BACKGROUND:Angiogenesis is the main treatment target of cardiovascular diseases.Bone morphogenetic protein 2 can modulate angiogenesis,but the regulatory effect of endothelial cell-specific bone morphogenetic protein 2 on angiogenesis is unclear. OBJECTIVE:To investigate the effect of endothelial-specific bone morphogenetic protein 2 on angiogenesis. METHODS:(1)Bioinformatics analysis:Cellular expression specificity and abundance of bone morphogenetic protein 2 were meta-analyzed by the PanglaoDB single-cell transcriptome database.The endothelial cell transcriptome sequencing dataset of the mouse hindlimb model and endocardial transcriptome dataset of mice overexpressing bone morphogenetic protein 2 were reanalyzed to evaluate the effect of endothelial cell bone morphogenetic protein 2 on the angiogenesis pathway.(2)Validation in vivo:After establishing the mouse hindlimb model,we compared the blood perfusion between the affected and sham limb at 7,14,and 21 days.The expression of the colocation of bone morphogenetic protein 2 and CD31 was explored by immunofluorescence and immunohistochemical staining.(3)Validation in vitro:The cultured human umbilical vein endothelial cells in vitro were divided into a control group,a hypoxia group,and a bone morphogenetic protein 2 inhibitor Noggin intervention group.After being cultured for 24 hours,the angiogenesis of endothelial cells in each group was observed. RESULTS AND CONCLUSION:(1)Endothelial cells are an important cell subgroup expressing bone morphogenetic protein 2.Both in the mouse hindlimb ischemia model and endocardial cells overexpressing bone morphogenetic protein 2,bone morphogenetic protein 2 was significantly up-regulated,and the angiogenesis pathway was significantly activated.(2)In the mouse hindlimb model,bone morphogenetic protein 2-positive blood vessels around neoangiogenesis increased significantly at 7 days of ischemia(P<0.05),and decreased significantly after 2 weeks of ischemia(P<0.001).(3)In umbilical vein endothelial cells cultured in vitro,after hypoxic intervention,the migration and sprouting of endothelial cells increased significantly,and the expression of angiogenesis factors vascular endothelial growth factor and platelet-derived growth factor was significantly increased.Noggin significantly reduced hypoxia-induced endothelial cell angiogenesis(P<0.001)and down-regulated the expression of vascular endothelial growth factor and platelet-derived growth factor(P<0.01).(4)These findings verify that endothelial cell-specific bone morphogenetic protein 2 can regulate angiogenesis,and targeting endothelial cell bone morphogenetic protein 2 is a promising way to improve angiogenesis.

Since the first successful transcatheter aortic valve replacement (TAVR) was performed globally in 2002, the TAVR technology has become increasingly mature. With more than a decade of development in China, its application experience, device research and development, procedural improvements, evidence-based medicine, and guideline updates have continuously progressed, leading to a significant increase in the number of procedures conducted. Compared to traditional surgical operations, TAVR has different postoperative monitoring points and principles for the prevention and management of complications, necessitating the formulation of corresponding monitoring and treatment protocols that align with the technical characteristics of the procedure. This guideline is based on clinical practice and incorporates both domestic and international literature as well as the experiences of Fuwai Hospital. It distills and organizes routine postoperative monitoring practices, process optimization, and complication management for TAVR, establishing a set of practical guidelines for postoperative monitoring in China. These guidelines have strong practical value for optimizing postoperative management strategies and preventing and managing complications, which is beneficial for early functional recovery of patients, shortening hospital stays, and reducing complication rates. They provide guidance and reference for domestic peers and support the standardized development and quality improvement of postoperative management for TAVR in China.

