Probability of cancer in high-risk patients predicted by the protein-based lung cancer biomarker panel in China: LCBP study.

BACKGROUND: The authors built a model for lung cancer diagnosis previously based on the blood biomarkers progastrin-releasing peptide (ProGRP), carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), and cytokeratin 19 fragment (CYFRA21-1). In the current study, they examined whether modification of the model to include relevant clinical information, risk factors, and low-dose chest computed tomography screening would improve the performance of the biomarker panel in large cohorts of Chinese adults. METHODS: The current study was a large-scale multicenter study (ClinicalTrials.gov identifier NCT01928836) performed in a Chinese population. A total of 715 participants were enrolled from 5 regional centers in Beijing, Henan, Nanjing, Shanghai, and Chongqing between October 2012 and February 2014. Serum biomarkers ProGRP, CEA, SCC, and CYFRA21-1 were analyzed on the ARCHITECT i2000SR. Relevant clinical information was collected and used to develop a patient risk model and a nodule risk model. RESULTS: The resulting patient risk model had an area under the receiver operating characteristic (ROC) curve of 0.7037 in the training data set and 0.7190 in the validation data set. The resulting nodule risk model had an area under the ROC curve of 0.9151 in the training data set and 0.5836 in the validation data set. Moreover, the nodule risk model had a relatively higher area under the ROC curve (0.9151 vs 0.8360; P = 0.001) compared with the American College of Chest Physician model in patients with lung nodules. CONCLUSIONS: Both the patient risk model and the nodule risk model, developed for the early diagnosis of lung cancer, demonstrated excellent discrimination, allowing for the stratification of patients with different levels of lung cancer risk. These new models are applicable in high-risk Chinese populations. Cancer 2018;124:262-70. © 2017 American Cancer Society.

Anlotinib as a third-line therapy in patients with refractory advanced non-small-cell lung cancer: a multicentre, randomised phase II trial (ALTER0302).

BACKGROUND: Anlotinib (AL3818) is a novel multitarget tyrosine kinase inhibitor, inhibiting tumour angiogenesis and proliferative signalling. The objective of this study was to assess the safety and efficacy of third-line anlotinib for patients with refractory advanced non-small-cell lung cancer (RA-NSCLC). METHODS: Eligible patients were randomised 1 : 1 to receive anlotinib (12 mg per day, per os; days 1-14; 21 days per cycle) or a placebo. The primary end point was progression-free survival (PFS). RESULTS: A total of 117 eligible patients enrolled from 13 clinical centres in China were analysed in the full analysis set. No patients received immune check-point inhibitors and epidermal growth factor receptor status was unknown in 60.7% of the population. PFS was better with anlotinib compared with the placebo (4.8 vs 1.2 months; hazard ratio (HR)=0.32; 95% confidence interval (CI), 0.20-0.51; P<0.0001), as well as overall response rate (ORR) (10.0%; 95% CI, 2.4-17.6% vs 0%; 95% CI, 0-6.27%; P=0.028). The median overall survival (OS) was 9.3 months (95% CI, 6.8-15.1) for the anlotinib group and 6.3 months (95% CI, 4.3-10.5) for the placebo group (HR=0.78; 95% CI, 0.51-1.18; P=0.2316). Adverse events were more frequent in the anlotinib than the placebo group. The percentage of grade 3-4 treatment-related adverse events was 21.67% in the anlotinib group. CONCLUSIONS: Anlotinib as a third-line treatment provided significant PFS benefits to patients with RA-NSCLC when compared with the placebo, and the toxicity profiles showed good tolerance.

Predictive Value of Combined LIPS and ANG-2 Level in Critically Ill Patients with ARDS Risk Factors.

