ObjectiveTo evaluate the clinical efficacy of Huayu Tongluo Formula （化瘀通络方， HTF） in patients with mid-stage diabetic kidney disease of blood stasis syndrome and explore its potential mechanisms. MethodsA multi-center， randomized， double-blind， placebo-controlled clinical trial was conducted. Ninety patients of mid-stage diabetic kidney disease of blood stasis syndrome were divided into a control group of 46 cases and a treatment group of 44 cases. Both groups received conventional western medicine treatment， the treatment group additionally taking HTF， while the control group taking a placebo of the formula. The treatment was administered once daily for 24 weeks. The primary outcomes included 24-hour urine total protein （24 h-UTP）， serum albumin （Alb）， glycated hemoglobin （HbA1c）， and serum creatinine （Scr）.The secondary outcomes included changes in levels of endothelin-1 （ET-1）， nitric oxide （NO）， vascular endothelial growth factor （VEGF）， and traditional Chinese medicine （TCM） syndrome scores before and after treatment. Clinical efficacy was evaluated based on TCM syndrome scores and overall disease outcomes. Adverse reactions and endpoint events were recorded. ResultsIn the treatment group after treatment， 24 h-UTP， ET-1， and VEGF levels significantly decreased （P＜0.05）， Alb and NO levels significantly increased （P＜0.05）； while the TCM syndrome scores for edema， lumbar pain， numbness of limbs， dark purple lips， dark purple tongue or purpura， and thin， rough pulse all significantly decreased （P＜0.05）. In the control group， no significant changes were observed in any of the indicators after treatment （P＞0.05）.Compared with the control group， the treatment group showed significant reductions in 24 h-UTP， ET-1， and VEGF levels， and increases in Alb and NO levels （P＜0.05）. The TCM syndrome scores for edema， lumbar pain， dark purple tongue or purpura， and thin， rough pulse were all lower in the treatment group than in the control group （P＜0.05）. The total effective rate of TCM syndrome in the treatment group was 59.09% （26/44）， and the overall clinical effective rate was 45.45% （20/44）. In the control group， these rates were 15.22% （7/46） and 8.7% （4/46）， respectively， with the treatment group showing significantly better outcomes （P＜0.05）. A total of 7 adverse events occurred across both groups， with no significant difference （P＞0.05）. No endpoint events occurred during the study. ConclusionOn the basis of conventional treatment of Western medicine， HTF can further reduce urinary protein levels and improve clinical symptoms in patients with mid-stage diabetic kidney disease of blood stasis syndrome. The mechanism may be related to its effects on endothelial function.

In the field of organ donation and transplantation, the determination of death faces the dilemma of the separation between medical standards and social cognition, which may hinder medical practice and lead to controversial legal evaluations. Establishing brain death criteria through the "hard law" model is the path currently adopted by many countries. However, this approach has limitations, such as the attribution of the right to define death in the law, the conflict between the technological iteration of brain death criteria and legal stability, and the neglect of the social construction of the concept of death. Based on the theory of gradual social engineering and social systems theory, establishing brain death criteria through the "soft law" model has both scientific adaptability and governance flexibility, and is conducive to cultivating social consensus on brain death criteria. In terms of implementation, it is essential to focus on the high-level positioning of the "soft law" formulation entities for brain death criteria, the professionalization of the implementation entities, the publicization of the formulation process, and the institutionalization of risk communication strategies. At the same time, it is necessary to strengthen the informed consent of close relatives and design a dispute resolution mechanism for misjudgments of brain death to guard against potential improper risks.

G protein-coupled receptors (GPCRs) are a large family of membrane protein receptors, and Takeda G protein-coupled receptor 5 (TGR5) is a member of this family. As a membrane receptor, TGR5 is widely distributed in different parts of the human body and plays a vital role in regulating metabolism, including the processes of energy consumption, weight loss and blood glucose homeostasis. Recent studies have shown that TGR5 plays an important role in glucose and lipid metabolism disorders such as fatty liver, obesity and diabetes. With the global obesity situation becoming more and more serious, a comprehensive explanation of the mechanism of TGR5 and filling the gaps in knowledge concerning clinical ligand drugs are urgently needed. In this review, we mainly explain the anti-obesity mechanism of TGR5 to promote the further study of this target, and show the electron microscope structure of TGR5 and review recent studies on TGR5 ligands to illustrate the specific binding between TGR5 receptor binding sites and ligands, which can effectively provide new ideas for ligand research and promote drug research.

