Maternal factor Trim75 contributes to zygotic genome activation program in mouse early embryos.

BACKGROUND: Zygotic genome activation (ZGA) is an important event in the early embryo development, and human embryo developmental arrest has been highly correlated with ZGA failure in clinical studies. Although a few studies have linked maternal factors to mammalian ZGA, more studies are needed to fully elucidate the maternal factors that are involved in ZGA. METHODS AND RESULTS: In this study, we utilized published single-cell RNA sequencing data from a Dux-mediated mouse embryonic stem cell to induce a 2-cell-like transition state and selected potential drivers for the transition according to an RNA velocity analysis. CONCLUSIONS: An overlap of potential candidate markers of 2-cell-like-cells identified in this research with markers generated by various data sets suggests that Trim75 is a potential driver of minor ZGA and may recruit EP300 and establish H3K27ac in the gene body of minor ZGA genes, thereby contributing to mammalian preimplantation embryo development.

Parkinson's disease gene, Synaptojanin1, dysregulates the surface maintenance of the dopamine transporter.

Missense mutations of PARK20/SYNJ1 (synaptojanin1/Synj1) have been linked to complex forms of familial parkinsonism, however, the molecular and cellular changes associated with dopaminergic dysfunction remains unknown. We now report fast depletion of evoked dopamine (DA) and altered maintenance of the axonal dopamine transporter (DAT) in the Synj1+/- neurons. While Synj1 has been traditionally known to facilitate the endocytosis of synaptic vesicles, we demonstrated that axons of cultured Synj1+/- neurons exhibit an increase of total DAT but a reduction of the surface DAT, which could be exacerbated by neuronal activity. We revealed that the loss of surface DAT is specifically associated with the impaired 5'-phosphatase activity of Synj1 and the hyperactive downstream PI(4,5)P2-PKCß pathway. Thus, our findings provided important mechanistic insight for Synj1-regulated DAT trafficking integral to dysfunctional DA signaling in early parkinsonism.

Neuroprotective Effects of Leptin on the APP/PS1 Alzheimer's Disease Mouse Model: Role of Microglial and Neuroinflammation.

Background: Microglia are closely linked to Alzheimer's disease (AD) many years ago; however, the pathological mechanisms of AD remain unclear. The purpose of this study was to determine whether leptin affected microglia in the hippocampus of young and aged male APP/PS1 mice. Objective: In a transgenic model of AD, we investigated the association between intraperitoneal injection of leptin and microglia. Methods: We intraperitoneal injection of leptin (1mg/kg) every day for one week and analyzed inflammatory markers in microglia in the hippocampus of adult (6 months) and aged (12 months) APP/PS1 mice. Results: In all leptin treatment group, the brain Aß levels were decrease. We found increased levels of IL-1ß, IL-6 and microglial activation in the hippocampus of adult mice. Using aged mice as an experimental model for chronic neuroinflammation and leptin resistance, the number of Iba-1+ microglia and the levels of IL-1ß/IL-6 in the hippocampus were greatly increased as compared to the adult. But between the leptin treatment and un-treatment, there were no difference. Conclusion: Leptin signaling would regulate the activation of microglia and the release of inflammatory factors, but it is not the only underlying mechanism in the neuroprotective effects of AD pathogenesis.

TRPM2 as a conserved gatekeeper determines the vulnerability of DA neurons by mediating ROS sensing and calcium dyshomeostasis.

Different dopaminergic (DA) neuronal subgroups exhibit distinct vulnerability to stress, while the underlying mechanisms are elusive. Here we report that the transient receptor potential melastatin 2 (TRPM2) channel is preferentially expressed in vulnerable DA neuronal subgroups, which correlates positively with aging in Parkinson's Disease (PD) patients. Overexpression of human TRPM2 in the DA neurons of C. elegans resulted in selective death of ADE but not CEP neurons in aged worms. Mechanistically, TRPM2 activation mediates FZO-1/CED-9-dependent mitochondrial hyperfusion and mitochondrial permeability transition (MPT), leading to ADE death. In mice, TRPM2 knockout reduced vulnerable substantia nigra pars compacta (SNc) DA neuronal death induced by stress. Moreover, the TRPM2-mediated vulnerable DA neuronal death pathway is conserved from C. elegans to toxin-treated mice model and PD patient iPSC-derived DA neurons. The vulnerable SNc DA neuronal loss is the major symptom and cause of PD, and therefore the TRPM2-mediated pathway serves as a promising therapeutic target against PD.

Nacre-inspired, strong, tough silk fibroin hydrogels based on biomineralization and the layer-by-layer assembly of ordered silk fabric.