To investigate the predictive value of the acute physiology and chronic health evaluation 2 (APACHE2) score and lung injury prediction score (LIPS) for acute respiratory distress syndrome (ARDS) when combined with biomarkers for this condition in patients with ARDS risk factors. In total, 158 Han Chinese patients with ARDS risk factors were recruited from the Respiratory and Emergency Intensive Care Units. The LIPS, APACHE2 score, primary diagnosis at admission, and ARDS risk factors were determined within 6 h of admission, and PaO2/FiO2 was determined on the day of admission. Blood was collected within 24 h of admission for the measurement of angiopoietin-2 (ANG-2), sE-selectin, interleukin-6 (IL-6), and interleukin-8 (IL-8) levels. ARDS was monitored for the next 7 days. Univariate and multivariate analyses and receiver operating characteristic (ROC) analyses were employed to construct a model for ARDS prediction. Forty-eight patients developed ARDS within 7 days of admission. Plasma ANG-2 level, sE-selectin level, LIPS, and APACHE2 score in ARDS patients were significantly higher than those in non-ARDS patients. ANG-2 level, LIPS, and APACHE2 score were correlated with ARDS (P < 0.001, P < 0.006, and P < 0.042, resp.). When the APACHE2 score was used in combination with the LIPS and ANG-2 level to predict ARDS, the area under the ROC curve (AUC) was not significantly increased. Compared to LIPS or ANG-2 alone, LIPS in combination with ANG-2 had significantly increased positive predictive value (PPV) and AUC for the prediction of ARDS. In conclusion, plasma ANG-2 level, LIPS, and APACHE2 score are correlated with ARDS. Combined LIPS and ANG-2 level displays favorable sensitivity, specificity, and AUC for the prediction of ARDS.

Prevention and management of lung cancer in China.

Lung cancer is the leading cause of cancer-related death worldwide. In China, the incidence of lung cancer has grown rapidly, resulting in a large social and economic burden. Several researchers have devoted their studies to lung cancer and have demonstrated that there are many risk factors for lung cancer in China, including tobacco use, environmental pollution, food, genetics, and chronic obstructive pulmonary disease. However, the lung cancer incidence is still growing rapidly in China, and there is an even higher incidence among the younger generation. One explanation may be the triple-neglect situation, in which medical policies that neglect prevention, diagnosis, and supportive care have increased patients' mortality and reduced their quality of life. Therefore, it is necessary to enhance the efficiency of prevention and early diagnosis not only by focusing more attention on treatment but also by drawing more attention to supportive care for patients with lung cancer.

[Efficacy and Safety of Tiotropium Bromide in the Treatment of Chronic Obstructive Pulmonary Disease--a Multi-center Randomized Clinical Trial].

OBJECTIVE: To investigate the efficacy and safety of domestic tiotropium inhalation capsule in patients with chronic obstructive pulmonary disease (COPD) with multi-center randomized clinical trial. METHODS: Patients with stable slight to moderate COPD were randomized into trial group (n=109) with tiotropium 18 pg Qd or control group (n =111) with ipratropium 40 µg Qid for a treatment of four weeks. The spirometry and scoring questionaire were recorded at different visits during the treatment. Rescue medication consumption and adverse events were recorded. Results Forced expiratory volume in 1 s (FEV1) of both groups increased obviously 30 min and 3 h after first dosing. After four weeks treatments, FEV, and forced vital capacity (FVC) in both groups were improved obviously, and the improvement in tiotropium group was significantly higher than that ipratropium group. COPD symptom scores were significantly reduced in both groups, and the improvement in tiotropium group was significantly better than that in ipratropium group. There was no significant difference in rescue medication consumption between the two groups. The ratios of adverse events were 22. 02% and 15. 32% in tiotropium and ipratropium group, respectively (P=0. 23). CONCLUSION: Domestic tiotropium inhalation capsule is efficient and safe in the treatment of COPD.

[Efficacies and toxicities of different platinum-based combination chemotherapies for patients with advanced non-small cell lung cancer].

OBJECTIVE: To explore the efficacies and toxicities of different platinum-based combination chemotherapeutic regiments for patients with advanced non-small cell lung cancer (NSCLC). METHODS: A total of 239 advanced NSCLC from January 2011 to December 2012 were reviewed in Xinqiao Hospital. The chemotherapeutic efficacies and adverse effects in the first-line treatment of advanced NSCLC by paclitaxel plus platinum (paclitaxel group, n = 113), gemcitabine plus platinum (gemcitabine group, n = 72) and docetaxel plus platinum (docetaxel group, n = 54) regiments were retrospectively analyzed and compared. Their efficacies and toxicities were analyzed by Chi-square test. And survival was estimated with Kaplan-Meier method. RESULTS: The objective response rate (ORR) of three groups were 42.5%, 43.1% and 35.2% respectively (P = 0.612). The disease control rate (DCR) were 84.1%, 75.0% and 74.1% respectively (P = 0.198). The median progression-free survival was 5.6, 5.8 and 3.2 months respectively (P = 0.000). The major adverse effects were myelosuppression, gastrointestinal reaction, alopecia and neurotoxicity, etc. The incidence rate of neurotoxicity among three groups were 34.5% (39/113), 11.1% (8/72) and 18.5% (10/54) respectively (P = 0.001).No significant inter-group difference of adverse effects existed (all P > 0.05), except for neurotoxicity. CONCLUSIONS: Three platinum-based combination chemotherapeutic regiments produce excellent efficacies with acceptable adverse effects. Their ORR and DCR were similar. And the median progression-free survival of paclitaxel and gemcitabine groups is significantly longer than that of docetaxel group.

