The synergistic mechanisms of propofol with cisplatin or doxorubicin in human ovarian cancer cells.

BACKGROUND: Most ovarian cancer cases are diagnosed at an advanced stage, leading to poor outcomes and a relatively low 5-year survival rate. While tumor resection in the early stages can be highly effective, recurrence following primary treatment remains a significant cause of mortality. Propofol is a commonly used intravenous anesthetic agent in cancer resection surgery. Previous research has shown that propofol anesthesia was associated with improved survival in patients undergoing elective surgery for epithelial ovarian cancer. However, the underlying antitumor mechanisms are not yet fully understood. METHODS: This study aimed to uncover the antitumor properties of propofol alone and combined with cisplatin or doxorubicin, in human SKOV3 and OVCAR3 ovarian cancer cells. We applied flowcytometry analysis for mitochondrial membrane potential, apoptosis, and autophagy, colony formation, migration, and western blotting analysis. RESULTS: Given that chemotherapy is a primary clinical approach for managing advanced and recurrent ovarian cancer, it is essential to address the limitations of current chemotherapy, particularly in the use of cisplatin and doxorubicin, which are often constrained by their side effects and the development of resistance. First of all, propofol acted synergistically with cisplatin and doxorubicin in SKOV3 cells. Moreover, our data further showed that propofol suppressed colony formation, disrupted mitochondrial membrane potential, and induced apoptosis and autophagy in SKOV3 and OVCAR3 cells. Finally, the effects of combined propofol with cisplatin or doxorubicin on mitochondrial membrane potential, apoptosis, autophagy, and epithelial-mesenchymal transition were different in SKOV3 and OVCAR3 cells, depending on the p53 status. CONCLUSION: In summary, repurposing propofol could provide novel insights into the existing chemotherapy strategies for ovarian cancer. It holds promise for overcoming resistance to cisplatin or doxorubicin and may potentially reduce the required chemotherapy dosages and associated side effects, thus improving treatment outcomes.

Inflammatory Biomarkers and Blood Physical Property Transformations Following On-Pump Coronary Artery Bypass Graft Surgery.

OBJECTIVE: This study aimed to compare the hemorheological and inflammatory changes before and after coronary artery bypass graft (CABG) surgery, as factors such as hypothermia, hemodilution, transfusion, and other variables affect blood viscosity and inflammation during the procedure. METHODS: A total of 25 patients who underwent CABG surgery were enrolled in this study. Whole blood was collected just before the CABG (D0), 2 days after surgery (D2), and 5 days after surgery (D5). The plasma viscosity (PV) and whole blood viscosity (WBV) were measured at shear rates ranging from 0.1 to 1000 s-1 using a rheometer, and the mean values were compared. Inflammatory markers were also assessed and analyzed in relation to the hemorheological changes. RESULTS: Compared with the baseline values, the PV significantly increased after 5 days. WBV showed a significant increase on day 2 and after 5 days. The WBV and fibrinogen were significantly correlated on day 2 and day 5 but not before surgery. Inflammatory markers such as CRP, WBC, platelets, and fibrinogen also demonstrated notable changes in relation to the hemorheological alterations. CONCLUSIONS: This study highlights the crucial finding that hyperviscosity, characterized by elevated PV and WBV, persists for almost one week after on-pump CABG surgery. Understanding the interplay between inflammation and hemorheological properties during the postoperative period is crucial for optimizing patient care. Future research should focus on exploring the underlying mechanisms and potential therapeutic interventions to mitigate the impact of inflammation on blood viscosity and improve patient outcomes following CABG surgery.

Extracorporeal Life Support for Severely Burned Patients with Concurrent Inhalation Injury and Acute Respiratory Distress Syndrome: Experience from a Military Medical Burn Center.