Hydrogels are attractive materials with structures and functional properties similar to biological tissues and widely used in biomedical engineering. However, traditional synthetic hydrogels possess poor mechanical strength, and their applications are limited. Herein, a multidimensional material design method is developed; it includes the in situ gelation of silk fabric and nacre-inspired layer-by-layer assembly, which is used to prepare silk fibroin (SF) hydrogels. The in situ gelation method of silk fabric introduces a directionally ordered fabric network in a silk substrate, considerably enhancing the strength of hydrogels. Based on the nacre structure, the layer-by-layer assembly method enables silk hydrogels to break through the size limit and increase the thickness, realizing the longitudinal extension of the hydrogels. The application of the combined biomineralization and hot pressing method can effectively reduce interface defects and improve the interaction between organic and inorganic interfaces. The multidimensional material design method helps increase the strength (287.78 MPa), toughness (18.43 MJ m-3), and fracture energy (50.58 kJ m-2) of SF hydrogels; these hydrogels can weigh 2000 times their own weight. Therefore, SF hydrogels designed using the aforementioned combined method can realize the combination of strength and toughness and be used in biological tissue engineering and structural materials.

The benefit of rhGH therapy in a Chinese child with 12q14 microdeletion syndrome: a case report.

OBJECTIVES: The 12q14 microdeletion syndrome is a rare genetic condition characterized by intrauterine growth restriction, proportionate short stature, failure to thrive, and intellectual disability. Few reports have discussed the therapeutic aspect of patients with 12q14 microdeletion syndrome. Herein, we report the first case of 12q14 microdeletion patient treated with rhGH without growth hormone deficiency. CASE PRESENTATION: The patient presented with feeding difficulties during infancy, failure to thrive, intellectual disability and subtle dysmorphic facial features. The patient first visited the clinic at 5 years and 3 months, his height was 91.4 cm (-4.9 SD) and weight 10.0 kg (-2.86 SD). The growth hormone level was within the normal range. Bone radiological testing revealed no significant abnormalities. Genetic analysis identified a 6.97 Mb deletion at the chromosome 12q14.1-q14.3 region in the proband. Recombinant human growth hormone therapy was initiated, which lasted for 12 months, and the new height was 101.0 cm (-4.0 SD) and weight 12.0 kg (-3.6 SD). CONCLUSIONS: This report first showed that patient with 12q14 microdeletion, although without growth hormone deficiency, can benefit from human growth hormone therapy.

Cartilage structure-inspired elastic silk nanofiber network hydrogel for stretchable and high-performance supercapacitors.

Flexible supercapacitors are an important portable energy storage but suffer from low capacitance, inability to stretch, etc. Therefore, flexible supercapacitors must achieve higher capacitance, energy density, and mechanical robustness to expand the applications. Herein, a hydrogel electrode with excellent mechanical strength was created by simulating the collagen fiber network and proteoglycan in cartilage using silk nanofiber (SNF) network and polyvinyl alcohol (PVA). The Young's modulus and breaking strength of the hydrogel electrode increased by 205 % and 91 % compared with PVA hydrogel owing to the enhanced effect of the bionic structure, respectively, which are 1.22 MPa and 1.3 MPa. The fracture energy and fatigue threshold reached 1813.5 J/m2 and 1585.2 J/m2, respectively. The SNF network effectively connected carbon nanotubes (CNTs) and polypyrrole (PPy) in series, affording a capacitance of 13.62 F/cm2 and energy density of 1.2098 mWh/cm2. This capacitance is the highest among currently reported PVA hydrogel capacitors, which can maintain >95.2 % after 3000 charge-discharge cycles. This capacitance Notably, the cartilage-like structure endowed the supercapacitor with high resilience; thus, the capacitance remained >92.1 % under 150 % deformation and >93.35 % after repeated stretching (3000 times), which was far superior to that of other PVA-based supercapacitors. Overall, this effective bionic strategy can endow supercapacitors with ultrahigh capacitance and effectively ensure the mechanical reliability of flexible supercapacitors, which will help expand the applications of supercapacitors.

Synaptojanin1 Modifies Endolysosomal Parameters in Cultured Ventral Midbrain Neurons.

The accumulation of α-synuclein (α-syn)-enriched protein aggregates is thought to arise from dysfunction in degradation systems within the brain. Recently, missense mutations of SYNJ1 encoding the SAC1 and 5'-phosphatase domains have been found in families with hereditary early-onset Parkinsonism. Previous studies showed that Synj1 haploinsufficiency (Synj1+/-) leads to accumulation of the autophagy substrate p62 and pathologic α-syn proteins in the midbrain (MB) and striatum of aged mice. In this study, we aim to investigate the neuronal degradation pathway using the Synj1+/- MB culture from mouse pups of mixed sex as a model. Our data show that GFP-LC3 puncta formation and cumulative mKeima puncta formation are unaltered at baseline in Synj1+/- MB neurons. However, GFP-LAMP1 puncta is reduced with a similar decrease in endogenous proteins, including lysosomal-associated membrane protein (LAMP)1, LAMP2, and LAMP2A. The LAMP1 vesicles are hyperacidified with enhanced enzymatic activity in Synj1+/- MB neurons. Using a combination of light and electron microscopy (EM), we show that endolysosomal changes are primarily associated with a lack of SAC1 activity. Consistently, expressing the SYNJ1 R258Q mutant in N2a cells reduces the lysosome number. Interestingly, the endolysosomal defects in Synj1+/- neurons does not impact the clearance of exogenously expressed wild-type (WT) α-syn; however, the clearance of α-syn A53T was impaired in the axons of Synj1+/- MB neurons. Taken together, our results suggest axonal vulnerability to endolysosomal defects in Synj1-deficient MB neurons.

