Metabolomics of astaxanthin biosynthesis and corresponding regulation strategies in Phaffia rhodozyma.

Astaxanthin is a valuable carotenoid and is used as antioxidant and health care. Phaffia rhodozyma is a potential strain for the biosynthesis of astaxanthin. The unclear metabolic characteristics of P. rhodozyma at different metabolic stages hinder astaxanthin's promotion. This study is conducted to investigate metabolite changes based on quadrupole time-of-flight mass spectrometry metabolomics method. The results showed that the downregulation of purine, pyrimidine, amino acid synthesis, and glycolytic pathways contributed to astaxanthin biosynthesis. Meanwhile, the upregulation of lipid metabolites contributed to astaxanthin accumulation. Therefore, the regulation strategies were proposed based on this. The addition of sodium orthovanadate inhibited the amino acid pathway to increase astaxanthin concentration by 19.2%. And the addition of melatonin promoted lipid metabolism to increase the astaxanthin concentration by 30.3%. It further confirmed that inhibition of amino acid metabolism and promotion of lipid metabolism were beneficial for astaxanthin biosynthesis of P. rhodozyma. It is helpful in understanding metabolic pathways affecting astaxanthin of P. rhodozyma and provides regulatory strategies for metabolism.

Sinus Tarsi Approach With Percutaneous Screw Fixation for Intra-Articular Calcaneal Fractures.

The aim of this study was to evaluate the outcomes of surgical treatment of intra-articular calcaneal fractures by using the sinus tarsi approach combined with percutaneous medial reduction by leverage technique and percutaneous screw fixation. We assessed the outcomes of 29 patients treated using sinus tarsi approach with percutaneous screw fixation. All patients were evaluated both clinically and radiologically. The Böhler and Gissane angle were evaluated postoperatively using radiographs. During the median follow-up period of 27.0 ± 10.3 months, no cases with failure to reduce or displace hardware were detected. All cases achieved the restoration of a normal Böhler and Gissane angle. The median preoperative Böhler angle was 12.3° ± 2.5° while postoperatively it was 30.5° ± 5.7° (p < .01). The median preoperative Gissane angle was 98.1° ± 7.5°, which was 125.9° ± 3.6° postoperatively (p < .01). At the last follow-up, the median American Orthopedic Foot and Ankle Society hindfoot score was 87.7 ± 5.9, and the median Maryland foot score was 88.6 ± 5.9. Our technique for intra-articular calcaneal fractures can effectively correct calcaneal tuberosity outward displacement, medial wall overlapping, and the hindfoot varus deformity with less soft tissue damage. This technique is a good alternative for the treatment of calcaneal fractures, resulting in minimal soft tissue damage, few wound complications, and excellent radiological and clinical outcomes.

Internal fixation of anterior acetabular fractures with a limited pararectus approach and the anatomical plates: preliminary results.

BACKGROUND: The surgical treatment of acetabular fracture has adverse outcomes and high risk, and minimally invasive method is a good way to reduce complications and improve hip joint function. This study is to investigate the treatment of certain acetabular fractures primarily involving the anterior column and quadrilateral plate using a limited pararectus approach and the anatomical plates. METHODS: A consecutive cohort of 17 patients with anterior displaced acetabular fractures were managed operatively with a limited approach and the anatomical plates. Ten patients had anterior column fractures, 1 patient had anterior wall fracture, 4 patients had transverse fractures and 2 patients had anterior column with posterior hemi-transverse fractures. The inferior half of the pararectus approach was adopted to open the medial window and to access the anterior column and the quadrilateral plate. The anatomical plates were used for internal fixation. Residual displacements were assessed on the postoperative CT scans using a standardized digital method. The surgical details, hip functional outcomes, and complications were noted. RESULTS: All of the patients were operated using the limited pararectus approach and the anatomical plates successfully. The mean operative time and blood loss were 90.9 min and 334.1 ml, respectively. The average postoperative residual gap and step displacement on CT were 2.9 mm and 0.7 mm, respectively. The radiological outcome was estimated according to the Matta score, ten of the cases were graded anatomical, six were graded imperfect, and one was graded poor. Follow up averaged 15 months. Functional outcomes were excellent for nine, good for six, and fair for two. It was noted that one case of peritoneal injury was repaired intraoperatively. CONCLUSIONS: The limited pararectus approach with the advantages of less trauma, direct exposure to the anterior column and quadrilateral plate. The anatomical plates can fit with the surface of the acetabulum, which saves the time of remodeling plates during operation and facilitate fracture reduction. The combination approach can be a good choice for limited surgery of displaced anterior acetabular fractures especially involving the quadrilateral plate.

Antimicrobial stewardship program in a Malaysian district hospital: First year experience.

