Pathogenesis and histological changes of nephropathy associated with COVID-19.

Coronavirus disease 2019 (COVID-19) can cause damage to multiple organ, not only to the lungs, but also to the kidneys. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause acute and chronic kidney disease through direct viral infection, indirect injury, and vaccination-related injury. Like lung injury, kidney injury is also an important aspect affecting the severity and prognosis of SARS-CoV-2. This article summarizes the pathogenesis, pathological manifestations, and clinical features of SARS-CoV-2 direct or indirect renal injury. Including direct injury, indirect injury, special comorbidities (receiving kidney transplantation and chronic kidney disease), and vaccine-related renal injury, and exploring the possible therapeutic effect of anti-SARS-CoV-2 therapy on renal injury. The purpose is to provide reference for understanding COVID-19-related renal injury, guiding clinical and pathological diagnosis and treatment, and evaluating prognosis.

Transanal intersphincteric under direct view in the jackknife position combined with laparoscopic total mesorectal excision for treating ultra-low rectal cancer.

Aim: To investigate the effect and clinical advantage of transanal intersphincteric (ISR) under direct view in the jackknife position combined with laparoscopic total mesorectal excision (TME) for treating ultra-low rectal cancer. Additionally, the feasibility of this surgical technique was evaluated. Method: This was a retrospective, single-center, single-arm pilot study. Ten patients with ultra-low rectal cancer underwent treatment by the same surgical team for direct view transanal ISR combined with laparoscopic TME in the Department of Anorectal Surgery, Huizhou Central People's Hospital between January 2021 and June 2021. The relevant clinical data were collected and analyzed. Results: All the patients underwent complete mesenteric resection without conversion to laparotomy. The circumferential and distal resection margins (CRM and DRM) were negative. The mean distance between the lower margin of the tumor and the anal margin was 2.8 ± 0.8 cm, and the mean margin of distal resection was 1.2 ± 0.2 cm. TNM pathological stages I, II, III, and IV were observed in 6, 2, 2, and 0 cases, respectively. The median follow-up period was 15 months (interquartile range, 8 months). The mean Wexner and Low Anterior Resection Syndrome scores at 12 months after ileostomy were 8.1 ± 2.1 and 22.4 ± 5.7, respectively. Conclusion: Transanal ISR under direct view in the jackknife position combined with laparoscopic TME is safe and feasible for the treatment of ultralow rectal cancer.

Comprehensive Management of Blood Pressure in Patients with Septic AKI.

Acute kidney injury (AKI) is one of the serious complications of sepsis in clinical practice, and is an important cause of prolonged hospitalization, death, increased medical costs, and a huge medical burden to society. The pathogenesis of AKI associated with sepsis is relatively complex and includes hemodynamic abnormalities due to inflammatory response, oxidative stress, and shock, which subsequently cause a decrease in renal perfusion pressure and eventually lead to ischemia and hypoxia in renal tissue. Active clinical correction of hypotension can effectively improve renal microcirculatory disorders and promote the recovery of renal function. Furthermore, it has been found that in patients with a previous history of hypertension, small changes in blood pressure may be even more deleterious for kidney function. Therefore, the management of blood pressure in patients with sepsis-related AKI will directly affect the short-term and long-term renal function prognosis. This review summarizes the pathophysiological mechanisms of microcirculatory disorders affecting renal function, fluid management, vasopressor, the clinical blood pressure target, and kidney replacement therapy to provide a reference for the clinical management of sepsis-related AKI, thereby promoting the recovery of renal function for the purpose of improving patient prognosis.

Traditional Chinese Medicine in Treating Primary Podocytosis: From Fundamental Science to Clinical Research.

Podocytes form a key component of the glomerular filtration barrier. Damage to podocytes is referred to as "podocyte disease." There are many causes of podocyte injury, including primary injury, secondary injury, and gene mutations. Primary podocytosis mostly manifests as nephrotic syndrome. At present, first-line treatment is based on glucocorticoid administration combined with immunosuppressive therapy, but some patients still progress to end-stage renal disease. In Asia, especially in China, traditional Chinese medicine (TCM) still plays an important role in the treatment of kidney diseases. This study summarizes the potential mechanism of TCM and its active components in protecting podocytes, such as repairing podocyte injury, inhibiting podocyte proliferation, reducing podocyte apoptosis and excretion, maintaining podocyte skeleton structure, and upregulating podocyte-related protein expression. At the same time, the clinical efficacy of TCM in the treatment of primary podocytosis (including idiopathic membranous nephropathy, minimal change disease, and focal segmental glomerulosclerosis) is summarized to support the development of new treatment strategies for primary podocytosis.

Interaction Between Intrinsic Renal Cells and Immune Cells in the Progression of Acute Kidney Injury.

