Background and aims Ischemic heart disease (IHD) presents a significant global health challenge, with myocardial ischemia-reperfusion injury (MIRI) being a major pathophysiological contributor and lacking effective interventions. While aerobic exercise training (AET) enhances cardiovascular health, its protective mechanism in MIRI remains elusive. This study aims to elucidate the protective effect of AET in MIRI and its underlying mechanism. Methods A mouse model of AET and MIRI was established to evaluate basic indices, cardiac ultrasound, and myocardial injury markers. Dot Blot, qRT-PCR, and Western blot were employed to assess m6A RNA methylation levels and related protein expression in myocardial tissue. In vitro, primary cardiomyocyte culture was utilized to mimic MIRI, evaluating cell viability, mitochondrial membrane potential, etc. Finally, myocardial tissues of MIRI mice were immunoprecipitated for m6A RNA methylation and sequenced to analyze related signaling pathways. Key results AET significantly improved cardiac function and mitigated myocardial injury and fibrosis. Moreover, AET protected myocardium from MIRI by reducing m6A RNA methylation levels and modulating METTL3 expression. In vitro experiments demonstrated that the decrease in m6A RNA methylation levels and METTL3 expression conferred resistance to hypoxia/reoxygenation-induced injury. Furthermore, sequencing results indicated elevated myocardial tissue m6A RNA methylation levels during MIRI, activation of the Nrf2-related signaling pathway, and AET-mediated regulation of the Nrf2/HO-1 signaling pathway, thereby attenuating MIRI through modulation of METTL3-related m6A methylation. Conclusion and significance AET attenuates MIRI by reducing the level of METTL3-related m6A RNA methylation in cardiomyocytes and activating the Nrf2/HO-1 antioxidant signaling pathway. This finding provides a novel insight and strategy for the prevention and treatment of IHD, holding significant clinical implications.

Abstract Background Arterial injury caused by heterotopic ossification (HO) following fractures is rarely reported, yet it can have catastrophic consequences. This case report presents a unique instance of femoral artery injury and hematoma organization, occurring a decade after intramedullary nail fixation for a femoral shaft fracture complicated by HO. Case presentation A 56-year-old male presented with right femoral artery injury and organized hematoma, a decade after suffering bilateral femoral shaft fractures with mild head injury in a traffic accident. He had received intramedullary nailing for the right femoral shaft fracture and plate fixation for the left side in a local hospital. Physical examination revealed two firm, palpable masses with clear boundaries, limited mobility, and no tenderness. Peripheral arterial pulses were intact. Radiography demonstrated satisfactory fracture healing, while a continuous high-density shadow was evident along the inner and posterior aspect of the right thigh. Computed tomography angiography identified a large mixed-density mass (16.8 × 14.8 × 20.7 cm) on the right thigh’s medial side, featuring central calcification and multiple internal calcifications. The right deep femoral artery coursed within this mass, with a smaller lesion noted on the posterior thigh. Surgical consultation with a vascular surgeon led to planned intervention. The smaller mass was completely excised, but the larger one partially, as it encased the femoral artery. The inability to remove all HO was due to excessive bleeding. Postoperatively, the patient experienced no complications, and one-year follow-up revealed a favorable recovery with restoration of full right lower limb mobility. Conclusion This case underscores the potential gravity of vascular injury associated with heterotopic ossification. Surgeons should remain vigilant regarding the risk of vascular injury during HO excision.

