Objective To investigate the correlation between the total load of cerebral small vessel disease(CSVD)and the early prognosis of patients with acute cerebral infarction(ACI).Methods A total of 150 patients with ACI admitted to the Department of Neurology,the First Hospital of Jiaxing from October 2020 to June 2022 were included,according to modified Rankin scale(mRs)score,patients were classified good prognosis group(mRs≤2 points)and poor prognosis group(mRs≥3 points),baseline data and clinical characteristics were compared between the 2 groups,and total CSVD load was assessed by cranial MRI,single factor and multi-factor analysis were performed with Logistic model.The relativity of CSVD load and early prognosis was analyzed with Pearson method.Results Age,length of stay,National Institute of Health stroke scale(NIHSS),hypersensitivity C-reactive protein,triglyceride and homocysteine were significantly higher in poor prognosis group than those in good prognosis group,the difference was significant(P<0.05).The scores of lacunar,cerebral microhemorrhage,white matter hyperintensity and CSVD in poor prognosis group were significantly higher than those in good prognosis group(P<0.05).Multivariate Logistic regression analysis showed that length of stay(OR=1.278,95％CI=1.054-1.548,P=0.012),admission NIHSS score(OR=1.354,95％CI=1.113-1.647,P=0.002),CSVD total load(OR=2.494,95％CI=1.666-3.735,P<0.001)were independent risk factors for poor early prognosis in patients with acute cerebral infarction.Conclusion CSVD load is associated with poor prognosis in patients with acute cerebral infarction.

ObjectiveKaroshi, death from overwork, is a serious problem with unclear identification standards and mechanisms. This study aims to establish a karoshi rat model by integrating weight-bearing swimming and sleep deprivation. This model will enable us to investigate the adverse effects of acute physical and mental fatigue on cardiac functions and explore the response mechanisms to overwork using integrated omics approaches, specifically metabonomics and proteomics. MethodsThe experimental design involved healthy male sprague-dawley (SD) rats subjected to weight-bearing swimming and sleep deprivation for 7 d. The rats were monitored for changes in physiological function indexes, including electrocardiogram and respiration. Protein digestion, iTRAQ labeling, and quantitative data analyses were performed to determine differentially expressed proteins (DEPs). Additionally, GC-MS analysis was conducted to identify differential metabolites. The integration analysis of differential metabolites and proteins shared by the fatigue group and the overwork group was performed to construct a relevant metabolic pathway network and integrate the proteomics and metabolomics data. Statistical analysis was carried out using one-way ANOVA and Duncan’s multiple range t-tests. ResultsThe rats subjected to weight-bearing swimming and sleep deprivation showed various physical and behavioral changes associated with fatigue, including hair disorder, decreased muscle tension, reduced food intake, and weight loss. Analysis of cardiac functions revealed cardiac hypertrophy and heart failure in the fatigue and karoshi groups, as evidenced by changes in heart color, myocardial fiber structure, heart rate, respiratory rate, and cardiac ultrasound measurements. Metabolomics analysis using GC-MS identified several differential metabolites in response to overwork, including amino acids involved in various metabolic pathways. Proteomic analysis using iTRAQ technology identified DEPs in the fatigue and karoshi groups, with a subset of DEPs shared by both groups. The GO analysis revealed that the up-regulated DEPs were primarily associated with mitochondria and peroxisomes in the cellular component category. The Reactome analysis further highlighted the enrichment of DEPs in the transfer of ferriheme from methemoglobin to hemopexin pathway. Integration analysis of the DEPs and differential metabolites revealed the activation of autophagy, increased mitochondrial oxidative phosphorylation, enhanced branched-chain amino acid degradation, and altered peroxisomal β-oxidation. These findings suggested complex metabolic adaptations to meet the increased energy demands during overwork while also dealing with oxidative stress. Furthermore, the reprogramming of energy metabolism was observed, with upregulation of fatty acid β-oxidation enzymes and glycolysis-related enzymes in the fatigue group, indicating a shift towards glucose metabolism. In contrast, the karoshi group showed a decreased dependence on fatty acids as an energy source and increased utilization of glucose. The model proposed in this study highlights the interconnected metabolic changes involving mitochondria, peroxisomes, and lysosomes in response to overwork. The findings contribute to our understanding of the mechanisms involved in overwork-related pathologies and provide a basis for further research in the field of karoshi. ConclusionOverall, metabolic reprogramming might provide sufficient energy to the heart, alleviate oxidative stress and damage to cardiac cells in response to excessive exertion and fatigue. Our findings provide an insight into response mechanism to overwork death and lay a foundation for further research on overwork death.