Background: and Purpose X-linked Charcot-Marie-Tooth disease type 1 (CMTX1) is characterized by peripheral neuropathy with or without episodic neurological dysfunction. We performed clinical, neuropathological, and genetic investigations of a series of patients with mutations of the gap-junction beta-1 gene (GJB1) to extend the phenotypic and genetic description of CMTX1. Methods: Detailed clinical evaluations, sural nerve biopsy, and genetic analysis were applied to patients with CMTX1. Results: We collected 27 patients with CMTX1 with GJB1 mutations from 14 unrelated families. The age at onset (AAO) was 20.9±12.2 years (mean±standard deviation; range, 2–45 years). Walking difficulties, weakness in the legs, and pes cavus were common initial symptoms. Compared with female patients, males tended to have a younger AAO (males vs. females=15.4±9.6 vs. 32.0±8.8 years, p=0.002), a longer disease course (16.8±16.1 vs. 5.5±3.8 years, p=0.034), and more-severe electrophysiological results. Besides peripheral neuropathy, six of the patients had special episodic central nervous system (CNS) evidence from symptoms, signs, and/or reversible white-matter lesions. Neuropathology revealed the loss of large myelinated fibers, increased number of regenerated axon clusters with abnormally thin myelin sheaths, and excessively folded myelin. Genetic analysis identified 14 GJB1 variants, 6 of which were novel. Conclusions These findings expand the phenotypic and genetic spectrum of CMTX1. Although CMTX1 was found to have high phenotypic and CNS involvement variabilities, detailed neurological examinations and nerve conduction studies will provide critical clues for accurate diagnoses. Further exploration of the underlying mechanisms of connexin 32 involvement in neuropathy or CNS dysfunction is warranted to develop promising therapies.

Humans ; East Asian People ; Surveys and Questionnaires ; Vitiligo/epidemiology*

Objective:To study the use of percutaneous transhepatic one-step biliary fistulation based on three-dimensional visualization technology (3D-PTOBF) in the treatment of complex hepatolithiasis.Methods:A retrospective analysis was conducted on 116 patients with complex hepatolithiasis treated in the First Affiliated Hospital of Guangzhou Medical University from January 2016 to December 2019. There were 56 patients in the 3D-PTOBF group (treated by 3D-PTOBF), and 60 patients in the traditional PTOBF group (received traditional PTOBF approach). The stone clearance rate, postoperative complication rate, intraoperative blood loss, hospitalization time, number of cholangioscopic treatment procedures and stone recurrence rate were compared between the two groups.Results:When compared with the traditional PTOBF group, the 3D-PTOBF group had significantly less procedures (1.43±0.71 vs. 2.07±1.22, P<0.05), and shorter hospital stay (4.6±2.3 d vs. 6.1±2.9 d, P<0.05). There were no significant differences in the immediate stone clearance, final stone clearance, postoperative complications and stone recurrence rates between the two groups (all P>0.05). Conclusion:3D-PTOBF was safe and feasible to treat complex hepatolithiasis. When compared with PTOBF, it had the advantages of shorter operation time and decreased hospital stay.

Objective:To summarize and analyze the clinical data of Chinese patients with colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy, and clarify the phenotypic and genetic characteristics of Chinese patients.Methods:Medical history of patients with CSF1R-related leukoencephalopathy diagnosed from April 1, 2018 to January 31, 2021 in the department of neurology of 22 hospitals in China was collected, and scores of Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment Scale (MoCA), magnetic resonance severity scale were evaluated. Group comparison was performed between male and female patients.Results:A total of 62 patients were included, and the male-female ratio was 1∶1.95. The age of onset was (40.35±8.42) years. Cognitive impairment (82.3%, 51/62) and motor symptoms (77.4%,48/62) were the most common symptoms. The MMSE and MoCA scores were 18.79±7.16 and 13.96±7.23, respectively, and the scores of two scales in male patients (22.06±5.31 and 18.08±5.60) were significantly higher than those in females (15.53±7.41 , t=2.954, P=0.006; 10.15±6.26, t=3.328 , P=0.003). The most common radiographic feature was bilateral asymmetric white matter changes (100.0%), and the magnetic resonance imaging severity scale score was 27.42±11.40, while the white matter lesion score of females (22.94±8.39) was significantly higher than that of males (17.62±8.74 , t=-2.221, P<0.05). A total of 36 CSF1R gene mutations were found in this study, among which c.2381T>C/p.I794T was the hotspot mutation that carried by 17.9% (10/56) of the probands. Conclusions:The core phenotypic characteristics of CSF1R-related leukoencephalopathy in China are progressive motor and cognitive impairment, with bilateral asymmetrical white matter changes. In addition, there exist gender differences clinically, with severer cognitive impairment and imaging changes in female patients. Thirty-six CSF1R gene mutations were found in this study, and c.2381T>C/p. I794T was the hotspot mutation.