BACKGROUND: Both inhalation injury and acute respiratory distress syndrome (ARDS) are risk factors that predict mortality in severely burned patients. Extracorporeal life support (ECLS) is widely used to rescue these patients; however, its efficacy and safety in this critical population have not been well defined. We report our experience of using ECLS for the treatment of severely burned patients with concurrent inhalation injury and ARDS. METHODS: This was a retrospective analysis of 14 patients collected from a single medical burn center from 2012 to 2019. All patients suffered from major burns with inhalation injury and ARDS, and were treated with ECLS. RESULTS: The median total body surface area of deep dermal or full thickness burns was 94.5%, ranging 47.7-99.0 %. The median revised Baux score was 122.0, ranging 90.0-155.0. All patients developed ARDS with a median partial pressure of arterial oxygen to a fraction of inspired oxygen ratio of 61.5, ranging 49.0-99.0. Indications for ECLS included sustained hypoxemia and unstable hemodynamics. The median interval for initiating ECLS was 2.5 days, ranging 1.0-156.0 days. The median duration of ECLS was 2.9 days, ranging 0.3-16.7 days. The overall survival to discharge was 42.8%. Causes of death included sepsis and multiple organ failure. ECLS-related complications included cannulation bleeding, catheter-related infection, and hemolysis. The incidence of risk factors reported in literature were higher in non-survivors, including Baux>120, albumin < 3.0 g/dL, and lactate > 8 mmol/L. CONCLUSIONS: For severely burned patients with concurrent inhalation injury and ARDS, ECLS could be a salvage treatment to improve sustained hypoxemia. However, the efficacy of hemodynamic support was limited. Identifying definite ECLS indications and rigorous patient selection would contribute to better clinical outcomes.

Apoptosis, Proliferation, and Autophagy Are Involved in Local Anesthetic-Induced Cytotoxicity of Human Breast Cancer Cells.

Breast cancer accounts for almost one quarter of all female cancers worldwide, and more than 90% of those who are diagnosed with breast cancer undergo mastectomy or breast conservation surgery. Local anesthetics effectively inhibit the invasion of cancer cells at concentrations that are used in surgical procedures. The limited treatment options for triple-negative breast cancer (TNBC) demonstrate unmet clinical needs. In this study, four local anesthetics, lidocaine, levobupivacaine, bupivacaine, and ropivacaine, were applied to two breast tumor cell types, TNBC MDA-MB-231 cells and triple-positive breast cancer BT-474 cells. In addition to the induction of apoptosis and the suppression of the cellular proliferation rate, the four local anesthetics decreased the levels of reactive oxygen species and increased the autophagy elongation indicator in both cell types. Our combination index analysis with doxorubicin showed that ropivacaine had a synergistic effect on the two cell types, and lidocaine had a synergistic effect only in MDA-MB-231 cells; the others had no synergistic effects on doxorubicin. Lidocaine contributed significantly to the formation of autophagolysosomes in a dose-dependent manner in MDA-MB-231 cells but not in BT-474 cells. Our study demonstrated that the four local anesthetics can reduce tumor growth and proliferation and promote apoptosis and autophagy.

Intrinsically Disordered Protein Condensate-Modified Surface for Mitigation of Biofouling and Foreign Body Response.

Mitigation of biofouling and the host's foreign body response (FBR) is a critical challenge with biomedical implants. The surface coating with various anti-fouling materials provides a solution to overcome it, but limited options in clinic and their potential immunogenicity drive the development of more alternative coating materials. Herein, inspired by liquid-liquid phase separation of intrinsically disordered proteins (IDPs) to form separated condensates in physiological conditions, we develop a new type of low-fouling biomaterial based on flexible IDP of FUS protein containing rich hydrophilic residues. A chemical structure-defined FUS IDP sequence tagged with a tetra-cysteine motif (IDPFUS) was engineered and applied for covalent immobilization on various surfaces to form a uniform layer of protein tangles, which boosted strong hydration on surfaces, as revealed by molecular dynamics simulation. The IDPFUS-coated surfaces displayed excellent performance in resisting adsorption of various proteins and adhesion of different cells, platelets, and bacteria. Moreover, the IDPFUS-coated implants largely mitigated the host's FBR compared with bare implants and particularly outperformed PEG-coated implants in reducing collagen encapsulation. Thus, this novel low-fouling and anti-FBR strategy provides a potential surface coating material for biomedical implants, which will also shed light on exploring similar applications of other IDP proteins.