Objective: To investigate whether tanshinone ⅡA can protect the apoptosis of mice cochlear pericytes induced by high glucose and its specific protective mechanism, so as to provide experimental evidence for the prevention and treatment of diabetic hearing loss. Methods: C57BL/6J male mice were used to prepare type 2 diabetes model, which were divided into normal (NG) group, diabetic (DM) group, diabetic+tanshinone ⅡA (HG+tanshinone ⅡA) group and tanshinone ⅡA group. Each group had 10 animals. Primary cochlear pericytes were divided into NG group, HG group (high glucose 35 mmol/L), HG+tanshinone ⅡA (1, 3, 5 μmol/L) group, HG+Tanshinone ⅡA+LY294002 (PI3K/AKT pathway inhibitor) group, LY294002 group, tanshinone ⅡA group and DMSO group. Auditory brainstem response (ABR) was used to measure hearing threshold. Evans blue was used to detect the permeability of blood labyrinth barrier in each group. TBA methods were used to detect oxidative stress levels in various organs of mice. Morphological changes of stria vascularis were observed by hematoxylin-eosin staining (HE). Evans blue was used to detect the vascular labyrinth barrier permeability in cochlea. The expression of apoptosis protein in stria vascularis pericytes was observed by immunofluorescence. Pericytes apoptosis rate was observed by flow cytometry. DCFH-DA was combined with flow cytometry to detect intracellular ROS content, and Western blot was used to detect the expression of apoptotic proteins (Cleaved-caspase3, Bax), anti-apoptotic proteins (BCL-2) and pathway proteins (PI3K, p-PI3K, AKT, p-AKT). SPSS software was used for statistical analysis. Independent sample t test was performed, and P<0.05 was considered statistically significant. Results: Animal experiments: Tanshinone ⅡA decreased the hearing threshold of DM group [(35.0±3.5) dB SPL vs. (55.3±8.1) dB SPL] (t=4.899, P<0.01), decreased the oxidative stress level in cochlea (t=4.384, P<0.05), improved the structure disorder, atrophy of cochlea vascular lines, vacuole increased phenomenon. Tanshinone ⅡA alleviated the increased permeability of the blood labyrinth barrier [Evans blue leakage (6.84±0.27) AU vs. (8.59±0.85) AU] in the cochlea of DM mice (t=2.770, P<0.05), reversed the apoptotic protein: Caspase3 (t=4.956, P<0.01) and Bax (t=4.388, P<0.05) in cochlear vascularis. Cell experiments: Tanshinone ⅡA decreased intracellular ROS content in a concentration-dependent way (t=3.569, P<0.05; t=4.772, P<0.01; t=7.494, P<0.01); Tanshinone ⅡA decreased apoptosis rate and apoptotic protein, and increased the expression of anti-apoptotic protein, p-PI3K/PI3K and p-AKT/AKT in concentration-dependent manner (all P values<0.05); LY294002 reversed the protective effect of tanshinone ⅡA on pericytes apoptosis (all P values<0.05). Conclusion: Tanshinone ⅡA can inhibit the apoptosis of cochlear pericytes induced by high glucose by reducing oxidative stress level and activating PI3K/AKT signaling pathway under high glucose environment, thus playing a protective role in diabetic hearing loss.
Animals ; Male ; Mice ; Apoptosis ; bcl-2-Associated X Protein ; Diabetes Mellitus, Type 2 ; Evans Blue ; Glucose ; Hearing Loss ; Mice, Inbred C57BL ; Pericytes/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Reactive Oxygen Species/metabolism* ; Signal Transduction

