Deep regional hyperthermia combined with modern concurrent chemoradiotherapy increases T-downstaging rate in locally advanced rectal cancer.

BACKGROUND: Deep regional hyperthermia might have an additional effect on radiotherapy in treating locally advanced rectal cancer (LARC). This study aimed to investigate the role of hyperthermia combined with modern preoperative concurrent chemoradiotherapy (CRT) for LARC. METHODS AND MATERIALS: From 2012 to 2018, 152 consecutive patients with LARC treated with neoadjuvant chemoradiation were enrolled and analyzed retrospectively. Pelvic radiotherapy (45-50 Gy) was delivered as volumetric modulated arc therapy (VMAT), concurrently with capecitabine chemotherapy. Fifty patients received hyperthermia combined with CRT (HCRT group) twice a week. Treatment response and outcomes were compared between the two groups. Furthermore, the relationships between peripheral blood neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR) in response to hyperthermia were analyzed. RESULTS: Patients treated with hyperthermia had a significantly higher T-downstaging rate than those without hyperthermia (82.0 vs. 62.7%; p = .016). Hyperthermia was an independent favorable predictor of T-downstaging (odds ratio [OR] = 2.473; 95% confidence interval [CI] 1.050-5.826; p = .038). In the HCRT group, a pre-therapeutic elevated NLR (≥3) was associated with a higher T-downstaging rate (100.0 vs. 73.5%, p = .043). However, NLR was not associated with the T-downstaging rate in the CRT group. Five-year rates of locoregional recurrence-free survival (96.8 vs. 94.7%, p = .959), disease-free survival (DFS; 61.4 vs. 79.3%, p = .242), and overall survival (OS; 92.7 vs. 89.8%, p = .831) were not statistically different between the CRT and HCRT groups. CONCLUSIONS: Hyperthermia can improve preoperative treatment response in LARC. Pretreatment NLR may be a predictive factor for hyperthermia.

Efficacy and safety of tratinterol hydrochloride tablets in bronchial asthma: a randomized double-blind and multicenter clinical trial.

PURPOSE: The aim of this study was to investigate the efficacy and safety of tratinterol hydrochloride in bronchial asthma (BA) treatment. METHODS: Patients enrolled in this study were distributed randomly into a treatment group (tratinterol hydrochloride) and an active control group (procaterol hydrochloride) and were treated for 2 weeks after running-in. The end points were changes in pulmonary function and clinical symptoms after administration. Safety indices were physical examinations, laboratory testing and spontaneous reporting. FINDINGS: We enrolled 732 subjects, -365 in the treatment group and 367 in the active control group. Forced expiratory volume (FEV1), significantly increased in both group after treatment (P < 0.05). Least-squares (LS) means were -0.03/in the full-analysis set (FAS) and -0.02 in the per-protocol set (PPS) set, and 95% confidence intervals (CIs) for these sets were -0.09 to 0.03 and -0.08 to 0.04, respectively. Forced expiratory volume (FVC), morning peak expiratory flow (PEF) and asthma scores were significantly different with pretreatment (P < 0.05). There was no difference in asymptomatic days or frequency of relief medicine use (P > 0.05). No serious adverse events occurred. IMPLICATIONS: Tratinterol hydrochloride was effective, safe and not inferior to procaterol hydrochloride in treating BA.

The accuracy and safety of CT-guided iodine-125 seed implantation assisted by 3D non-coplanar template for retroperitoneal recurrent carcinoma.