Cerebral Oximetry-Monitored Nitroglycerin Infusion and Tissue Perfusion during Rewarming of Cardiopulmonary Bypass in Cardiac Surgery: A Prospective Randomized Trial.

BACKGROUND: Nitroglycerin facilitates microcirculation and oxygen delivery through vasodilation. The purpose of this study was to clarify the effects of nitroglycerin-induced vasodilation and potential hypotension on tissue perfusion under cerebral oximetry monitoring during rewarming in cardiopulmonary bypass. METHODS: Elective cardiac surgical patients were randomly assigned to either a nitroglycerin group (n = 32) with an intravenous infusion of 1-5 mcg/kg/min or a control group (n = 31) with 0-0.1 mcg/kg/min infusion, since the initiation of rewarming. Perioperative arterial blood gas data were collected in addition to hemodynamic variables, cerebral oximetry values, urine output, and postoperative outcomes. RESULTS: Nearly one-fifth (6/32) of patients in the nitroglycerin group experienced transient (≤5 min) profound hypotension (mean arterial blood pressure ≤40 mmHg) after the initiation of infusion. There were no significant differences between groups in terms of perioperative levels of cerebral oximetry, cardiac index, plasma glucose, lactate, bicarbonate, base excess, or post-bypass activated coagulation time. In the nitroglycerin group, urine output was nonsignificantly higher during cardiopulmonary bypass (p = 0.099) and within 8 h after surgery (p = 0.157). Perioperative transfused blood products, postoperative inotropic doses, extubation time, and intensive care unit stay were comparable for the two groups. CONCLUSIONS: Initiation of intravenous nitroglycerin infusion (at 1-5 mcg/kg/min) during rewarming in hypothermic cardiopulmonary bypass resulted in transient profound hypotension in one-fifth of patients and did not improve perioperative cerebral oxygenation, tissue perfusion, and coagulation in cardiac surgery.

Restrictive cardiomyopathy caused by diffuse calcification of the left ventricle after 20 years of haemodialysis.

Valvular and vascular calcifications are common among patients with end-stage renal disease, but diffuse calcification of the left ventricle is rarely reported. We report on a rare case of restrictive cardiomyopathy resulting from severe myocardial calcification and review the literature. A 77-year-old man was diagnosed with end-stage renal disease after having received regular haemodialysis for 20 years. He was referred to our emergency room due to exertional dyspnoea and exacerbated shortness of breath. A chest X-ray revealed severe pulmonary oedema and bilateral massive pleural effusion. Transthoracic echocardiography revealed impaired diastolic function of the left ventricle but preserved systolic function with a 50% ejection fraction. Repeat chest computed tomography demonstrated exacerbation of the calcification from the mitral annulus to the whole circular left ventricle. A coronary angiogram revealed non-significant stenosis, and right heart catheterisation demonstrated elevated pulmonary capillary wedge pressure. He was discharged after two weeks of conservative medication.

Mitochondrial Dysfunction Involved in the Cytotoxicity of Tramadol in Human Endometrial Carcinoma Cells.

Tramadol is a common anesthetic used to treat cancer pain, including endometrial cancer, but its function in endometrial cancer remains unclear. The purpose of this study was to elucidate the antitumor effects of tramadol on human endometrial cancer cells. Colony formation, BrdU, cell cycle profiles, apoptosis, ROS, and Western blot analyses were used to study the response of endometrial cancer cells to tramadol. JC-1 and seahorse metabolic flux assays were used to detect the effect of tramadol on mitochondria in endometrial cancer cells. Combination index was used to detect the interaction of tramadol with chemotherapy drugs in endometrial cancer cells. In this study, we found that tramadol was able to inhibit proliferation and induce cell cycle arrest, ROS generation, and apoptosis in two types of endometrial cancer cells. In addition, tramadol treatment also induced mitochondrial dysfunction in endometrial cancer cells by causing a loss of mitochondrial membrane potential and a decreased oxygen consumption rate. More importantly, the synergetic effect of tramadol with doxorubicin or cisplatin was further confirmed in endometrial cancer cells by the results of the combination index and apoptosis assay. In summary, our findings indicate that tramadol has an antitumor effect on endometrial cancer cells, which might serve as a potential adjuvant therapy strategy for endometrial cancer.

