Protein SUMOylation promotes cAMP-independent EPAC1 activation.

Protein SUMOylation is a prevalent stress-response posttranslational modification crucial for maintaining cellular homeostasis. Herein, we report that protein SUMOylation modulates cellular signaling mediated by cAMP, an ancient and universal stress-response second messenger. We identify K561 as a primary SUMOylation site in exchange protein directly activated by cAMP (EPAC1) via site-specific mapping of SUMOylation using mass spectrometry. Sequence and site-directed mutagenesis analyses reveal that a functional SUMO-interacting motif in EPAC1 is required for the binding of SUMO-conjugating enzyme UBC9, formation of EPAC1 nuclear condensate, and EPAC1 cellular SUMOylation. Heat shock-induced SUMO modification of EPAC1 promotes Rap1/2 activation in a cAMP-independent manner. Structural modeling and molecular dynamics simulation studies demonstrate that SUMO substituent on K561 of EPAC1 promotes Rap1 interaction by increasing the buried surface area between the SUMOylated receptor and its effector. Our studies identify a functional SUMOylation site in EPAC1 and unveil a novel mechanism in which SUMOylation of EPAC1 leads to its autonomous activation. The findings of SUMOylation-mediated activation of EPAC1 not only provide new insights into our understanding of cellular regulation of EPAC1 but also will open up a new field of experimentation concerning the cross-talk between cAMP/EPAC1 signaling and protein SUMOylation, two major cellular stress response pathways, during cellular homeostasis.

[The effect of glycopyrrolate on intestinal spasm and hemodynamics in painless colonoscopy].

Objective: To investigate the effects of glycopyrrolate on intestinal spasm and hemodynamics in painless colonoscopy. Methods: A total of 100 patients who were scheduled to undergo painless colonoscopy were selected as the study subjects and randomly divided into two groups by a computerized number method. Ten patients in both groups dropped out because of disruption of the study protocol, and 45 patients from each group were included in the final analysis. Before anesthesia induction, patients in group glycopyrrolate (group G) were injected with 0.2 mg glycopyrrolate, while those in congtrol group (group C) were injected with an equal amount of saline. The heart rate, systolic blood pressure, and diastolic blood pressure were recorded at T0 (baseline period), T1 (after anesthesia induction), T2 (colonoscopy over sigmoid colon), T3 (colonoscopy over the liver region), T4 (after the end of examination), and T5 (at the awakening phase), and the degree of intestinal spasm was assessed intraoperatively using the Likert's four-point scale. The numerical rating scale (NRS) was used to assess preoperative and postoperative pain. The incidence of adverse events was recorded. Results: The general data at baseline were not statistically different between the two groups (P>0.05). During the procedure, patients in group G had lower intraoperative intestinal spasm scores than those in group C (P=0.028). Intraoperative hypotension and bradycardia occurrence were lower in group G than in group C (P<0.05), and intraoperative norepinephrine use was also lower than in the group C (P=0.034). Postoperative visual analog scale pain scores were lower in group G (P=0.047), but patients who used glycopyrrolate had a higher proportion of dry mouth (P=0.035). Conclusion: During painless colonoscopy, preoperative administration of glycopyrrolate significantly improved intraoperative hemodynamic fluctuations, reduced the incidence of hypotension and bradycardia, and relieved postoperative pain. However, glycopyrrolate use resulted in the risk of dry mouth.

[The association of cholesterol crystals and non-culprit plaque characteristics in AMI patients: an OCT study].