CT-Based Calculation Model Assists Precise Treatment for Anterior and Posterior Ankle Bony Impingement.

OBJECTIVE: Ankle arthroscope is the preferred tool for ankle surgeons to treat ankle impingement. However, there is no relevant report on how to improve the accuracy of arthroscopic osteotomy through preoperative planning. The aims of this study were to investigate a novel method to obtain the bone morphology in anterior and posterior ankle bony impingement through computed tomography (CT) calculation model, use this method to guide surgical decision-making, and compare the postoperative efficacy and actual bone cutting volume with conventional surgery. METHODS: This retrospective cohort study includes 32 consecutive cases with anterior and posterior ankle bony impingement by arthroscopy from January 2017 to December 2019. Mimics software was utilized to calculate the bony morphology and measure the volume of the osteophytes by two trained software engineers. The patients were divided into the precise group (n = 15) and the conventional group (n = 17) according to whether obtain and quantify the osteophytes' morphology with CT based calculation model preoperative. All patients were evaluated clinically using visual analog scale (VAS) score, American Orthopaedic Foot and Ankle Society (AOFAS) score, active dorsiflexion and plantarflexion angle before and after surgery at both 3 months and 12 months postoperatively. We obtained the shape and volume of bone cutting through Boolean calculation. Clinical outcomes and radiological data were compared between the two groups. RESULTS: The VAS score, AOFAS score, active dorsiflexion angle and plantarflexion angle were significantly improved in both groups postoperatively. In comparison of the VAS score, AOFAS score, and active dorsiflexion angle, the precise group were higher than the conventional group in the follow-up at 3 and 12 months postoperatively with statistical difference. The difference between the virtual bone cutting volume and the actual bone cutting volume of the anterior edge of distal tibia in the conventional group and precise group were 244.20 ± 147.66 mm3 and 76.53 ± 168.51 mm3 , respectively, there was statistical difference between the two groups (t = -2.927, p = 0.011). CONCLUSION: Using a novel method of obtaining and quantifying the bony morphology with CT-based calculation model for anterior and posterior ankle bony impingement can help guide surgical decision-making preoperatively and assist precise bone cutting during the operation, which can improve the efficacy and evaluate the accuracy of osteotomy postoperatively.

Cocaine-regulated trafficking of dopamine transporters in cultured neurons revealed by a pH sensitive reporter.

Cocaine acts by inhibiting plasma membrane dopamine transporter (DAT) function and altering its surface expression. The precise manner and mechanism by which cocaine regulates DAT trafficking, especially at neuronal processes, are poorly understood. In this study, we engineered and validated the use of DAT-pHluorin for studying DAT localization and its dynamic trafficking at neuronal processes of cultured mouse midbrain neurons. We demonstrate that unlike neuronal soma and dendrites, which contain a majority of the DATs in weakly acidic intracellular compartments, axonal DATs at both shafts and boutons are primarily (75%) localized to the plasma membrane, whereas large varicosities contain abundant intracellular DAT within acidic intracellular structures. We also demonstrate that cocaine exposure leads to a Synaptojanin1-sensitive DAT internalization process followed by membrane reinsertion that lasts for days. Thus, our study reveals the previously unknown dynamics and molecular regulation for cocaine-regulated DAT trafficking in neuronal processes.

Application status and prospect of biodegradable polymer stents in pancreatobiliary disease / 中华肝胆外科杂志

Endoscopic stent implantation is one of the main methods for the treatment of biliary and pancreatic diseases. At present, the commonly used biliary and pancreatic stents are mainly plastic and metal stents which are still have some deficiencies in clinical applications, and the emergence of the new type of biodegradable polymer materials is expected to achieve the purpose of treatment to overcome these shortcomings. It is a potential hope to break through the bottleneck of endoscopic treatment of choleopancreatic diseases. Previous animal experiments and human clinical studies have preliminarily shown its safety and effectiveness, which can effectively solve some problems of bile and pancreatic duct stenosis and so on. Biodegradable polymer stents have been widely studied, but their clinical application progress is slow and not yet popular, and it has gradually become a research hotspot in recent years . This article discusses the research status and development direction of biodegradable polymer stents in biliary and pancreatic diseases.

