Zhi Mao

Erratum to: Autophagy Reduces Neuronal Damage and Promotes Locomotor Recovery via Inhibition of Apoptosis after Spinal Cord Injury in Rats

Autophagy is an intracellular catabolic mechanism that maintains the balance of proteins, lipids and aging organelles. 3-Methyladenine (3-MA) is a selective inhibitor of autophagy, whereas rapamycin, an antifungal agent, is a specific inducer of autophagy, inhibiting the protein mammalian target of rapamycin. In the present study, we examined the role of autophagy, inhibited by 3-MA and enhanced by rapamycin, in a model of acute spinal cord injury in rats. We found that rapamycin could significantly increase the expression of microtubule-associated protein 1 light chain 3 (LC3) and Beclin1 at the injury site. At the same time, the number of neurons and astrocytes with LC3 positive in the spinal cord was upregulated with time. In addition, administration of rapamycin produced an increase in the Basso, Beattie and Bresnahan scores of injured rats, indicating high recovery of locomotor function. Furthermore, expression of the proteins Bcl-2 and Bax was upregulated and downregulated, respectively. By contrast, the results for rats treated with 3-MA, which inhibits autophagy, were the opposite of those seen with the rapamycin-treated rats. These results show that induction of autophagy can produce neuroprotective effects in acute spinal cord injury in rats via inhibition of apoptosis.

A Systematic Review and Meta-Analysis of Ilizarov Methods in the Treatment of Infected Nonunion of Tibia and Femur.

Background Infected nonunion of tibia and femur are common in clinical practice, however, the treatment of these diseases has still been a challenge for orthopaedic surgeons. Ilizarov methods can eradicate infection, compensate bone defects and promote the bone union through progressive bone histogenesis. The objective of this systematic review was to review current available studies reporting on Ilizarov methods in the treatment of infected nonunion of tibia and femur, and to perform meta-analysis of bone and functional results and complications to evaluate the efficacy of Ilizarov methods. Methods A comprehensive literature search was performed from the SCI, PubMed, Cochrane Library; and Embase between January 1995 and August 2015. Some major data were statistically analyzed using weighted means based on the sample size in each study by SPSS 13.0, including number of patients, mean age, mean previous surgical procedures, mean bone defects, mean length of follow-up, bone union, complications per patient, external fixation time, and external fixation index(EFI). Bone results (excellent, good, fair and poor rate), functional results (excellent, good, fair and poor rate) and complications were analyzed by Stata 9.0. Findings A total of 590 patients from 24 studies were included in this systematic review. The average of bone union rate was 97.26% in all included studies. The poor rate in bone results and functional results was 8% (95%CI, 0.04–0.12; I2 = 44.1%, P = 0.065) and 10% (95%CI, 0.05–0.14; I2 = 34.7%, P = 0.121) in patients with infected nonunion of tibia and femur treated by Ilizarov methods. The rate of refracture, malunion, infectious recurrence, knee stiffness, amputation, limb edema and peroneal nerve palsy was respectively 4%, 7%, 5%, 12%, 4%, 13% and 13%. Conclusions Our systematic review showed that the patients with infected nonunion of tibia and femur treated by Ilizarov methods had a low rate of poor bone and functional results. Therefore, Ilizarov methods may be a good choice for the treatment of infected nonunion of tibia and femur.

Advancing computer-assisted orthopaedic surgery using a hexapod device for closed diaphyseal fracture reduction

Surgical complications such as healing problems, in fractures treated using the Arbeitsgemeinschaft für Osteosynthesefragen (AO) technique, present functional and economic challenges to patients and treatment dilemmas for surgeons. Computer‐assisted orthopaedic surgery using minimally invasive techniques focused on biological osteosynthesis is a novel direction for fracture treatment.