Background Osteomyelitis (OM) poses a significant clinical challenge, especially among individuals with diabetes mellitus (DM). While both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) have been linked to an elevated risk of OM, the precise causal relationships remain uncertain. Methods We conducted Mendelian randomization (MR) analyses using summary statistics from genome-wide association studies (GWAS) to explore the causal effects of T1DM, T2DM, their complications, and glycemic traits on OM risk. The study utilized the inverse variance weighted (IVW) method, along with weighted median and MR-Egger for causal estimation, and performed various sensitivity analyses to ensure robustness. Multivariable MR (MVMR) analysis assessed direct effects, while two-step mediation MR analyses investigated the mediating role of DM between rheumatoid arthritis (RA) and OM. Results The MR analysis unveiled distinct causal effects of T1DM and T2DM on OM risk. Genetically determined T2DM, rather than its complications, significantly increased OM risk (primary dataset: IVW: OR = 1.13, 95% CI 1.056–1.209, p = 4E-04; validation dataset: IVW: OR = 1.317, 95% CI 1.14–1.522, p =2E-04; Meta-analysis: OR=1.206; 95% CI 1.037–1.402; p =0.014), with no observable heterogeneity or horizontal pleiotropy. MVMR analysis confirmed the robustness of the causal association between T2DM and OM, even after adjusting for potential confounders such as body mass index. Conversely, T1DM and its complications showed no significant causal link with OM in either the primary dataset (IVW: p = 0.071), the validation dataset (IVW: p = 0.276), or the meta-analysis (IVW: p = 0.242). Additionally, there was no robust evidence supporting the causal risk of glycemic traits on OM. Mediation MR analysis underscored T2DM as a pivotal contributor to the differential effects of RA on OM. Conclusions Mendelian randomization analysis provides compelling evidence of a significant causal relationship between genetically determined T2DM and increased OM risk, while T1DM exhibits distinct causal effects. Additionally, our findings highlight the role of T2DM in mediating the association between RA and OM. Further research is warranted to elucidate the underlying mechanisms and guide targeted interventions for OM prevention and management in diabetic populations. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement We thank the Jilin Province Science and Technology Development Grant (grant Nos. 20210101452JC and YDZJ202301ZYTS096) for funding this study. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study used openly available human data that were originally located at:<https://www.finngen.fi/en/access_results>, <https://gwas.mrcieu.ac.uk/> I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors <https://www.finngen.fi/en/access_results> <https://gwas.mrcieu.ac.uk/> <https://www.ebi.ac.uk/gwas/home> * T1DM : type 1 diabetes mellitus T2DM : type 2 diabetes mellitus OM : osteomyelitis IVW : Inverse variance weighted IVs : Instrumental variables SNPs : Single Nucleotide Polymorphisms UVMR : Univariable MR MVMR : Multivariable MR OR : Odds ratio CI : confidence interval GWAS : Genome-Wide Association Study UKBB : United Kingdom Biobank

患者，女性，年龄45岁，体重60 kg，ASA分级Ⅱ级。因"月经量增多6个月，发现子宫肌瘤渐进性增大6个月"入院。既往病史：左下肢静脉血栓病史6个月，规律溶栓治疗，半月前停药。术前化验检查：ECG提示校正的QT间期(QTc) 491 ms，血红蛋白66 g/L。经输血治疗后血红蛋白达到84 g/L。拟在全麻下行开腹子宫肌瘤切除术。该患者贫血貌，入室后精神状态紧张，心率104次/min，血压138/90 mmHg(1 mmHg＝0.133 kPa)。麻醉诱导：静脉注射依托咪酯0.3 mg/kg、芬太尼3 μg/kg、顺式阿曲库铵0.15 mg/kg，置入三号喉罩并用胶带固定。呼吸机参数设定：FiO 2 60%，V T 450 ml，通气频率12次/min，I∶E 1∶2。监测血压109/70 mmHg，心率50次/min，监测仪显示T波倒置，随后出现室颤波形，即刻开始心肺复苏，建立有创动脉压监测，并将喉罩更换为气管插管。共静脉注射肾上腺素3 mg，2次360 J电除颤后恢复窦性心率。约40 min后患者苏醒，拔除气管导管。血气分析结果：pH值7.41，PCO 2 35 mmHg，PO 2 206 mmHg，K + 3.2 mmol/L，Ca 2+ 0.98 mmol/L，乳酸2.8 mmol/L，Hb 96 g/L。送入ICU观察期间，患者再次突发意识丧失，床旁心电图可见尖端扭转型室速(Tdp)，抢救成功后再次行心电图检查，T波呈双峰样改变，QTc 634 ms，可诊断为长QT间期综合征(LQTS)。静脉输注硫酸镁2.5 g和氯化钾1.5 g治疗，经治疗后未出现心脏不良事件，口服倍他乐克11.875 mg，1次/d。距第1次心肺复苏3 d后心电图显示QT/QTc 482/580 ms。5 d后QTc逐渐恢复至470 ms，各项化验检查结果正常，患者要求出院，待进一步调整后再行手术。