OBJECTIVE: To explore the effect of robot-assisted internal fixation in lateral decubitus position for the treatment of ankylosing spondylitis (AS) complicated with thoracolumbar fractures. METHODS: The clinical data of 26 patients with ankylosing spondylitis complicated with thoracolumbar fractures treated from January 2018 to June 2020 was retrospectively analyzed. According to different surgical methods, these patients were divided into observation group and control group. There were 8 patients in observation group, which were treated with robot-assisted percutaneous screw fixation in lateral decubitus position, including 4 males and 4 females, aged form 55 to 85 years old with an mean of (66.25±9.42) years, the course of disease was (4.00±0.76) days on average, 2 cases were T₁₁ fracture, 2 cases were T₁₂, 3 cases were L₁ and 1 case was L₂. And there were 18 patients in control group, which were treated with conventional percutaneous screw fixation in prone position, including 6 males and 12 females, aged from 48 to 81 years old with a mean of (61.22±9.53) years, the course of disease was (4.11±0.83) days on average, 2 cases were T₁₀ injury, 3 cases were T₁₁, 4 cases were T₁₂, 7 cases were L₁, and 2 cases were L₂. The intraoperative blood loss, operation time, position time and postoperative neurological complications were compared between two groups. Postoperative visual analogue scale (VAS) at 1d and 3 months, and Oswestry Disability Index (ODI) before and 3 months after operation were observed. According to Gertzbein-Robbins standard to evaluate the accuracy of pedicle screw placement. RESULTS: There was no nerve injury due to pedicle screw placement in both groups. The intraoperative blood loss in observation group and control group was (34.13±4.61) ml and (78.17±22.02) ml, operation time was(92.13±9.82) min and (106.22±11.55) min, position time was(10.00±2.14) min and (15.17±2.66) min, the differences was statistically significant(P<0.05);VAS of the two groups were (2.38±0.52) points and (4.56±0.98) points one day after surgery, respectively, with statistically significant differences (P<0.05), while VAS and ODI three months after surgery showed no statistically significant differences (P>0.05). The screw accuracy was 96.88%(62/64) in observation group and 81.48%(88/108) in control group, the difference was statistically significant(P<0.05). CONCLUSION Robot-assisted internal fixation in lateral decubitus position for the treatment of ankylosing spondylitis complicated with thoracolumbar fractures can shorten the position time and operation time, significantly improve the accuracy of internal fixation screw placement, relieve the early postoperative pain, reduce intraoperative blood loss and postoperative complications, and facilitate the fast track rehabilitation of patients.
Aged ; Aged, 80 and over ; Female ; Fracture Fixation, Internal ; Humans ; Lumbar Vertebrae/surgery* ; Male ; Middle Aged ; Pedicle Screws ; Retrospective Studies ; Robotics ; Spinal Fractures/surgery* ; Spondylitis, Ankylosing/surgery* ; Thoracic Vertebrae/surgery* ; Treatment Outcome

Central nervous system (CNS) fungal infections are challenging and difficult to diagnose and treat. This article introduces the high risk factors, pathogen spectrum and laboratory indicators that cause CNS fungal infection. As patients with CNS fungal infections are often accompanied by immunodeficiency, it is especially necessary for clinical early detection, early prevention, and early diagnosis, and timely and effective implementation of optimized diagnosis and treatment programs to prevent further deterioration of the disease.
Central Nervous System ; Central Nervous System Fungal Infections/microbiology* ; Central Nervous System Infections ; Fungi ; Humans ; Risk Factors