Objective: To analyze plaque characteristics of non-culprit coronary lesions with cholesterol crystals in patients with acute myocardial infarction(AMI) by using optical coherence tomography(OCT). We also investigated the potential association between cholesterol crystals with plaque rupture and healed plaque at non-culprit segment. Methods: This study was a retrospective cohort study. Between January 2017 and December 2017, patients with AMI who underwent 3-vessel OCT imaging were included in this study. Patients were divided into two groups according to the presence or absence of cholesterol crystals at the non-culprit lesions. All patients underwent coronary angiography and OCT examination, and non-culprit plaque characteristics were compared between the two groups. The generalized estimating equation log-binomial multirariate regression model was used to assess the relationship between non-culprit lesions with cholesterol crystals and plaque rupture and plaque healing. The follow-up data collection ended in October 2023. Kaplan-Meier survival curves were plotted, and log-rank tests were used to compare the cumulative incidence of major adverse cardiovascular events between the two groups. Results: A total of 173 AMI patients were included (aged (56.8±11.6) years; 124 men (71.7%)). Among 710 non-culprit lesions identified by OCT, there were 102 (14.4%) in cholesterol crystals group and 608 (85.6%) in non-cholesterol crystals group. Compared with non-culprit lesions without cholesterol crystals, those with cholesterol crystals had smaller minimum lumen diameter, severer diameter stenosis, and longer lesion length (all P<0.01). The prevalence of plaque rupture (17.6% (18/102) vs. 4.9% (30/608), P=0.001) and thin-cap fibroatheroma (31.4% (32/102) vs. 11.5% (70/608), P<0.01) was higher in the cholesterol crystals groups than in the non-cholesterol crystals group. In addition, vulnerable plaque characteristics such as (44.1% (45/102) vs. 25.8% (157/608), P<0.01), macrophages were more frequently observed in non-culprit lesions with cholesterol crystals. The generalized estimating equation log-binomial multivariate regression analyses showed that non-culprit cholesterol crystals were positively correlated with healed plaque (OR=1.583, 95%CI: 1.004-2.495, P=0.048). Conversely, cholesterol crystals were not associated with plaque rupture (OR=1.632, 95%CI: 0.745-3.576, P=0.221). The follow-up time was 2 142 (1 880, 2 198) days. Non-culprit cholesterol crystals were not related to the major adverse cardiovascular events in patients with AMI (log-rank P=0.558). Conclusions: Among AMI patients, non-culprit lesions with cholesterol crystals presented with severer luminal stenosis and increased plaque vulnerability. The presence of non-culprit cholesterol crystals was associated with rather than plaque rupture.

Experimental Limits on Solar Reflected Dark Matter with a New Approach on Accelerated-Dark-Matter-Electron Analysis in Semiconductors.

Recently a dark matter-electron (DM-electron) paradigm has drawn much attention. Models beyond the standard halo model describing DM accelerated by high energy celestial bodies are under intense examination as well. In this Letter, a velocity components analysis (VCA) method dedicated to swift analysis of accelerated DM-electron interactions via semiconductor detectors is proposed and the first HPGe detector-based accelerated DM-electron analysis is realized. Utilizing the method, the first germanium based constraint on sub-GeV solar reflected DM-electron interaction is presented with the 205.4 kg·day dataset from the CDEX-10 experiment. In the heavy mediator scenario, our result excels in the mass range of 5-15 keV/c^{2}, achieving a 3 orders of magnitude improvement comparing with previous semiconductor experiments. In the light mediator scenario, the strongest laboratory constraint for DM lighter than 0.1 MeV/c^{2} is presented. The result proves the feasibility and demonstrates the vast potential of the VCA technique in future accelerated DM-electron analyses with semiconductor detectors.

[Effectiveness of the central government-funded echinococcosis control programme in Tianzhu Tibetan Autonomous County, Gansu Province from 2007 to 2022].