Risk factors of acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone and construction of prediction model / 中华消化外科杂志

Objective:To investigate the risk factors of acute biliopancreatic complica-tions in patients of pregnancy combined with gallbladder stone and construction of prediction model.Methods:The retrospective case-control study was constructed. The clinical data of 98 patients of pregnancy combined with gallbladder stone who were admitted to the First Hospital of Lanzhou University from September 2011 to October 2022 and 53 patients of pregnancy combined with gallbladder stone who were admitted to Gansu Provincial Hospital May 2014 to October 2021 were collected. The age of 151 patients was 29(25,32)years. Observation indicators: (1) situations of patients of pregnancy combined with gallbladder stone; (2) risk factors of acute biliopancreatic com-plications in patients of pregnancy combined with gallbladder stone; (3) construction of prediction model for acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the rank sum test. Univariate and multi-variate analyses were conducted using the Logistic regression model. Nomogram prediction model was conducted, and the receiver operating characteristic (ROC) curve was used to evaluate discri-mination of the nomogram predic-tion model. The calibration curve and clinical decision curve were used to evaluate calibration and net clinical benefit of the nomogram prediction model. Internal validation of the prediction model was performed by applying 10-fold cross-validation. Results:(1) Situations of patients of pregnancy combined with gallbladder stone. The total cholesterol, triglyceride, high density lipoprotein cholesterol, low density lipoprotein cholesterol, prepregnancy body mass index (<18.5 kg/m 2, 18.5?24.0 kg/m 2, >24.0 kg/m 2), gesta-tional period (early, mid, late), primipara (positive, negative), stone type (solitary, non solitary), diameter of stone (≤10 mm, >10 mm), gallbladder wall thickness (≥4 mm, <4 mm) were (4.9±1.4)mmol/L, 1.88(1.22,2.93)mmol/L, 1.48(1.22,1.83)mmol/L, (2.8±0.9)mmol/L, 13, 75, 58, 37, 45, 69, 86, 65, 37, 114, 89, 62, 38, 113 in the 151 patients of pregnancy combined with gallbladder stone. Of the 151 patients, the age, prepregnancy body mass index (<18.5 kg/m 2, 18.5?24.0 kg/m 2, >24.0 kg/m 2), primipara (positive, negative), stone type (solitary, non solitary), diameter of stone (≤10 mm, >10 mm), gallbladder wall thickness (≥4 mm, <4 mm) were 31(28,37)years, 3, 30, 36, 29, 40, 32, 37, 26, 43, 4, 65 in 69 cases without symptom, versus 27(24,31)years, 10, 45, 22, 57, 25, 5, 77, 63, 19, 34, 48 in 82 cases combined with acute biliopancreatic complications, showing significant differences in the above indicators between them ( Z=?3.636, ?2.385, χ2=11.544, 32.862, 23.729, 25.310, P<0.05). Five of the 82 patients of pregnancy combined with gallbladder stone missed data of prepregnancy body mass index. Of the 82 patients, there were 42 patients of simple acute cholecystitis, 40 patients of common bile duct stone and/or acute biliary pancreatitis including 18 cases of common bile duct stone, 13 cases of acute biliary pancreatitis and 9 cases of common bile duct stone combined with acute biliary pancreatitis. (2) Risk factors of acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone. Results of multivariate analysis showed that primipara, non solitary stone, diameter of stone ≤10 mm, gallbladder wall thickness ≥4 mm were independent risk factors of acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone ( odds ratio=3.102, 6.305, 3.674, 6.686, 95% confidence interval as 1.280?7.519, 1.886?21.080, 1.457?9.265, 1.984?22.528, P<0.05). Results of multivariate analysis in further analysis showed that primipara, non solitary stone, gallbladder wall thickness ≥4 mm were independent risk factors of simple acute cholecystitis in patients of pregnancy combined with gallbladder stone ( odds ratio=3.671, 8.905, 7.137, 95% confidence interval as 1.386?9.723, 2.332?34.006, 1.902?26.773, P<0.05), and age, non solitary stone, diameter of stone ≤10 mm, gallbladder wall thickness ≥4 mm were independent risk factors of common bile duct stone and/or acute biliary pancreatitis in patients of pregnancy combined with gallbladder stone ( odds ratio=0.883, 5.361, 5.472, 8.895, 95% confidence interval as 0.789?0.988, 1.062?27.071, 1.590?18.827, 2.064?38.325, P<0.05). (3) Construction of prediction model for acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone. The nomogram prediction model for acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone was constructed based on the clinical factors of age, primipara, stone type, diameter of stone and gallbladder wall thickness. The area under the curve (AUC) of ROC curve of prediction model was 0.869 (95% confidence interval as 0.813?0.923), indicating that the prediction model with good predictive ability. Results of Hosmer-Lemeshow test showed a good fit ( χ2=5.680, P>0.05), indicating that the prediction model with good calibration. Results of decision curve analysis showed the prediction model with high net clinical benefit. Results of internal validation of the prediction model based on 10-fold cross-validation showed the AUC of ROC curve for the cross-validation sample was 0.833, indicating that the prediction model with good stability. Conclusions:Primigravida, non solitary stone, diameter of stone ≤10 mm, gallbladder wall thickness ≥4 mm are independent risk factors of acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone. The prediction model for acute biliopancreatic complications has good predictive ability.