BACKGROUNDS & OBJECTIVE: Antimicrobial resistance is an alarming public health threat that requires urgent global solution. Implementation of antimicrobial stewardship program (ASP) is an essential practice element for healthcare institutions in gate-keeping judicious antimicrobial use. This study highlighted the development, first year experience, and result of the implementation of ASP utilizing persuasive and restrictive approaches in a Malaysian district hospital. METHODS: An observational study was conducted between January 2015 to December 2015 on implementation of ASP among hospitalized inpatients age 12 years old and above. RESULTS: Recommendations were provided for 60% of cases (110 patients) with the average acceptance rate of 83.33%. Majority of the interventions were to stop the antimicrobial therapy (30.3%), and the most common audited antimicrobials was Piperacillin/Tazobactam (25.5%), followed by Meropenem (11.82%), Amoxicillin/Clavulanate and Vancomycin (8.18%) respectively. The concordance rate towards authorization policy was increased in 2015 (71.59% of cases) as compared before the implementation of ASP in 2014 (60.6% of cases). Restrictive enforcement under ASP had been shown to improve significantly adherence rate towards antimicrobials authorization policy (p-value: 0.004). CONCLUSION: ASP was successfully implemented in a district hospital. Future studies on its clinical outcomes are important to evaluate its effectiveness as well as focus on the improvement to the pre-existing strategies and measures.

Multifunctional Extracellular Matrix Hydrogel with Self-Healing Properties and Promoting Angiogenesis as an Immunoregulation Platform for Diabetic Wound Healing.

Treating chronic wounds is a global challenge. In diabetes mellitus cases, long-time and excess inflammatory responses at the injury site may delay the healing of intractable wounds. Macrophage polarization (M1/M2 types) can be closely associated with inflammatory factor generation during wound healing. Quercetin (QCT) is an efficient agent against oxidation and fibrosis that promotes wound healing. It can also inhibit inflammatory responses by regulating M1-to-M2 macrophage polarization. However, its limited solubility, low bioavailability, and hydrophobicity are the main issues restricting its applicability in wound healing. The small intestinal submucosa (SIS) has also been widely studied for treating acute/chronic wounds. It is also being extensively researched as a suitable carrier for tissue regeneration. As an extracellular matrix, SIS can support angiogenesis, cell migration, and proliferation, offering growth factors involved in tissue formation signaling and assisting wound healing. We developed a series of promising biosafe novel diabetic wound repair hydrogel wound dressings with several effects, including self-healing properties, water absorption, and immunomodulatory effects. A full-thickness wound diabetic rat model was constructed for in vivo assessment of QCT@SIS hydrogel, in which hydrogels achieved a markedly increased wound repair rate. Their effect was determined by the promotion of the wound healing process, the thickness of granulation tissue, vascularization, and macrophage polarization during wound healing. At the same time, we injected the hydrogel subcutaneously into healthy rats to perform histological analyses of sections of the heart, spleen, liver, kidney, and lung. We then tested the biochemical index levels in serum to determine the biological safety of the QCT@SIS hydrogel. In this study, the developed SIS showed convergence of biological, mechanical, and wound-healing capabilities. Here, we focused on constructing a self-healing, water-absorbable, immunomodulatory, and biocompatible hydrogel as a synergistic treatment paradigm for diabetic wounds by gelling the SIS and loading QCT for slow drug release.

Effect and Optimal Timing of Extracorporeal Shock-Wave Intervention to Patients With Spasticity After Stroke: A Systematic Review and Meta-analysis.

OBJECTIVE: This study investigated the efficacy of extracorporeal shock wave therapy as well as the optimal intervention timing for extracorporeal shock wave therapy for patients with spasticity after stroke. DESIGN: A search of randomized controlled trials was conducted in different electronic databases. We performed a meta-analysis to measure the effect of extracorporeal shock wave therapy versus sham interventions on spasticity and limb functionality. The meta-regression analysis was performed to determine the adequate intervention timing of extracorporeal shock wave therapy. The follow-up period of the outcomes was divided into the short (<2 wks), mid (>2 wks and ≤4 wks), and long (>4 wks and ≤3 mos) terms. RESULTS: Thirteen studies with 677 participants were evaluated. Spasticity significantly improved throughout the follow-up duration. Limb functionality significantly improved in the short-term follow-up period. The meta-regression analysis showed that patients with stroke duration less than 45 mos may be benefited from extracorporeal shock wave therapy in improving limb function in all follow-up periods. CONCLUSIONS: Extracorporeal shock wave therapy is an effective method for reducing spasticity in patients with stroke, and the effect could be maintained for up to 3 mos. Its effects on limb functionality could persist for at least 2 wks. Patients who had stroke for less than 45 mos may have significant benefit from extracorporeal shock wave therapy in all follow-up periods.