OBJECTIVE: To evaluate the effectiveness of the central government-funded echinococcosis control programme in Tianzhu Tibetan Autonomous County, Gansu Province from 2007 to 2022, so as to provide insights into echinococcosis control. METHODS: Administrative villages were sampled using a multi-stage cluster random sampling method from Tianzhu Tibetan Autonomous County, Gansu Province from 2007 to 2022, and all residents at ages of 12 years and older in the sampled villages were screened for echinococcosis, and schools were sampled using a cluster sampling method, and all children at ages of 12 years and older in the sampled schools were screened for echinococcosis. Domestic dogs were sampled using a systematic random sampling method, and one domestic dog stool sample was collected from each household. Stray dog stool samples were collected outside the villages, and Echinococcus coproantigens were detected using enzyme-linked immunosorbent assay in domestic and stray dogs. In addition, echinococcosis was screened in sheep and cattle in designated slaughterhouses in Tianzhu Tibetan Autonomous County. The trends in the prevalence of echinococcosis in humans and livestock and the positive rate of Echinococcus coproantigens in dogs were examined with the Cochran-Armitage trend test. In addition, individuals screened for echinococcosis were randomly sampled from 2007 to 2022 for survey on the awareness of echinococcosis control knowledge. RESULTS: A total of 290 356 person-times were screened for echinococcosis among residents at ages of 12 years and older in Tianzhu Tibetan Autonomous County, Gansu Province from 2007 to 2022, with 1 094 residents detected with cystic echinococcosis, and the detection of echinococcosis appeared a tendency towards a gradual decline over years (χ2 = 358.602, P < 0.001). A total of 32 931 person-times were screened for echinococcosis among children at ages of 12 years and older in Tianzhu Tibetan Autonomous County, Gansu Province from 2007 to 2022, with 296 children detected with echinococcosis, and the detection of echinococcosis appeared a tendency towards a gradual decline over years (χ2 = 267.673, P < 0.001). A total of 33 230 domestic dog stool samples were tested for Echinococcus coproantigens in Tianzhu Tibetan Autonomous County, Gansu Province from 2007 to 2022, with 1 777 Echinococcus coproantigens-positive samples tested, and the positive rate of Echinococcus coproantigens appeared a tendency towards a decline in domestic dogs over years (χ2 = 2 210.428, P < 0.001), while the positive rate of Echinococcus coproantigens showed a tendency towards a rise in domestic animals from 2016 to 2022 (χ2 = 37.745, P < 0.001). The positive rate of Echinococcus coproantigens remained relatively stable in stray dogs in Tianzhu Tibetan Autonomous County, Gansu Province from 2019 to 2022 (χ2 = 0.315, P = 0.575). A total of 10 973 sheep were screened for echinococcosis in Tianzhu Tibetan Autonomous County from 2007 to 2022, with 334 sheep detected with echinococcosis, and the detection of echinococcosis appeared a tendency towards a decline in sheep over years (χ2 = 53.579, P < 0.001); however, there was no significant change in the detection of echinococcosis during the period from 2015 through 2022 (χ2 = 1.520, P = 0.218). A total of 2 400 cattle were screened for echinococcosis in Tianzhu Tibetan Autonomous County from 2017 to 2022, with 231 cattle detected with echinococcosis, and the detection of echinococcosis showed a tendency towards a decline over years (χ2 = 5.579, P < 0.05). The awareness of echinococcosis control knowledge increased from 44.37% in 2007 to 94.00% in 2022 among residents at ages of 12 years and older and from 52.50% in 2007 to 92.50% in 2022 among children at ages of 12 years and older in Tianzhu Tibetan Autonomous County, respectively. CONCLUSIONS: There has been a reduction in the detection of echinococcosis in humans and domestic animals and the positive rate of Echinococcus coproantigens in dogs and a rise in the awareness of the echinococcosis control knowledge following the implementation of the central government-funded echinococcosis control programme in Tianzhu Tibetan Autonomous County, Gansu Province; however, integrated echinococcosis control measures are still required for further control of the prevalence of echinococcosis.

An optimal de Quervain's tenosynovitis splint with ergonomic thumb support and evenly distributed pressure.

Splinting is a conventional treatment for de Quervain's tenosynovitis (dQt). However, existing splints have problems such as excessive thermal discomfort and poor fit, which have been pointed out in previous studies. This study proposes a new functional splint consisting of both hard and soft materials with the aim of providing wear comfort with a good fit and sufficient stability of the injured hand. Thumb support of the splint is an important component that controls and protects the affected thumb. To develop an ergonomically shaped thumb support, 16 participants with dQt were recruited for three-dimensional (3D) scanning of their hands. The angles of the wrist and the curvature of the thumb were measured using computer software, and the results were used as a reference for the design of the prototype supports. Excessive pressure on particular regions, such as bony areas, may cause discomfort or pain. To ensure the wear comfort of the proposed splint, a finite element model (FEM) was built to simulate the wear process of the splint and hence to predict the pressure distribution exerted from the splint onto the hand of the wearer. The simulated results show that the pressure is evenly distributed over the hand, indicating that patients are likely to wear the proposed splint comfortably during their treatment period.

Development and validation of a nomogram and risk stratification system to predict overall survival after surgical repair for pediatric patients with medulloblastoma based on easily accessible variables.