Influencing factors of textbook outcomes in liver surgery after radical resection of gallbladder carcinoma: a national multicenter study / 中华消化外科杂志

Objective:To investigate the influencing factors of textbook outcomes in liver surgery (TOLS) after radical resection of gallbladder carcinoma.Methods:The retrospective case-control study was conducted. The clinicopathological data of 530 patients who underwent radical resection of gallbladder carcinoma in 15 medical centers, including the First Affiliated Hospital of Army Medical University et al, from January 2014 to January 2020 were collected. There were 209 males and 321 females, aged (61±10)years. Patients underwent radical resection of gallbladder carcinoma, including cholecystectomy, hepatectomy, invasive bile duct resection, and lymph node dissection. Observation indicators: (1) situations of TOLS; (2) influencing factors of TOLS. Measure-ment data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data between groups was conducted using the Mann-Whitney U test. The univariate analysis was conducted using the corresponding statistical methods based on data type, and variables with P<0.10 were included in multivariate analysis. Multivariate analysis was conducted using the Logistic stepwise regression model. Results:(1) Situations of TOLS. All 530 patients underwent radical resection of gallbladder carcinoma, and there were 498 cases achieving R 0 resection, 508 cases without ≥grade 2 intra-operative adverse events, 456 cases without postoperative grade B and grade C biliary leakage, 513 cases without postoperative grade B and grade C liver failure, 395 cases without severe com-plications within postoperative 90 days, 501 cases did not being re-admission caused by severe com-plications within postoperative 90 days. Of the 530 patients, 54.53%(289/530) of patients achieved postoperative TOLS, while 45.47%(241/530) of patients did not achieve postoperative TOLS. (2) Influencing factors of TOLS. Results of multivariate analysis showed that American Society of Anesthesiologists classification >grade Ⅱ, preoperative jaundice, T staging as T3?T4 stage, N staging as N2 stage, liver resection as right hemi-hepatectomy, and neoadjuvant therapy were independent factors influencing TOLS in patients undergoing radical resection of gallbladder carcinoma ( odds ratio=2.65, 1.87, 5.67, 5.65, 2.55, 3.34, 95% confidence interval as 1.22?5.72, 1.18?2.95, 2.51?12.82, 2.83?11.27, 1.41?4.63, 1.88?5.92, P<0.05). Conclusion:American Society of Anesthesiologists classification >grade Ⅱ, preoperative jaundice, T staging as T3?T4 stage, N staging as N2 stage, liver resection as right hemi-hepatectomy, and neoadjuvant therapy are independent factors influencing TOLS in patients undergoing radical resection of gallbladder carcinoma.

Clinical characteristics of choledocholithiasis combined with periampullary diverticulum and influencing factor analysis for difficult cannulation of endoscopic retrograde cholangiopan-creatography: a report of 1 920 cases / 中华消化外科杂志