Vasopressors in septic shock: a systematic review and network meta-analysis

Objective Vasopressor agents are often prescribed in septic shock. However, their effects remain controversial. We conducted a systematic review and Bayesian network meta-analysis to compare the effects among different types of vasopressor agents. Data sources We searched for relevant studies in PubMed, Embase, and the Cochrane Library databases from database inception until December 2014. Study selection Randomized controlled trials in adults with septic shock that evaluated different vasopressor agents were selected. Data extraction Two authors independently selected studies and extracted data on study characteristics, methods, and outcomes. Data synthesis Twenty-one trials (n=3,819) met inclusion criteria, which compared eleven vasopressor agents or vasopressor combinations (norepinephrine [NE], dopamine [DA], vasopressin [VP], epinephrine [EN], terlipressin [TP], phenylephrine [PE], TP+NE, TP + dobutamine [DB], NE+DB, NE+EN, and NE + dopexamine [DX]). Except for the superiority of NE over DA, the mortality of patients treated with any vasopressor agent or vasopressor combination was not significantly different. Compared to DA, NE was found to be associated with decreased cardiac adverse events, heart rate (standardized mean difference [SMD]: −2.10; 95% confidence interval [CI]: −3.95, −0.25; P=0.03), and cardiac index (SMD: −0.73; 95% CI: −1.14, −0.03; P=0.004) and increased systemic vascular resistance index (SVRI) (SMD: 1.03; 95% CI: 0.61, 1.45; P<0.0001). This Bayesian meta-analysis revealed a possible rank of probability of mortality among the eleven vasopressor agents or vasopressor combinations; from lowest to highest, they are NE+DB, EN, TP, NE+EN, TP+NE, VP, TP+DB, NE, PE, NE+DX, and DA. Conclusion In terms of survival, NE may be superior to DA. Otherwise, there is insufficient evidence to suggest that any other vasopressor agent or vasopressor combination is superior to another. When compared to DA, NE is associated with decreased heart rate, cardiac index, and cardiovascular adverse events, as well as increased SVRI. The effects of vasopressor agents or vasopressor combinations on mortality in patients with septic shock require further investigation.

Outcome of posterior cruciate ligament reconstruction using the single- versus double bundle technique: A meta-analysis

Objective To test the hypothesis that double bundle posterior cruciate ligament (PCL) reconstruction yields better improvement in stability and functional recovery of the knee than the single bundle technique. Methods PubMed®, Embase®, the Cochrane Library, CNKI, Wanfang and CBM disc databases were searched for comparative trials of PCL reconstruction using the single- versus double bundle technique. Data were extracted and meta-analysis was performed for stability improvement and functional recovery. Results The meta-analysis included 435 patients in three randomized controlled trials (RCTs) and eight non-RCTs. Double bundle reconstruction provided significantly better 90° posterior stability than the single bundle technique (weighted mean difference 0.81, 95% confidence interval, [CI] 0.2, 1.42). Double bundle reconstruction resulted in a significantly higher likelihood of International Knee Documentation Committee (IKDC) examination grade A than the single bundle technique (odds ratio 0.41, 95% CI 0.24, 0.72). Conclusions The small amount of data available indicates that double bundle reconstruction is superior to the single bundle technique after isolated PCL injury. These findings should be interpreted with caution due to the low quality and limited sample size of the studies concerned.

Operative Versus Nonoperative Treatment in Complex Proximal Humeral Fractures

This updated meta-analysis investigated whether operative treatment is superior to nonoperative treatment in complex proximal humeral fractures. The authors searched the Cochrane Central Register of Controlled Trials, PubMed, and EMBASE. Randomized controlled trials that evaluated operative vs nonoperative treatment for exclusively 3- or 4-part proximal humeral fractures were considered. Six studies with a total of 287 patients who had proximal humeral fractures were included. According to the meta-analysis, no statistically significant differences were found between operative and nonoperative treatment in Constant-Murley shoulder scores (Constant scores); Disabilities of the Arm, Shoulder, and Hand scores; total complication events; mortality; infection; nonunion; avascular necrosis; osteoarthritis; redisplacement of fractures; or dislocation or resorption of tuberosity. For health-related quality of life, EuroQol-5D (EQ-5D) favored operative treatment, but 15D scores showed no significant difference. Compared with nonoperative treatment, open reduction and internal fixation required significantly more additional surgeries (risk ratio, 6.50; 95% confidence interval, 1.54-27.50; P=.01), and more penetrations into joint space occurred (risk ratio, 9.56; 95% confidence interval, 2.27-40.13; P=.002). The limited evidence suggests that no convincing findings support the use of either open reduction and internal fixation or hemiarthroplasty for the treatment of complex proximal humeral fractures. The findings of the current study should be interpreted cautiously because of the modest sample size and the short follow-up period.

