries were 96.44%-102.37%with the RSDs of 2.05%-3.74%.CONCLUSION This study can provide a reference for the quality control for Xieriga-4 Powder.

Objective:To analyze the clinical and laboratory characteristics of patients with cryoglobulinemia.Methods:It is a cross-sectional study. The patients diagnosed with cryoglobulinemia in our hospital were enrolled from July 2017 to March 2023. The baseline information of patients, included age, gender, qualitative, and quantitative results of serum cryoglobulins, initial clinical manifestations, etiology, serum complement 3 and 4, and the renal pathological manifestations. The clinical and laboratory characteristics of patients with different types of cryoglobulinemia were analyzed.Results:There were 62 patients (30.7%) with type Ⅰ cryoglobulinemia, 58 patients (28.7%) with type Ⅱ cryoglobulinemia, and 82 patients (40.6%) with type Ⅲ cryoglobulinemia enrolled in this study. Among these patients, 56 of primary cryoglobulinemia, 76 of autoimmune diseases, 29 of tumor-related diseases, and 52 of infectious diseases were observed. Clinical symptoms related to skin lesions (124 cases, 61.4%) and kidney damage (87 cases, 43.1%) were the most common initial clinical manifestations and arthralgia/arthritis (50 cases, 24.8%), peripheral neuropathy (33 cases, 16.3%), fatigue (28 cases, 13.9%), fever (23 cases, 11.4%) were also observed in some patients. The clinical symptoms varied in different types of cryoglobulinemia. 29.0% patients (18/62) with type Ⅰ had fatigue, which was higher than those with type Ⅱ (10.3%, 6/58) and type Ⅲ (4.9%, 4/82) ( P<0.05); Kidney damage occurred in 56.9% (33/58) patients with type Ⅱ and 52.4% (43/82) patients with type Ⅲ, which was higher than that in type Ⅰ patients (17.7%, 11/62) ( P<0.05); Only 4 patients (4.9%, 4/82) with type Ⅲ had peripheral neuropathy, which was lower than those with type Ⅰ (17.7%, 11/62) and type Ⅱ (31.0%, 18/58) ( P<0.05). The quantity of cryoglobulins in patients with type Ⅲ cryoglobulinemia [122 (82, 177) mg/L] was significantly lower than that in patients with type Ⅰ [695(229, 3 499) mg/L] ( P<0.001) and type Ⅱ cryoglobulinemia [350 (107, 1 874) mg/L] ( P<0.001). Complement 4 decreased in 49.0% (99/202) of patients and complement 3 decreased in 42.6% (86/202) of patients. Membranoproliferative glomerulonephritis (36.0%, 9/25) and endocapillary proliferative glomerulonephritis (32.0%, 8/25) were the main renal pathological manifestations of cryoglobulin nephropathy. Conclusions:The most common clinical manifestations of cryoglobulinemia are skin and kidney damage. The clinical manifestations of patients with cryoglobulinemia vary in different types of cryoglobulins. Serum complement decreases in nearly half of cryoglobulinemia patients.

Objective To study the effects of Chrysanthemum Flos on blood pressure of spontaneously hypertensive rats(SHR)and evaluate its antioxidant activity in vitro and in vivo.Methods SHR were randomly divided into model,control and experimental-L,-H groups with 10 rats per group,and 10 WKY rats as blank group.Experimental-H,-L groups were given 2.10 and 0.525 g·kg-1 Chrysanthemum Flos extract by gavage;control group received 5.25 mg·kg-1 losartan by gavage;blank and model groups were given the same volume of 0.9％NaCl solution by gavage.Rats in each group were gavaged once a day for 8 weeks.After 8 weeks of continuous intragastric administration,the systolic blood pressure(SBP)and diastolic blood pressure(DBP)were observed.The contents of catalase(CAT),superoxide dismutase(SOD),glutathione peroxidase(GSH)and malondialdehyde(MDA)in serum were measured with kit colorimetry method.The in vitro free radical scavenging rates of Chrysanthemum Flos extract were detected by 1,1-diphenyl-2-picrylhydrazyl(DPPH)and 2,2'-amino-di(2-ethyl-benzothiazoline sulphonic acid-6)ammonium salt(ABTS)methods.Results The SBP of blank,model,control and experimental-H,-L groups were(132.00±2.45),(204.00±4.55),(171.00±2.16),(181.00±3.74)and(184.67±4.78)mmHg;the DBP were(73.33±4.03),(175.67±3.40),(120.33±0.94),(125.33±2.87)and(125.67±2.36)mmHg;the contents of serum CAT were(9.24±3.99),(8.40±2.98),(9.24±2.42),(8.59±2.70)and(8.49±1.47)U·mL-1;the contents of serum SOD were(122.40±12.30),(75.30±28.37),(125.39±31.35),(110.92±26.14)and(103.37±22.31)U·mL-1;the contents of serum GSH were(117.93±10.18),(78.29±23.68),(118.57±26.08),(109.89±20.52)and(98.73±14.71)U·mL-1;the contents of serum MDA were(8.36±2.08),(8.45±3.38),(8.22±3.04),(7.09±3.21)and(7.24±3.32)nmol·L 1,respectively.Compared with model group,the differences of above indicators in control group and experimental-H,-L groups were statistically significant(P＜0.05,P＜0.01).Chrysanthemum Flos extract showed certain free radical scavenging ability in vitro.The highest scavenging rates of DPPH and ABTS were 90.29％and 92.67％,respectively.Conclusion Chrysanthemum Flos extract had good antihypertensive activity.The antioxidation ability might be its antihypertensive mechanisms.

Objective:To explore the regulation mechanism of the quorum sensing regulator AphA on the functional activity of type Ⅵ secretion system VflT6SS2 in Vibrio fluvialis. Methods:Western Blot analysis was used to detect the relative expression and secretion of VflT6SS2 signature component hemolysin-coregulated protein (Hcp) in wild type (WT), Δ aphA, and corresponding complementary strains. Quantitative reverse transcription PCR and luminescence activity assay of the promoter- lux fusion system was used to measure the mRNA expression levels and promoter activity of the VflT6SS2 core and accessory gene-cluster representative genes tssB2, hcp ( tssD2) and vgrG ( tssI2), and the quorum sensing regulator HapR in WT and Δ aphA strains. A point mutation experiment combined with a luminescence activity assay was used to verify the regulatory binding site of AphA in the tssD2b promoter region. Electrophoretic mobility shift assay (EMSA) was used to determine AphA binding to the hapR promoter. Results:The mRNA expression levels of tssB2, hcp( tssD2), vgrG ( tssI2), and hapR as well as the protein expression and secretion levels of Hcp in Δ aphA strain, were significantly higher than those in the WT strain. The promoter activities of the VflT6SS2 core cluster, tssD2a, tssI2a, and hapR were higher in Δ aphA strain than in the WT strain, while the promoter activity of tssD2b showed the opposite trend. The promoter sequence analysis of tssD2a and tssD2b found significant differences in the region from -335 bp to -229 bp, and two potential AphA binding sites on tssD2b. The promoter activity of tssD2b decreased significantly after the point mutation of the two potential AphA binding sites. EMSA results showed that AphA binds directly to the promoter region of hapR. Conclusions:AphA indirectly inhibits the regulation of the VflT6SS2 core and accessory gene clusters at the promoter level by directly repressing the expression of hapR. AphA showed opposite regulation patterns for tssD2a and tssD2b, and AphA could positively regulate the expression of tssD2b by directly binding to the tssD2b promoter region (-335 bp to -229 bp).