Long-term outcome of children with acute promyelocytic leukemia: a randomized study of oral versus intravenous arsenic by SCCLG-APL group.

Realgar-Indigo naturalis formula (RIF), an oral traditional Chinese medicine mainly containing Realgar (As4S4), is highly effective in treating adult acute promyelocytic leukemia (APL). However, the treatment efficacy and safety of RIF have not been verified in pediatric patients. SCCLG-APL group conducted a multicenter randomized non-inferiority trial to determine whether intravenous arsenic trioxide (ATO) can be substituted by oral RIF in treating pediatric APL. Of 176 eligible patients enrolled, 91 and 85 were randomized to ATO and RIF groups, respectively. Patients were treated with the risk-adapted protocol. Induction, consolidation, and 96-week maintenance treatment contained all-trans-retinoic acid and low-intensity chemotherapy, and either ATO or RIF. The primary endpoint was 5-year event-free survival (EFS). The secondary endpoints were adverse events and hospital days. After a median 6-year follow-up, the 5-year EFS was 97.6% in both groups. However, the RIF group had significantly shorter hospital stays and lower incidence of infection and tended to have less cardiac toxicity. All 4 relapses occurred within 1.5 years after completion of maintenance therapy. No long-term arsenic retentions were observed in either group. Substituting oral RIF for ATO maintains treatment efficacy while reducing hospitalization and adverse events in treating pediatric APL patients, which may be a future treatment strategy for APL.

[Effect of epidural drainage and dural tenting suture on epidural hematoma in 145 cases of craniotomy].

OBJECTIVE: To evaluate the efficacy of dural tenting suture and epidural drainage in craniotomy. METHODS: In 145 cases of intracranial lesions, dural tenting suture and epidural drainage were performed to prevent epidural hematoma. RESULTS: Postoperative computed tomography (CT) showed no epidural hematoma required surgery in both groups. CONCLUSION: Both dural tenting suture and epidural drainage are effective in preventing epidural hematoma. Hemostasis is the key step. Dural tenting suture without epidural drainage relieves psychological stress. It decreases the risk of intracranial infection and avoids some unusual complications.

Effects of edaravone on postoperative cognitive function in elderly patients undergoing hip joint replacement surgery: A randomized controlled trial.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a complication of central nervous system in patients after surgery. Edaravone as a brain-protective agent may have protective effect on postoperative cognitive function. The study was designed to explore the effects of edaravone on postoperative cognitive function in elderly patients undergoing hip joint replacement surgery and potential mechanism. PATIENTS AND METHODS: Patients undergoing hip joint replacement surgery were randomly allocated into 2 groups: the edaravone group (group E) and the control group (group C). Group E received intravenous edaravone at a dose of 0.5 mg/kg after induction of anesthesia, while group C received normal saline. The cognitive function was evaluated with the Mini-Mental State Examination (MMSE) 1day before surgery,3 days and the 7 days after surgery. Patients' plasma samples were collected to detect the levels of S100ß protein (S100ß), interleukin-6 (IL-6), matrix metalloproteinase-9 (MMP-9), superoxide dismutase (SOD) and malondialdehyde (MDA) before the induction of anesthesia, at the end of surgery and on postoperative day 3. RESULTS: The MMSE scores in group E were higher than those of group C 3 days after surgery (25.98 ± 1.99 vs 24.86 ± 1.86, p = 0.003). There were remarkable rises (p < 0.05) in plasma IL-6, S100ßand MMP-9 levels at the end of surgery and on postoperative day 3 in the two groups, however, edaravone pretreatment could reduce these levels to a certain extent compared with group C (p < 0.05).In group E, the SOD concentration was higher at the end of surgery (16.03 ± 2.46U/ml vs. 13.65 ± 2.53U/ml, p = 0.0001), while the MDA level was lower on postoperative day 3 than those in group C (7.01 ± 2.37 nmol/ml vs. 11.34 ± 3.18 nmol/ml, p = 0.0001). CONCLUSION: The results indicated that preoperative intervention with edaravone may improve the postoperative cognitive function in elderly patients undergoing hip joint replacement surgery.

Card9 as a critical regulator of tumor development.

Caspase recruitment domain-containing protein 9 (Card9) is a myeloid cell-specific signaling protein that plays a critical role in NF-κB and MAPK activation. This leads to initiation of the inflammatory cytokine cascade, and elicits the host immune response against microbial invasion, especially in fungal infection. Current research indicates that Card9 plays an important role in tumor progression. Here, we review the data from preclinical and clinical studies of Card9 and suggest the potential for Card9-targeted interventions in the prevention or treatment of certain tumors.