Identification of Hypoxia-Related Molecular Classification and Associated Gene Signature in Oral Squamous Cell Carcinoma.

The high heterogeneity of oral squamous cell carcinoma (OSCC) is the main obstacle for individualized treatment. Recognizing the characteristics of different subtypes and investigating the promising strategies for each subclass are of great significance in precise treatment. In this study, we systematically evaluated hypoxia-mediated patterns together with immune characteristics of 309 OSCC patients in the TCGA training set and 97 patients in the GSE41613 testing set. We further identified two different hypoxia subtypes with distinct immune microenvironment traits and provided treatment programs for the two subclasses. In order to assess hypoxia level individually, we finally constructed a hypoxia-related risk score, which could predict the clinical outcome and immunotherapy response of OSCC patients. In summary, the recognition of different hypoxia patterns and the establishment of hypoxia-related risk score might enhance our understanding of the tumor microenvironment of OSCC and provide more personalized treatment strategies in the future.

Application of Straight-needle, Three-tailed, Knot-free, Peritoneal Sutures in Laparoscopic Transabdominal Preperitoneal Hernia Repair.

Laparoscopic transabdominal preperitoneal hernia repair (TAPP) is one of the most widely used methods in inguinal hernia surgery. After the mesh is placed, the peritoneum must be resutured to avoid contact with the tissues and organs in the abdominal cavity. If the peritoneal suture time is too long, the operation and anesthesia time will be prolonged, increasing the burden on the patient. Moreover, improper suture methods cause serious consequences, such as intestinal obstruction and mesh infection. The straight-needle suture method transforms the three-dimensional spatial configuration of the needle holder and the arc needle tip into a two-dimensional planar structure, which greatly reduces the difficulty of suturing. The three-tailed knot can be anchored at the beginning of the suture by its friction and button effect, which has an exact fixation effect. Thus, the suture does not easily slip, and the time to complete the suturing is shortened. Compared with the traditional suture method, the operator can suture the peritoneum more quickly, beginners can pass through the difficult learning curve faster, and skilled operators can also shorten the total operation time of TAPP to a certain extent. Thus, this suture method is extremely amenable to clinical application.

Expression and prognostic value of Chromobox family members in gastric cancer.

BACKGROUND: The Chromobox (CBX) protein family, which is a crucial part of the epigenetic regulatory complex, plays an important role in the occurrence and development of cancer; however, the function and prognostic value of CBX family members in gastric cancer is not clear. METHODS: we investigated the relationship between CBX members and gastric cancer using a range of tools and databases: Oncomine, Kaplan-Meier plotter, cBioPortal, ULCAN, Metascape, and GEPIA. RESULTS: The results showed that, relative to normal gastric tissue, mRNA expression levels of CBX1-6 were significantly higher in gastric cancer tissue, whereas the level of CBX7 was significantly lower. Furthermore, overexpression of CBX3-6 and underexpression of CBX7 mRNAs was significantly related to the poor prognosis and survival of gastric cancer patients, making these CBX family members useful biomarkers. Finally, overexpression of CBX1 mRNA was significantly related to the poor prognosis of gastric cancer patients treated with adjuvant 5-fluorouracil-based chemotherapy. CONCLUSIONS: The members of the CBX family can be used as prognosis and survival biomarkers for gastric cancer and CBX1 may be a biomarker for choosing the chemotherapy regimen of gastric cancer patients.

Caprin-1 promotes HepG2 cell proliferation, invasion and migration and is associated with poor prognosis in patients with liver cancer.