Serum Metabolomic and Lipidomic Profiling Reveals the Signature for Postoperative Obesity among Adult-Onset Craniopharyngioma.

Craniopharyngioma patients often suffer from a diminished quality of life after surgery, which is usually associated with metabolic disorders and hypothalamic obesity. However, the precise etiology of these conditions remains elusive. To identify the metabolic changes after surgery, we conducted a cross-sectional study using metabolomic and lipidomic analysis to profile metabolic alterations in adult-onset craniopharyngioma patients with postoperative obesity. A cohort of 120 craniopharyngioma patients who had undergone surgery were examined. Differential analyses, including clinical characteristics, serum metabolome, and lipidome, were conducted across distinct body mass index (BMI) groups. Our findings indicated no statistically significant differences in age, sex, and fasting blood glucose among postoperative craniopharyngioma patients when stratified by BMI. However, a noteworthy difference was observed in uric acid and blood lipid levels. Further investigation revealed that alterations in metabolites and lipids were evidently correlated with increased BMI, indicating that postoperative obesity of craniopharyngioma patients affected their whole-body metabolism. Additionally, the multi-omics analysis identified specific metabolites and lipids, including uric acid and DG(18:2/20:4), as contributors to the metabolic disorders associated with postoperative obesity of craniopharyngioma patients. This work provides valuable insight into the involvement of metabolites and lipids in metabolic disorders subsequent to craniopharyngioma surgery.

Promoter methylation profiles between human lung adenocarcinoma multidrug resistant A549/cisplatin (A549/DDP) cells and its progenitor A549 cells.

Although aberrant DNA methylation has been implicated in the pathophysiology of lung cancer, the role of methylation in multidrug resistance (MDR) of lung cancer has remained unclear. To investigate whether certain distinct DNA methylation pattern is associated with acquired MDR of lung adenocarcinoma, methylated-DNA immunoprecipitation-chromatin immunoprecipitation (MeDIP-ChIP) was utilised to compare the genome-wide promoter methylation of the human lung adenocarcinoma MDR A549/cisplatin (A549/DDP) cells with its progenitor A549 cells. The comparison identified 3617 genes with differentially methylated promoter, of which 1581 were hypermethylated and 2036 were hypomethylated. Then, bisulphite sequencing polymerase chain reaction (PCR) (BSP) and quantitative reverse transcription (RT)-PCR (Q-PCR) were used to validate the promoter methylation of five candidate genes and to determine whether the expression of genes was associated with the promoter methylation. BSP confirmed that the promoter methylation incidence of the hypermethylated genes, G protein-coupled receptor 56 isoform 3 (GPR56), metallothionein 1G (MT1G), and RAS association domain family gene 1 (RASSF1), was significantly higher in A549/DDP cells compared with A549 cells (p<0.001, p=0.0099, and p=0.0165), whereas no significant difference was found in that of the other two genes, CCNL2 and BAD (p=0.0594 and p=0.5546). Additionally, Q-PCR showed that the mRNA expression of the three hypermethylated genes was significantly lower in A549/DDP cells compared with A549 cells (all p<0.001). In conclusion, this study reported for the first time that a distinct promoter methylation pattern is associated with MDR of lung adenocarcinoma A549/DDP cells and suggested that GPR56, MT1G, and RASSF1 might be the potential methylation markers associated with acquired MDR of lung adenocarcinoma.

Polymorphisms of angiotensin converting enzyme and nitric oxide synthase 3 genes as risk factors of high-altitude pulmonary edema: a case-control study and meta-analysis.