Sepsis-associated encephalopathy (SAE) is one of the complications of sepsis, causes cognitive dysfunction ranging from mild attention deficits to progression into coma, which severely impairs patients' ability to live and mental health, and increases the long-term disability and mortality rates. Although the clinical attention to SAE has been increasing in recent years, effective interventions to improve cognitive dysfunction in sepsis survivors are still in the preclinical stage. The pathogenesis of SAE is numerous and complex, and mitochondrial dysfunction, as one of the key pathogenic mechanisms, plays a role in the cognitive development process through oxidative stress imbalance, energy metabolism disorders, and activation of apoptosis signaling pathway. The present review systematically integrates the recent studies on mitochondrial dysfunction in the development of cognitive disorders. This review systematically integrates the cutting-edge research results in recent years, discusses the mitochondrial structural disruption, mitochondrial kinetic abnormalities, respiratory chain dysfunction, and comprehensively comprehends the research progress of mitochondria-targeted antioxidant, mitochondrial autophagy activator, mitochondrial biosynthesis modifier and other novel intervention strategies in improving cognitive function of SAE patients, with the aim of providing theoretical basis for the breakthrough of the current status of clinical treatment of SAE and the targeting of mitochondria for treatment. The aim is to provide theoretical basis for breaking through the status of SAE clinical treatment and targeting mitochondrial therapy.
Humans ; Sepsis-Associated Encephalopathy/metabolism* ; Mitochondria/metabolism* ; Sepsis/complications* ; Oxidative Stress ; Cognitive Dysfunction ; Autophagy

ObjectiveTo analyze the quantity-quality transfer of standard decoction of Ginseng Radix et Rhizoma（GRR） decoction pieces produced by fresh and traditional cutting， and to provide reference for quality control and application development of the decoction pieces produced by fresh cutting. MethodTen batches of representative GRR decoction pieces produced by fresh and traditional cutting and their standard decoctions were prepared by standard process， and high performance liquid chromatography（HPLC） fingerprint of the standard decoction was established and performed on an Agilent EC-C₁₈ column（4.6 mm×150 mm， 2.7 μm） with acetonitrile（A）-0.1% phosphoric acid aqueous solution（B） as the mobile phase for gradient elution（0-23 min， 18%-21%A； 23-35 min， 21%-28%A； 35-80 min， 28%-32%A）， and the detection wavelength was 203 nm. Then similarity evaluation， principal component analysis（PCA） and partial least squares-discriminant analysis（PLS-DA） of fingerprint of the standard decoction were performed to screen the differential components with variable importance in the projection（VIP） value>1. Quantitative analysis was carried out on the screened known differential components， and combined with the indicators of the dry extract rate and the transfer rate， to explore the differences in the quantity-quality transfer between the standard decoction of GRR decoction pieces produced by fresh and traditional cutting. ResultThe fingerprint similarity of the standard decoction of GRR decoction pieces produced by fresh and traditional cutting was more than 0.950， and 18 common peaks were identified， including 9 identified common peaks. The results of PCA and PLS-DA showed that there were some differences in the contents of index components between the two standard decoctions. The contents of ginsenoside Rg₁， Re and Ro in GRR decoction pieces produced by fresh cutting were higher than those in traditional decoction pieces， while the contents of ginsenoside Rb₁， Rc ， Rb₂ and Rd were lower than those in traditional decoction pieces. The contents of ginsenoside Rg₁， Re， Rb₁ and Ro in the standard decoction of GRR decoction pieces produced by fresh cutting were higher than those in the standard decoction of traditional decoction pieces， while the contents of ginsenoside Rc ， Rb₂ and Rd were comparable between the two standard decoctions. Compared with the standard decoction of the traditional decoction pieces， the average transfer rates of ginsenoside Rg₁， Rb₁， Rc， Rb₂ and dry extract rate of the standard decoction of GRR decoction pieces produced by fresh cutting were significantly increased（P<0.05）， and the average transfer rate of ginsenoside Re and Rd also increased， but the difference was not statistically significant. ConclusionThe dry extract rate， content and transfer rate of index components of standard decoction of GRR decoction pieces produced by fresh cutting are better than those of the standard decoction of traditional decoction pieces， which can provides data support for the subsequent clinical application of fresh cutting products.