OBJECTIVE: This study aimed to develop and validate a nomogram and risk stratification system for the overall survival of pediatric patients with medulloblastoma after surgical repair. PATIENTS AND METHODS: In this multicenter, retrospective study, consecutive patients who underwent surgery for medulloblastoma at Shanghai Children's Medical Center and the First Affiliated Hospital of Fujian Medical University from 2010 to 2022 formed the training and external validation datasets, respectively. Univariable and multivariable Cox regression analyses were performed to identify variables associated with mortality in the training dataset. A nomogram prediction model was developed based on independent variables in the multivariable Cox regression analysis to predict the 1-, 3-, and 5-year overall survival. The area under receiver operating characteristic curve (AUC) and calibration curve were used to evaluate the discrimination and calibration of the nomogram. A risk stratification system based on the median risk score was also established to divide patients into two risk groups. RESULTS: In the training dataset, Cox regression analyses identified tumor size, brainstem involvement and chemotherapy as independent predictors for overall survival. The AUC of the nomogram was 0.75 at 1 year, 0. 75 at 3 years, 0.77 at 5 years in the training dataset, 0.74 at 1 year, 0.70 at 3 years, and 0.70 at 5 years in the validation dataset. The calibration curve for the probability of 1-, 3-, and 5-year survival showed good agreement between the nomogram prediction and actual observation in the training and validation datasets. The risk stratification system could perfectly classify patients into two risk groups, and the overall survival in the two groups had a good division. CONCLUSIONS: This low-cost, convenient, and noninvasive nomogram can be translated into clinical practice as a tool for risk stratification and individualized prognosis prediction for children with medulloblastoma.

Comparison of outcomes between preservation or division of the uterine round ligament in laparoscopic groin hernia repair in females: a meta-analysis and trial sequential analysis.

PURPOSE: The purpose of this study was to perform a meta-analysis comparing the short-term and long-term outcomes in laparoscopic groin hernia repair with or without preservation of the uterine round ligament (URL) in females. METHODS: We searched several databases including PubMed, Web of Science, Cochrane Library, and and CNKI databases. This meta-analysis included randomized clinical trials, and retrospective comparative studies regarding preservation or division of the URL in laparoscopic groin hernia repair in females. Outcomes of interest were age, BMI, type of hernia, type of surgery, operating time, estimated blood loss, time of hospitalization, seroma, concomitant injury, mesh infection, recurrence, uterine prolapse, foreign body sensation, chronic pain, and pregnancy. Meta-analyses and trial sequential analysis were performed with Review Manager v5.3 and TSA software, respectively. RESULTS: Of 192 potentially eligible articles, 9 studies with 1104 participants met the eligibility criteria and were included in the meta-analysis. There were no significant difference in age (MD-6.58, 95% CI - 13.41 to 0.24; P = 0.06), BMI (MD 0.05, 95%CI - 0.31 to 0.40; P = 0.81), blood loss (MD-0.04, 95% CI - 0.75 to 0.66; P = 0.90), time of hospitalization (MD-0.22, 95% CI-1.13 to 0.69; P = 0.64), seroma (OR 0.71, 95% CI 0.41 to 1.24; P = 0.23), concomitant injury (OR 0.32, 95% CI 0.01 to 8.24; P = 0.68), mesh infection (OR 0.13, 95% CI 0.01 to 2.61; P = 0.18), recurrence (OR 1.13, 95% CI 0.18 to 7.25; P = 0.90), uterine prolapse(OR 0.71, 95% CI 0.07 to 6.94; P = 0.77), foreign body sensation (OR 1.95, 95% CI 0.53 to 7.23; P = 0.32) and chronic pain(OR 1.03 95% CI 0.4 to 2.69; P = 0.95). However, this meta-analysis demonstrated a statistically significant difference in operating time (MD 6.62, 95% CI 2.20 to 11.04; P = 0.0003) between the preservation group and division group. Trial sequential analysis showed that the cumulative Z value of the operating time crossed the traditional boundary value and the TSA boundary value in the third study, and the cumulative sample size had reached the required information size (RIS), indicating that the current conclusion was stable. CONCLUSION: In summary, laparoscopic groin hernia repair in women with the preservation of the round uterine ligament requires a longer operating time, but there was no advantage in short-term or long-term complications, and there was no clear evidence on whether it causes infertility and uterine prolapse.

Protein SUMOylation promotes cAMP-independent EPAC1 activation.

Exchange protein directly activated by cAMP (EPAC1) mediates the intracellular functions of a critical stress-response second messenger, cAMP. Herein, we report that EPAC1 is a cellular substrate of protein SUMOylation, a prevalent stress-response posttranslational modification. Site-specific mapping of SUMOylation by mass spectrometer leads to identifying K561 as a primary SUMOylation site in EPAC1. Sequence and site-directed mutagenesis analyses reveal a functional SUMO-interacting motif required for cellular SUMOylation of EPAC1. SUMO modification of EPAC1 mediates its heat shock-induced Rap1/2 activation in a cAMP-independent manner. Structural modeling and molecular dynamics simulation studies demonstrate that SUMO substituent on K561 of EPAC1 promotes Rap1 interaction by increasing the buried surface area between the SUMOylated receptor and its effector. Our studies identify a functional SUMOylation site in EPAC1 and unveil a novel mechanism in which SUMOylation of EPAC1 leads to its autonomous activation. The findings of SUMOylation-mediated activation of EPAC1 not only provide new insights into our understanding of cellular regulation of EPAC1 but also will open up a new field of experimentation concerning the cross-talk between cAMP/EPAC1 signaling and protein SUMOylation, two major cellular stress response pathways, during cellular homeostasis.

