The efficacy of vancomycin-loaded biphasic calcium phosphate bone substitute in the promotion of new bone growth and the prevention of postoperative infection.

Background: Due to the increasing need for suitable alternatives to bone grafts, artificial bones made of biphasic calcium phosphate (BCP) are currently being extensively researched. These porous bone substitutes have also demonstrated considerable incorporation with the host bone, and new bone is able to grow within the porous structure. They therefore offer a potential therapeutic approach for bone defects. Methods: Vancomycin-loaded Bicera™, a BCP bone substitute, was investigated in order to prevent implant-associated osteomyelitis and postoperative infection after orthopedic surgery. The loading capacity of Bicera™ was measured to understand its potential antibiotic adsorption volume. An antibiotic susceptibility test was also carried out to analyze the effect of Bicera™ loaded with different concentrations of vancomycin on the growth inhibition of methicillin-resistant Staphylococcus aureus (MRSA). Vancomycin-loaded Bicera™ was implanted into rabbits with bone defects, and general gross, radiographic, and histological evaluation was undertaken at 4, 12, and 24 weeks after implantation. Results: The maximum loading capacity of vancomycin-loaded Bicera™ was 0.9 ml of liquid regardless of the vancomycin concentration. Antibiotic susceptibility tests showed that vancomycin-loaded Bicera™ inhibited the growth of MRSA for 6 weeks. In addition, animal studies revealed that new bone grew into the vancomycin-loaded Bicera™. The percentage of new bone formation from 4 to 24 weeks after implantation increased from 17% to 36%. Conclusion: Vancomycin-loaded Bicera™ could effectively inhibit the growth of MRSA in vitro. It was found to incorporate into the host bone well, and new bone was able to grow within the bone substitute. The results of this study indicate that vancomycin-loaded Bicera™ is a potential bone substitute that can prevent implant-associated osteomyelitis and postoperative infection.

Monitored Anesthetic Care Combined with Scalp Nerve Block in Awake Craniotomy: An Effective Attempt at Enhanced Recovery After Neurosurgery.

BACKGROUND: Enhanced recovery after surgery has been attempted in neurosurgery at a greater rate. However, concern exists regarding the feasibility of using enhanced recovery after neurosurgery (ERANS). How to manage available resources to safely perform ERANS and improve clinical outcomes has been the subject of much debate and discussion. METHODS: Owing to the paucity of data available on the use of ERANS protocols, we performed the present feasibility study. We studied the outcomes of the protocols used within a tertiary referral neurosurgery center. Data from patients who had undergone awake craniotomy within an ERANS protocol were prospectively recorded in our institution from September 2017 to December 2018. We also evaluated the safety and effectiveness of the novel ERANS protocol. RESULTS: A total of 20 patients (mean age, 49.5 ± 17.8 years) were included in the present study. Intraoperative hypertension, hypotension, and bradycardia were present in 4 (20%), 1 (5%), and 1 (5%) patient, respectively. The postoperative morbidities included epilepsy in 1 (5%), pain in 3 (15%), and nausea or vomiting in 2 (10%). No significant changes had occurred in the mean arterial pressure, heart rate, blood glucose, or lactic acid level throughout the procedure. The median length of intensive care unit stay and postoperative hospital stay were 1 and 9.5 days, respectively. No 30-day readmissions or reoperations occurred during the present study. CONCLUSIONS: Applying an ERANS protocol was feasible, associated with a low incidence of complications, and acceptable intensive care unit and postoperative hospital lengths of stay. The findings from the present study might provide a new approach for the further research of ERANS.

MiR-27a-3p promotes the osteogenic differentiation by activating CRY2/ERK1/2 axis.