The present study aimed to investigate the role of caprin-1 in liver cancer and its association with the clinicopathological features and prognosis of liver cancer, as well as the underlying mechanism of caprin-1 function. Caprin-1 expression levels in a tissue microarray containing 40 liver cancer tissues, 10 peritumoral tissues and 20 normal liver tissues were analyzed using immunohistochemistry. The clinical data of 154 patients with liver cancer were also collected from The Cancer Genome Atlas database. Kaplan-Meier analysis and a Cox proportional hazards regression model were used to assess the association between caprin-1 expression levels and survival in patients with liver cancer. The effects of caprin-1 knockdown on the mRNA levels of cyclin D1 and cyclin D2 as well as the proliferation, invasion and migration of HepG2 cells were also investigated. The expression level of caprin-1 in liver cancer tissues was significantly higher compared with normal liver tissues or cells (P<0.01). High caprin-1 expression levels were associated with advanced clinical stage (P<0.001) and enhanced tumor invasion (P<0.001). Kaplan-Meier analysis showed that the overall survival time and disease-free survival time in patients with liver cancer with high caprin-1 expression were significantly shorter compared with patients with low caprin-1 expression levels (P=0.002 and P=0.033, respectively). The Cox proportional hazards regression model showed that high caprin-1 expression levels were an independent prognostic factor for liver cancer (P<0.001). Knockdown of caprin-1 in HepG2 cells significantly downregulated mRNA expression levels of cyclin D1 and cyclin D2, inhibited cell proliferation and invasion and the cells were arrested at G0/G1 phase. In conclusion, caprin-1 may be a novel prognostic indicator for patients with liver cancer.

Ultrasound-mediated delivery of RGD-conjugated nanobubbles loaded with fingolimod and superparamagnetic iron oxide nanoparticles: targeting hepatocellular carcinoma and enhancing magnetic resonance imaging.

Nanobubbles (NBs) are considered to be a new generation of ultrasound-responsive nanocarriers that can effectively target tumors, accurately release multi-drugs at desired locations, as well as simultaneously perform diagnosis and treatment. In this study, we designed theranostic NBs (FTY720@SPION/PFP/RGD-NBs) composed of RGD-modified liposomes as the shell, and perflenapent (PFP), superparamagnetic iron oxide nanoparticles (SPION), and fingolimod (2-amino-2[2-(4-octylphenyl)ethyl]-1,3-propanediol, FTY720) encapsulated as the core. The prepared FTY720@SPION/PFP/RGD-NBs were black spheres with a diameter range of 160-220 nm, eligible for enhanced permeability and retention (EPR) effects. The calculated average drug loading efficiency (LE) and encapsulation efficiency (EE) of the FTY720@SPION/PFP/RGD-NBs were 9.18 ± 0.61% and 88.26 ± 2.31%, respectively. With the promotion of low-intensity focused ultrasound (LIFU), the amount and the rate of FTY720 released from the prepared NB complex were enhanced when compared to the samples without LIFU treatment. In vitro magnetic resonance imaging (MRI) trials showed that the prepared FTY720@SPION/PFP/RGD-NBs had a high relaxation rate and MRI T2-weighted imaging (T2WI) scanning sensitivity conditions. The cell viability studies demonstrated that both HepG2 and Huh7 cells co-cultured with FTY720@SPION/PFP/RGD-NB (100 µg mL-1) + LIFU treatment had the lowest survival rate compared with the other groups at 24 h and 48 h, showing that FTY720@SPION/PFP/RGD-NB had the strongest anti-tumor efficiency among the prepared NBs. The cytotoxicity study also demonstrated that the prepared NBs had low toxicity to normal fibroblast 3T3 cells. Cellular uptake studies further indicated that both LIFU treatment and RGD modification could effectively improve the tumor-targeted effects, thereby enhancing the antitumor efficacy. The qRT-PCR results indicated that LIFU-mediated FTY720@SPION/PFP/RGD-NB could significantly cause the activation of Caspase3, Caspase9 and p53 compared to the control group, inducing HepG2 apoptosis. These results together indicated that FTY720@SPION/PFP/RGD-NBs combined with LIFU may serve as a multifunctional drug delivery platform for hepatocellular carcinoma treatment and provide a new strategy for tumor visualization by MRI.