Objective:To investigate the clinical characteristics of choledocholithiasis com-bined with periampullary diverticulum and influencing factor for difficult cannulation of endoscopic retrograde cholangiopancreatography (ERCP).Methods:The retrospective case-control study was conducted. The clinical data of 1 920 patients who underwent ERCP for choledocholithiasis in 15 medical centers, including the First Hospital of Lanzhou University, et al, from July 2015 to December 2017 were collected. There were 915 males and 1 005 females, aged (63±16)years. Of 1 920 patients, there were 228 cases with periampullary diverticulum and 1 692 cases without periampullary diverticulum. Observation indicators: (1) clinical characteristics of patients with choledocholithiasis; (2) intraoperative and postoperative situations of patients undergoing ERCP for choledocholithiasis; (3) influencing factor analysis for difficult cannulation in patients undergoing ERCP for choledocholithiasis. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and com-parison between groups was conducted using the Wilcoxon rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. The Logistic regression model was used for univariate and multivariate analyses. Results:(1) Clinical characteristics of patients with choledocholithiasis. Age, body mass index, cases with complications as chronic obstructive pulmonary disease, diameter of common bile duct, cases with diameter of common bile duct as <8 mm, 8?12 mm, >12 mm, diameter of stone, cases with number of stones as single and multiple were (69±12)years, (23.3±3.0)kg/m 2, 16, (14±4)mm, 11, 95, 122, (12±4)mm, 89, 139 in patients with choledocholithiasis combined with periampullary diverticulum, versus (62±16)years, (23.8±2.8)kg/m 2, 67, (12±4)mm, 159, 892, 641, (10±4)mm, 817, 875 in patients with choledocholithiasis not combined with periampullary diver-ticulum, showing significant differences in the above indicators between the two groups ( t=?7.55, 2.45, χ2=4.54, t=?4.92, Z=4.66, t=?7.31, χ2=6.90, P<0.05). (2) Intraoperative and postoperative situations of patients undergoing ERCP for choledocholithiasis. The balloon expansion diameter, cases with intraoperative bleeding, cases with hemorrhage management of submucosal injection, hemostatic clip, spray hemostasis, electrocoagulation hemostasis and other treatment, cases with endoscopic plastic stent placement, cases with endoscopic nasal bile duct drainage, cases with mechanical lithotripsy, cases with stone complete clearing, cases with difficult cannulation, cases with delayed intubation, cases undergoing >5 times of cannulation attempts, cannulation time, X-ray exposure time, operation time were 10.0(range, 8.5?12.0)mm, 56, 6, 5, 43, 1, 1, 52, 177, 67, 201, 74, 38, 74, (7.4±3.1)minutes, (6±3)minutes, (46±19)minutes in patients with choledocholithiasis combined with periampullary diverticulum, versus 9.0(range, 8.0?11.0)mm, 243, 35, 14, 109, 73, 12, 230, 1 457, 167, 1 565, 395, 171, 395, (6.6±2.9)minutes, (6±5)minutes, (41±17)minutes in patients with choledocholithiasis not combined with periampullary diverticulum, showing significant differences in the above indicators between the two groups ( Z=6.31, χ2=15.90, 26.02, 13.61, 11.40, 71.51, 5.12, 9.04, 8.92, 9.04, t=?3.89, 2.67, ?3.61, P<0.05). (3) Influencing factor analysis for difficult cannulation in patients undergoing ERCP for choledocholithiasis. Results of multivariate analysis showed total bilirubin >30 umol/L, number of stones >1, combined with periampullary diverticulum were indepen-dent risk factors for difficult cannulation in patients with periampullary diverticulum who underwent ERCP for choledocholithiasis ( odds ratio=1.31, 1.48, 1.44, 95% confidence interval as 1.06?1.61, 1.20?1.84, 1.06?1.95, P<0.05). Results of further analysis showed that, of 1 920 patients undergoing ERCP for choledocholithiasis, the incidence of postoperative pancreatitis was 17.271%(81/469) and 8.132%(118/1 451) in the 469 cases with difficult cannulation and 1 451 cases without difficult cannula-tion, respectively, showing a significant difference between them ( χ2=31.86, P<0.05). In the 1 692 patients with choledocholithiasis not combined with periampullary diverticulum, the incidence of postopera-tive pancreatitis was 17.722%(70/395) and 8.250%(107/1 297) in 395 cases with difficult cannula-tion and 1 297 cases without difficult cannulation, respectively, showing a significant difference between them ( χ2=29.00, P<0.05). In the 228 patients with choledocholithiasis combined with peri-ampullary diverticulum, the incidence of postoperative pancreatitis was 14.865%(11/74) and 7.143%(11/154) in 74 cases with difficult cannulation and 154 cases without difficult cannulation, respectively, showing no significant difference between them ( χ2=3.42, P>0.05). Conclusions:Compared with patients with choledocholithiasis not combined with periampullary divertioulum, periampullary divertioulum often occurs in choledocholithiasis patients of elderly and low body mass index. The proportion of chronic obstructive pulmonary disease is high in choledocholithiasis patients with periampullary diverticulum, and the diameter of stone is large, the number of stone is more in these patients. Combined with periampullary diverticulum will increase the difficult of cannulation and the ratio of patient with mechanical lithotripsy, and reduce the ratio of patient with stone complete clearing without increasing postoperative complications of choledocholithiasis patients undergoing ERCP. Total bilirubin >30 μmol/L, number of stones >1, combined with periampullary diverticulum are independent risk factors for difficult cannulation in patients of periampullary diverticulum who underwent ERCP for choledocholithiasis.

Performance of the clinical assessment scale for autoimmune encephalitis in a pediatric autoimmune encephalitis cohort.

Background: The Clinical Assessment Scale for Autoimmune Encephalitis (CASE), a new scale used for rating the severity of autoimmune encephalitis (AE), has demonstrated good validity and reliability in adults with AE, but there is a shortage of data on its performance in children with AE. This study aimed to assess the reliability and validity of the CASE in a cohort of children with AE. Methods: Forty-seven pediatric inpatients with AE who visited Guizhou Provincial People's Hospital between January 1, 2017, and October 31, 2021, were enrolled in the study. The CASE and mRS scores were obtained through a review of detailed medical records from the Health Information System by two pediatric neurologists. Finally, the performance of the CASE in this pediatric AE cohort was analyzed. Results: The results showed that anti-NMDA receptor encephalitis was the most common (61.70%) type of AE in children. The most common clinical manifestations were language problems (85.1%), psychiatric symptoms (80.9%), and dyskinesia/dystonia (78.7%). The CASE had good item reliability and interevaluator reliability; the Cronbach's alpha value of the total score was 0.825, and the intraclass correlation (ICC) was 0.980. The Cronbach's alpha value by item ranged from 0.16 to 0.406; items 1 and 9 had the lowest and highest Cronbach's alpha values, respectively. The criterion validity between CASE and mRS total scores, as quantified by Pearson correlation, was 0.459, indicating slight to good criterion validity. The area under the curve (AUC) was 0.992 (95% confidence interval: 0.974-1.00). A cutoff value of 14 was selected to determine whether a patient needed admission to the ICU; this cutoff had a sensitivity of 100% and a specificity of 92%. The changes in EEG, MRI, and antibody titers were not related to the severity of AE. A CASE score cutoff of 9 was selected to indicate whether second-line treatment would be needed. Conclusion: The CASE has good reliability and validity in children with AE; however, some items of the CASE may not apply to this population. Thus, an in-depth study of the CASE is needed in children with AE.