PURPOSE: To investigate the accuracy, dosimetric parameters, and safety of 3D-printing non-coplanar template (3D-PNCT)-assisted CT guidance for radioactive iodine-125 (125I) seed implantation brachytherapy (RSI-BT) for retroperitoneal recurrent carcinomas METHODS AND MATERIALS: We enrolled 15 patients with 17 retroperitoneal recurrent carcinomas after external beam radiotherapy (EBRT). All patients received CT-guided 125I RSI-BT assisted by 3D-PNCT successfully. We compared the original needle insertion position, angular, and the needle tip distance deviations of preoperative plan with that of intraoperative in brachytherapy treatment planning system (B-TPS). The dosimetric parameters of RSI-BT were evaluated on preoperative plan, intraoperative real-time plan, and postoperative plan, including D90, D100 (the dose to 90% and 100% of the target volume), V100, V150, and V200 (the volume receives 100%, 150%, and 200% of the prescribed doses). The quality assurance of RSI-BT evaluated on conformal index (CI), external index (EI), and homogeneity index (HI) of the targets were compared among preoperative plan, intraoperative real-time plan, and postoperative plan. The perioperation complications and RSI-BT-related toxicity were assessed. RESULTS: The median follow-up was 8.2 months (range 1-18.5 months). One patient was lost to follow-up after RSI-BT. Fourteen patients were assessed for response rate and toxicity. The mean entrance point distance deviation for all 165 needles was 4.50 ± 4.10 mm (range, 0-30). The mean angular deviation was 2.70 ± 3.00° (range, 0-20). The needle tip distance deviation was 6.90 ± 6.00 mm (range, - 30-28). D90 for preoperative plan, intraoperative plan, and postoperative plan were 140.55 ± 23.93, 124.25 ± 28.04, and 128.98 ± 22.75, respectively. There was significant difference between D90 of preoperative plan with that of intraoperative plan (p = 0.036). Four lesions reached CR, six lesions reached PR, three lesions were SD, and three lesions were PD. Four patients with moderate pain became mild, and two with mild pain relieved completely after RSI-BT. The other parameters showed no differences among preoperative plan, intraoperative plan, and postoperative plan. The perioperative complications were observed in four patients, including three patients of grade 1 and one patient of grade 2. No ≥ grade 3 side effects were observed. CONCLUSION: CT-guided 125I RSI-BT assisted by 3D-PNCT was a safe, accurate, and feasible strategy for recurrent carcinomas located in the retroperitoneal regions.

Rivaroxaban for the treatment of symptomatic deep-vein thrombosis and pulmonary embolism in Chinese patients: a subgroup analysis of the EINSTEIN DVT and PE studies.

BACKGROUND: The worldwide EINSTEIN DVT and EINSTEIN PE studies randomized 8282 patients with acute symptomatic deep-vein thrombosis (DVT) and/or pulmonary embolism (PE) and, for the first time in trials in this setting, included patients in China. This analysis evaluates the results of these studies in this subgroup of patients. METHODS: A total of 439 Chinese patients who had acute symptomatic DVT (n=211), or PE with or without DVT (n=228), were randomized to receive rivaroxaban (15 mg twice daily for 21 days, followed by 20 mg once daily) or standard therapy of enoxaparin overlapping with and followed by an adjusted-dose vitamin K antagonist, for 3, 6, or 12 months. The primary efficacy outcome was symptomatic recurrent venous thromboembolism. The principal safety outcome was major or non-major clinically relevant bleeding. RESULTS: The primary efficacy outcome occurred in seven (3.2%) of the 220 patients in the rivaroxaban group and in seven (3.2%) of the 219 patients in the standard-therapy group (hazard ratio, 1.04; 95% confidence interval 0.36-3.0; p=0.94). The principal safety outcome occurred in 13 (5.9%) patients in the rivaroxaban group and in 20 (9.2%) patients in the standard-therapy group (hazard ratio, 0.63; 95% confidence interval 0.31-1.26; p=0.19). Major bleeding was observed in no patients in the rivaroxaban group and in five (2.3%) patients in the standard-therapy group. In fragile patients (defined as age >75 years, creatinine clearance <50 mL/min, and/or body weight ≤50 kg), the principal safety outcome occurred in four (8.9%) of the 45 patients who received rivaroxaban compared with seven (15.2%) of the 46 patients who received standard therapy. CONCLUSIONS: In Chinese patients with acute symptomatic DVT and/or PE, rivaroxaban was as efficacious as enoxaparin followed by vitamin K antagonist therapy, with a similar safety profile. The relative efficacy and safety of rivaroxaban compared with enoxaparin/vitamin K antagonist were consistent with that found in the rest of the world. TRIAL REGISTRATION NUMBER: EINSTEIN PE, ClinicalTrials.gov NCT00439777; EINSTEIN DVT, ClinicalTrials.gov NCT00440193.