A growing number of studies have confirmed that immune cells play various key roles in the pathophysiology of acute kidney injury (AKI) development. After the resident immune cells and intrinsic renal cells are damaged by ischemia and hypoxia, drugs and toxins, more immune cells will be recruited to infiltrate through the release of chemokines, while the intrinsic cells promote macrophage polarity conversion, and the immune cells will promote various programmed deaths, phenotypic conversion and cycle arrest of the intrinsic cells, ultimately leading to renal impairment and fibrosis. In the complex and dynamic immune microenvironment of AKI, the bidirectional interaction between immune cells and intrinsic renal cells affects the prognosis of the kidney and the progression of fibrosis, and determines the ultimate fate of the kidney.

Potential Therapeutic Strategies for Renal Fibrosis: Cordyceps and Related Products.

At present, there is no effective drug for the treatment of renal fibrosis; in particular, a safe and effective treatment for renal fibrosis should be established. Cordyceps has several medical effects, including immunoregulatory, antitumor, anti-inflammatory, and antioxidant effects, and may prevent kidney, liver, and heart diseases. Cordyceps has also been reported to be effective in the treatment of renal fibrosis. In this paper, we review the potential mechanisms of Cordyceps against renal fibrosis, focusing on the effects of Cordyceps on inflammation, oxidative stress, apoptosis, regulation of autophagy, reduction of extracellular matrix deposition, and fibroblast activation. We also discuss relevant published clinical trials and meta-analyses. Available clinical studies support the possibility that Cordyceps and related products provide benefits to patients with chronic kidney diseases as adjuvants to conventional drugs. However, the existing clinical studies are limited by low quality and significant heterogeneity. The use of Cordyceps and related products may be a potential strategy for the treatment of renal fibrosis. Randomized controlled trial studies with good methodological quality, favorable experimental design, and large sample size are needed to evaluate the efficacy and safety of Cordyceps.

Programmed Cell Death in Sepsis Associated Acute Kidney Injury.

Sepsis-associated acute kidney injury (SA-AKI) is common in patients with severe sepsis, and has a high incidence rate and high mortality rate in ICU patients. Most patients progress to AKI before drug treatment is initiated. Early studies suggest that the main mechanism of SA-AKI is that sepsis leads to vasodilation, hypotension and shock, resulting in insufficient renal blood perfusion, finally leading to renal tubular cell ischemia and necrosis. Research results in recent years have shown that programmed cell death such as apoptosis, necroptosis, pyroptosis and autophagy play important roles. In the early stage of sepsis-related AKI, autophagy bodies form and inhibit various types of programmed cell death. With the progress of disease, programmed cell death begins. Apoptosis promoter represents caspase-8-induced apoptosis and apoptosis effector represents caspase-3-induced apoptosis, however, caspase-11 and caspase-1 regulate gasdermin D-mediated pyroptosis. Caspase-8 and receptor interacting kinase 1 bodies mediate necroptosis. This review focuses on the pathophysiological mechanisms of various programmed cell death in sepsis-related AKI.

Long Non-coding RNA MEG3 Promotes Renal Tubular Epithelial Cell Pyroptosis by Regulating the miR-18a-3p/GSDMD Pathway in Lipopolysaccharide-Induced Acute Kidney Injury.

Background and Objective: Acute kidney injury (AKI) is a complication of sepsis. Pyroptosis of gasdermin D (GSDMD)-mediated tubular epithelial cells (TECs) play important roles in pathogenesis of sepsis-associated AKI. Long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3), an imprinted gene involved in tumorigenesis, is implicated in pyroptosis occurring in multiple organs. Herein, we investigated the role and mechanisms of MEG3 in regulation of TEC pyroptosis in lipopolysaccharide (LPS)-induced AKI. Materials and Methods: Male C57BL/6 mice and primary human TECs were treated with LPS for 24 h to establish the animal and cell models, respectively, of sepsis-induced AKI. Renal function was assessed by evaluation of serum creatinine and urea levels. Renal tubule injury score was assessed by Periodic acid-Schiff staining. Renal pyroptosis was assessed by evaluating expression of caspase-1, GSDMD, and inflammatory factors IL-1ß and IL-18. Cellular pyroptosis was assessed by analyzing the release rate of LDH, expression of IL-1ß, IL-18, caspase-1, and GSDMD, and using EtBr and EthD2 staining. MEG3 expression in renal tissues and cells was detected using RT-qPCR. The molecular mechanisms of MEG3 in LPS-induced AKI were assessed through bioinformatics analysis, RNA-binding protein immunoprecipitation, dual luciferase reporter gene assays, and a rescue experiment. Results: Pyroptosis was detected in both LPS-induced animal and cell models, and the expression of MEG3 in these models was significantly up-regulated. MEG3-knockdown TECs treated with LPS showed a decreased number of pyroptotic cells, down-regulated secretion of LDH, IL-1ß, and IL-18, and decreased expression of GSDMD, compared with those of controls; however, there was no difference in the expression of caspase-1 between MEG3 knockdown cells and controls. Bioinformatics analysis screened out miR-18a-3P, and further experiments demonstrated that MEG3 controls GSDMD expression by acting as a ceRNA for miR-18a-3P to promote TECs pyroptosis. Conclusion: Our study demonstrates that lncRNA MEG3 promoted renal tubular epithelial pyroptosis by regulating the miR-18a-3p/GSDMD pathway in LPS-induced AKI.