G protein-coupled receptors regulate a variety of cellular responses and have been considered as therapeutic targets for human diseases. Lysophosphatidic acid receptor 1 (LPA1) is a receptor for bioactive lysophospholipid, LPA. LPA/LPA1-mediated signaling contributes to inflammatory and fibrotic responses in lung diseases; thus understanding regulation of LPA1 stability is important for modulating LPA/LPA1 signaling. Our previous study has shown that LPA1 is degraded in the Nedd4 like (Nedd4L) E3 ubiquitin ligase-mediated ubiquitin-proteasome system. In the current study, we attempt to identify a peptide that stabilizes LPA1 through disrupting LPA1 association with Nedd4L. LPA treatment induces both endogenous and overexpressed LPA1 degradation, which is attenuated by a proteasome inhibitor, suggesting that LPA1 is degraded in the proteasome. LPA increases phosphorylation of extracellular signal-regulated kinase 1/2 (Erk1/2) and I-κB kinase in lung epithelial cells, and this effect is promoted by overexpression of a peptide (P1) that mimics C-terminal of LPA1. P1, not a control peptide, attenuates LPA-induced LPA1 ubiquitination and degradation, suggesting that P1 stabilizes LPA1. Further, P1 diminishes Nedd4L-mediated degradation of LPA1 and Nedd4L/LPA1 association. In addition to increasing LPA1 signaling, P1 enhances LPA-induced cell migration and gene expression of Elafin, matrix metallopeptidase 1, and serpin family B member 2 in lung epithelial cells. These data suggest that disruption of LPA1 interaction with Nedd4L by P1 increases LPA1 stability and LPA/LPA1 signaling.

Pulmonary fibrosis is a chronic, progressive, and irreversible interstitial lung disease. Transforming growth factor-β1 (TGF-β1) plays a major role in lung fibroblast cell differentiation to myofibroblast cells and production of extracellular matrix, which are hallmarks of pulmonary fibrosis. G protein-coupled receptor kinase-2 (GRK2) has been shown to play controversial roles in TGF-β1-induced signal transduction in different cell types; however, the role of GRK2 in TGF-β1-induced activation of lung fibroblast cells and development of pulmonary fibrosis has not been revealed. In this study, we found that GRK2 levels were increased in lungs and isolated fibroblast cells in a murine model of pulmonary fibrosis, as well as TGF-β1-treated lung fibroblasts. GRK2 levels were not changed in lungs in the injury phase of pulmonary fibrosis. Posttreatment with GRK2 inhibitor reduced extracellular matrix (ECM) accumulation in lungs in bleomycin-challenged mice, suggesting that GRK2 activation contributes to the progressive phase of pulmonary fibrosis. Inhibition or downregulation of GRK2 attenuates fibronectin, collagen, and α-smooth muscle actin expression in TGF-β1-induced lung fibroblast cells or myofibroblast cells isolated from patients with pulmonary fibrosis. Furthermore, we showed that GRK2 regulates Smad3 expression, indicating that inhibition of GRK2 attenuates ECM accumulation through downregulation of Smad3 expression. This study reveals that GRK2 is a therapeutic target in treating pulmonary fibrosis and inhibition of GRK2 dampens pulmonary fibrosis by suppression of Smad3 expression, eventually attenuating TGF-β1 signal pathway and ECM accumulation.