Comparison of lateral and posterior surgical approach in management of extra-articular distal humeral shaft fractures.

OBJECTIVE The objective of this study was to compare treatment results and complication rates between lateral and posterior approaches in surgical treatment of extra-articular distal humeral shaft fractures. MATERIAL AND METHODS Between June 2008 and May 2012, a total of 68 patients with extra-articular distal humeral shaft fractures were treated by lateral and posterior approaches. Of the patients, 30 were operated by a lateral approach (group I) and 26 patients were operated by a posterior approach (group II). There was no statistical significance between the two groups in sex distribution, age, the mechanism of the injury, injured arms, AO/ASIF (Arbeitsgemeinschaft für Osteosynthesefragen/Association for the Study of Internal Fixation) classification, and the time from injury to surgery (P>0.05). Operation time, intraoperative bleeding volume, hospitalisation, clinical outcomes, and complications were compared between the two groups. The elbow functional results were evaluated by the Mayo Elbow Performance Score (MEPS). RESULTS All patients were followed up. The average of follow-up in group I was 15.53±2.636 months (range, 12-22 months), and was 16.12±2.889 months (range, 12-22 months) in group II. There was no significant difference in the operation time, intraoperative bleeding time, and hospitalisation between the two groups (P>0.05). In group I, the mean time of bone union was 12.87±1.852 weeks (range, 10-16 weeks), the mean degrees of elbow flexion was 139.20°±3.274° (range, 134-146°), the mean degrees of elbow extension was 4.77°±1.906° (range, 0-8°), and the mean points of MEPS was 87.00±7.724 (range, 70-100 points). In group II, the mean time of bone union was 12.96±2.218 weeks (range, 10-16 weeks), the mean degrees of elbow flexion was 137.85°±4.076° (range, 130-145°), the mean degrees of elbow extension was 5.15°±2.327° (range, 0-9°), and the mean points of MEPS was 86.15±7.656 (range, 70-100 points). There was no significant difference in the bone union, range of elbow flexion, range of elbow extension and MEPS between the two groups (P>0.05). The overall complication rate in group I was lower than that in group II (P=0.041). CONCLUSIONS Both lateral and posterior surgical approaches acquired satisfied treatment results in the management of extra-articular distal humeral shaft fractures, and there was a lower complication rate using the lateral approach.

Ethyl pyruvate protects against sepsis by regulating energy metabolism

Background Ethyl pyruvate (EP) is a derivative of pyruvic acid that has been demonstrated to be a potential scavenger of reactive oxygen species as well as an anti-inflammatory agent. In this study, we investigated the protective effects of EP and its role in regulating the energy metabolism in the livers of cecal-ligation-and-puncture-induced septic mice. Methods The animals were treated intraperitoneally with 0.2 mL of Ringer’s lactate solution or an equivalent volume of Ringer’s lactate solution containing EP immediately after cecal ligation and puncture. Each mouse in the Sham group was only subjected to a laparotomy. At 30-, 60-, 180-, and 360-minute time points, we measured the histopathological alterations of the intestines, and the plasma levels of interleukin (IL)-1β, IL-6, IL-10, and tumor necrosis factor-α, and the total antioxidative capacity, malondialdehyde content, and lactate and lactate/pyruvate levels in livers. Furthermore, we detected the levels of adenosine triphosphate, total adenylate, and energy charge in the livers. Results Our results demonstrated that the administration of EP significantly improved the survival rate and reduced intestinal histological alterations. EP inhibited the plasma levels of IL-1β, IL-6, and tumor necrosis factor-α and increased the IL-10 level. EP significantly inhibited the elevation of the malondialdehyde, lactate, and lactate/pyruvate levels and enhanced the total antioxidative capacity levels in the liver tissues. The downregulation of the adenosine triphosphate, total adenylate, and energy charge levels in the liver tissues was reversed in the septic mice treated with EP. Conclusion The results suggest that EP administration effectively modulates the energy metabolism, which may be an important component in treatment of sepsis.

