Case report: Genotype-phenotype characteristics of nine novel PKD1 mutations in eight Chinese patients with autosomal dominant polycystic kidney disease.

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder. The PKD1 gene is responsible for the majority of ADPKD cases, and the mutations in this gene exhibit high genetic diversity. This study aimed to investigate the association between genotype and phenotype in ADPKD patients with PKD1 gene mutations through pedigree analysis. Methods: Eight Chinese pedigrees affected by ADPKD were analyzed using whole-exome sequencing (WES) on peripheral blood DNA. The identified variants were validated using Sanger sequencing, and clinical data from the patients and their families were collected and analyzed. Results: Nine novel mutation sites in PKD1 were discovered across the pedigrees, including c.4247T > G, c.3298_3301delGAGT, c.4798A > G, c.7567G > A, c.11717G > C, c.7703 + 5G > C, c.3296G > A, c.8515_8516insG, and c.5524C > A. These mutations were found to be associated with a range of clinical phenotypes, including chronic kidney disease, hypertension, and polycystic liver. The age of onset and disease progression displayed significant heterogeneity among the pedigrees, with some individuals exhibiting early onset and rapid disease progression, while others remained asymptomatic or had milder disease symptoms. Inheritance patterns supported autosomal dominant inheritance, as affected individuals inherited the mutations from affected parents. However, there were instances of individuals carrying the mutations who remained asymptomatic or exhibited milder disease phenotypes. Conclusion: This study highlights the importance of comprehensive genotype analysis in understanding the progression and prognosis of ADPKD. The identification of novel mutation sites expands our knowledge of PKD1 gene mutations. These findings contribute to a better understanding of the disease and may have implications for personalized therapeutic strategies.

Effects of combined binding of chlorogenic acid/caffeic acid and gallic acid to trypsin on their synergistic antioxidant activity, enzyme activity and stability.

The combined application of multiple natural polyphenols in functional foods may provide better health benefits. The binding of polyphenols with different structures to proteins will affect their respective functions. Spectroscopy and molecular docking were used to investigate the competitive binding of chlorogenic acid (CGA)/caffeic acid (CA) and gallic acid (GA) to trypsin. The effects of different molecular structures and the order of adding the three phenolic acids on the binding were assessed. The stability of trypsin and its docked complexes with CGA/CA/GA was evaluated by molecular dynamics simulation. The effects of the binding process on the activity and thermal stability of trypsin, as well as on the antioxidant activity and stability of CGA/CA/GA were explored. The competitive binding of CGA/CA and GA to trypsin affected their synergistic antioxidant effects. The results may provide a reference for the combined application of CGA/CA and GA in food and pharmaceutical fields.

Multispectroscopic and synergistic antioxidant study on the combined binding of caffeic acid and (-)-epicatechin gallate to lysozyme.

The binding of caffeic acid (CA) and/or (-)-epicatechin gallate (ECG) to lysozyme was investigated by multispectroscopic methods and molecular docking. The effects of the single and combined binding on the structure, activity and stability of lysozyme and the synergistic antioxidant activity of CA and ECG were also studied. Fluorescence quenching spectra, time-resolved fluorescence spectra, and UV-vis absorption difference spectra all ascertained the static quenching mechanism of lysozyme by CA/ECG. Thermodynamic parameters indicated that CA and ECG competitively bound to lysozyme, and CA had a stronger binding affinity, which was consistent with the results of molecular docking. Hydrogen bonding, van der Waals' force and electrostatic interaction were the main driving forces for the binding process. Synchronous fluorescence spectra displayed that the interaction of CA/ECG exposed the tryptophan residues of lysozyme to a more hydrophilic environment. Circular dichroism spectroscopy, Fourier transform infrared spectroscopy and dynamic light scattering indicated that the binding of CA and/or ECG to lysozyme resulted in the change of the secondary structure and increased the particle size of lysozyme. The binding of CA and/or ECG to lysozyme inhibited the enzyme activity and enhanced the thermal stability of lysozyme. The combined application of CA and ECG showed antioxidant synergy which was influenced by the encapsulation of lysozyme and cellular uptake. In summary, this work provides theoretical guidance for lysozyme as a carrier for the combined application of CA and ECG.

Antioxidant activity, stability, in vitro digestion and cytotoxicity of two dietary polyphenols co-loaded by ß-lactoglobulin.

The combination of multiple dietary polyphenols may have synergistic beneficial effects. And the beneficial effects can be further improved by the encapsulation of proteins. The interactions of procyanidin B2 (PB2) and/or dihydromyricetin (DMY) with ß-lactoglobulin (ß-LG) were investigated using multi-spectroscopic techniques and molecular docking. The structural change of ß-LG in the presence of PB2 and/or DMY was demonstrated by dynamic light scattering, Fourier transform infrared spectroscopy and circular dichroism spectroscopy. Response surface analysis was used to optimize the synergistic antioxidant activity between PB2 and DMY. Besides, the antioxidant activity, stability, in vitro digestion and cytotoxicity of PB2 and DMY in the binary and ternary systems were investigated. These studies will elucidate the interaction mechanism of PB2 and/or DMY with ß-LG. The research results can provide theoretical support for the development of functional foods and beverages with synergistic activity, improved stability and bioaccessibility, thereby promoting human health and preventing diseases.