FOXO3a belongs to a family of transcription factors characterized by a conserved forkhead box DNA-binding domain. It has been known to regulate various cellular processes including cell proliferation, apoptosis and differentiation. Post-translational modifications of FOXO3a and their roles in the regulation of FOXO3a activity have been well-documented. FOXO3a can be phosphorylated, acetylated and ubiquitinated, however, the ISGylation of FOXO3a has not been reported. Protein overexpression, ISGylation and half-life were measured to determine the post-translational modification of FOXO3a. Human fibroblast cells were treated with transforming growth factor (TGF)-β1 to determine the role of FOXO3a ISGylation in TGF-β1 signaling. FOXO3a's half-life is around 3.7 hours. Inhibition of the proteasome, not lysosome, extends its half-life. ISGylation, but not ubiquitination of FOXO3a, is increased in the presence of the proteasome inhibitor. Overexpression of ISG15 increases FOXO3a degradation, while overexpression of USP18 stabilizes FOXO3a through de-ISGylation. These results suggest that FOXO3a is degraded in the ISGylation and proteasome system, which can be reversed by USP18, an ISG15-specific deubiquitinase. This study reveals a new molecular mechanism by which ISGylation regulates FOXO3a degradation. Furthermore, we show that the overexpression of FOXO3a attenuated TGF-β1-induced fibronectin expression in human lung fibroblast cells without altering Smad2/3 expression and activation. FOXO3a can be ISGylated, which can regulate FOXO3a stability. USP18/FOXO3a pathway is a potential target for treating TGF-β1-mediated fibrotic diseases such as idiopathic pulmonary fibrosis.

Smad4 plays a central role in the regulation of extracellular matrix (ECM) protein expression and cell differentiation; however, the molecular regulation of Smad4 protein stability by a deubiquitinase has not been reported. In the current study, we reveal that a deubiquitinase USP13 stabilizes Smad4, ultimately modulating ECM protein expression in lung fibroblast cells. USP13 was increased in primary adult lung fibroblasts isolated from bleomycin-challenged mice and transforming growth factor (TGF)-beta 1-treated primary mouse lung fibroblasts. In a bleomycin-induced murine model of lung fibrosis, USP13-deficient mice showed reduced ECM levels such as fibronectin (FN) and collagen compared with wild-type mice. The reductions in both protein levels and mRNA expression of ECM were observed in the isolated lung fibroblasts from USP13-deficient mice, suggesting that downregulation of USP13 reduces ECM levels through inhibiting its transcription. To investigate the molecular mechanisms by which USP13 modulates ECM expression, we focused on the role of USP13 on Smad4 expression. Overexpression of USP13 increased FN and Smad4 protein levels in lung fibroblasts, while downregulation of USP13 reduced Smad4 protein levels, without altering Smad4 mRNA expression, suggesting that USP13 regulates Smad4 protein stability. Knockdown of USP13 decreased Smad4 half-life and promoted Smad4 ubiquitination. Both Smad4 and USP13 were co-localized in the cytoplasm in treated cell, and co-translocated into the nucleus in response to TGF-beta 1. The results indicate that USP13 promotes ECM expression by stabilizing Smad4 in lung fibroblasts and plays a role in the maintenance of the extracellular matrix in lungs.

Protein ubiquitination regulates protein stability, cellular localization, and enzyme activity. Deubiquitinases catalyze the removal of ubiquitin from target proteins and reverse ubiquitination. USP13, a deubiquitinase, has been shown to regulate a variety of cellular responses including inflammation; however, the molecular regulation of USP13 has not been demonstrated. In this study, we revealed that USP13 is degraded in response to lipopolysaccharide (LPS) in Kupffer cells. USP13 levels are significantly decreased in inflamed organs, including liver tissues from septic mice. LPS reduces USP13 protein stability, not transcription, in Kupffer cells. Furthermore, LPS increases USP13 polyubiquitination. Inhibition of proteasome, but not lysosome or immunoproteasome, attenuates LPS-induced USP13 degradation, suggesting USP13 degradation is mediated by the ubiquitin-proteasome system. A catalytically inactive form of USP13 exhibits similar degree of degradation compared with USP13 wild-type, suggesting that USP13 degradation is not dependent on its activity. Furthermore, USP13 degradation is dependent on new protein synthesis. Inhibition of c-Jun N-terminal kinase (JNK) attenuates USP13 degradation, indicating that JNK-dependent new protein synthesis is necessary for USP13 degradation. This study reveals a molecular mechanism of regulation of USP13 degradation in Kupffer cells in response to bacterial endotoxin.