Red Cell Distribution Width as an Independent Predictor of Long-Term Mortality in Hip Fracture Patients: A Prospective Cohort Study.

Red blood cell distribution width (RDW) has been found to be a significant prognostic factor of mortality in many cardiovascular diseases. However, a link between RDW at admission with long‐term mortality in the hip fracture population has not been well established. Therefore, we sought to evaluate the long‐term prognostic value of RDW in a well‐defined hip fracture cohort, and to compare the effect of RDW in patients with and without anemia. A prospective cohort study was performed on 1479 hip fracture patients admitted at the General Hospital of Chinese PLA between January 2000 and October 2011 with a follow‐up study over a 2‐year period. A total of 1479 patients were used for the evaluation of 2‐year all‐cause mortality, while 804 patients with more than 4 years of follow‐up were extracted for further evaluation of 4‐year all‐cause mortality. Cox proportional regression was used to evaluate the association between admission RDW and long‐term mortality, adjusting for potential confounding variables. Higher RDW values were strongly associated with increased all‐cause mortality. After adjusting for age, mean corpuscular volume, admission hemoglobin, comorbidities, and complications, RDW had a significant independent association with both 2‐year mortality with a hazard ratio (HR) of 1.183 (95% confidence interval [CI], 1.017 to 1.376) and 4‐year mortality with an HR of 1.244 (95% CI, 1.052 to 1.471). In stratified analysis, the effect of RDW was even more pronounced, with 2‐year mortality HR of 1.341 (95% CI, 1.095 to 1.643) and 4‐year mortality HR of 1.345 (95% CI, 1.071 to 1.688) in non‐anemic patients. In non‐anemic patients, elevated RDW values are significantly associated with increased odds of all‐cause mortality, implying that RDW may be a possible laboratory biomarker for risk stratification in non‐anemic hip fracture patients. Further studies are needed to confirm the current finding in different and larger hip fracture cohorts.

Intramedullary nailing versus plating for distal tibia fractures without articular involvement: a meta-analysis

BackgroundThe choice between intramedullary (IM) nailing or plating of distal tibia fractures without articular involvement remains controversial. A meta-analysis of randomized controlled trials (RCTs) and observational studies was performed to compare IM nailing with plating for distal tibia fractures without articular involvement and to determine the dominant strategy.Materials and methodsThe PubMed, Embase, Cochrane Library databases, Chinese Wan-Fang Database, and China National Knowledge Infrastructure were searched.ResultsTwenty-eight studies, which included 1863 fractures, met the eligible criteria. The meta-analysis did not identify a statistically significant difference between the two treatments in terms of the rate of deep infection, delayed union, removal of instrumentation, or secondary procedures either in the RCT or retrospective subgroups. IM nailing was associated with significantly more malunion events and a higher incidence of knee pain in the retrospective subgroup and across all the studies, but not significantly in the RCT subgroup, and a lower rate of delayed wound healing and superficial infection both in the RCT and retrospective subgroups relative to plating. A meta-analysis of the functional scores or questionnaires was not possible because of the considerable variation among the included studies, and no significant differences were observed.ConclusionsEvidence suggests that both IM nailing and plating are appropriate treatments as IM nailing shows lower rate of delayed wound healing and superficial infection and plating may avoid malunion and knee pain. These findings should be interpreted with caution, however, because of the heterogeneity of the study designs. Large, rigorous RCTs are required.