Objective To develop a machine learning(ML)-based prediction model for assessing the therapeutic effects of resveratrol(RES)on the pathological damage of acute pancreatitis(AP),and to optimize RES administration strategies for AP through validation using an animal model.Methods AAn ML-based prediction model was constructed using published data.Interpretability analysis was applied to identify high-efficacy zones within the parameter space of administration dose and frequency,which was followed by rigorous screening to select the optimal dosing strategy that balanced therapeutic efficacy and experimental feasibility.A total of 32 C57BL/6 mice were randomly assigned to 4 groups(n=8 per group),including a control group(Ctrl),an AP model group induced by caerulein(CER)and referred to as CER-AP,a treatment group receiving RES via intraperitoneal injection(RES i.p.),and a treatment group receiving RES via intragastric gavage(RES i.g.).The Ctrl group received intraperitoneal injection of normal saline.The CER-AP and the treatment groups were induced with 10 intraperitoneal injections of CER at 50 μg/kg.RES was administered to the RES i.p.and RES i.g.groups according to the optimal dose and timing predicted by the ML model.Blood and tissue samples were collected 12 hours after the experiment started.Results The gradient boosting decision tree model,optimized via Hyperopt,yielded the best performance,predicting that the optimal dose and administration frequency were 19.992 mg/kg and 3.828 times,respectively.Accordingly,a regimen of 20 mg/kg RES,administered four times,was used in the animal experiments.Compared with the Ctrl group,the CER-AP group exhibited higher pancreatic pathology scores and elevated levels of serum amylase,lipase,pancreatic myeloperoxidase,and trypsin,with all differences reaching statistical significance(all P<0.05).The administration of 20 mg/kg RES via both intraperitoneal injection and intragastric gavage mitigated pancreatic inflammatory cell infiltration and necrosis,improved the overall pathology score,and reduced serum amylase,lipase,and pancreatic myeloperoxidase levels to varying degrees(all P<0.05).Conclusion A regimen of 20 mg/kg RES administered four times effectively alleviates the severity of CER-induced AP.The therapeutic benefits appear to arise from a multi-target regulatory network that simultaneously suppresses inflammatory cascades,mitigates oxidative stress,and reduces apoptosis,thereby reducing pancreatic tissue damage and systemic inflammatory responses.

Tissue engineering bone technology, grounded in seed cells, cytokines, and scaffold supports, provides an effective solution for addressing extensive bone defects, demonstrating significant potentials in the field of bone repair. However, this technology still faces numerous challenges. Focusing on vascularization in engineered bones, this article reviews various methods to enhance vascularization within tissue-engineered bones, including multicellular co-culture, application of angiogenic factors, advanced 3D printing, and aid of surgical interventions. This article also analyses the latest research developments and the limitations of the methods, and speculates future research directions for tissue engineered bone.

Virtual reality (VR) is a technology, which can simulate human vision, touch, hearing and other sensory functions, and it synthesizes a computer-generated 3D world to provide immersive experiences.VR technology has the characteristics of interactivity, immersion and imagination, and its application in medical education and simulation training improves the quality and efficiency of learning.At the same time, VR technology also plays a certain role in clinical treatment such as surgery, rehabilitation, psychology, sedation and analgesia.With the development of VR technology, its application in pediatric medicine field is expected to solve some difficulties of pediatric practitioners.For example, the application of virtual standard patient in pediatric training, and VR technology relieving pain and anxiety.

