Activation of GABAergic neurons in the zona incerta accelerates anesthesia induction with sevoflurane and propofol without affecting anesthesia maintenance or awakening in mice / 南方医科大学学报

OBJECTIVE@#To explore the regulatory effects of GABAergic neurons in the zona incerta (ZI) on sevoflurane and propofol anesthesia.@*METHODS@#Forty-eight male C57BL/6J mice divided into 8 groups (n=6) were used in this study. In the study of sevoflurane anesthesia, chemogenetic experiment was performed in 2 groups of mice with injection of either adeno-associated virus carrying hM3Dq (hM3Dq group) or a virus carrying only mCherry (mCherry group). The optogenetic experiment was performed in another two groups of mice injected with an adeno-associated virus carrying ChR2 (ChR2 group) or GFP only (GFP group). The same experiments were also performed in mice for studying propofol anesthesia. Chemogenetics or optogenetics were used to induce the activation of GABAergic neurons in the ZI, and their regulatory effects on anesthesia induction and arousal with sevoflurane and propofol were observed; EEG monitoring was used to observe the changes in sevoflurane anesthesia maintenance after activation of the GABAergic neurons.@*RESULTS@#In sevoflurane anesthesia, the induction time of anesthesia was significantly shorter in hM3Dq group than in mCherry group (P < 0.05), and also shorter in ChR2 group than in GFP group (P < 0.01), but no significant difference was found in the awakening time between the two groups in either chemogenetic or optogenetic tests. Similar results were observed in chemogenetic and optogenetic experiments with propofol (P < 0.05 or 0.01). Photogenetic activation of the GABAergic neurons in the ZI did not cause significant changes in EEG spectrum during sevoflurane anesthesia maintenance.@*CONCLUSION@#Activation of the GABAergic neurons in the ZI promotes anesthesia induction of sevoflurane and propofol but does not affect anesthesia maintenance or awakening.

Dopaminergic Neurons in the Ventral Tegmental-Prelimbic Pathway Promote the Emergence of Rats from Sevoflurane Anesthesia / 神经科学通报·英文版

Dopaminergic neurons in the ventral tegmental area (VTA) play an important role in cognition, emergence from anesthesia, reward, and aversion, and their projection to the cortex is a crucial part of the "bottom-up" ascending activating system. The prelimbic cortex (PrL) is one of the important projection regions of the VTA. However, the roles of dopaminergic neurons in the VTA and the VTADA-PrL pathway under sevoflurane anesthesia in rats remain unclear. In this study, we found that intraperitoneal injection and local microinjection of a dopamine D1 receptor agonist (Chloro-APB) into the PrL had an emergence-promoting effect on sevoflurane anesthesia in rats, while injection of a dopamine D1 receptor antagonist (SCH23390) deepened anesthesia. The results of chemogenetics combined with microinjection and optogenetics showed that activating the VTADA-PrL pathway prolonged the induction time and shortened the emergence time of anesthesia. These results demonstrate that the dopaminergic system in the VTA has an emergence-promoting effect and that the bottom-up VTADA-PrL pathway facilitates emergence from sevoflurane anesthesia.

Factors for and prevention of muscular calf vein thrombosis after unilateral total knee arthroplasty / 中华创伤骨科杂志