The skin is the largest organ comprised of three main layers: epidermis, dermis and subcutaneous tissue. Characteristic microscopic and ultrastructural alterations are present in certain skin structures, such as nerve fibers, blood vessels and sweat glands, not only in vasculitis, but in several other metabolic neurologic diseases. In recent years, advances in immunohistochemistry and electron microscopy have made these dermatopathological changes identifiable and clear-cut. It was then recognized that such pathological feature could be present in many tissues in addition to those nerve systems clinically affected. Skin biopsy has become a recognized diagnostic procedure for peripheral neuropathy and central nervous system diseases. This article reviews the dermatopathology in neurological disorders under light and electron microscope to promote application of skin biopsy in clinical diagnosis for neurologist.

Objective To observe the effect of supplemental Revolvin D1 (RvD1) on Toll-like receptor 4 (TLR4) in skeletal muscle of type 2 diabetic mice.Methods 35 male C57BL/6 mice were randomly divided into control group (NC group) and high glucose and high fat diet group.After 8 weeks,mice in high glucose and high fat diet group were given intraperitoneal injection of streptozotocin (STZ) 100 mg/ kg.Then they were randomly divided into two groups:Type 2 diabetes group (T2DM group) and type 2 diabetes + RvD1 intervention group (T2DM + RvD1 group).Mice in T2DM group mice were injected with phosphate buffer saline 0.2 ml and T2DM + RvD1 group mice were injected with Revolvin D1 100 ng/day respectively.The levels of fasting blood glucose,serum insulin and inflammatory factors were detected.The mRNA expression level of TLR4 was detected by real-time quantitative polymerase chain reaction (RT-qPCR) method,and the expression of TLR4 protein was detected by Western blot.Results The levels of insulin resistance index,interleukin(IL)-6 and tumor necrosis factor-α (TNF-α) in T2DM group and T2DM + RvD1 group increased (P ＜ 0.05).Compared with the T2DM group,the levels of insulin resistance index,IL-6 and TNF-α in T2DM + RvD1 group decreased (P ＜0.05).The expression of TLR4 protein in T2DM group and T2DM + RvD1 group was higher than that in NC group (P ＜ 0.05).The expression of TLR4 protein in T2DM + RvD1 group,was lower than that in T2DM group (P ＜0.05).The mRNA level of TLR4 in mice was consistent with the above results by RT-qPCR.Conclusions Moderate supplementation of RvD1 can not only decrease the level of inflammatory factors in type 2 diabetic mice,but also reduce the expression of TLR4 and insulin resistance in skeletal muscle of type 2 diabetic mice.

Objective To investigate the effect of parents accompany comfort anesthesia technique on child anesthesia induction compliance.Methods Two hundreds and thirteen children cases undergoing elective operation under general anesthesia were selected,aged 2-12 years old,ASA grade Ⅰ-Ⅱ,developmental normal,without mental system and cognitive dysfunction,and randomly divided into the experimental group 1,2 and control group.The children cases in the experimental group 1 conducted the anesthesia induction by their parents accompany on the operation day,while those in the experimental 2 conducted the anesthesia induction on the operation day after conducting the comfort anesthesia technique guidance.The control group was performed the conventional follow up before operation,the anesthesia induction was performed by the operation nurses and anesthesia doctor accompany on the operation day.Results There were statistically significant differences between the cases of slightly large age,with surgical experience,parents non-anxiety and psychological internal control type with the control group(P＜0.05).The difference between conducting the anesthesia induction guidance and non-conducting the anesthesia induction guidance was not statistically significant(P＞0.05).Conclusion The parents accompany comfort anesthesia induction technique can effectively increase the compliance during the anesthesia induction period in the children patients with slightly large age,operation experience,parents non-anxiety and psychological internal control type.