OBJECTIVE To reveal the role of the basal forebrain(BF)GABAergic neurons in the regulation of isoflurane anesthesia and to elucidate the underlying neural pathways.METHODS The activity of BF GABAer-gic neurons was monitored during isoflurane anesthesia using a genetically encoded calcium indicator in Vgat-Cre mice of both sexes.The activity of BF GABAer-gic neurons was manipulated by chemogenetic and opto-genetic approaches.Sensitivity,induction time and emer-gence time of isoflurane anesthesia were estimated by righting reflex.The electroencephalogram(EEG)power and burst-suppression were monitored by EEG recording.The effects of activation of GABAergic BF-thalamic reticu-lar nucleus(TRN)pathway on isoflurane anesthesia were investigated with optogenetics.RESULTS The activity of BF GABAergic neurons was generally inhibited during isoflurane anesthesia,obviously decreased during the induction of anesthesia and gradually restored during the emergence from anesthesia.Activation of BF GABAergic neurons with chemogenetics and optogenetics promoted behavioral emergence from isoflurane anesthesia,with decreased sensitivity to isoflurane,delayed induction and accelerated emergence from isoflurane anesthesia.Optogenetic activation of BF GABAergic neurons prom-oted cortical activity during isoflurane anesthesia,with decreased EEG delta power and burst suppression ratio during 0.8%and 1.4%isoflurane anesthesia,respectively.Similar to the effects of activating BF GABAergic cell bod-ies,photostimulation of BF GABAergic terminals in the TRN also strongly promoted cortical activation and behav-ioral emergence from isoflurane anesthesia.CONCLU-SION The GABAergic neurons in the BF is a key neural substrate for general anesthesia regulation that facilitates behavioral and cortical emergence from general anesthe-sia via the BF-TRN pathway.

Metformin is currently a strong candidate anti-tumor agent in multiple cancers. However, its anti-tumor effectiveness varies among different cancers or subpopulations, potentially due to tumor heterogeneity. It thus remains unclear which hepatocellular carcinoma (HCC) patient subpopulation(s) can benefit from metformin treatment. Here, through a genome-wide CRISPR-Cas9-based knockout screen, we find that DOCK1 levels determine the anti-tumor effects of metformin and that DOCK1 is a synthetic lethal target of metformin in HCC. Mechanistically, metformin promotes DOCK1 phosphorylation, which activates RAC1 to facilitate cell survival, leading to metformin resistance. The DOCK1-selective inhibitor, TBOPP, potentiates anti-tumor activity by metformin in vitro in liver cancer cell lines and patient-derived HCC organoids, and in vivo in xenografted liver cancer cells and immunocompetent mouse liver cancer models. Notably, metformin improves overall survival of HCC patients with low DOCK1 levels but not among patients with high DOCK1 expression. This study shows that metformin effectiveness depends on DOCK1 levels and that combining metformin with DOCK1 inhibition may provide a promising personalized therapeutic strategy for metformin-resistant HCC patients.
Animals ; Antineoplastic Agents/therapeutic use* ; Carcinoma, Hepatocellular/metabolism* ; Cell Line, Tumor ; Clustered Regularly Interspaced Short Palindromic Repeats ; Genome ; Humans ; Liver Neoplasms/metabolism* ; Metformin/therapeutic use* ; Mice ; Phosphorylation ; Synthetic Lethal Mutations ; Transcription Factors/metabolism* ; rac GTP-Binding Proteins/metabolism*

Objective:To investigate whether the Garden indexes can serve as a criterion for rotational displacement of femoral neck fracture.Methods:Ten cadaveric specimens of healthy human proximal femur were used for this study. They came from 3 males and 2 females who had died at the age from 45 to 70 years old. A Kirschner wire of 2.0 mm in diameter was implanted into the center of the femoral head. Osteotomy was conducted perpendicular to the middle line of the femoral neck. The rotational angles were marked on the distal osteotomy surface. Each cadaveric specimen was rotated sequentially at pronation and supination angles of 0°, 10°, 20°, 30°, 40°, 50°, 70° and 90°, respectively. X-ray images of anterior-posterior and lateral views were taken to record all the rotations of the specimens. Picture Archiving and Communication Systems (PACS) were used to measure the Garden indexes and compare them among anterior-posterior and lateral X-ray films of different pronation and supination angles. Changes in the area of the femoral head fovea at different rotation angles were observed as well.Results:There were no significant differences in the auterior-posterior or latera Garden indexes from 0° to pronation or supination 30°, with all the Garden values >155° ( P>0.05); from pronation of 40° to pronation of 90°, the Garden indexes were 152.36°±1.41°, 146.04°±1.64°, 143.95°±0.60° and 141.73°±0.60° for anterior-posterior views and 172.54°±0.86°, 168.57°±0.98°, 157.18°±1.17° and 156.47°±1.63° for lateral views, showing a significant difference between rotational angles ( P<0.05); from supination of 40° to supination of 90°, the Garden indexes were 151.67°±1.06°, 147.32°±1.82°, 142.77°±0.75° and 139.88°±1.48° for anterior-posterior views and 172.28°±0.79°, 166.76°±1.02°, 155.67°±1.74° and 154.16°±1.27° for lateral views, showing a significant difference between rotational angles ( P<0.05). The area of the femoral head fovea decreased gradually with the increase in pronation angle, and increased gradually with the increase in supination angle. Conclusions:The Garden indexes cannot serve as an accurate indication of rotational displacement in reduction of femoral neck fracture when the pronation or supination angles ranges from 0° to 30°. Changes in the area of the femoral head fovea can help determine the rotational displacement of the femoral neck fracture.