Objective:To investigate the factors for and prevention of muscular calf vein thrombosis (MCVT) after unilateral total knee arthroplasty (TKA).Methods:Between January 2018 and October 2020, 551 patients were admitted to Department of Orthopedics, The First Affiliated Hospital to Zhengzhou University for unilateral TKA. They were 187 males and 364 females, aged from 32 to 90 years (average, 64.6 years) and with 234 left and 317 right knees affected. They were assigned into a MCVT group ( n=77) and a non-MCVT group ( n=474) according to whether or not MCVT had happened at 7 days after operation. Recorded were the patients’ baseline information, tourniquet time, intraoperative blood loss, postoperative prothrombin time (PT), postoperative thrombin time (TT), postoperative fibrinogen (FIB), D-dimer, platelet count (PLT), postoperative bed time, knee society score (KSS), erythrocyte sedimentation rate (ESR) fall time, and C-reactive protein (CRP) fall time so as to analyze the risk factors for MCVT. Results:There were significant differences between the 2 groups in age [(66.8±7.0) versus (64.2±9.6) years], body mass index (BMI) [(28.7±2.2) versus (25.0±2.4) kg/m 2], smoking (20/57 versus 41/433), diabetes (56/21 versus 172/302), primary hypertension (45/32 versus 174/300), coronary heart disease (50/27 versus204/270), hyperlipidemia (33/44 versus 149/325), varicosity (50/27 versus 166/308), tourniquet time [(97.9±22.6) versus (83.1±10.6) min], intraoperative blood loss [(73.2±40.6) versus (62.4±11.5) mL], postoperative PT [(10.7±0.8) versus (11.9±1.0) s], TT [(15.2±1.3) versus (17.2±2.4) s], FIB [(3.7±0.8) versus (3.2±0.5) g/L], D-dimer [(1.1±1.0) versus (0.8±0.3) μg/L], PLT [(233.4±68.5) versus (178.5±27.8) 10 9/L], postoperative bed time [(17.3±2.6) versus (14.6±3.8) h], KSS [(3.32±0.7) versus (3.61±0.56) points], ESR fall time [(2.90±0.74) versus (1.55±0.64) d] and CRP fall time [(2.90±0.74) versus (1.55±0.64) d] (all P<0.05). Multivariate logistic regression analysis showed that old age (95% CI: 0.890 to 1.112, P=0.034), high BMI (95% CI: 1.012 to 1.214, P=0.046), diabetes (95% CI: 1.002 to 2.590, P=0.020), D-dimer (95% CI: 1.239 to 10.292, P=0.001) and postoperative PLT (95% CI: 1.012 to 1.112, P=0.014) were independent risk factors for MCVT. Reduced postoperative bed time (95% CI: 1.009 to 1.469, P=0.040) was a protective factor. Conclusions:As old age, high BMI, diabetes, and high postoperative levels of D-dimer and PLT may be independent risk factors for MCVT, patients with such characteristics should be alert to MCVT. Early ambulation should be encouraged in patients after unilateral TKA to reduce postoperative bed time for prevention of the disease.

Implantation of antibiotic calcium sulfate carriers in two-stage revision for periprosthetic knee joint infection / 中华创伤骨科杂志

Objective:To investigate the feasibility of replacing the femoral prosthesis and implanting antibiotic calcium sulfate carriers in a two-stage revision for periprosthetic infection following total knee arthroplasty (TKA).Methods:Between May 2017 and January 2020, 35 patients were admitted to Department of Orthopaedic Surgery, The First Affiliated Hospital to Zhengzhou University for periprosthetic infection after TKA. They were 12 males and 23 females, aged from 49 to 84 years (average, 67.9 years). The two-stage revision for periprosthetic infection was performed for all of them and replacement of femoral prosthesis and implantation of antibiotic calcium sulfate carriers were carried out in stage-one revision. Recorded were postoperative culture of micro-organisms, white blood cell count (WBC), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) before stage-one and stage-two revisions; the Hospital for Special Surgery (HSS) knee score, range of motion (ROM) and American Knee Society Score (KSS) were compared between preoperation and the last follow-up.Results:Postoperative negative culture was found in 22 cases (62.9%), and positive one in 13 cases (37.1%) of which 4 were caused by Staphylococcus aureus, 2 by Staphylococcus epidermidis, 2 by Candida glabrata, 2 by Candida parapsilosis, one by Candida albicans, one by Mycobacterium tuberculosis and one by Escherichia coli. WBC, ESR and CRP decreased on average from 13.67×10 9/L, 49.71 mm/h and 45.13 mg/L before stage-one revision to 6.44×10 9/L, 18.79 mm/h and 7.82 mg/L before stage-two revision. All patients were followed up for an average of 22.4 months (from 8 to 41 months). At the last follow-up, ROM, HSS and KSS were significantly increased from preoperative 73.2°±15.9°, 59.5±14.6 and 36.1±6.0 to 105.6°±13.2°, 84.3±10.0 and 86.1±5.6, respectively ( P<0.05). None of the patients showed any sign of re-infection at the last follow-up. Conclusion:For patients with periprosthetic infection following total knee arthroplasty, replacing femoral prosthesis and implantation of antibiotic calcium sulfate carriers can well control infection, facilitating recovery of range of motion and function after surgery.