High-altitude pulmonary edema (HAPE) is a non-cardiogenic type of pulmonary edema developing altitudes > 2,500 m. Angiotensin converting enzyme (ACE) and nitric oxide synthase 3 (NOS3) play important roles in regulating pulmonary vascular tone. To assess associations between genetic variants in the ACE and NOS3 genes and HAPE risk, 27 HAPE patients and 108 matched controls were genotyped and analyzed. The indicated HAPE association of the NOS3 G894T (Glu298Asp) single nucleotide polymorphism (SNP), which may change NO production, was further evaluated by a meta-analysis of six studies involving 399 HAPE patients and 495 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were determined with fixed-effects models. Stratification analyses of ethnicity and geographic location were performed. Significant associations were observed for the dominant model in two ACE tag SNPs influencing serum ACE concentrations (rs8066114 polymorphism: GG+CG vs. CC; rs4461142 polymorphism: TT+CT vs. CC). Furthermore, Single-locus analysis indicated significantly different distributions of G allele frequency between the cases (29.63%) and controls (17.13%) for the ACE rs8066114 polymorphism. The case-control distributions of genotype frequencies and T allele frequency of NOS3 G894T (Glu298Asp) polymorphism were significantly higher in the cases than controls, and the NOS3 G894T (Glu298Asp) SNP showed elevated HAPE risk under the dominant model (TT+GT vs. GG). Meta-analysis showed overall association of NOS3 G894T SNP with HAPE risk under the allele contrast and dominant genetic models, which remained significant for Asians. In conclusion, ACE rs8066114 and rs4461142 and NOS3 rs1799983 (G894T) polymorphisms may be associated with increased HAPE risk in Asians.

[Diagnostic value of computed tomography-guided percutaneous lung biopsy for malignant lung tumors].

OBJECTIVE: To explore the diagnostic efficiency of percutaneous lung biopsy for malignant lung tumors under the guidance of computed tomography (CT). METHODS: The clinical data of 623 patients undergoing CT-guided percutaneous lung biopsy at Department of Respiratory Medicine, Xinqiao Hospital, Third Military Medical University from January 2010 to November 2012 were analyzed to examine the influencing factors for the occurrences of pneumothorax and hemoptysis, including patient age, gender, site of puncture, tumor location and size, depth and number of puncture, chronic obstructive pulmonary disease (COPD) and doctor's clinical experience. RESULTS: A total of 623 cases were recruited. There were 410 male and 213 female with an average age of 60 ± 11 (15-87) years. Among them, 618 were diagnosed as malignant lung tumors with a positive rate of 99.2%. Pathological classifications were adenocarcinoma (n = 387, 62.1%), squamous carcinoma (n = 166, 26.6%), small cell lung cancer (n = 30, 4.8%), undifferentiated cancer (n = 18, 2.9%) adenosquamous carcinoma (n = 2, 0.3%), sarcomatoid carcinoma (n = 6, 0.9%), leiomyosarcoma (n = 3, 0.5%), neuroendocrine carcinoma (n = 2, 0.3%), low differentiated carcinoid (n = 1, 0.2%), cribriform carcinoma (n = 1, 0.2%), malignant lymphoma (n = 1, 0.2%) and metastatic renal cell carcinoma (n = 1, 0.2%) respectively. Another 5 patients (0.8%) had an initial diagnosis of chronic inflammation according to their pathological features of lung punctures. Their definite diagnoses were lung squamous cell carcinoma (n = 3), adenocarcinoma (n = 1) and small cell carcinoma (n = 1) respectively. The major complications were pneumothorax and hemoptysis. Among 73 cases of pneumothorax (n = 73, 11.7%), 65 cases (n = 65, 10.4%) of mild pneumothorax (lung compression < 20%) were cured by sufficient oxygen inhalation and repose while 8 cases (1.3%) suffered lung compression ≥ 75% recovered via closed thoracic drainage. Eighty-four patients (13.5%) suffered from the complications of slight or self-limited hemoptysis with blood-tinged sputum. The symptoms of hemoptysis disappeared after oral hemostatic or other treatments. Another 5 patients (0.8%) suffered from moderate hemoptysis (100-500 ml) and their symptoms disappeared after rest or an intravenous infusion of haemostatic. None of them died of massive hemoptysis or biopsy. The occurrence of pneumothorax was significantly correlated with the diameter of lesions ( ≤ 2 cm) (P = 0.006), depth of needle (>3 cm) (P = 0.044), number of puncture needles ( ≥ 3 needles) (P = 0.025), inadequate clinical experience of puncturing doctors (P = 0.003) and COPD (P = 0.036); the occurrence of hemoptysis was obviously correlated with the diameter of lesions ( ≤ 2 cm) (P = 0.031), depth of needle (>3 cm) (P = 0.018), number of puncture needles ( ≥ 3 needles) (P = 0.015) and inadequate clinical experience of puncturing doctors (P = 0.014). However, the relationship was unremarkable between the occurrences of pneumothorax and hemoptysis and patient gender, age, sites of puncture and tumor location. CONCLUSION: With a high diagnostic value, CT-guided percutaneous lung biopsy is both safe and effective for malignant lung tumors.