BACKGROUND: Osteoporosis seriously disturbs the life of people. Meanwhile, inhibition or weakening of osteogenic differentiation is one of the important factors in the pathogenesis of osteoporosis. It was reported that miR-27a-3p reduced the symptoms of osteoporosis. However, the mechanism by which miR-27a-3p in osteogenic differentiation remains largely unknown. METHODS: To induce the osteogenic differentiation in MC3T3-E1 cells, cells were treated with osteogenic induction medium (OIM). RT-qPCR was used to evaluate the mRNA expression of miR-27a-3p and CRY2 in cells. The protein levels of CRY2, Runt-related transcription factor 2 (Runx2), osteopontin (OPN), osteocalcin (OCN) and the phosphorylation level of extracellular regulated protein kinases (ERK) 1/2 in MC3T3-E1 cells were evaluated by western blotting. Meanwhile, calcium nodules and ALP activity were tested by alizarin red staining and ALP kit, respectively. Luciferase reporter gene assay was used to analyze the correlation between CRY2 and miR-27a-3p. RESULTS: The expression of miR-27a-3p and the phosphorylation level of ERK1/2 were increased by OIM in MC3T3-E1 cells, while CRY2 expression was decreased. In addition, OIM-induced increase of calcified nodules, ALP content and osteogenesis-related protein expression was significantly reversed by downregulation of miR-27a-3p and overexpression of CRY2. In addition, miR-27a-3p directly targeted CRY2 and negatively regulated CRY2. Meanwhile, the inhibitory effect of miR-27a-3p inhibitor on osteogenic differentiation was reversed by knockdown of CRY2 or using honokiol (ERK1/2 signal activator). Furthermore, miR-27a-3p significantly inhibited the apoptosis of MC3T3-E1 cells treated by OIM. Taken together, miR-27a-3p/CRY2/ERK axis plays an important role in osteoblast differentiation. CONCLUSIONS: MiR-27a-3p promoted osteoblast differentiation via mediation of CRY2/ERK1/2 axis. Thereby, miR-27a-3p might serve as a new target for the treatment of osteoporosis.

Multiple In-Gap States Induced by Topological Surface States in the Superconducting Topological Crystalline Insulator Heterostructure Sn_{1-x}Pb_{x}Te-Pb.

Superconducting topological crystalline insulators (TCIs) have been proposed to be a new type of topological superconductor where multiple Majorana zero modes may coexist under the protection of lattice symmetries. The bulk superconductivity of TCIs has been realized, but it is quite challenging to detect the superconductivity of topological surface states inside their bulk superconducting gaps. Here, we report high-resolution scanning tunneling spectroscopy measurements on lateral Sn_{1-x}Pb_{x}Te-Pb heterostructures using superconducting tips. Both the bulk superconducting gap and the multiple in-gap states with energy differences of ∼0.3 meV can be clearly resolved on TCI Sn_{1-x}Pb_{x}Te at 0.38 K. Quasiparticle interference measurements further confirm the in-gap states are gapless. Our work demonstrates that the unique topological superconductivity of a TCI can be directly distinguished in the density of states, which helps to further investigate the multiple Dirac and Majorana fermions inside the superconducting gap.

Early tracheostomy is associated with better prognosis in patients with brainstem hemorrhage.

Brainstem hemorrhage is presumed to be invariably associated with a poor prognosis in people with spontaneous hypertensive cerebral hemorrhage. The optimal timing of tracheostomy placement in brainstem hemorrhage patients, who generally require endotracheal intubation for airway protection, remains uncertain. Our research aim was to analyze the impact of early tracheostomy versus late tracheostomy on brainstem hemorrhage patients related outcomes and prognostic factors at 30 days. We identified early tracheostomy and how it could benefit the patients with brainstem hemorrhage and ameliorate the predictors of functional recovery at 30 days. Data on 136 patients with brainstem hemorrhage and Glasgow Coma Scale score ≤ 8, were retrospectively collected from 2012 to 2019. Patients were divided into the early tracheostomy group and the late tracheostomy group. Patients in the early tracheostomy group had a significantly lower neurosurgical intensive care unit stay (both overall and survival) compared with the late tracheostomy group (15.6 days vs. 19.0 days, P = 0.041, overall and 14.5 vs. 19.5 days, P = 0.023, survival). Also, the good outcomes (modified Rankin Score ≤ 3) were higher in the early tracheostomy group (P = 0.036). Multivariate analysis demonstrated that less hemorrhagic volume, high Glasgow Coma Scale score on admission, young age, and early tracheostomy were significantly associated with a better 30-day functional outcome. In conclusion, an early tracheostomy in patients with brainstem hemorrhage can reduce neurosurgical intensive care unit stay, and in addition to improvements in prognosis at 30 days.