Biomimetic grandient scaffolds for articular cartilage tissue engineering / 中华骨科杂志

Due to good mechanical properties and biocompatibility, tissue engineering scaffolds have become the vital method for repairing and regenerating articular cartilage defects. With the continuous development of tissue engineering technology, many scaffolds preparation and formation methods have been developed and tested in the past decade, however, the preparation of ideal regenerative scaffolds remain controversial. As load-bearing tissue inside the body joints, the matrix structure and cell composition of articular cartilage are hierarchical, and there are several smooth natural gradients from the cartilage surface to the subchondral bone layer, including cell phenotype and number, specific growth factors, matrix composition, fiber arrangement, mechanical properties, nutrient and oxygen consumption. Therefore, in the design of regenerative scaffolds, it is necessary to achieve these gradients to regenerate articular cartilage in situ. In recent studies, many new biomimetic gradient scaffolds have been used to simulate the natural gradient of articular cartilage. These scaffolds show different mechanical, physicochemical or biological gradients in the structure, and have achieved good repair effects. The related articles on tissue engineering for the treatment of articular cartilage defects were retrieved by searching databases with key wordsarticular cartilage injury, cartilage repair and gradient scaffolds. In this work,the structural, biochemical, biomechanical and nutrient metabolism gradients of natural articular cartilage were studied and summarized firstly. Then, the latest design and construction of articular cartilage gradient scaffolds were classified. Besides that, the material composition (such as hydrogels, nanomaterials, etc.) and the preparation process (such as electrospinning, 3D printing, etc.) of grandient scaffolds were further enhanced. Finally, the prospect and challenge of biomimetic gradient scaffolds in cartilage engineering are discussed, which provides a theoretical basis for the successful application of gradient scaffolds in clinical transformation.

Chemoattractant-mediated in situ tissue engineering for articular cartilage regeneration / 中华骨科杂志

The treatment of articular cartilage (AC) injury caused by various reasons is still a major clinical problem. The emergence of cartilage tissue engineering brings new hope for the treatment of AC injury. In general, AC tissue engineering can be divided into two categories, including cell-based tissue engineering and cell-free tissue engineering. Although cell-based tissue engineering can repair cartilage damage to a certain extent, existing therapeutic strategies still suffer from limited cell sources, high costs, risk of disease transmission, and complex procedures. However, the cell-free tissue engineering avoids these shortcomings and brings hope for in-situ AC regeneration. Non-cellular tissue engineering is mainly used to recruit endogenous stem cells/progenitor cells (SCPCs) to reach the site of cartilage injury, and provide a suitable regenerative microenvironment to promote cell proliferation and chondrogenic differentiation, then the maturation of new cartilage tissue was promoted. Therefore, it is also called as cell-homing in situ tissue engineering. Successful recruitment of endogenous SCPCs is the first step in in-situ cartilage tissue engineering. This review aims to introduce chemokine response of cartilage injury, systematically summarize traditional chemoattractant (chemokines and growth factors etc.) and emerging chemoattractant (functional peptides, exosomes and nucleic acid adapters etc.), evaluate the combination mode between chemoattractant and delivery devices, discuss the prospects and challenges of chemoattractant-mediated in situ tissue engineering and provide theoretical basis for the design of endogenous SCPCs homing-based in situ tissue engineering.

Efficacy of sevoflurane in preventing depression-like behavior in mice: the relationship with BDNF/TrkB signaling pathway / 中华麻醉学杂志

Objective To evaluate the efficacy of sevoflurane in preventing depression-like behavior in mice and the relationship with brain-derived neurotrophic factor (BDNF)/tyrosine kinase B (TrkB) signaling pathway.Methods Forty-four clean-grade male C57BL/6 mice,weighing 18-22 g,aged 8-10 weeks,were divided into 2 groups (n =22 each) using a random number table method:control group (group C) and sevoflurane group (group S).Mice in group C inhaled oxygen for 30 min,and mice in group S inhaled 2.5％ sevoflurane for 30 min.The forced swimming test and novelty-suppressed feeding test were performed after the mice were fully awake.The brains were immediately removed under anesthesia at the end of inhalation of oxygen or sevoflurane,and the prefrontal cortex and hippocampus were isolated for detection of the expression of BDNF,TrkB and phosphorylated TrkB (p-TrkB) by Western blot.Results Compared to group C,the immobility time and feeding latency were significantly shortened,the expression of p-TrkB in the prefrontal cortex and hippocampus was up-regulated (P＜0.05),and no significant change was found in the feeding consumption or expression of BDNF and TrkB in the prefrontal cortex and hippocampus in group S (P＞0.05).Conclusion Sevoflurane produces a preventive effect on depression-like behavior in mice,and the mechanism is related to increased phosphorylation of TrkB in BDNF/TrkB signaling pathway.