Spatial scale applicability of 4-Scale geometrical optics model canopy reflectance simulation.

Accurately clarifying the applicable spatial scale of 4-Scale model is conducive to improving the accuracy of its application in canopy reflectance simulation of different vegetation types, and to further improving the inversion accuracy of leaf area index, canopy density, and other parameters. Two forest plots (one for broad-leaved forest and one for mixed forest) with each area of 100 m×100 m in Maoershan Experimental Forest Farm, Shangzhi, Heilongjiang, were divided into the spatial scales of 10, 20, 30, 40 and 50 m, respectively. The 4-Scale model was used to simulate forest canopy reflectance. Local mean method, the nearest neighbor method, bilinear interpolation method, and cubic convolution method were used to convert Sentinel-2 images with spatial resolution of 10 m to other scales, with the results being evaluated. The simulated canopy reflectance and remote sensing pixel reflectance were compared and analyzed. The spatial scale of mixed forest and broad-leaved forest suitable for high-precision inversion parameters of 4-Scale model was determined. The results showed that the 4-Scale model underestimated the pixel forest canopy reflectance as a whole. The canopy reflectance of mixed forest and broad-leaved forest had the worst simulation effect at the 20 m scale. Both the root mean square error (RMSE) and the mean absolute error from (MAE) of red and near-infrared band were large. When the scale was >20 m, the simulation effect became better. The applicability of the model was the best when the mixed forest was 40 m and the broad-leaved forest was 30 m. The mean and standard deviation of the reflectance difference between the simulated value and the remote sensing pixel were the minimum in the red and near near-infrared bands, with the minimum RMSE and MAE. The simulation results of mixed forest and broad-leaved forest at 10 m scale were not stable, the rule of mean and standard deviation was inconsistent, and the difference between RMSE and MAE was large under the same band.

Prulifloxacin versus levofloxacin in the treatment of respiratory and urinary tract infections: a multicentre, double-blind, randomized controlled clinical trial.

BACKGROUND: Prulifloxacin is a promising fluoroquinolone antibiotic. A multicentre, double-blind, randomized clinical study was designed to evaluate its efficacy and safety compared to that of levofloxacin for the treatment of respiratory and urinary infections of Chinese patients. METHODS: A total of 267 patients were enrolled and each was randomly assigned to either the treatment or the control group. Prulifloxacin 264.2 mg (equivalent to ulifloxacin 200 mg) b.i.d. or levofloxacin hydrochloride 200 mg b.i.d. was administered orally for 5-14 days according to a patient's condition. The clinical response, bacterial eradication and incidence of adverse events were evaluated. RESULTS: Two hundred and forty-three patients completed the study. For the modified intention-to-treat population, the cure and effective rates were 45.53 and 82.93% in the prulifloxacin group and 49.18 and 83.61% in the levofloxacin group. For the per-protocol analysis population, the cure and effective rates were 45.90 and 83.61% in the prulifloxacin group and 49.59 and 83.47% in the levofloxacin group. The bacterial eradication rates were 96.59 and 95.35%, and the drug-related adverse event rates were 7.87 and 5.51% in the prulifloxacin and levofloxacin group, respectively. The cure rate and efficacy rate of respiratory and urinary tract infections of the levofloxacin group were better than those of the prulifloxacin group. However, the difference between the 2 groups was not statistically significant (p > 0.05). CONCLUSION: Prulifloxacin is as effective and well tolerated as levofloxacin in the treatment of respiratory and urinary tract infections.

[Micro-locking plate external fixation for the treatment of proximal phalanx comminuted fractures].