Currently, nailing through the suprapatellar approach and minimally invasive plating have been generally accepted in the management of displaced proximal tibial fractures. This investigation was aimed at comparing these two treatment methods in terms of their effectiveness and safety. We randomized 328 patients into one of two groups: one underwent intramedullary nailing via the suprapatellar approach (IMN group), while the other underwent locking compressive plate (LCP group) placement. The primary outcome was the Iowa Knee Score at 12 months. The clinical history, amount of intra-operative blood loss, rate of fracture healing, and post-operative complications were assessed as secondary outcomes. Participants were assessed at one, two, three, six and 12 months after surgery. Follow-up data for a year were available for 152 and 154 patients in the IMN group and LCP group, respectively. No intergroup difference was detected with regard to the Iowa Knee Scores (91 ± 8.2 in the IMN group and 90 ± 7.3 in the LCP group, respectively (p = 0.26)), at 12 months. Duration of operation (83.5 ± 35.3 min), amount of blood loss (55 ± 43 mL), duration of fluoroscopy (53.7 ± 3.9 s), and cases with difficult reduction (n = 46) in the IMN group did not differ significantly from those in the LCP group (80.1 ± 43.6 min; 65 ± 56 mL; 48 ± 12 s; 32) (p < 0.05). The two groups had similar post-operative complications and rate of fracture union, with the pre-injury activity level being restored in most patients. Removal of the implants was performed in 31.6% and 63.0% of the cases in the IMN and LCP groups, respectively, indicating a significant intergroup difference. Both IMN through the suprapatellar approach and minimally invasive LCP were found to yield no significant intergroup difference of clinical outcomes in the treatment of proximal, extra-articular tibial fractures. However, the requirement of implant removal was more relevant to LCP.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and accounts for 85% of all lung carcinomas. The hepatocyte growth factor receptor (c-Met) has been considered as a potential therapeutic target for NSCLC. Proteasome inhibition induces cell apoptosis and has been used as a novel therapeutic approach for treating diseases including NSCLC; however, the effects of different proteasome inhibitors on NSCLC have not been fully investigated. The aim of this study is to determine a precise strategy for treating NSCLC by targeting c-Met using different proteasome inhibitors. Three proteasome inhibitors, bortezomib, MG132, and ONX 0914, were used in this study. Bortezomib (50 nM) significantly reduced c-Met levels and cell viability in H1299 and H441 cells, while similar effects were observed in H460 and A549 cells when a higher concentration (100 nM) was used. Bortezomib decreased c-Met gene expression in H1299 and H441 cells, but it had no effect in A549 and H460 cells. MG-132 at a low concentration (0.5 M) diminished c-Met levels in H441 cells, while neither a low nor a high concentration (20 M) altered c-Met levels in A549 and H460 cells. A higher concentration of MG-132 (5 M) was required for decreasing c-Met levels in H1299 cells. Furthermore, MG-132 induced cell death in all four cell types. Among all the four cell lines, H441 cells expressed higher levels of c-Met and appeared to be the most susceptible to MG-132. MG-132 decreased c-Met mRNA levels in both H1299 and H441 cells. ONX 0914 reduced c-Met levels in H460, H1299, and H441 cells but not in A549 cells. c-Met levels were decreased the most in H441 cells treated with ONX 0914. ONX 0914 did not alter cell viability in H441; however, it did induce cell death among H460, A549, and H1299 cells. This study reveals that different proteasome inhibitors produce varied inhibitory effects in NSCLS cell lines.