Superconductivity of Topological Surface States and Strong Proximity Effect in Sn1- x Pbx Te-Pb Heterostructures.

Superconducting topological crystalline insulators are expected to form a new type of topological superconductors to host Majorana zero modes under the protection of lattice symmetries. The bulk superconductivity of topological crystalline insulators can be induced through chemical doping and the proximity effect. However, only conventional full gaps are observed, so the existence of topological superconductivity in topological crystalline insulators is still controversial. Here, the successful fabrication of atomically flat lateral and vertical Sn1- x Pbx Te-Pb heterostructures by molecular beam epitaxy is reported. The superconductivity of the Sn1- x Pbx Te-Pb heterostructures can be directly investigated by scanning tunneling spectroscopy. Unconventional peak-dip-hump gap features and fourfold symmetric quasiparticle interference patterns taken at the zero energy in the superconducting gap support the presence of the topological superconductivity in superconducting Sn1- x Pbx Te. Strong superconducting proximity effect and easy preparation of various constructions between Sn1- x Pbx Te and Pb make the heterostructures to be a promising candidate for topological superconducting devices to detect and manipulate Majorana zero modes in the future.

Tauroursodeoxycholic acid enhances the development of porcine embryos derived from in vitro-matured oocytes and evaporatively dried spermatozoa.

Evaporative drying (ED) is an alternative technique for long-term preservation of mammalian sperm, which does not require liquid nitrogen or freeze-drying equipment, but offers advantages for storage and shipping at ambient temperature and low cost. However, the development of zygotes generated from these sperms was poor. Here, we demonstrated that the supplementation of tauroursodeoxycholic acid (TUDCA), an endogenous bile acid, during embryo culture improved the developmental competency of embryos derived from in vitro matured pig oocytes injected intracytoplasmically with boar ED spermatozoa by reducing the production of reactive oxygen species, the DNA degradation and fragmentation, and the expression of apoptosis-related gene Bax and Bak, and by increasing the transcription of anti-apoptosis gene Bcl-XL and Bcl-2. Furthermore, TUDCA treatment promoted the blastocyst quality manifested by the total cell numbers and the ratio of inner cell mass. Taken together, our data suggest that evaporative drying would be a potentially useful method for the routine preservation of boar sperm in combination with further optimization of subsequently embryo culture conditions.

Glycine increases preimplantation development of mouse oocytes following vitrification at the germinal vesicle stage.

Ice-free cryopreservation, referred to as vitrification, is receiving increased attention in the human and animal assisted reproduction. However, it introduces the detrimental osmotic stress by adding and removing high contents of cryoprotectants. In this study, we evaluated the effects of normalizing cell volume regulation by adding glycine, an organic osmolyte, during vitrification of mouse germinal vesicle stage oocyte and/or subsequent maturation on its development. The data showed that glycine supplementation in either vitrification/thawing or maturation medium significantly improved the cytoplasmic maturation of MII oocytes manifested by spindle assembly, chromosomal alignment, mitochondrial distribution, euploidy rate, and blastocyst development following fertilization in vitro, compared to the control without glycine treatment. Furthermore, glycine addition during both vitrification/thawing and maturation further enhanced the oocyte quality demonstrated by various markers, including ATP contents and embryo development. Lastly, the effect of anti-apoptosis was also observed when glycine was added during vitrification. Our result suggests that reducing osmotic stress induced by vitrification could improve the development of vitrified mouse oocyte.

Research on cultivating medical students' self-learning ability using teaching system integrated with learning analysis technology.