OBJECTIVE: To explore clinical efficacy of external placement of micro-locking plate combined with small incision reduction in treating proximal phalanx comminuted fractures. METHODS: From January 2018 to December 2019, 17 patients with proximal phalanx comminuted fractures were treated with micro-locking plate combined with small incision open reduction, including 13 males and 4 females, aged from 16 to 64 years old with an average of (37.2±20.1) years old. Two patients were accompanied by soft tissue extrusion and opening injuries, which were treated with fixed treatment after the first-stage emergency debridement. Curative effect was evaluated according to total active flexion scale (TAFS) of American Hand Surgery Association at 6 months after operation;and fracture healing, nailing, local soft tissue healing, complications were observed. RESULTS: All patients were followed up from 6 to 12 months with an avaerge of(9.3±3.6) months. Two patients occurred delayed union, 1 occurred local skin necrosis and was treated with the second-stage skin grafting to repair wound surface. No external screw breakage or infection was reported, skin soft tissue healed favorably and reached bony union, the union time from 12 to 24 weeks with an average of (15.7±2.1) weeks. According to TAFS standard, 9 patients got excellent result, 5 good and 3 poor at 6 months after operation. CONCLUSION: External micro-locking plate combined with small incision reduction in treating proximal phalanx comminuted fracture, which has advantages of good condition of skin and soft tissue, simple operation, early functional exercise, good range of motion of interphalanx joint, and function score of recovery period is high.

[Kirschner wire combined with PEEK anchor for the treatment of Wagstaffeâ ¡fracture].

OBJECTIVE: To explore clinical effect of Kirschner wire combined with PEEK anchor with thread to fix fibula bone block in WagstaffeⅡfracture. METHODS: From January 2018 to December 2020, 29 patients with WagstaffeⅡfracture of ankle joint were treated with Kirschner wire fixation of avulsed fibular bone block, PEEK with thread anchor repair and reinforcement, and plaster external fixation, including 18 males and 11 females, aged from 27 to 69 years old with an average of (46.3±10.2) years old. All of them were unilateral operations, and the time from injury to operation ranged from 3 to 5 days with an average of(4.05±0.63) days. Clinical efficacy was evaluated by using American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot functional scoring system and visual analogue scaleat scoring system before and after operation at 6 months. RESULTS: All patients were followed up from 6 to 12 months with an average of (9.7±2.1) months. Two patients occurred pain of ankle joint during walking, which was relieved after strengthening rehabilitation exercise and anti-nflammatory and analgesic drug treatment. AOFAS score was incrased from(62.16±19.73) preoperativyly to(91.35±6.37) at 6 months after operation (t=5.51, P<0.01);15 patients got excellent results, 12 moderate and 2 good. VAS was decreased (5.91±1.57) preoperativly to (0.41±0.37) at 6 months after operation(t=10.54, P<0.01). CONCLUSION: Kirschner wire combined with PEEK anchor with thread to fix fibula bone block in WagstaffeⅡfracture strengthen repair of inferior tibiofibular syndesmosis ligament and anterior talofibular ligament, and effectively relieved ankle joint pain, obtain good function recovery, the avulsion fracture block was fixed securely, and receive good clinical effect.

[Clinical analysis of external micro-locking plate in the treatment of fifth metatarsal comminuted fractures].

OBJECTIVE: To explore the clinical efficacy of external micro-locking plate combined with closed reduction in the treatment of fifth metatarsal comminuted fracture with severe soft tissue injury. METHODS: From January 2018 to December 2019, 13 patients received micro-locking plate combined with closed reduction treatment due to the fifth metatarsal comminuted fracture with severe soft tissue injury. There were 11 males and 2 females patients, ranging in age from 21 to 69 years. According to the fracture AO fracture classification, 9 cases belonged to type 87(S)-C2.2 and 4 cases belonged to type 87(S)-C2.1. The fifth metatarsal cuneiform articular surface was not involved, and all of them were comminuted fractures of the fifth metatarsal shaft. All soft tissues were damaged to varying degrees. Three patients got small defect of skin and soft tissue, and they were treated with debridement and suture after one-stage emergency surgery. The fracture healing and complications were observed, and the clinical efficacy was evaluated according to the midfoot function score of American Orthopaedic Foot & Ankle Society (AOFAS) at the latest follow-up. RESULTS: All patients were followed up, and the duration ranged from 3 to 12 months. One patient had delayed union. One patient had local skin necrosis and was treated with second-stage skin grafting to repair the wound surface. No external screw breakage or infection was reported, the skin soft tissue healed satisfactorily and reached bony union, with the union time ranging from 8 to 19 weeks. The postoperative functional recovery was rated according to the midfoot score of AOFAS, the score ranged from 49 to 98, and 7 patients got an excellent result, 4 good, 1 fair and 1 poor. CONCLUSION: The external micro-locking plate combined with closed reduction in the treatment of fifth metatarsal comminuted fracture with severe soft tissue injury has the advantages of simple operation, good stability and low infection rate, which is helpful to the repair of soft issue injury, and the fixation can be removed early in outpatient clinic. To sum up, this surgical procedure is suitable for patients with severe soft tissue injury and comminuted fracture to avoid periosteum stripping. The space occupying is smaller than the micro-external fixator, which is convenient for patients with early functional exercise.