Background Poplital artery transection injury is potentially catastrophic, or even life-threatening. Severe traumas, including open fracture, gunshot, stabs, and knee dislocation and complex fracture of proximal tibia or distal femur, are the common causes of high rate of amputation due to popliteal artery trauma. No report mentions vascular injury associated with minimally displaced tibial plateau fracture in adult. Case presentation A 30-year-old male presented with popliteal artery transection injury associated with minimally displaced tibial plateau fracture. He presented to emergency department, 6 h after fall from ground into a 1-m height hole. Physical examination suggested acute ischemia, with signs of paleness, coldness, anesthesia, hemorrhagic bullae below the right knee level. There was severe swelling and ecchymosis in popliteal fossa and around the leg with significant calf tenderness and pedal edema. Tibialis posterior, dorsalis pedis, and popliteal arterial pulses were not palpable. Radiograph suggested minimally displaced tibial plateau fracture with no evidence of knee dislocation. The patient was taken up for emergency surgery after consultation with vascular surgeon. During the closed reduction external fixation and compartment decompression, popliteal artery trunk was found transected and end-to-end repair was performed. During the post-operational period, no complication was developed and the patient was followed-up for 1 year. At the one-year follow-up, he acquired good stability of his right knee with full range of motion. Conclusion Significant swelling and ecchymosis should alert the surgeons to the possibility of vascular injury in knee joint injury, even if there is no fracture or dislocation, or fracture is minimally displaced.

Primary cilia have been found to function as mechanosensors in low‐magnitude high‐frequency vibration (LMHFV)‐induced osteogenesis. The PGE2 also regulates bone homeostasis and mechanical osteogenesis through its receptor EP4 signaling, but its involvement in LMHFV‐induced or in primary cilia‐induced osteogenesis has not been investigated. We hypothesized that LMHFV stimulates osteoblast (OB) differentiation by activating the COX2‐PGE2‐EP pathway in a manner dependent on primary cilia and that primary cilia are also affected by the PGE2 pathway. In this study, through western blot analysis, RNA interference, enzyme‐linked immunosorbent assay, real‐time quantitative polymerase chain reaction, and cytochemical staining, we observed that COX2, mPGES‐1, and PGE2 levels were markedly elevated in cells treated with LMHFV and were greatly decreased in LMHFV‐treated cells following IFT88 silencing. EP4 expression was significantly increased in OBs following LMHFV treatment, but IFT88 silencing significantly blocked this increase. EP4 localized to the bases of primary cilia. LMHFV reduced the length and abundance of primary cilia, but the cells could self‐repair their primary cilia after mechanical damage. EP4 antagonism significantly blocked the LMHFV‐induced increase in IFT88 expression and blocked the recovery of primary cilia length and the proportion of cells with primary cilia. In addition, COX2 or EP4 antagonism disrupted LMHFV‐induced osteogenesis. These results demonstrate the integration of and crosstalk between primary cilia and the COX2‐PGE2‐EP4 signaling pathway under mechanical stimulation.

Background Intramedullary nails have become the main treatment for intertrochanteric fractures. However, a distal locking procedure during nailing gradually raised controversy. In this study, a systematic review and meta-analysis of clinical trials was performed to summarize existing evidence, aiming to determine the safety and efficacy of distal locking or unlocking in the nailing of stable intertrochanteric fractures. Methods Appropriate articles were identified using the most common public databases, such as PubMed, Embase, the Cochrane Library, and Google Scholar from the inception of each database to April 2019, without restriction of language, publication date, and considering ongoing trials. Eligible studies were represented by randomized controlled trials or retrospective cohort studies, comparing distal locking and unlocking for the treatment of acute stable intertrochanteric fractures in adult patients. Information regarding methodological quality, patient demographics, and clinical outcomes were extracted independently by two reviewers. Subsequently, patients were divided into a locking and unlocking group. Results This study included 9 articles, comprising a total of 1978 patients with a similar baseline. The results showed that the unlocking group had a shorter operation time, less intraoperative bleeding, lower transfusion rate, and less thigh pain after the treatment of femoral intertrochanteric fracture when compared with the distal locking group. No significant differences were observed in safety-related outcomes, including mortality, infection rate, cutting out, loss of reduction, backing out of lag screws, cephalic screw breakage, nail breakage, and peri-implant fractures between the two groups. In addition, efficacy-related outcomes including nonunion, delayed healing rates, and the Harris functional score were not significantly different between the two groups. Conclusions Our pooled analysis demonstrated that distal unlocking of stable intertrochanteric fractures can shorten the operation time, reduce intraoperative bleeding, and reduce the blood transfusion rate. The use of locked or unlocked intramedullary nailing does not affect long-term outcomes regarding complications and function.