Association between infarct location and haemorrhagic transformation of acute ischaemic stroke after intravenous thrombolysis.

AIM: To evaluate the association between computed tomography (CT)-based imaging variables at the time of admission and haemorrhagic transformation (HT) after intravenous thrombolysis (IVT). MATERIALS AND METHODS: One hundred and eight patients who were treated with IVT for acute ischaemic stroke (AIS) during January 2021 to July 2023 were analysed retrospectively. The infarct location was classified as cortical or subcortical in accordance with the Alberta Stroke Program Early CT Score (ASPECTS) system. Logistic regression and receiver operating characteristic curve analyses were performed to determine the relationship between ischaemic variables and HT. RESULTS: Of the total, 18 (16.7%) patients had HT and seven (6.5%) had symptomatic intracerebral haemorrhage (sICH). Multivariate analysis revealed that cortical ASPECTS was independently associated with HT (odds ratio [OR], 0.197; 95% confidence interval [CI], 0.076-0.511; p=0.001) and cortical ASPECTS was independently associated with sICH (OR, 0.066; 95% CI, 0.009-0.510; p=0.009). To predict HT and sICH, cortical ASPECTS (HT area under the curve [AUC] = 0.881, sICH AUC = 0.971) provided a higher AUC compared with ASPECTS (HT AUC = 0.850, sICH AUC = 0.918). CONCLUSION: Cortical ASPECTS seen on CT at the time of admission is associated with HT and sICH after IVT.

Genome-wide association study for charcoal rot resistance in soybean harvested in Kazakhstan.

Charcoal rot (CR) caused by the fungal pathogen Macrophomina phaseolina is a devastating disease affecting soybean (Glycine max (L.) Merrill.) worldwide. Identifying the genetic factors associated with resistance to charcoal rot is crucial for developing disease-resistant soybean cultivars. In this research, we conducted a genome-wide association study (GWAS) using different models and genotypic data to unravel the genetic determinants underlying soybean resistance to сharcoal rot. The study relied on a panel of 252 soybean accessions, comprising commercial cultivars and breeding lines, to capture genetic variations associated with resistance. The phenotypic evaluation was performed under natural conditions during the 2021-2022 period. Disease severity and survival rates were recorded to quantify the resistance levels in the accessions. Genotypic data consisted of two sets: the results of genotyping using the Illumina iSelect 6K SNP (single-nucleotide polymorphism) array and the results of whole-genome resequencing. The GWAS was conducted using four different models (MLM, MLMM, FarmCPU, and BLINK) based on the GAPIT platform. As a result, SNP markers of 11 quantitative trait loci associated with CR resistance were identified. Candidate genes within the identified genomic regions were explored for their functional annotations and potential roles in plant defense responses. The findings from this study may further contribute to the development of molecular breeding strategies for enhancing CR resistance in soybean cultivars. Marker-assisted selection can be efficiently employed to accelerate the breeding process, enabling the development of cultivars with improved resistance to сharcoal rot. Ultimately, deploying resistant cultivars may significantly reduce yield losses and enhance the sustainability of soybean production, benefiting farmers and ensuring a stable supply of this valuable crop.

Network pharmacological and molecular docking verification of the mechanism of Osteoking in preventing deep vein thrombosis of lower limb.