Along with the advancement of information technology and the era of big data education, using learning process data to provide strategic decision-making in cultivating and improving medical students' self-learning ability has become a trend in educational research. Educator Abuwen Toffler said once, the illiterates in the future may not be the people not able to read and write, but not capable to know how to learn. Serving as educational institutions cultivating medical students' learning ability, colleges and universities should not only instruct specific professional knowledge and skills, but also develop medical students' self-learning ability. In this research, we built a teaching system which can help to restore medical students' self-learning processes and analyze their learning outcomes and behaviors. To evaluate the effectiveness of the system in supporting medical students' self-learning, an experiment was conducted in 116 medical students from two grades. The results indicated that problems in self-learning process through this system was consistent with problems raised from traditional classroom teaching. Moreover, the experimental group (using this system) acted better than control group (using traditional classroom teaching) to some extent. Thus, this system can not only help medical students to develop their self-learning ability, but also enhances the ability of teachers to target medical students' questions quickly, improving the efficiency of answering questions in class.

Olanzapine for preventing nausea and vomiting induced by moderately and highly emetogenic chemotherapy.

Nausea and vomiting are common adverse events in chemotherapy. In spite of the serious effects on the quality of life and further treatment, they remain overlooked by physicians, and no standard treatment has been developed. Neurokinin-1 (NK-1) receptor antagonists and palonosetron are the major agents in the standard regimen for treating moderately and highly emetogenic chemotherapy-induced nausea and vomiting (CINV). However, NK-1 receptor antagonists first became commercially available at the end of 2013 and palonosetron has not been extensively applied in China. Olanzapine was recommended as a therapy for moderate and severe CINV in antiemesis-clinical practice guidelines in oncology in 2014 for the first time. It is an atypical antipsychotic agent, which can block multiple receptors on neurotransmitters. During more than 10 years, olanzapine has demonstrated significant effects in preventing CINV and treating breakthrough and refractor CINV, which was observed in case reports, precise retrospective studies, and phase I, II and III clinical trials, with no grade 3 to 4 adverse events. In particular, it is superior to aprepitant and dexamethasone in delayed nausea and vomiting. Therefore, this compound is worthy of further investigation.

Aprepitant in the prevention of vomiting induced by moderately and highly emetogenic chemotherapy.

Chemotherapy is a major therapeutic approach for malignant neoplasms; however, due to the most common adverse events of nausea and vomiting, scheduled chemotherapeutic programs may be impeded or even interrupted, which severely impairs the efficacy. Aprepitants, 5-HT3 antagonists and dexamethasone are primary drugs used to prevent chemotherapy-induced nausea and vomiting (CINV). These drugs have excellent efficacy for control of acute vomiting but are relatively ineffective for delayed vomiting. Aprepitant may remedy this deficiency. Substance P was discovered in the 1930s and its association with vomiting was confirmed in the 1950s. This was followed by a period of non-peptide neurokinin-1 (NK-1) receptor antagonist synthesis and investigation in preclinical studies and clinical trials (phases I, II and III). The FDA granted permission for the clinical chemotherapeutic use of aprepitant in 2003. At present, the combined use of aprepitant, 5-HT3 antagonists and dexamethasone satisfactorily controls vomiting but not nausea. Therefore, new therapeutic approaches and drugs are still needed.

[Repairing soft tissue defect coverage in lower leg with a bridge shaped medial hemisleus muscle flap transplantation].

OBJECTIVE: To summarize clinical application results of repairing soft tissue defect in lower leg with a bridge shaped medial hemisleus muscle flap pedicle transplantation. METHODS: From January 2008 to January 2012,12 patients with soft-tissue defect in lower leg underwent reconstruction with a bridge shaped medial hemisleus muscle flap pedicle transplantation. There were 8 males and 4 females with an average age of 34 years old ranging from 22 to 50 years old. Time after injury was from 2 to 12 weeks (means, 3.5 weeks ). The immediate coverage of the muscle flaps were performed by a meshed split-thickness skin graft. The donor site was closed directly. RESULTS: All the muscle flaps had survived completely. Follow-up period ranged form 1.8 to 4.0 years (means, 2.8 years) postoperatively. The tibia and fibula fractures were confirmed healing. A good contour was confirmed at the recipient area. The results were evaluated with LEM questionnaire, excellent results were obtained in 6 cases, good in 5 cases and fair in 1 case. Satisfactory clinical results were obtained in 11 cases. CONCLUSION: This technique is particularly useful for repairing soft tissue defect in the injured leg when only one vessel remains, and can reduce injury to donor site.