目前已有研究证实限制性输液的优势,随着术后快速康复的发展,限制性输液不但不会增加术中后出现肝肾功能异常风险,而且有利于患者术后的恢复 [1,2] 。在麻醉过程中,患者的交感神经受到抑制,血管平滑肌松弛,血管扩张,液体存在相对不足。为维持循环稳定,使循环系统维持在稳定的生理状态,α受体激动剂成为良好的选择。去甲肾上腺素激动α受体,对β1受体激动作用很弱,对β2受体几乎无作用,具有很强的血管收缩

A 64-year-old male smoker who was previously healthy underwent intracranial aneurysm clipping after subarachnoid hemorrhage. Thoracic computerized tomography which was taken a day before the surgery revealed small bullae and low attenuation area in bilateral lower lobes. Soon after the completion of the surgery, the patient began to breathe, and then developed cough, 5 min later oxygen saturation decreased, and diminished breath sounds were detected in the left lung. Tube thoracostomy was performed and eventually resolved the complication. Bilateral pneumothorax, pneumomediastinum, and subcutaneous emphysema were confirmed by computerized tomography later. Early recognition and intervention of perioperative pneumothorax and pneumomediastinum can improve the patient's outcome.

Our objective was to investigate the role of primary cilia in low-magnitude, high-frequency vibration (LMHFV) treatment of MC3T3-E1 osteoblasts (OBs). We used chloral hydrate (CH), which has a well-characterized function in chemically removing primary cilia, to elucidate the role of primary cilia in LMHFV-induced OB osteogenic responses through cell viability assay, Western blot analysis, real-time quantitative RT-PCR, and histochemical staining methods. We observed a significant, 30% decrease in the number of MC3T3-E1 OBs with primary cilia (reduced from 64.3 ± 5%) and an approximately 50% reduction in length of primary cilia (reduced from 3 ± 0.8 μm) after LMHFV stimulation. LMHFV stimulation upregulated protein expression of the bone matrix markers collagen 1 (COL-1), osteopontin (OPN), and osteoclacin(OCN) in MC3T3-E1 OBs, indicating that LMHFV induces osteogenesis. High-concentration or long-duration CH exposure resulted in inhibition of MC3T3-E1 OB survival. In addition, Western blot analysis and RT-PCR revealed that CH treatment prevented LMHFV-induced osteogenesis. Furthermore, decreased alkaline phosphate activity, reduced OB differentiation, mineralization, and maturation were observed in CH-pretreated and LMHFV-treated OBs. We showed that LMHFV induces morphological changes in primary cilia that may fine-tune their mechanosensitivity. In addition, we demonstrated the significant inhibition by CH of LMHFV-induced OB mineralization, maturation, and differentiation, which might reveal the critical role of primary cilia in the process.

Anesthetics have long been proven to have additional effects other than anesthesia on different organs and tissues of the human body. Barrier tissues play critical roles in human health and diseases, yet the impacts of anesthetics on barrier tissues are still not clear. This review article is aimed at summarizing different effects of anesthetics on the skin, the respiratory, and intestinal membranes from two aspects: inflammation/immunity and ischemia-reperfusion. Among volatile, intravenous, and local anesthetics, volatile anesthetics are less influential on barrier ischemia-perfusion function. Although direct comparisons between volatile and the other two types of anesthetics are still lacking, volatile anesthetics appear to have stronger anti-inflammatory effects on different barrier tissues through various mechanisms. These results suggested that when treating patients with barrier tissue complications, volatile anesthetics can provide better therapeutic outcomes.