The Antibody Assay in Suspected Autoimmune Encephalitis From Positive Rate to Test Strategies.

Objective: The aim of this study was to analyze the positive rate and test strategies of suspected autoimmune encephalitis (SAE) based on an antibody assay. Methods: Patients who were diagnosed with suspected autoimmune encephalitis in Guizhou Province between June 1, 2020, and June 30, 2021 and who had anti-neuronal autoantibodies detected by Guizhou KingMed Diagnostics Group Co., Ltd. were included in this study. The positive rate and the test strategies were analyzed based on the results of the anti-neuronal antibody assay. Results: A total of 263 patients with SAE were included, 58.2% (153/263) of whom were males, with a median age of 33 years (1-84 years). 84% (221/263) of all patients completed both serum and CSF tests. A total of 46.0% (121/263) of SAE patients received the AE-6 examination package. The antibody-positive rate was 9.9% (26/263) in the current cohort, with an observed incidence of antibody positive of 0.2 in 100,000 (26/11,570,000, 95% CI: 0.15-0.30), and the estimated incidence was 0.9 in 100,000 (95% CI: 0.84-0.95) of the total population. A total of 9 different anti-neuronal antibodies were detected. Anti-NMDAR antibody was the most common antibody in 46.2% (12/26) of subjects, 70.0% (7/10) of whom were children, followed by anti-Caspr2 antibody in 30.8% (8/26); the remaining 7 antibodies were detected in 23.1% (6/26) of the population. There were no obvious differences among age, sex or season in the positive rate of anti-neuronal antibodies. The cost of antibody testing per capita was $439.30 (SD±$195.10). The total cost of AE-14 was the highest at $48.016.81 (41.56%) among all examination packages. Conclusions: This study described the positive rate associated with AE-related anti-neuronal antibodies and test strategies in the current cohort, which provides a basis for clinicians in clinical practice.

Air-Stable 2D Cr5 Te8 Nanosheets with Thickness-Tunable Ferromagnetism.

2D magnetic materials have aroused widespread research interest owing to their promising application in spintronic devices. However, exploring new kinds of 2D magnetic materials with better stability and realizing their batch synthesis remain challenging. Herein, the synthesis of air-stable 2D Cr5 Te8 ultrathin crystals with tunable thickness via tube-in-tube chemical vapor deposition (CVD) growth technology is reported. The importance of tube-in-tube CVD growth, which can significantly suppress the equilibrium shift to the decomposition direction and facilitate that to the synthesis reaction direction, for the synthesis of high-quality Cr5 Te8 with accurate composition, is highlighted. By precisely adjusting the growth temperature, the thickness of Cr5 Te8 nanosheets is tuned from ≈1.2 nm to tens of nanometers, with the morphology changing from triangles to hexagons. Furthermore, magneto-optical Kerr effect measurements reveal that the Cr5 Te8 nanosheet is ferromagnetic with strong out-of-plane spin polarization. The Curie temperature exhibits a monotonic increase from 100 to 160 K as the Cr5 Te8 thickness increases from 10 to 30 nm and no apparent variation in surface roughness or magnetic properties after months of exposure to air. This study provides a robust method for the controllable synthesis of high-quality 2D ferromagnetic materials, which will facilitate research progress in spintronics.

Influencing factors for endoscopic retrograde cholangiopancreatography-related adverse events in novice trainees and establishment of its prediction model: a prospective study / 中华消化外科杂志