Short-term intermittent fasting (IF) is beneficial to weight control in patients with nonalcoholic fatty liver disease, but the impact of long-term IF is not clear. In this study, healthy C57BL/6N mice with 4-month alternate day fasting (ADF) were used to study the effects of long-term IF on systemic and liver lipid metabolism. The results showed that, compared with the Ad Libitum group, the weight and food conversion rate of mice in the ADF group were markedly decreased and increased respectively, and the liver index and the liver content of triglyceride were significantly increased by pathological examination. qRT-PCR analysis revealed that the mRNA expression of the lipogenesis gene Pparγ and lipolysis gene Atgl was up-regulated in the ADF group (P < 0.05). Western blot analysis showed that the ratio of microtubule associated protein LC3-II/LC3-I was increased, while the abundance of autophagy adaptor protein p62 was decreased in the ADF group. In addition, autophagy signal positive regulation key factor AMPK phosphorylation was increased (P < 0.05), and negative regulation factor mTOR phosphorylation was decreased (P < 0.05) in the ADF group, indicating that hepatocyte autophagy activity was elevated. Taken together, ADF for 4 months results in an excessive liver triglyceride accumulation, accompanied by a marked decrease in liver mTOR phosphorylation and a significant increase in hepatic autophagy.
Mice ; Animals ; Intermittent Fasting ; Mice, Inbred C57BL ; Liver/pathology* ; TOR Serine-Threonine Kinases ; Lipid Metabolism ; Autophagy ; Triglycerides

Objective: To compare the detection rate of advanced neoplasia and the number of people needing endoscopy in colorectal cancer screening giving at different starting age in population at high risk. Methods: Based on the screening project of early diagnosis and treatment of colorectal cancer in Jiashan county, Zhejiang province, two rounds of colorectal cancer screening were conducted between January 2007 and December 2020. After excluding participants who were not at high risk or had incomplete information, 27 130 participants and 31 205 participants were finally enrolled in round one and in round two, respectively. The spline analysis based on the generalized additive model was used to describe the trend of detection rate of advanced neoplasia with age. The detection rate and number of people needing endoscopy for the groups with starting age at 50, 45 and 40 years were calculated, and the differences in the detection rate were tested by χ² goodness of fit test. Results: A total of 21 077 (77.69%) participants in round one and 25 249 (80.91%) participants in round two received endoscopy, in whom 1 097 (detection rate=52.05‰) and 1 151 (detection rate=45.59‰) had advanced neoplasia (cancers and advanced adenomas), respectively. The detection rate increased significantly with age, and the detection rate in round one were significantly higher than that in round two (P<0.05). The overall detection rates of advanced neoplasia for the groups with starting age at 50, 45 and 40 years were 61.11‰, 56.14‰ and 52.05‰ in round one, and 49.10‰, 46.75‰ and 45.59‰ in round two, respectively. The rates were significantly higher for the group with starting age at 50 years than that with starting age at 40 years in both round one and round two (P<0.05). The numbers of people needing endoscopy of advanced neoplasia for the groups with starting age at 50, 45 and 40 years were 17, 18, and 20 in round one, and 21, 22 and 22 in round two. Conclusions: The detection rate of advanced neoplasia increased with age. Starting screening at lower age might contribute to decreased detection rate and increased number of people needing endoscopy. However, the difference was limited.
Adult ; Colorectal Neoplasms/epidemiology* ; Early Detection of Cancer ; Humans ; Mass Screening ; Middle Aged ; Occult Blood