Objective To study the predictive value of hemodynamic monitoring in the responsiveness of fluid therapy in neonatal septic shock.Method The 96 neonates with septic shock admitted to the NICU from Wuhan Children's Hospital and Tongji Hospital between March 2014 to May 2017 were enrolled.Hemodynamics parameters of neonates pre-,1 hour and 6 hour post-fluid therapy were supervised by ultrasonic cardiac output monitor.The hemodynamics parameters included cardiac index (CI),systemic vascular resistance (SVR),stroke volume (SV),stroke volume variation (SVV),stroke volume index (SVI) and corrected flow time (FTc).The SVI variation (△ SVI) were calculated based on the SVI among pre-and post-fluid therapy.According to the △ SVI,these samples were assigned into two groups,responsive group with a △ SVI ≥10％,and the other was nonresponsive group respectively.T-test was applied to analyze the differences of hemodynamic parameters between two groups.The associations between SVV、FTc and △ SVI were evaluated by bivariate correlation.Receiver operating characteristic curve (ROC) was used to evaluate the predictive value of SVV and FTc in fluid responsiveness.All statistical analyses were performed by SPSS 19.0,P＜0.05 was considered as statistically significant.Result A total of 96 cases were enrolled,of which 54 were fluid responsive group,while 42 were nonresponsive group.(1) Before fluid resuscitation,the FTc in responsive and nonresponsive groups were (317.1±22.2) ms and (326.8± 21.2) ms (P＜0.05) respectively,SVV were(18.3±2.0)％ and (15.0±2.6)％ (P＜0.05).SVV was significantly associated with △ SVI (r=0.542,P＜0.05).(2) There were statistically significant differences in heart rate,mean arterial pressure,cardiac output,cardiac index,stroke volume and systemic vascular resistance index before treatment,1 h and 6 h after treatment (P＜0.05).(3) The area under the ROC of SVV (AUC) was 0.838 (95％CI 0.749～0.906).A sensitivity of 98.2％,and specificity 73.8％ when SVV defined as 15.5％,with a significant difference when compared with FTc (AUC=0.642,95％CI 0.538～0.737) (P＜0.01).Conclusion SVV could be a reliable predictive index in estimating fluid responsiveness of neonatal septic shock and could be helpful parameter in clinic diagnosis.

With the development of science and technology, and the emergence of artificial intelligence, wearable technology is becom-ing a hot topic in the field of rehabilitation medicine. Wearable technology is characterized by miniaturization, intelligency and convenience, and has been widely researched and applied in many fields, such as neurological rehabilitation, orthopaedic rehabilitation, spinal cord injury rehabilitation and rehabilitation for senile degenerative diseases. The further research may focus on the reliability of signals under dynamic monitoring, the comfortable feeling during long-term use of wearable devices, the data security based on personal privacy, and so on.

The measurement of intramedullary pressure is particularly important in the research of spinal cord injury. This article ana-lyzed the influence factors and the measurement methods of intramedullary pressure. The influence factors included edema, vascular regula-tion and bleeding, spinal dural, pia mater spinalis, cerebrospinal fluid, canalis vertebralis and body position, etc. The measurement methods included direct measurement methods, as the sensor placed in the parenchyma of spinal cord, intradural extramedullary or lumbar catheter, and measuring in vitro, and indirect measurement methods, as computer modeling and intraocular pressure measuring.

Two­photon microscopy is a new technique which combines laser scanning con-focal microscopy and two-photon excitation technique. Two-photon fluorescence microscopy has the advantages of little light damage, small bleaching area, strong penetrability, high resolution, high fluorescence collection efficiency, and high image contrast. It is suitable for dark field imaging and multi-labeled compound measurement, and has been widely used in small animals in vivo optical imaging, such as research for tumour, gene therapy, stem cells, drug development, spinal cord injury, etc.