Objective:To investigate the influencing factors for endoscopic retrograde cholangiopancreatography (ERCP)-related adverse events in novice trainees and establishment of its prediction model.Methods:The prospective study was conducted. The clinical data of 12 novice trainees of ERCP in the First Hospital of Lanzhou University from July 2016 to July 2019 were selected. The operation was performed by 12 novice trainees of ERCP under the guidance of the endoscopic experts. Observation indicators: (1) ERCP-related adverse events in novice trainees; (2) analysis of influencing factors for ERCP-related adverse events in novice trainees; (3) establishment of a prediction model for ERCP-related adverse events in novice trainees. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed by the t test. Measurement data with skewed distribution were represented as M(range), and com-parison between groups was analyzed by the Mann-Whitney U test. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed by the chi-square test. The Logistic regression model was used for univariate and multivariate analyses. The regression coefficients were used to construct a prediction model. The receiver operating characteristic curve was drawn, and the area under curve was used to evaluate the predictive ability. Results:(1) ERCP-related adverse events in novice trainees. Of the 300 patients with ERCP operated by 12 novice trainees, 52 cases had ERCP-related adverse events and 248 cases had no ERCP-related adverse events. Cases in grade 1?2 or grade 3?4 of ERCP difficulty classification, score for intubation time, score for cannulation time, cases with or without completion of the cannulation, cases with or with-out basket stone removal, cases with or without stenosis expansion, score for contrast-enhanced interpretation, score for implementation of reasonable treatment and score for expected purpose reached were 22, 30, 8(range, 5?10), 20(rang, 9?20), 24, 28, 11, 41, 0, 52, 39±17, 39±19 and 44±23 for novice trainees with ERCP-related adverse events, versus 146, 102, 6(range, 4?9), 12(range, 8?20), 163, 85, 94, 154, 20, 228, 52±22, 80±20, 52±23 for novice trainees without ERCP-related adverse events, showing significant differences in the above indicators between them ( χ2=4.79, Z=?2.46, ?2.72, χ2=7.01, 5.30, 4.49, t=?4.00, ?2.97, ?2.29, P<0.05). (2) Analysis of influencing factors for ERCP-related adverse events in novice trainees. Results of univariate analysis showed that the diffi-culty classification of ERCP, intubation time, cannulation time, completion of cannulation, basket stone extraction, contrast-enhanced interpretation, implementation of reasonable treatment and expected purpose reached were related factors for ERCP-related adverse events in novice trainees ( odds ratio=1.95, 1.11, 1.08, 0.45, 0.44, 0.97, 0.98, 0.98, 95% confidence intervals as 1.07?3.58, 1.02?1.22, 1.02?1.14, 0.24?0.82, 0.22?0.90, 0.96?0.99, 0.96?0.99, 0.97?1.00, P<0.05). Results of multi-variate analysis showed that difficulty classification of ERCP and contrast-enhanced interpretation were independent influencing factors for ERCP-related adverse events in novice trainees ( odds ratio=2.08, 0.95, 95% confidence intervals as 1.10?3.96, 0.92?0.99, P<0.05). (3) Establishment of a predic-tion model for ERCP-related adverse events in novice trainees. According to the important outcome indicators of clinical training and results of multivariate analysis, 4 indicators including difficulty classification of ERCP, intubation time, cannulation time and contrast-enhanced interpretation were included to establish a prediction model for ERCP-related adverse events in novice trainees, which indicated that trainees with the predicted score >0.4 were in high risk of ERCP-related adverse events. The area under receiver operating characteristic curve of the prediction model was 0.72(95% confidence interval as 0.65?0.79, P<0.05), with the best cut-off value as 0.40, the sensitivity as 76.9% and the specificity as 63.3%. Conclusion:The difficulty classification of ERCP and contrast-enhanced interpretation are independent influencing factors for ERCP-related adverse events in novice trainees. Novice trainees with a predicted score >0.4 are high-risk groups of ERCP-related adverse events.

Endoscopic surgery strategies of delayed iatrogenic bile duct injury / 中华消化外科杂志

The treatment of iatrogenic bile duct injury is complex, especially for delayed iatrogenic bile duct injury, and the timing and treatment measures are crucial. Endoscopic surgery treatment, interventional treatment and surgery all play important roles. Endoscopic surgery treatment has become the main choice for iatrogenic bile duct injury because of its advantages of small trauma, fast recovery, short operation time and precise efficacy, etc. At the same time, endoscopic surgery treatment can create opportunities and conditions for secondary bile duct repair surgery, and can also control the occurrence of post-repair complications. With the further populari-zation and application of endoscopic technology, the development of imaging three-dimensional reconstruction technology and visualization analysis, endoscopic surgery treatment will definitely become the main treatment for delayed iatrogenic bile duct injury.

Mini-review: Synaptojanin 1 and its implications in membrane trafficking.

This mini-review aims to summarize a growing body of literature on synaptojanin 1 (Synj1), a phosphoinositide phosphatase that was initially known to have a prominent role in synaptic vesicle recycling. Synj1 is coded by the SYNJ1 gene, whose mutations and variants are associated with an increasing number of neurological disorders. To better understand the mechanistic role of Synj1 in disease pathogenesis, we review details of phosphoinositide signaling pathways and the reported involvement of Synj1 in membrane trafficking with a specific focus on Parkinson's disease (PD). Recent studies have tremendously advanced our understanding of Synj1 protein structure and function while broadening our view of how Synj1 regulates synaptic membrane trafficking and endosomal trafficking in various organisms and cell types. A growing body of evidence points to inefficient membrane trafficking as key pathogenic mechanisms in neurodegenerative diseases associated with abnormal Synj1 expression. Despite significant progress made in the field, the mechanism by which Synj1 connects to trafficking, signaling, and pathogenesis is lacking and remains to be addressed.