CqZF-HD14 enhances drought tolerance in quinoa seedlings through interaction with CqHIPP34 and CqNAC79.

Drought stress is a key agricultural problem that restricts plant development and crop yield. Research on quinoa (Chenopodium quinoa), a nutrient-rich crop with strong stress resistance, has been limited in terms of the molecular regulation of its adaptation to drought stress. This study identified the zinc finger-homeodomain (ZF-HD) family in quinoa and a drought-responsive Chenopodium quinoa ZF-HD14 (CqZF-HD14) through expression profiles. Transient overexpression of CqZF-HD14 promotes photosynthetic pigment accumulation under drought stress, strengthens the antioxidant system, and in turn enhances drought tolerance. Comprehensive genome-wide family analysis and expression profiling identified CqNAC79 and CqHIPP34 regulated by CqZF-HD14, and their interactions were further determined by bimolecular fluorescence complementation (BIFC). Moreover, physiological and biochemical analyses and transient overexpression also revealed that CqNAC79 and CqHIPP34 resist drought by promoting the accumulation of photosynthetic pigments and maintaining antioxidant capacity under drought stress. The synergistic effect of CqZF-HD14 with CqNAC79 or CqHIPP34 further enhanced the drought tolerance of quinoa seedlings. Taken together, the results indicate that CqZF-HD14, CqNAC79 and CqHIPP34 may be important contributors to the drought tolerance regulatory network in quinoa, and these findings add new members to the drought tolerance gene pool.

Malate-mediated CqMADS68 enhances aluminum tolerance in quinoa seedlings through interaction with CqSTOP6, CqALMT6 and CqWRKY88.

Aluminum (Al) stress in acidic soils has severe negative effects on crop productivity. In this study, the alleviating effect and related mechanism of malate on Al stress in quinoa (Chenopodium quinoa) seedlings were investigated. The findings indicated that malate alleviated the growth inhibition of quinoa seedlings under Al stress, maintained the enzymatic and nonenzymatic antioxidant systems, and aided resistance to the damage caused by excessive reactive oxygen species (ROS). Under Al stress, malate significantly increased the contents of chlorophyll and carotenoids in quinoa shoots by 103.8% and 240.7%, and significantly increased the ratios of glutathione (GSH)/oxidized glutathione (GSSG), and ascorbate (AsA)/dehydroascorbate (DHA) in roots by 59.9% and 699.2%, respectively. However, malate significantly decreased the superoxide radical (O2•-), hydrogen peroxide (H2O2), malondialdehyde (MDA) and Al contents in quinoa roots under Al stress by 32.7%, 60.9%, 63.1% and 49%, respectively. Moreover, the CqMADS family and the Al stress-responsive gene families (CqSTOP, CqALMT, and CqWRKY) were identified from the quinoa genome. Comprehensive expression profiling identified CqMADS68 as being involved in malate-mediated Al resistance. Transient overexpression of CqMADS68 increased Al tolerance in quinoa seedlings. More importantly, we found that CqMADS68 regulated the expression of CqSTOP6, CqALMT6 and CqWRKY88 and further demonstrated the interaction of CqMADS68 with CqSTOP6, CqALMT6 and CqWRKY88 by bimolecular fluorescence complementation (BIFC) experiments. Moreover, transient overexpression and physiological and biochemical analyses demonstrated that CqSTOP6, CqALMT6 and CqWRKY88 could also improve Al tolerance by maintaining the antioxidant capacity of quinoa seedlings. Taken together, these findings reveal that CqMADS68, CqSTOP6, CqALMT6 and CqWRKY88 may be important contributors to the Al tolerance regulatory network in quinoa, providing new insights into Al stress resistance.