The implication of seniority of supervising attending surgeon on the reexploration rate following elective coronary artery bypass grafting.

BACKGROUND AND AIMS: During coronary artery bypass graft (CABG) surgery, the residual hemostasis procedures, from weaning cardiopulmonary bypass to closing sternotomy, are always completed by residents and supervised by attending surgeons. We want to evaluate the teaching effectiveness for residents under the supervision of attending surgeons with different levels of seniority. MATERIALS AND METHODS: Between January 1st 2001 and December 31st 2010, 2279 consecutive CABG surgeries were performed in our medical center. In total, 83 patients underwent a reexploration for postoperative bleeding. All causes of bleeding were identified and recorded. Competent attending surgeons were defined as having >3 years' experience and young attending surgeons with ≦3 years' experience. We compared the reexploration rate and aimed to identify the common sources of bleeding by the two groups. We also assessed the impact of attending experience on the outcomes and major complications after reexploration. RESULTS: There were 36 surgical bleeding and 17 non-surgical bleeding in the young group and 16 surgical bleeding and 14 non-surgical bleeding in the competent group. The young group experienced more mediastinal drainage before a reexploration and a longer time interval to a reexploration. However, both are without statistical significance. Furthermore, the young group has a significant longer hospital stay. The most common intra-pericardium surgical bleeding included two-stage cannulation, side branch of the left internal mammary artery (LIMA), and side branch of vein grafts. The most common extra-pericardium surgical bleeding included a puncture hole by sternal wires, LIMA bed, and fragile sternum. CONCLUSION: Young attending surgeons indeed had both higher incidence of reexploration and surgical bleeding after a CABG. However, the supervisor experience only impacted hospital stay, not major complications or mortality after a reexploration. This might imply the competent attending surgeons provide higher teaching effectiveness for the hemostasis procedure after CABG.

Benefit of extracorporeal membrane oxygenation in major burns after stun grenade explosion: Experience from a single military medical center.

INTRODUCTION: Explosion injury is very common on the battlefield and is associated with major burn and inhalation injuries and subsequent high mortality and morbidity rates. Here we report six victims who suffered from explosion injuries caused by stun grenade; all were treated with extracorporeal membrane oxygenation (ECMO) as salvage therapy. This study was aimed to evaluate the indications and efficacy of ECMO in acute and critically ill major burn patients. METHODS: This was a retrospective analysis of six patients from Tri-Service General Hospital, National Defense Medical Center in Taiwan. All suffered from major burns with 89.0±19.1% average of total body surface area over second degree (TBSA; range, 50-99%). ECMO was used due to inhalation injury in five patients and cardiogenic shock in one patient. The average interval to start ECMO was 26.5±19.0h (range, 14-63h). Venoarterial ECMO was used on in four patients due to unstable hemodynamic status, whereas venovenous ECMO was used in two patients for sustained hypoxemia. RESULTS: All patients had rhabdomyolysis with acute renal failure. The average duration of ECMO was 169.6±180.9h (range, 27-401h). All patients developed coagulopathy and needed debridement surgery during ECMO support, and five underwent torso escharotomy due to inspiratory compromise. Only one patient whose second and third degree burns covered 50% TBSA was successfully weaned from ECMO and survived; he was discharged after 221 hospital days. All patients who died had second and third degree burns covering over 90% of their TBSA. Three patients died of multiple organ failure, one died of septic shock, and the other died of cardiogenic shock. Overall survival rate was 16.7%. CONCLUSIONS: In acute and critically ill major burn patients, ECMO could be considered as a salvage therapy, particularly in those with inhalation injury and burn-related acute respiratory distress syndrome. However, ECMO does not seem to provide benefits for circulatory support in those with hemodynamic compromise. The use of ECMO in these patients is still investigational, as our data provided no benefit in terms of the outcomes or survival, particularly in those with more than 90% TBSA burns.