ObjectiveTo analyze and determine the differential components of freeze-dried and sun-dried Panacis Quinquefolii Radix（PQR）， and to compare the differences in their pro-angiogenic activities. MethodFingerprints of freeze-dried and sun-dried PQR were established based on ultra performance liquid chromatography（UPLC）， and chemometrics methods such as principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were combined to determine the differential saponin composition of the two decoction pieces， and six representative saponins were selected and their contents in freeze-dried and sun-dried PQR were determined by UPLC. Transgenic zebrafish line Tg（fli1a∶EGFP） embryos fertilized for 24 h were selected， and different doses of 70% methanol extracts of freeze-dried and sun-dried PQR（10， 30 mg·L^-1） were used to intervene in normal zebrafish and in a zebrafish model of intersegmental vascular（ISV） injury induced by vascular endothelial growth factor（VEGF） receptor tyrosine kinase inhibitor Ⅱ（PTK787）， then the development of subintestinal vein（SIV） and ISV of zebrafish was observed， SIV diameter， mean number of crossings and mean number of germinations were determined， and the ISV vascular index was calculated， in order to compare the pro-angiogenic activities of the two decoction pieces. ResultThe similarity of the fingerprints of freeze-dried and sun-dried PQR decoction pieces was>0.950， and 17 common peaks were identified， of which 6 common peaks were designated as peak 6（ginsenoside Rg₁）， peak 7（ginsenoside Re）， peak 8（ginsenoside Rb₁）， peak 11（ginsenoside Rc）， peak 13（ginsenoside Rb₂）， and peak 16（ginsenoside Rd）， respectively. A total of 11 differential saponin components were screened by PCA and OPLS-DA， indicating that there were some differences in the contents of the components in the two decoction pieces. The results of determination showed that the contents of ginsenosides Rg₁， Re， Rb₁ and Rb₂ in freeze-dried PQR were higher than those in sun-dried PQR， while the contents of ginsenosides Rc and Rd were lower than those in sun-dried PQR（P<0.05， P<0.01）. In the study of the pro-angiogenic effect on normal zebrafish embryos， compared with the blank group， and the SIV vessel diameter， mean germination rate and mean crossover rate were significantly higher in the high-dose groups of freeze-dried and sun-dried PQR（P<0.01）， and the vessel diameter， mean numbers of crossings and germinations in the freeze-dried PQR group were higher than those of the sun-dried PQR group（P<0.05）. In the study of the pro-angiogenic effect on zebrafish embryos with ISV injury， the development of ISV in the model group was significantly inhibited when compared with the blank group， compared with the model group， different dose groups of freeze-dried and sun-dried PQR could promote the growth and sprouting of ISV， and the number of normal blood vessels in the freeze-dried PQR group was significantly higher than that in the sun-dried PQR group at the same dosage（P<0.05）. ConclusionFreeze-drying can effectively avoid the loss and secondary transformation of ginsenosides in PQR， and its angiogenic activity is better than that of sun-dried PQR， which can provide a reference for the production and development of high-quality PQR decoction pieces.