Vasculogenic mimicry is a prognostic factor for postoperative survival in patients with glioblastoma.

A previous report has confirmed the existence and clinical significance of vasculogenic mimicry (VM) in glioma. However, its conclusions about the negative clinical significance of VM in glioblastoma are based on a small group of patients and, thus, might be unconvincing. The aim of the present study was to reevaluate the clinical significance of VM in glioblastoma. Patients were classified as VM-positive or VM-negative according to CD34 and periodic acid-Schiff staining. The association between VM and the clinical characteristics of the patients was analyzed. Univariate and multivariate analyses were carried out to identify the independent prognostic factors for overall survival using the Cox regression hazard model. Survival times were estimated using the Kaplan-Meier method and compared using the log-rank test. Of all 86 glioblastomas, 23 were found to have VM. The presence of VM in glioblastoma was not associated with gender, age, Karnofsky performance status, hydrocephalus, tumor burden, microvessel density, tumor relapse, or the extent of tumor resection. The univariate and multivariate analyses revealed that VM is an independent prognostic factor for overall survival. The median survival time for patients with VM was 11.17 months compared with 16.10 months for those without VM (P = 0.017). In addition to VM, an age of 65 years or older, a KPS of 60 or less, a large tumor burden are significant prognostic factors for patient survival. Our data suggest that VM might be an independent adverse prognostic factor in newly diagnosed GBM, further prospective studies are needed to answer this question.

Repair of a large soft tissue defect in the leg with cross-leg bridge free transfer of a latissimus dorsi myocutaneous flap: a case report.

A 48-year-old man sustained a traffic accident injury to his left leg. It was an open fracture of the left tibia and fibula accompanied by a large soft tissue defect (27 cm multiply 7 cm). Doppler examination revealed the posterior tibial artery was occluded due to thrombosis. Three weeks after injury, the latissimus dors myocutaneous flap was elevated with a T-shaped vascular pedicle and was interposed between the two vascular ends of the posterior tibial vessel of the contralateral leg. Two end to end anastomoses were performed between the two vascular ends of the posterior tibial vessel of the contralateral leg and the latissimus dors myocutaneous flap's T-shaped vascular pedicle. The latissimus dorsi myocutaneous flap was used for repair of a large soft tissue defect of the left leg. The vascular pedicle was cut off after 28 days and the flap survived completely. After 3-years'follow-up postoperatively, a good contour was confirmed at the recipient area. The right tibia and fibula fractures were confirmed healing radiologically. The posterior tibial artery of contralateral leg was demonstrated patent by clinical and Doppler examinations.

Repair of a soft tissue defect of medial malleolus with cross-leg bridge free transfer of anterolateral thigh muscle flap: a case report.

A 38-year-old man sustained a traffic accident injury to his right medial malleolus and leg. It was an open fracture of the right tibia and fibula accompanied by a large soft tissue defect of the right medial malleolus sized 12 cm multiply 4 cm. Doppler examination revealed that the tibialis posterior vessel was occluded due to thrombosis. The anterior tibial artery was patent. Three weeks after injury, the left anterolateral thigh muscle flap was harvested and transplanted to the right medial malleolus defect area for repair of the soft tissue defect, and an end-to-side anastomosis was performed between the posterior tibial vessel of the contralateral leg and the muscle flap's vascular pedicle. A split thickness free skin graft was used to cover the muscle flap and around the flap's vascular pedicle. The vascular pedicle was cut off after 28 days and the muscle flap survived completely. After 3-year follow-up postoperatively, the right tibia and fibula fractures were confirmed healing radiologically. The posterior tibial artery of contralateral leg was patent by clinical and Doppler examinations. This technique can be used to preserve the flow and patency of recipient arteries.