Association of PBEF gene polymorphisms with acute lung injury, sepsis, and pneumonia in a northeastern Chinese population.

BACKGROUND: Several studies have suggested that pre-B-cell colony-enhancing factor (PBEF) gene polymorphisms are associated with susceptibility to and prognosis of acute lung injury (ALI) in several populations of Caucasians. The aim of this study was to detect the distribution of PBEF alleles and to evaluate any potential relationship between PBEF polymorphisms and ALI, sepsis, and pneumonia in the Han population of Northeast China. METHODS: Genotyping of two PBEF promoter single-nucleotide polymorphisms (SNPs), rs61330082 (C-1535T) and rs9770242 (T-1001G), were performed in patients with ALI (n=130), sepsis alone (n=107), bacterial pneumonia (n=195) and 150 healthy volunteers using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: We found no variation in the T-1001G allele of PBEF. The homozygous TT genotype was the only genotype. This result is different from that observed in Caucasians. The frequency of the -1543T allele was lower in patients with ALI and sepsis than that in healthy subjects ALI vs. healthy controls: OR=0.60, 95% CI 0.43-0.84, p=0.003; and sepsis vs. healthy controls: OR=0.69, 95% CI 0.49-0.99, p=0.04, respectively). The frequency of TT genotype of -1543T was significantly lower in patients with ALI and sepsis than in healthy subjects (ALI vs. healthy controls: OR=0.23, 95% CI 0.10-0.54, p=0.001; and sepsis vs. healthy controls: OR=0.36, 95% CI 0.15-0.83, p=0.02, respectively). CONCLUSIONS: This study suggested that -1543T allele might be a protective factor for ALI and sepsis, but it apparently had no connection with pneumonia in northeastern Chinese Han patients.

The Accuracy of Individualized 3D-Printing Template-Assisted I125 Radioactive Seed Implantation for Recurrent/Metastatic Head and Neck Cancer.

PURPOSE: To evaluate the accuracy of individualized 3D-printing template-assisted I125 radioactive seed implantation (3D-PT assisted I125 RSI) for recurrent/metastatic head and neck cancer. MATERIALS AND METHODS: From February 2017 to January 2020, clinical data of 41 patients (mean age, 58.5 ± 16.1 years; 28 males) with recurrent (48.8%)/metastatic (51.2%) head and neck cancer underwent individualized 3D-PT assisted I125 RSI under CT guidance in a single institute were retrospectively reviewed. Total 430 seed needles [mean, 10.5 (range 3-17) per patient] were inserted. RESULTS: All seed needles were inserted manually in a single attempt with the technical success rate of 100% without major perioperative complications. The mean needle's entrance deviation was 0.090 cm (95% Confidence Interval, 0.081-0.098). The mean intraoperative depth and angle of the needle were consistent with that of planned (6.23 ± 0.24 vs. 6.21 ± 0.24 cm, p = 0.903; 83.14 ± 3.64 vs. 83.09 ± 3.66 degrees, p = 0.985, respectively). The mean deviation between the needle's planned and intraoperative depth and angle was 0.168 ± 0.024 cm and 1.56 ± 0.14 degrees, respectively. The postoperative dosimetry parameters, including D90, D100, V100, V150, V200, conformity index, external index, and homogeneity index, were all well-coordinated with planned dosimetry without significant difference (p = 0.515, 0.662, 0.958, 0.865, 0.872, 0.278, 0.456, and 0.989, respectively). CONCLUSIONS: Within the limitation of this study, individualized 3D-PT assisted I125 RSI may be accurate in obtaining favorable postoperative dosimetry for patients with recurrent/metastatic head and neck cancer. CLINICAL TRIAL REGISTRATION: [website], identifier [registration number].

Accuracy and dosimetric parameters comparison of 3D-printed non-coplanar template-assisted computed tomography-guided iodine-125 seed ablative brachytherapy in pelvic lateral recurrence of gynecological carcinomas.