OBJECTIVE: The aim of this study was to predict the mechanism of Osteoking in preventing deep vein thrombosis (DVT) of the lower limb by network pharmacology and molecular docking. MATERIALS AND METHODS: The relevant active components and targets of Osteoking were collected through the TCMSP database, and the relevant disease targets of DVT were collected through the GeneCards, OMIM, and DisGeNET databases. The intersecting gene targets of Osteoking and DVT were obtained using Venny 2.1.0 software. PPI network construction and core target selection using Cytoscape 3.9.0 software. The Metascape database was used for GO and KEGG enrichment analysis of relevant targets. Finally, the molecular docking of the main active components and key targets was carried out. RESULTS: There are 361 potential targets and 71 core targets of Osteoking in preventing deep vein thrombosis of the lower limb. Signal pathways are involved in various diseases such as cancer, diabetic complications, atherosclerosis, and more. Some of the most common pathways include AGE-RAGE signaling pathway and Calcium signaling pathway. Molecular docking results showed that the main active components of Osteoking had relatively stable binding activities with the key targets. CONCLUSIONS: Osteoking can play a role through multiple targets and multiple signal pathways to prevent the formation of deep venous thrombosis of the lower limb after fracture.

[Safety and effectiveness of emergency stenting for acute anterior circulation large artery disease].

Objective: To explore the safety and effectiveness of early stent implantation in patients with acute anterior circulation large artery disease. Methods: Patients were recruited from the RESCUE-RE study (a registration study for Critical Care of Acute Ischemic Stroke After Recanalization). Patients who were diagnosed with acute ischemic stroke within 24 hours of onset and given endovascular treatment after consultation from July 2018 to May 2019 from 18 sub-centers nationwide were retrospectively enrolled. According to whether the stents were placed during the operation, the patients were divided into two groups: stenting group and non-stenting group. The baseline between the two groups was matched by propensity score. The matching variables included age, sex, baseline National Institutes of Health Stroke Scale (NIHSS) score, baseline Glasgow Coma Scale (GCS) score, history of stroke, smoking and onset to hospital time. The primary clinical outcome was 90-day good neurological outcome [defined as modified Rankin score (mRS) 0-2]. Secondary outcomes include 90-day mortality, 24-hour re-occlusion of the responsible artery, and symptomatic intracranial hemorrhage. The differences in clinical endpoints between the two groups were compared. Result: A total of 899 patients with acute anterior circulation artery stenosis or occlusion were included in the study, with a mean age of(66±12)years,and 532(59.18%) were male. There were 193 patients in the stenting group and 706 patients in the non-stenting group. After the baseline data between the two groups were matched by propensity score, 169 patients were enrolled in each of two groups respectively. After matching, the proportion of patients in the stenting group with etiological diagnosis of large atherosclerosis [82.53% (137/166) vs 55.69% (93/167)] and the proportion of patients with previous history of hypertension [63.31% (107/169) vs 47.93% (81/169)] in the stenting group were higher than those in the non-stenting group (both P<0.05). While the proportion of patients in the non-stenting group with cardiogenic embolism [37.73%(63/167) vs 11.45%(19/166)]and the proportion of patients with atrial fibrillation [18.93% (32/169) vs 10.65%(18/169)]was higher(all P<0.05). In the stenting group, the time from onset to recanalization was longer[519 (408, 620)min vs 469 (365, 690)min], and the proportion of general anesthesia [50.89% (86/169) vs 35.50% (60/169)] was higher in the stenting group(both P<0.05). In addition, in the stenting group, the proportion of patients receiving mechanical thrombectomy[67.46% (114/169) vs 88.76% (150/169)] and arterial thrombolysis [2.37% (4/169) vs 18.93% (32/169)] was lower than non-stenting group during the operation, while the proportion of patients receiving balloon dilation [53.85% (91/169) vs 13.61% (23/169)]was higher(both P<0.05). The proportion of patients in stent group receiving antiplatelet drugs before operation was higher [13.46% (21/169) vs 8.70% (14/169)](both P<0.05). In terms of clinical outcome, compared with the non-stenting group, the proportion of patients in the stenting group with good neurological function in 90 days was lower [44.79% (73/169) vs 56.36% (93/169)], and the proportion of death at 90 days was higher[15.98% (27/169) vs 8.88% (15/169)] (both P<0.05). There was no significant difference between the two groups in 24-hour re-occlusion[8.88% (15/169) vs 9.47% (16/169)] and symptomatic intracranial hemorrhage[5.92% (10/169) vs 4.76% (8/169)](both P>0.05). Conclusion: For patients with acute anterior circulation artery disease, early stent therapy may increase the proportion of patients with adverse neurological outcomes.

[Application of augmented reality navigation combined with indocyanine green fluorescence imaging technology in the accurate guidance of laparoscopic anatomical segment 8 liver resection].