Involvement of several putative transporters of different families in ß-cyclocitral-induced alleviation of cadmium toxicity in quinoa (Chenopodium quinoa) seedlings.

Cadmium (Cd) has a serious negative impact on crop growth and human food security. This study investigated the alleviating effect of ß-cyclocitral, a potential heavy metal barrier, on Cd stress in quinoa seedlings and the associated mechanisms. Our results showed that ß-cyclocitral alleviated Cd stress-induced growth inhibition in quinoa seedlings and promoted quinoa seedling root development under Cd stress. Moreover, it maintained the antioxidant system of quinoa seedlings, including the enzymatic, i.e., superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), ascorbate peroxidase (APX), and nonenzymatic, i.e., reduced glutathione (GSH) and ascorbic acid (ASA), antioxidants, which eliminate the damage from excessive reactive oxygen species (ROS). Our results showed that ß-cyclocitral could reduce the amount of Cd absorbed by roots. Furthermore, we systematically identified five transporter families from the quinoa genome, and the RT-qPCR results showed that ZIP, Nramp and YSL gene families were downregulated by ß-cyclocitral to reduce Cd uptake by roots. Thus, ß-cyclocitral promoted the growth, photosynthetic capacity and antioxidant capacity of the aboveground parts of quinoa seedlings. Taken together, these results suggested that the ß-cyclocitral-induced decrease in Cd uptake may be caused by the downregulation of several selected transporter genes.

Atrial performance in healthy subjects following high altitude exposure at 4100 m: 2D speckle-tracking strain analysis.

High altitude (HA) exposure has been considered as a cardiac stress and might impair ventricular diastolic function. Atrial contraction is involved in ventricular passive filling, however the atrial performance to HA exposure is poorly understood. This study aimed to evaluate the effect of short-term HA exposure on bi-atrial function. Physiological and 2D-echocardiographic data were collected in 82 healthy men at sea level (SL, 400 m) and 4100 m after an ascent within 7 days. Atrial function was measured using volumetric and speckle-tracking analyses during reservoir, conduit and contractile phases of cardiac cycle. Following HA exposure, significant decreases of reservoir and conduit function indexes were observed in bi-atria, whereas decreases of contractile function indexes were observed in right atrium (RA), estimated via RA active emptying fraction (SL 41.7 ± 13.9% vs. HA 35.4 ± 12.2%, p = 0.001), strain during the contractile phase [SL 13.5 (11.4, 17.8) % vs. HA 12.3 (9.3, 15.9) %, p = 0.003], and peak strain rate during the contractile phase [SL - 1.76 (- 2.24, - 1.48) s-1 vs. HA - 1.57 (- 2.01, - 1.23) s-1, p = 0.002], but not in left atrium (LA). In conclusion, short-term HA exposure of healthy individuals impairs bi-atrial performance, mostly observed in RA. Especially, atrial contractile function decreases in RA rather than LA, which seems not to compensate for decreased ventricular filling after HA exposure. Our findings may provide a novel evidence for right-sided heart dysfunction to HA exposure.

A multicenter, randomized controlled clinical study on biapenem and imipenem/cilastatin injection in the treatment of respiratory and urinary tract infections.

BACKGROUND: Biapenem is an injectable carbapenem antibiotic. A clinical study was designed to evaluate its efficacy and safety in the treatment of respiratory and urinary infections compared to imipenem/cilastatin. METHODS: A total of 216 patients with respiratory or urinary tract infections were enrolled into this multicenter, open-label, randomized controlled clinical study. Each patient was randomly assigned to either the treatment or control group; 106 patients in each group were included in the ITT analyses. The patients were given biapenem 300 mg or imipenem/cilastatin 500 mg/500 mg two or three times daily, i.v. g.t.t. for 7-14 days according to their conditions. RESULTS: The cure and effective rates were 67.92 and 88.68% in the biapenem group and 76.02 and 93.40% in the imipenem/cilastatin group, the bacterial eradication rates were 93.83 and 98.82%, and the adverse-event rates were 6.54 and 7.41%, respectively. There were no significant differences between the two groups (p > 0.05). CONCLUSION: Biapenem is as effective and well-tolerated as imipenem/cilastatin for the treatment of intermediate and severe bacterial infections.