Co-encapsulation of (-)-epigallocatechin-3-gallate and piceatannol/oxyresveratrol in ß-lactoglobulin: effect of ligand-protein binding on the antioxidant activity, stability, solubility and cytotoxicity.

The co-encapsulation of multiple bioactive components in a carrier may produce synergistic effects and improve health benefits. In this study, the interactions of ß-lactoglobulin (ß-LG) with epigallocatechin-3-gallate (EGCG) and/or piceatannol (PIC)/oxyresveratrol (OXY) were investigated by multispectroscopic techniques, isothermal titration calorimetry, and molecular docking. The static quenching mechanism of ß-LG by EGCG, PIC and OXY was confirmed by fluorescence spectroscopy and UV-vis absorption difference spectroscopy. The binding sites of these three polyphenols in ß-LG were identified by site marking fluorescence experiments and molecular docking. The thermodynamic parameters of the ß-LG + EGCG/PIC/OXY binary complex and ß-LG + EGCG + PIC/OXY ternary complex were obtained from fluorescence data and used to analyze the main driving force for complex formation. The exothermic binding process was further confirmed by isothermal titration calorimetry. The α-helical content, particle size and morphology of free and ligand-bound ß-LG were determined by circular dichroism spectroscopy, dynamic light scattering and transmission electron microscopy, respectively. The effect of EGCG, PIC and OXY on the conformation of ß-LG was studied by Fourier transform infrared spectroscopy. In addition, the maximum synergistic antioxidant activity between EGCG and PIC/OXY was obtained by response surface analysis. The effects of ß-LG in the binary and ternary systems on the antioxidant activity, stability, solubility and cytotoxicity of the polyphenols were also studied. Finally, the different cytotoxicities of the complexes and nanoparticles of the binary and ternary systems were compared. The results of this study are expected to provide a theoretical basis for the development of ß-LG-based carriers co-encapsulating a variety of bioactive components.

Delayed stillbirth by hysterectomy following early-term uterine rupture with fetal demise in secundigravida.

Uterine rupture and postterm pregnancy pose a number of life-threatening complications to both mother and child, including severe intra-abdominal bleeding and peritonitis, birth injury, hypoxia, and fetal loss. This report presents a rare case of a 20-year-old female experiencing fetal demise at 60 weeks of pregnancy, with uterine rupture and bone tissue discharge from her vagina without severe intra-abdominal bleeding and peritonitis. The mild clinical course despite complete uterine rupture was due to the firm adhesion of the amniotic sac to the uterus caused by inflammation. The adhesion of the intestines to the rupture site prevented dehiscence of the ruptured wound. Suppuration and bone tissue discharge relieved the pressure on the patient's abdominal cavity and prevented subsequent occurrence of severe peritonitis. Radiologists mistakenly regarded the thick amniotic sac wall on the right side of the uterine wall as a right cornual pregnancy with uterine rupture caused by chronic inflammation. This report aims to bring awareness of this rare condition to medical students and radiologists.

Neurometabolic alterations in bipolar disorder with anxiety symptoms: A proton magnetic resonance spectroscopy study of the prefrontal whiter matter.

To identify the pathophysiological mechanism of bipolar disorder (BD) patients with anxiety symptoms, we analyzed the differences of brain biochemical metabolism in BD patients with and without anxiety symptoms. We collected 39 BD patients who had been untreated with drugs in one month and were divided into the anxiety symptoms group (20 cases) and non-anxiety symptoms group (19 cases) according to whether they had anxiety symptoms. We used proton magnetic resonance spectroscopy (1H-MRS) to detect the biochemical metabolite ratios of the prefrontal whiter matter (PWM) in all patients. The right PWM mI/Cr ratios in BD patients with anxiety symptoms were higher than those in BD patients without anxiety symptoms and the Cho/Cr ratios in the left PWM were negatively correlated with age and age of onset in BD patients with anxiety symptoms. These findings indicated that BD patients with anxiety symptoms have increased levels of inositol metabolism in the right PWM. Furthermore, the level of membrane phospholipid catabolism in the left PWM of BD patients with anxiety symptoms decreased with increasing age and onset age. Our results provide some references for the pathophysiological mechanism in BD patients with anxiety symptoms.

3D printing technology used in severe hip deformity.

This study was designed to assess the use of a 3D printing technique in total hip arthroplasty (THA) for severe hip deformities, where new and improved approaches are needed. THAs were performed from January 2015 to December 2016. Bioprosthesis artificial hip joints were used in both conventional and 3D printing hip arthroplasties. A total of 74 patients (57 cases undergoing conventional hip replacements and 17 undergoing 3D printing hip replacements) were followed-up for an average of 24 months. The average age of the patients was 62.7 years. Clinical data between the patients treated with different approaches were compared. Results showed that the time to postoperative weight bearing and the Harris scores of the patients in the 3D printing group were better than those for patients in the conventional hip replacement group. Unfortunately, the postoperative infection and loosening rates were higher in the 3D printing group. However, there were no significant differences in femoral neck anteversion, neck shaft, acetabular or sharp angles between ipsilateral and contralateral sides in the 3D printing group (P>0.05). The femoral neck anteversion angle was significantly different between the two sides in the conventional hip replacement group (P<0.05). Based on these results, we suggest that the 3D printing approach provides a better short-term curative effect that is more consistent with the physiological structure and anatomical characteristics of the patient, and we anticipate that its use will help improve the lives of many patients.