Objective: To investigate the application value of augmented reality navigation combined with indocyanine green(ICG) fluorescence imaging technology in laparoscopic anatomical segment 8 liver resection. Methods: Clinical and pathological data from 8 patients with hepatocellular carcinoma located in segment 8 of the liver admitted to the First Department of Hepatobiliary Surgery,Zhujiang Hospital,Southern Medical University from October 2021 to October 2022 were collected restrospectively. Among them,there were 5 males and 3 females,aged between 40 and 72 years. During the operation,the self-developed laparoscopic augmented reality surgical navigation system was used to integrate the three-dimensional liver model with the laparoscopic scene,and ICG fluorescence imaging technology was used to guide the anatomical liver resection of segment 8. The predicted liver resection volume and actual liver resection volume,related surgical indicators and postoperative complications were analyzed. Results: Among the 8 patients, 4 underwent laparoscopic anatomical segment 8 liver resection,1 underwent laparoscopic anatomical ventral subsegment of segment 8 liver resection,2 underwent laparoscopic anatomical ventral subsegment combined with medial subsegment of segment 8 liver resection, and 1 underwent laparoscopic anatomical dorsal subsegment of segment 8 liver resection. All operations were completed under the guidance of augmented reality navigation combined with ICG fluorescence imaging,without conversion to open surgery. The operation time was (276.3±54.8)minutes(range:200 to 360 minutes). Intraoperative blood loss was (75.0±35.4)ml(range:50 to 150 ml). No blood transfusion was performed during the operation. The length of postoperative hospital stay was (7.6±0.8)days(range:7 to 9 days). There were no deaths or postoperative complications such as bleeding or biliary fistula during the perioperative period. Conclusion: Augmented reality navigation combined with ICG fluorescence imaging technology can guide the implementation of laparoscopic anatomical segment 8 liver resection.

[Comparison of therapeutic effect of metformin hydrochloride/vildagliptin and liraglutide on type 2 diabetes mellitus in obese patients].

OBJECTIVE: To evaluate the therapeutic effects of two therapeutic strategies based on metformin hydrochloride/vildagliptin and liraglutide on type 2 diabetes mellitus (T2DM) in obese patients. METHODS: We retrospectively collected the clinical data of 107 obese patients (BMI>25 kg/m2) with T2DM treated in Second Affiliated Hospital of Wannan Medical College (Wuhu, China) during 2019-2021, including 53 patients treated continuously with metformin hydrochloride/vildagliptin and 54 with liraglutide for 3 months. The changes in BMI, waist circumference, fasting blood glucose (FBG), postprandial blood glucose, HbA1C, fasting C-peptide, postprandial C-peptide, fasting insulin and postprandial insulin of the patients after treatment were compared between the two groups. RESULTS: In both of the groups, the patients all showed significant reductions of BMI, waist circumference, FBG, postprandial blood glucose and HbA1C (all P < 0.05) with improved fasting and postprandial C-peptide levels after the treatments (P < 0.05). The two treatment regimens showed comparable blood glucoselowering effects, but liraglutide produced better effect in reducing waist circumference (P < 0.01). Neither of two regimens obviously affected insulin level of the patients (P>0.05). CONCLUSION: Both metformin hydrochloride/vildagliptin and liraglutide have good therapeutic effects on T2DM in obese patients and can achieve good blood glucose and weight control, but liraglutide has a better effect for weight control.

Fracture incidence and fracture-related mortality decreased with decreases in population mobility during the early days of the COVID-19 pandemic: an epidemiological study.

INTRODUCTION: We investigated the impact of coronavirus disease 2019 (COVID-19) social distancing measures on fracture incidence and fracture-related mortality, as well as associations with population mobility. METHODS: In total, 47 186 fractures were analysed across 43 public hospitals from 22 November 2016 to 26 March 2020. Considering the smartphone penetration of 91.5% in the study population, population mobility was quantified using Apple Inc's Mobility Trends Report, an index of internet location services usage volume. Fracture incidences were compared between the first 62 days of social distancing measures and corresponding preceding epochs. Primary outcomes were associations between fracture incidence and population mobility, quantified by incidence rate ratios (IRRs). Secondary outcomes included fracture-related mortality rate (death within 30 days of fracture) and associations between emergency orthopaedic healthcare demand and population mobility. RESULTS: Overall, 1748 fewer fractures than projected were observed during the first 62 days of COVID-19 social distancing (fracture incidence: 321.9 vs 459.1 per 100 000 person-years, P<0.001); the relative risk was 0.690, compared with mean incidences during the same period in the previous 3 years. Population mobility exhibited significant associations with fracture incidence (IRR=1.0055, P<0.001), fracture-related emergency department attendances (IRR=1.0076, P<0.001), hospital admissions (IRR=1.0054, P<0.001), and subsequent surgery (IRR=1.0041, P<0.001). Fracture-related mortality decreased from 4.70 (in prior years) to 3.22 deaths per 100 000 person-years during the COVID-19 social distancing period (P<0.001). CONCLUSION: Fracture incidence and fracture-related mortality decreased during the early days of the COVID-19 pandemic; they demonstrated significant temporal associations with daily population mobility, presumably as a collateral effect of social distancing measures.