Electrospun scaffolds for multiple tissues regeneration in vivo through topography dependent induction of lineage specific differentiation.

Physical topographic cues from various substrata have been shown to exert profound effects on the growth and differentiation of stem cells due to their niche-mimicking features. However, the biological function of different topographic materials utilized as bio-scaffolds in vivo have not been rigorously characterized. This study investigated the divergent differentiation pathways of mesenchymal stem cells (MSCs) and neo-tissue formation trigged by aligned and randomly-oriented fibrous scaffolds, both in vitro and in vivo. The aligned group was observed to form more mature tendon-like tissue in the Achilles tendon injury model, as evidenced by histological scoring and collagen I immunohistochemical staining data. In contrast, the randomly-oriented group exhibited much chondrogenesis and subsequent bone tissue formation through ossification. Additionally, X-ray imaging and osteocalcin immunohistochemical staining also demonstrated that osteogenesis in vivo is driven by randomly oriented topography. Furthermore, MSCs on the aligned substrate exhibited tenocyte-like morphology and enhanced tenogenic differentiation compared to cells grown on randomly-oriented scaffold. qRT-PCR analysis of osteogenic marker genes and alkaline phosphatase (ALP) staining demonstrated that MSCs cultured on randomly-oriented fiber scaffolds displayed enhanced osteogenic differentiation compared with cells cultured on aligned fiber scaffolds. Finally, it was demonstrated that cytoskeletal tension release abrogated the divergent differentiation pathways on different substrate topography. Collectively, these findings illustrate the relationship between topographic cues of the scaffold and their inductive role in tissue regeneration; thus providing an insight into future development of smart functionalized bio-scaffold design and its application in tissue engineering.

Acute pulmonary injury with refractory hypoxaemia after implantation of Levitronix CentriMag ventricular assist device: successful treatment with veno-venous extracorporeal membrane oxygenation.

Although acute pulmonary injury after cardiopulmonary bypass has been detailed in the literature, it was seldom mentioned in the context of following implantation of a ventricular assist device. We report on a 65-year-old male with end-stage ischemic cardiomyopathy who underwent implantation of Levitronix CentriMag (Levitronix, Waltham, MA) for cardiac support and was listed for heart transplantation. Acute pulmonary injury with profound hypoxaemia was noted 6 h after the implantation. Despite optimal medical treatment and maximal ventilator support, refractory hypoxaemia persisted, and veno-venous extracorporeal membrane oxygenation (oxygenator: Affinity-NT; centrifugal pump: BPX-80 Bio-Pump, Medtronic, Minneapolis, MN, USA) was applied for ventilation support. The patient was weaned from the extracorporeal membrane oxygenation 4 days later and from the ventilator on the next 2 days. He underwent a successful orthotopic heart transplant after a total of 77 days on Levitronix left ventricular device cardiac support.

Scleraxis-overexpressed human embryonic stem cell-derived mesenchymal stem cells for tendon tissue engineering with knitted silk-collagen scaffold.

AIM: Despite our previous study that demonstrates that human embryonic stem cells (hESCs) can be used as seed cells for tendon tissue engineering after stepwise induction, suboptimal tendon regeneration implies that a new strategy needs to be developed for tendon repair. We investigated whether overexpression of the tendon-specific transcription factor scleraxis (SCX) in hESC-derived mesenchymal stem cells (hESC-MSCs) together with knitted silk-collagen sponge scaffold could promote tendon regeneration. METHODS AND RESULTS: hESCs were initially differentiated into MSCs and then engineered with scleraxis (SCX+hESC-MSCs). Engineered tendons were constructed with SCX+hESC-MSCs and a knitted silk-collagen sponge scaffold and then mechanical stress was applied. SCX elevated tendon gene expression in hESC-MSCs and concomitantly attenuated their adipogenic and chondrogenic potential. Mechanical stress further augmented the expression of tendon-specific genes in SCX+hESC-MSC-engineered tendon. Moreover, in vivo mechanical stimulation promoted the alignment of cells and increased the diameter of collagen fibers after ectopic transplantation. In the in vivo tendon repair model, the SCX+hESC-MSC-engineered tendon enhanced the regeneration process as shown by histological scores and superior mechanical performance compared with control cells, especially at early stages. CONCLUSION: Our study offers new evidence concerning the roles of SCX in tendon differentiation and regeneration. We demonstrated a novel strategy of combining hESCs, genetic engineering, and tissue-engineering principles for tendon regeneration, which are important for the future application of hESCs and silk scaffolds for tendon repair.