Objective:To evaluate the role of NOD-like receptor protein 3 (NLRP3) inflammasomes in curcumin-induced reduction of sevoflurane-induced postoperative cognitive dysfunction in rats.Methods:Forty SPF healthy male Sprague-Dawley rats, aged 17-18 months, with body mass index of 580-600 g, were divided into 4 groups ( n=10 each) by a random number table method: control group (C group), postoperative cognitive dysfunction group (P group), curcumin group (CU group), and curcumin+ NLRP3 inflammasome activator group (CN group). The rat model of postoperative cognitive dysfunction was prepared by inhaling 1.5% sevoflurane to explore the abdominal cavity. Curcumin suspension 300 mg/kg was given by intragastric administration in CU group and CN group, and the rats received intragastric administration of nidrisin sodium 5 mg/kg simultaneously in CN group, once a day for 6 consecutive days. Rats received the equal volume of normal saline instead in C group and P group. The frequency of crossing the original platform and time spent in the target quadrant were measured by the Morris water maze test. The histopathological changes of hippocampus were observed by HE staining, neuronal apoptosis was detected by TUNEL staining, and the expression of NLRP3, Bcl-2 and Bax was detected by Western blot. Results:Compared with C group, the frequency of crossing the original platform was significantly reduced, the time spent in the target quadrant was shortened, the apoptosis rate of neurons was increased, and the expression of NLRP3 and Bax was up-regulated, and the expression of Bcl-2 was down-regulated in P group ( P<0.05). Compared with P group, the frequency of crossing the original platform was significantly increased, the time spent in the target quadrant was prolonged, the apoptosis rate of neurons was decreased, and the expression of NLRP3 and Bax was down-regulated, and the expression of Bcl-2 was up-regulated in CU group ( P<0.05). Compared with CU group, the frequency of crossing the original platform was significantly reduced, the time spent in the target quadrant was shortened, the apoptosis rate of neurons was increased, and the expression of NLRP3 and Bax was up-regulated, and the expression of Bcl-2 was down-regulated in CN group ( P<0.05). Conclusions:The NLRP3 inflammasome is involved in curcumin-induced reduction of postoperative cognitive dysfunction in sevoflurane-anesthetized rats.

This report describes a case of an elderly patient whose cardiac pacemaker lead had dislocated and whose battery had depleted.After evaluation,the patient required implantation of a leadless pacemaker.The procedure was successfully completed using solely transthoracic ultrasound guidance,marking the first leadless pacemaker implantation done with only ultrasound guidance,and achieved favorable clinical outcomes.

The incidence of osteoporotic thoracolumbar vertebral fracture (OTLVF) in the elderly is gradually increasing. The kyphotic deformity caused by various factors has become an important characteristic of OTLVF and has received increasing attention. Its clinical manifestations include pain, delayed nerve damage, sagittal imbalance, etc. Currently, the definition and diagnosis of OTLVF with kyphotic deformity in the elderly are still unclear. Although there are many treatment options, they are controversial. Existing guidelines or consensuses pay little attention to this type of fracture with kyphotic deformity. To this end, the Lumbar Education Working Group of the Spine Branch of the Chinese Medicine Education Association and Editorial Committee of Chinese Journal of Trauma organized the experts in the relevant fields to jointly develop Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fractures with kyphotic deformity in the elderly ( version 2024), based on evidence-based medical advancements and the principles of scientificity, practicality, and advanced nature, which provided 18 recommendations to standardize the clinical diagnosis and treatment.

Traumatic cerebrospinal fluid leakage commonly presents in traumatic brain injury patients, and it may lead to complications such as meningitis, ventriculitis, brain abscess, subdural hematoma or tension pneumocephalus. When misdiagnosed or inappropriately treated, traumatic cerebrospinal fluid leakage may result in severe complications and may be life-threatening. Some traumatic cerebrospinal fluid leakage has concealed manifestations and is prone to misdiagnosis. Due to different sites and mechanisms of trauma and degree of cerebrospinal fluid leak, treatments for traumatic cerebrospinal fluid leakage varies greatly. Hence, the Craniocerebral Trauma Professional Group of Neurosurgery Branch of Chinese Medical Association and the Neurological Injury Professional Group of Trauma Branch of Chinese Medical Association organized relevant experts to formulate the " Chinese expert consensus on the diagnosis and treatment of traumatic cerebrospinal fluid leakage in adults ( version 2023)" based on existing clinical evidence and experience. The consensus consisted of 16 recommendations, covering the leakage diagnosis, localization, treatments, and intracranial infection prevention, so as to standardize the diagnosis and treatment of traumatic cerebrospinal fluid leakage and improve the overall prognosis of the patients.