Buntanetap, a Novel Translational Inhibitor of Multiple Neurotoxic Proteins, Proves to Be Safe and Promising in Both Alzheimer's and Parkinson's Patients.

BACKGROUND: Previously we reported the clinical safety and pharmacological activity of buntanetap (known as Posiphen or ANVS401) in healthy volunteers and mild cognitive impaired (MCI) patients (21). The data supported continued clinical evaluation of buntanetap for treating Alzheimer's Disease (AD). Neurodegenerative diseases such as AD and Parkinson's disease (PD) share several pathological manifestations, including increased levels of multiple neurotoxic protein aggregates. Therefore, a treatment strategy that targets toxic species common to both disorders can potentially provide better clinical outcomes than attacking one neurotoxic protein alone. To test this hypothesis, we recently completed a clinical study in early AD and early PD participants and report the data here. OBJECTIVES: We evaluated safety, pharmacokinetics, biomarkers, and efficacy of buntanetap in treating early AD and PD patients. DESIGN: Double-blind, placebo-controlled, multi-center study. SETTING: 13 sites in the US participated in this clinical trial. The registration number is NCT04524351 at ClinicalTrials.gov. PARTICIPANTS: 14 early AD patients and 54 early PD patients. INTERVENTION: AD patients were given either 80mg buntanetap or placebo QD. PD patients were given 5mg, 10mg, 20mg, 40mg, 80mg buntanetap or placebo QD. MEASUREMENTS: Primary endpoint is safety and tolerability; secondary endpoint is pharmacokinetics of buntanetap in plasma; exploratory endpoints are 1) biomarkers in cerebrospinal fluid (CSF) in both AD and PD patients 2) psychometric tests specific for AD (ADAS-Cogs and WAIS coding test) or PD (MDS-UPDRS and WAIS coding test). RESULTS: Buntanetap was safe and well tolerated. Biomarker data indicated a trend in lowering levels of neurotoxic proteins and inflammatory factors and improving axonal integrity and synaptic function in both AD and PD cohorts. Psychometric tests showed statistically significant improvements in ADAS-Cog11 and WAIS coding in AD patients and MDS-UPDRS and WAIS coding in PD patients. CONCLUSIONS: Buntanetap is well tolerated and safe at doses up to 80mg QD in both AD and PD patients. Cmax and AUC increase with dose without evidence for a plateau up to 80mg QD. The drug shows promising evidence in exploratory biomarker and efficacy measures. Further evaluation of buntanetap in larger, longer-term clinical trials for the treatment of AD and PD are warranted.

Ultrasound-based hepatic fat quantification: current status and future directions.

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of disease from fatty accumulation (steatosis), necro-inflammation though to fibrosis. It is of increasing global prevalence as a hepatic manifestation of the metabolic syndrome. Although accurate histopathology and magnetic resonance imaging techniques for hepatic fat quantification exist, these are limited by invasiveness and availability, respectively. Ultrasonography is potentially ideal for assessing and monitoring hepatic steatosis given the examination is rapid and readily available. Traditional ultrasound methods include qualitative B-mode for imaging markers, such as increased hepatic parenchymal echogenicity compared to adjacent renal cortex are commonplace; however, there is acknowledged significant interobserver variability and they are suboptimal for detecting mild steatosis. Recently quantitative ultrasound metrics have been investigated as biomarkers for hepatic steatosis. These methods rely on changes in backscatter, attenuation, and speed of sound differences encountered in a steatotic liver. Prospective studies using quantitative ultrasound parameters show good diagnostic performance even at low steatosis grades and in NAFLD. This review aims to define the clinical need for ultrasound-based assessments of liver steatosis, to describe briefly the physics that underpins the various techniques available, and to assess the evidence base for the effectiveness of the techniques that are available commercially from various ultrasound vendors.