The aim of this study was to elucidate the mechanism of nuciferine on alleviating obesity based on modulating gut microbiota, ameliorating chronic inflammation, and improving gut permeability. In this study, the obese model mice were induced by high-fat diet and then randomly divided into model group, and nuciferine group; some other mice of the same week age were fed with normal diet as normal group. In the modeling process, the mice were administered intragastrically(ig) for 12 weeks. In the course of both modeling and treatment, the body weight and food intake of mice in each group were measured weekly. After modeling and treatment, the Lee's index, weight percentage of inguinal subcutaneous fat, and the level of blood lipid in each group were measured. The pathological changes of adipocytes were observed by HE staining to evaluate the efficacy of nuciferine treatment in obese model mice. 16 S rRNA sequencing analysis was conducted to study the changes in diversity and abundance of gut microbiota after nuciferine treatment. Enzyme-linked immunosorbent assay(ELISA) and quantitative Real-time polymerase chain reaction(qPCR) were used to detect the levels of inflammatory factors interleukin-6(IL-6), interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α) and the expression of related genes in adipose tissue of mice in each group, so as to evaluate the effect of nuciferine on chronic inflammation of mice in obese model group. qPCR was used to detect the expression of occludin and tight junction protein 1(ZO-1)gene in colon tissure, so as to evaluate the effect of nuciferine on intestinal permeability of mice in obese group. Nuciferine decreased the body weight of obese mice, Lee's index, weight percentage of inguinal subcutaneous fat(P<0.05), and reduced the volume of adipocytes, decreased the level of total cholesterol(TC), triglyceride(TG), and low density lipoprotein cholesterol(LDL-C)(P<0.05) in serum, improved dysbacteriosis, increased the relative abundance of Alloprevotella, Turicibacter, and Lactobacillus, lowered the relative abundance of Helicobac-ter, decreased the expression of inflammatory cytokines IL-6, IL-1β, and TNF-α genes in adipose tissue(P<0.01), decreased the levels of inflammatory cytokines IL-6, IL-1β, and TNF-α in serum(P<0.05), and increased the expression of occludin and ZO-1 genes related to tight junction in colon tissue(P<0.01). Nuciferine could treat obesity through modulating gut microbiota, decreasing gut permeability and ameliorating inflammation.
Animals ; Aporphines ; Diet, High-Fat/adverse effects* ; Gastrointestinal Microbiome ; Mice ; Mice, Inbred C57BL ; Mice, Obese ; Obesity/genetics*

OBJECTIVE: To compare the femoral and tibial tunnel positions of anterior cruciate ligament reconstruction using the modified transtibial (MTT) technique and anteromedial (AM) portal technique. METHODS: Between January 2017 and September 2020, 78 patients with anterior cruciate ligament rupture underwent single-bundle reconstruction with the modified transtibial technique in 39 cases (group MTT) and through anteromedial approach in 39 cases (group AM). There were 25 males and 14 females in group MTT, with an average age of (37.0±2.3) years old; 27 males and 12 females in group AM, with an average age of (37.5±2.2) years old. CT scan of the affected knee was conducted one week after the surgery to measure and compare the femoral tunnels positioning (Fx, Fy), tibial tunnels positioning in the frontal plane(Tx1), tibial tunnels positioning in the sagittal plane (Ty1), and tibial tunnels positioning in the axial plane (Tx2, Ty2) in patients undergoing anterior cruciate ligament reconstruction through Mimics software. RESULTS: Three-dimensional CT reconstruction after the surgery showed that the average Fx and Fy were(25.2±2.1)% and (34.9±3.0)% respectively and the Tx1 and Ty1 were (45.5±3.3)% and (44.7± 3.0)% respectively, while the Tx2 and Ty2 were (47.0±3.0)% and (39.9±4.2)% respectively in group MTT. In group AM, the average Fx and Fy were (26.0±2.0)% and (36.1±3.9)% respectively and the Tx1 and Ty1 were (46.5±3.1)% and (45.6± 3.1)% respectively, while the Tx2 and Ty2 were (47.4±2.5)% and (39.6±3.9)% respectively. There were no statistically significant differences in the femoral and tibial tunnels between the two groups ( CONCLUSION Both the MTT and AM technique can achieve good anatomical positioning of the femoral and tibial tunnels, without significant differences in the positioning of the bone tunnels.
Adult ; Anterior Cruciate Ligament/surgery* ; Anterior Cruciate Ligament Injuries/surgery* ; Anterior Cruciate Ligament Reconstruction ; Female ; Femur/surgery* ; Humans ; Knee Joint/surgery* ; Male ; Software ; Tibia/surgery* ; Tomography, X-Ray Computed

Anterior Cruciate Ligament Injuries ; Biomechanical Phenomena ; Humans ; Knee Joint/surgery* ; Posterior Cruciate Ligament/surgery* ; Posterior Cruciate Ligament Reconstruction ; Reconstructive Surgical Procedures ; Robotics