Vasculogenic mimicry and its clinical significance in medulloblastoma.

Vasculogenic mimicry (VM), a process involving the formation of a tubular structure by highly invasive and genetically dysregulated tumor cells, can supplement the function of blood vessels to transport nutrients and oxygen to maintain the growth of tumor cells in many malignant tumors. We aimed to explore the existence of VM and its clinical significance in medulloblastoma in this study. VM was identified in 9 out of 41 (22%) medulloblastoma tissues. Immunohistochemical studies revealed that the presence of VM was associated with the expression of MMP-2, MMP-14, EphA2 and laminin 5γ2. Tumor tissues with VM were associated with lower microvessel density (MVD), which was indirect evidence of the blood supply function of VM. Survival analysis and log-rank tests showed that patients with VM had shorter overall survival time than those without VM. Multivariate analysis and the Cox proportional hazards model identified VM as independent prognostic factor for overall survival. Our results confirmed the existence of VM for the first time and revealed that VM is a strong independent prognostic factor for survival in patients with medulloblastoma.

Hand reconstruction using heterotopic replantation of amputated index and little fingers.

In cases of severe segmental injury across the hand and wrist, but one or other fingers are still in peak condition, the fingers can be selected for replantation at the forearm bones to restore pinch function. Here we reported an unusual case with a severe crush-avulsion amputated injury to the right hand caused by a machine accident. We conducted hand reconstruction using heterotopic replantation of the amputated index and little fingers. During 19 months follow-up, the bone union healed well with satisfactory outcome. The interphalangeal and metacarpophalangeal joint of the fingers after the heterotopic replantation had a good holding activity. This is a worthwhile procedure and the patient is satisfied with the result. The major disadvantage of this method is the poor appearance of the reconstructed fingers.

Molecular targeting of malignant glioma cells with an EphA2-specific immunotoxin delivered by human bone marrow-derived mesenchymal stem cells.

Immunotoxins have shown great promise as an alternative treatment for brain malignancies such as gliomas, but their failure to penetrate into the tumor mass remains a major problem. Mesenchymal stem cells exhibit tropism to tumor tissue and may serve as a cellular vehicle for the delivery and local production of antitumor agents. In this study, we used human bone marrow-derived mesenchymal stem cells (hMSCs) as a vehicle for the targeted delivery of EphrinA1-PE38, a very specific immunotoxin against the EphA2 receptor that is overexpressed in gliomas. hMSCs were transduced with adenovirus to express secretable EphrinA1-PE38. Our invitro assays confirmed the expression, release and selective killing effect of the immunotoxin produced by hMSCs. Furthermore, the intratumoral injection of engineered hMSCs was effective at inhibiting tumor growth in a malignant glioma tumor model. These results indicate that gene therapy utilizing EphrinA1-PE38-secreting hMSCs may provide a novel approach for the local treatment of malignant gliomas.

[Adjustment methods of proportional pressure support on weaning during acute aggravation in chronic respiratory failure patients with chronic obstructive pulmonary disease].

OBJECTIVE: To study the effects of two adjustment methods of proportional pressure support (PPS) on patients with acute aggravation in chronic respiratory failure of chronic obstructive pulmonary disease. METHODS: Seventy-five patients were randomized to two groups, 30 in proportional adjustment group and 45 in target adjustment group, respectively. Suitable flow assist (FA) and volume assist (VA) were adjusted with proportional adjustment and target adjustment methods respectively according to the ventilation parameters until the weaning of ventilation. RESULTS: There were no significant differences in resistance, elastic, FA as well as VA on weaning point, duration of mechanical ventilation, and successful weaning rate between the two groups (all P>0.05). CONCLUSION: The same aim and successful weaning rate could be gained in the target adjustment group compared with the proportional adjustment group. More clinical experience and more intensive care would be needed in the target adjustment group.