PURPOSE: To investigate the accuracy of needle distribution and dosimetric parameter differences of 3D-printing non-coplanar template (3D-PNCT)-assisted computed tomography (CT)-guided iodine-125 seed ablative brachytherapy (125I-SAB) in gynecological cancer patients with non-central pelvic recurrence between pre-operative plan and post-operative plan. MATERIAL AND METHODS: Thirty-eight patients with forty-one non-central pelvic recurrent gynecological carcinomas after radiotherapy were enrolled in this study. All patients received 3D-PNCT-assisted CT-guided 125I-SAB from January 2016 to January 2019. The position, angle, and depth of seed needles were measured in both pre-operative plan and intra-operative real-time plan in brachytherapy treatment planning system (B-TPS). Dosimetric parameters of D90, D100, V100, V150, and V200 as well as quality parameters of conformal index (CI), external index (EI), and homogeneity index (HI) were compared between pre-operative plan and post-operative plan. Peri-operation complications and radiation-related toxicity were assessed. RESULTS: Median follow-up time was 12 months (range, 5-34 months). Prescribed dose was 100-170 Gy (median, 120 Gy). Radioactivity of 125I seed was 0.4-0.7 mCi (median, 0.55 mCi). Mean depth deviation for 499 needles was 0.8 ±1.0 cm. Mean angular deviation was 2.2 ±2.1 degrees. Mean tip distance deviation of needles was 0.4 ±0.3 cm. There were significant differences between pre-operative and post-operative plans in CI (p = 0.001) and EI (p = 0.005). No significant differences were shown in D90, D100, V100, V150, V200, and HI between pre-operative and post-operative plans. Only few patients suffered from ≤ grade 2 toxicities. CONCLUSIONS: 3D-PNCT-assisted CT-guided 125I-SAB is safe and feasible for non-central pelvic recurrence of gynecological cancer. All complications are tolerable and mild.

Randomized, Multicenter Clinical Study of Tratinterol Hydrochloride Tablets for the Treatment of Bronchial Asthma.

PURPOSE: The aim of this study was to determine the efficacy and safety profile of tratinterol hydrochloride tablets in the treatment of bronchial asthma. METHODS: This multicenter, randomized, double-blind clinical research study was completed at 6 centers in the People's Republic of China from March 2009 to June 2010, and a randomized trial of procaterol hydrochloride tablets produced by Otsuka Pharmaceutical Co Ltd was conducted. The study was approved by the Medical Ethics Committee of the First Hospital of China Medical University. The clinical trial registration number is 2007L04263. FINDINGS: A total of 223 patients were selected for this study, with 112 patients in the treatment group and 111 in the control group. The lung function of the 2 groups after treatment significantly increased in all (P < 0.05); however, there was no significant difference in the changes between the 2 groups (P > 0.05). The occurrence of related adverse events at varying degrees in the control group was higher than in the treatment group. IMPLICATIONS: It is safe and effective to use tratinterol hydrochloride tablets to treat bronchial asthma.

MicroRNA-575 targets BLID to promote growth and invasion of non-small cell lung cancer cells.

This study was designed to detect miR-575 expression and function in non-small cell lung cancer (NSCLC). A higher expression of miR-575 in NSCLC tissues was observed compared with adjacent non-neoplastic tissues. Furthermore, re-introduction of miR-575 significantly promoted cell proliferation, migration, and invasion in the NSCLC line. Moreover, we showed that BLID is negatively regulated by miR-575 at the posttranscriptional level, via a specific target site within the 3'UTR. Overexpression of BLID counteracted miR-575-induced proliferation and invasion in NSCLC cells. The expression of BLID is frequently downregulated in NSCLC tumors and cell lines and inversely correlates with miR-575 expression. The findings of this study contribute to the current understanding of the functions of miR-575 in NSCLC.

Efficacy and tolerability of tratinterol hydrochloride tablets in bronchial asthma: a multicenter, randomized, double-blind, dose-finding clinical trial.