Flexible and Robust Biomaterial Microstructured Colored Textiles for Personal Thermoregulation.

Integrating personal thermoregulation technologies into wearable textiles has enabled extensive and profound technological breakthroughs in energy savings, thermal comfort, wearable electronics, intelligent fabrics, and so forth. Nevertheless, previous studies have suffered from long-standing issues such as limited working temperature, poor comfort, and weak reliability of the textiles. Here, we demonstrate a skin-friendly personal insulation textile and a thermoregulation textile that can perform both passive heating and cooling using the same piece of textile with zero energy input. The insulation textile material is composed of biomaterial microstructured fibers that exhibit good thermal insulation, low thermal emissivity, and good dyeability. By filling these microstructure fibers with biocompatible phase-change materials and coating them with polydimethylsiloxane, the insulation textile becomes a thermoregulation textile that shows good water hydrophobicity, high mechanical robustness, and high working stability. The proposed thermoregulation textile exhibits slow heating/cooling rates with improved thermal comfort, offering feasible and adaptive options for personal cooling/heating scenarios and enabling scalable manufacturing for practical applications.

Dapagliflozin-citric acid cocrystal showing better solid state properties than dapagliflozin.

Dapagliflozin (DAP) is a potent and selective sodium-glucose contransporter-2 inhibitor, for treating type 2 diabetes. DAP propanediol monohydrate (DAP-PDO-H2O, 1:1:1) is the solid form used in the current tablet product to address the severe hygroscopicity problem of DAP free form. DAP-PDO-H2O, however, suffers the problem of instability when exposed to high temperature, which renders it amorphous. In this work, we report on the preparation and evaluation of a new 1:1 cocrystal between DAP and citric acid (DAP-CA). The DAP-CA cocrystal exhibits superior stability against high temperature and high relative humidity without compromising dissolution and tableting performance. Thus, DAP-CA is a promising solid form for developing the next generation DAP tablet products with improved performance.

Three-dimensional computational reconstruction of lateral skull base with plastinated slices.

The goals of this study were to build the 3D reconstructed model of lateral skull base and to explore the spatial relationships of the important structures for providing the morphological basis for lateral skull base surgery and clinical image diagnosis. Blocks with edges of about 80 mm containing the lateral skull base region and adjacent structures were sawn out from both sides of the heads and sectioned on transverse plane at a thickness of 700 microm using a plastination technique. On an SGI workstation, a Contours-Marching cubes algorithm was selected to reconstruct the 3D model of the lateral skull base. Accurate alignment of the structures in the serial macroscopic sections was obtained by the employment of the plastination technique. The quality of the reconstructed images was distinct and perfect, specifically, the spatial positions and complicated adjacent relationships of various structures of the lateral skull base can be shown in direct viewing when they are displayed in background of the cranial bony substance. The time spent in displaying or rotating one image including 50 sections was 1.5 sec; all reconstructed structures can be represented individually or jointly and rotated in any plane. The plastination technique and computer-aided 3D reconstruction have an obvious advantage in the study of the complex anatomy of the lateral skull base. Plastination technique provides cross-section images of a higher resolution than those obtained from CT scanning. The computerized 3D reconstruction is important in studying the spatial anatomy of the lateral skull base and can serve as a standard for models created with other techniques.

Plastination and computerized 3D reconstruction of the temporal bone.

The purpose of this study was to generate a computerized 3D reconstruction of the temporal bone and intratemporal structures. A plastination technique was used to obtain equidistant serial thin sections of 1.2 mm thickness and, on an SGI workstation, a Contour-Marching Cubes algorithm was selected to reconstruct the temporal bone and intratemporal structures in three dimensions. All reconstructed structures can be represented individually or jointly and rotated in any plane. Any diameter and angle of a structure can be conveniently measured. The capability of reconstructing individual and combined images of intratemporal structures, viewing them from all surgical angles, and accurately measuring their spatial relationships gives skull base and otologic surgeons important guidance. The reconstructed model can also be used for resident education, rehearsal of an unfamiliar surgery, and for developing a new surgical approach.

[Visualization of the parapharyngeal space of the Chinese visible human].

OBJECTIVE: To build digitized visible model of the parapharyngeal space(PPS) of Chinese visible human. METHOD: Cross-sectional images from the Chinese visible human data set were reviewed and the structures of the parapharyngeal space were confirmed on a section-by-section basis. Three-dimensional computer reconstructions of the parapharyngeal space and surrounding structures were generated from these data using PC and imaging software. RESULT: The three-dimensional reconstructed images displayed perfectly the anatomical relationships of the parapharyngeal space, parotid, muscles, mandible and vessels. All reconstructed structures can be represented individually or jointly, any diameter and angle of the structures reconstructed could be measured conveniently. CONCLUSION: The Chinese visible human data set can provide complete and accurate data. The digitized model of the parapharyngeal space and its surroundings offer unique insights into the complex anatomy, and provide morphological data for image diagnosis and operation of the parapharyngeal space.