Objective:To evaluate the role of ketamine in postoperative cognitive dysfunction (POCD) and to clarify the association with subdiaphragmatic vagus nerve in mice.Methods:One hundred and forty-four SPF healthy male C57BL/6J mice, aged 18 months, weighing 32-35 g, were divided into 8 groups ( n=18 each) using a random number table method: sham operation group (group C), surgery group (group S), ketamine + surgery group (group SK), ketamine + surgery + subdiaphragmatic vagotomy group (group SK+ SDV), pseudo germ-free mice+ normal saline group (group GM+ V), pseudo germ-free mice that received fecal microbiota transplantation (FMT) from group S mice group (group GM+ S), pseudo germ-free mice that received FMT from group SK mice group (group GM+ SK), and pseudo germ-free mice received subdiaphragmatic vagotomy and FMT from group SK mice group (group GM+ SDV+ SK). Tibial fracture internal fixation was performed under anesthesia with 2.0% isoflurane. Ketamine 50 mg/kg was intraoperatively administered at the beginning of the suture in group SK. The fecal samples were collected at 24 h after surgery to prepare fecal bacteria filtrate in S and SK groups. The dorsal and ventral branches of subdiaphragmatic vagus nerve were cut prior to ketamine administration in SK+ SDV group and prior to FMT in GM+ SDV+ SK group. Broad-spectrum antibiotics dissolved in drinking water were given ad libitum to mice for 14 consecutive days at 2 weeks before FMT or subdiaphragmatic vagotomy and replaced once every 2 days to establish the pseudo germ-free model. Pseudo germ-free mice were gavaged with normal saline or fecal suspension 200 μl obtained from mice for 14 consecutive days at fixed time starting from 14 days after antibiotic intervention in GM+ SK and GM+ SDV+ SK groups. While normal saline was given instead for 14 consecutive days in GM+ V group. The fecal samples were collected after tibial fracture internal fixation or at 24 h after completion of FMT for 16S rRNA gene sequence analysis. The contents of interleukin-6 (IL-6), IL-17, tumor necrosis factor-alpha (TNF-α), IL-4 and IL-10 in the hippocampus were measured by enzyme linked-immuno-sorbent assay at 24 h after surgery or FMT. The spatial memory and learning ability was assessed by the Morris water maze test at 24 h after surgery or FMT. Results:Compared with group Sham, Simpson′s diversity index, Shannon index and Ace index were significantly decreased, the contents of IL-6, IL-17 and TNF-α were increased, contents of IL-4 and IL-10 were decreased, the escape latency in the training and testing phases and swimming distance were prolonged, and the time spent in the target quadrant was shortened in group S ( P<0.05). Compared with group S, Simpson′s diversity index, Shannon index and Ace index were significantly increased, the contents of IL-6, IL-17 and TNF-α were decreased, contents of IL-4 and IL-10 were increased, the escape latency in the training and testing phases and swimming distance were shortened, and the time spent in the target quadrant was prolonged in group SK ( P<0.05). Compared with group SK, Simpson′s diversity index, Shannon index and Ace index were significantly decreased, the contents of IL-6, IL-17 and TNF-α were increased, contents of IL-4 and IL-10 were decreased, the escape latency in the training and testing phases and swimming distance were prolonged, and the time spent in the target quadrant was shortened in group SK+ SDV ( P<0.05). Compared with group GM+ V, the contents of IL-6, IL-17 and TNF-α were significantly increased, contents of IL-4 and IL-10 were decreased, the escape latency in the training and testing phases and swimming distance were prolonged, and the time spent in the target quadrant was shortened in group GM+ S ( P<0.05). Compared with group GM+ S, the contents of IL-6, IL-17 and TNF-α were significantly decreased, contents of IL-4 and IL-10 were increased, the escape latency in the training and testing phases and swimming distance were shortened, and the time spent in the target quadrant was prolonged in group GM+ S ( P<0.05). Compared with group GM+ SK, the contents of IL-6, IL-17 and TNF-α were significantly increased, contents of IL-4 and IL-10 were decreased, the escape latency in the training and testing phases and swimming distance were prolonged, and the time spent in the target quadrant was shortened in group GM+ SDV+ SK ( P<0.05). Conclusions:Ketamine can improve intestinal flora disorders and reduce POCD in mice, and the mechanism may be related to subdiaphragmatic vagal nerve conduction.