PURPOSE: The aims of this study were to determine the efficacy and tolerability of different dosages of, and to identify the best dosage of, tratinterol hydrochloride tablets in the treatment of bronchial asthma. METHODS: This multicenter, randomized, double-blind, dose-finding clinical research study was completed at 3 centers in the People's Republic of China from March 2008 to February 2009. Each center selected patients with bronchial asthma whose forced expiratory volume in 1 second (FEV1) values were <80% of predicted normal (pretreatment). Patients were assigned to 1 of 3 groups, based on daily dosage: low, 50 µg/d; intermediate, 100 µg/d; and high, 150 µg/d. Doses were administered orally twice daily for 10 days. The primary end points were the changes from baseline (0 minutes) in peak expiratory flow (PEF) and FEV1 at 30 minutes and 1, 2, 4, 6, and 12 hours after administration. Secondary end points were changes from baseline in forced vital capacity and asthma scores. Tolerability was monitored throughout the study period using physical examinations, laboratory testing, and spontaneous reporting. FINDINGS: A total of 72 patients were selected in this study (24 per group; 40 men; 32 women; mean age, 43.48 years). The efficacy analysis (per-protocol set) included 20, 20, and 22 patients in the low-, intermediate-, and high-dosage groups, respectively. In terms of the primary and secondary end points, the intermediate dosage was most efficacious, followed by the high and low dosages, respectively. All 3 dosages were well-tolerated. IMPLICATIONS: In these patients with bronchial asthma, 100 µg/d was the dosage of tratinterol hydrochloride tablets most efficacious in terms of improvement in lung function. All 3 dosages were well-tolerated.

Genome-wide identification and expression analysis of microRNA involved in small cell lung cancer via deep sequencing.

Small cell lung cancer is a major cause of mortality worldwide. microRNAs (miRNAs) are involved in various biological processes through regulating gene expression. In the present study, to identify the miRNAs involved in human small cell lung cancer at the genome-wide level, Solexa sequencing was employed to sequence two small RNA (sRNA) libraries from small cell lung cancer tissues (LC sRNA library) and the corresponding normal tissues (NT sRNA library). Deep sequencing of the two sRNA libraries identified a number of conserved miRNAs and differential expression analysis of these miRNAs revealed 81 miRNAs differentially expressed in small cell lung cancer, of which more than half were downregulated. The expression trends determined by sequencing were validated by reverse transcription-quantitative polymerase chain reaction analysis. The annotations for the targets of these miRNAs were predicted. This study provides valuable information for understanding the regulatory mechanisms of miRNAs involved in human small cell lung cancer.

Mutations of EGFR or KRAS and expression of chemotherapy-related genes based on small biopsy samples in stage IIIB and IV inoperable non-small cell lung cancer.

PURPOSES: Epidermal growth factor receptor (EGFR) and KRAS mutations may predict the outcome of targeted drug therapy and also may be associated with the efficacy of chemotherapy in patients with non-small cell lung cancer (NSCLC). This report investigated the relation of EGFR or KRAS mutation and expression of chemotherapy-related genes, including excision repair cross-complementing 1 (ERCC1), thymidylate synthetase (TYMS), ribonucleotide reductase subunit M1 (RRM1) and class III ß-tubulin (TUBB3), as a potential explanation for these observations. METHODS: A total of 143 patients with stage IIIB and IV NSCLC from bronchoscopy or percutaneous lung biopsy obtained tumor samples were analyzed concurrently for EGFR or KRAS mutations, and mRNA expression of ERCC1, TYMS, RRM1 and TUBB3. EGFR or KRAS mutations were detected with xTAG liquidchip technology (xTAG-LCT), and mRNA expression levels of four genes were detected by branched DNA-liquidchip technology (bDNA-LCT). RESULTS: Of 143 patients, 63 tumors were positive for EGFR-activating mutations, and 16 tumors were positive for KRAS mutations. EGFR-activating mutations are more frequent in females, adenocarcinoma and non-smokers patients, and KRAS mutations are more frequent in smoking patients. ERCC1 mRNA levels were significantly associated with histological type and tumor differentiation, whereas TYMS levels were significantly associated with age. NSCLC specimens that harboring EGFR-activating mutations are more likely to express low ERCC1 and high TUBB3 mRNA levels, whereas tumors from patients with NSCLC harboring KRAS mutation are more likely to express high ERCC1 mRNA levels. CONCLUSIONS: Mutations and expression of chemotherapy-related genes may provide a basis for the selection of suitable molecular markers for individual treatment in a population with stage IIIB and IV NSCLC.