Force and scleraxis synergistically promote the commitment of human ES cells derived MSCs to tenocytes.

As tendon stem/progenitor cells were reported to be rare in tendon tissues, tendons as vulnerable targets of sports injury possess poor self-repair capability. Human ESCs (hESCs) represent a promising approach to tendon regeneration. But their teno-lineage differentiation strategy has yet to be defined. Here, we report that force combined with the tendon-specific transcription factor scleraxis synergistically promoted commitment of hESCs to tenocyte for functional tissue regeneration. Force and scleraxis can independently induce tendon differentiation. However, force alone concomitantly activated osteogenesis, while scleraxis alone was not sufficient to commit, but augment tendon differentiation. Scleraxis synergistically augmented the efficacy of force on teno-lineage differentiation and inhibited the osteo-lineage differentiation by antagonized BMP signaling cascade. The findings not only demonstrated a novel strategy of directing hESC differentiation to tenocyte for functional tendon regeneration, but also offered insights into understanding the network of force, scleraxis and bmp2 controlling tendon-lineage differentiation.

[An analysis of disease spectrum of patients admitted to the General Internal Medicine Unit at Peking Union Medical College Hospital from 2004 to 2008, and the value of general internal medicine unit in comprehensive hospitals].

OBJECTIVE: To analyze the disease spectrum of patients admitted to the General Internal Medicine Unit at Peking Union Medical College Hospital, which is the first academic division of general internal medicine in the department of medicine within Chinese medical colleges and universities, and the value of general internal medicine unit in comprehensive hospitals. METHODS: A retrospective data review of patients admitted to the General Internal Medicine Unit from 2004 to 2008 was conducted from hospital information system and partially by chart review manually. Analysis of disease spectrum was performed thereafter. RESULTS: A total of 2593 patients were included in our study. It consisted of 1075 men and 1518 women, with an average age of 45.1 years old. Forty point three percent of these patients were from Beijing, the local city, and the remaining 59.7% were from outside of Beijing. Sixty-four point nine percent (1683/2593) of these patients did not have a clear diagnosis on admission, including 758 fever of unknown origin (FUO) cases and 925 non-FUO cases. The final diagnostic rate of the FUO cases was 89.2% [676/758, with the first three leading causes as diseases of the musculoskeletal system and connective tissue (29.8%), certain infectious and parasitic diseases (26.3%), and neoplasm (14.5%)]. The final diagnostic rate of the 928 non-FUO cases was 86.8% (803/925), with the first three leading causes as musculoskeletal system and connective tissue (24.9%), neoplasm (15.5%), and diseases of blood and blood-forming organs (11.4%). Despite most diagnoses fitting into the above categories, the array of diseases was broad with as many as 550 discharge diagnoses from 2004 to 2008. CONCLUSIONS: During 2004 - 2008, there was a high proportion of cases that presented to the General Internal Medicine Unit at Peking Union Medical College Hospital with an unclear diagnosis, and the spectrum of diseases diagnosed was very broad. This kind of patient admitting model might not only benefit patients with no clear admission diagnosis and patients with multidisciplinary medical problems for whom it is usually difficult to be admitted by a specialty unit, but would also benefit medical students and residents by providing a good clinical medicine teaching base. These features show the value of general internal unit in comprehensive hospitals.