[Role of neoadjuvant rectal score in prognosis and adjuvant chemotherapy decision-making in locally advanced rectal cancer following neoadjuvant short-course radiotherapy and consolidation chemotherapy].

Objectives: To assess the prognostic impact of the neoadjuvant rectal (NAR) score following neoadjuvant short-course radiotherapy and consolidation chemotherapy in locally advanced rectal cancer (LARC), as well as its value in guiding decisions for adjuvant chemotherapy. Methods: Between August 2015 and August 2018, patients were eligible from the STELLAR phase III trial (NCT02533271) who received short-course radiotherapy plus consolidation chemotherapy and for whom the NAR score could be calculated. Based on the NAR score, patients were categorized into low (＜8), intermediate (8-16), and high (＞16) groups. The Kaplan-Meier method, log rank tests, and multivariate Cox proportional hazard regression models were used to evaluate the impact of the NAR score on disease-free survival (DFS). Results: Out of the 232 patients, 24.1%, 48.7%, and 27.2% had low (56 cases), intermediate (113 cases), and high NAR scores (63 cases), respectively. The median follow-up period was 37 months, with 3-year DFS rates of 87.3%, 68.3%, and 53.4% (P＜0.001) for the low, intermediate, and high NAR score groups. Multivariate analysis demonstrated that the NAR score (intermediate NAR score: HR, 3.10, 95% CI, 1.30-7.37, P=0.011; high NAR scores: HR=5.44, 95% CI, 2.26-13.09, P＜0.001), resection status (HR, 3.00, 95% CI, 1.64-5.52, P＜0.001), and adjuvant chemotherapy (HR, 3.25, 95% CI, 2.01-5.27, P＜0.001) were independent prognostic factors for DFS. In patients with R0 resection, the 3-year DFS rates were 97.8% and 78.0% for those with low and intermediate NAR scores who received adjuvant chemotherapy, significantly higher than the 43.2% and 50.6% for those who did not (P＜0.001, P=0.002). There was no significant difference in the 3-year DFS rate (54.2% vs 53.3%, P=0.214) among high NAR score patients, regardless of adjuvant chemotherapy. Conclusions: The NAR score is a robust prognostic indicator in LARC following neoadjuvant short-course radiotherapy and consolidation chemotherapy, with potential implications for subsequent decisions regarding adjuvant chemotherapy. These findings warrant further validation in studies with larger sample sizes.

[Effect of Echinococcus granulosus hydatid cyst fluid protein on allergic rhinitis induced by ovalbumin in mice].

OBJECTIVE: To investigate the protective effect of Echinococcus granulosus hydatid cyst fluid protein (HCFP) on ovalbumin (OVA)-induced allergic rhinitis (AR) in mice. METHODS: Twenty-four BALB/c mice at ages of 8 to 10 weeks, each weighing approximately 20 g, were randomly divided into four groups, including groups A (blank control group), B (blank intervention group), C (AR model group) and D (AR+HCFP intervention group), with 6 mice in each group. On days 0, 2, 4, 6, 8, 10 and 12, mice in groups A, B, C and D were injected with 200 µL sterile phosphate buffered saline (PBS), 200 µL sterile PBS containing 20 µg HCFP, 200 µL sterile PBS containing 50 µg OVA and 5 mg Al(OH)3 gel, and 200 µL sterile PBS containing 50 µg OVA, 5 mg Al(OH)3 gel and 20 µg HCFP, respectively. On days 14 to 20, mice in groups A, B, C and D were administered with 40 µL sterile PBS, 40 µL sterile PBS containing 20 µg HCFP, 40 µL sterile PBS containing 2 mg OVA and 40 µL sterile PBS containing 2 mg OVA and 20 µL HCFP by nasal drop, respectively. Mouse behavioral changes were observed and behavioral scores were estimated. The serum levels of interferon-γ (IFN-γ), interleukin-4 (IL-4), IL-5, IL-10, transforming growth factor-ß (TGF-ß) and OVA-specific IgE antibody (OVA-sIgE) were measured using enzyme-linked immunosorbent assay (ELISA), and the pathological changes of mouse nasal mucosa were observed by hematoxylin and eosin (HE) staining. RESULTS: The mean behavioral score was significantly greater in Group C (6.83 ± 0.50) than in groups A (1.17 ± 0.52) and B (1.33 ± 0.52) (P < 0.05), while a lower mean behavioral score was estimated in Group D (3.50 ± 0.50) than in Group C (P < 0.05). There were significant differences among the groups in terms of serum IFN-γ (F = 4.08, P < 0.05), IL-4 (F = 275.90, P < 0.05), IL-5 (F = 96.82, P < 0.05), IL-10 (F = 77.67, P < 0.05), TGF-ß (F = 9.98, P < 0.05) and OVA-sIgE levels (F = 44.69, P < 0.05). The serum IFN-γ level was significantly lower in Group C than in groups A, B and C (P < 0.05), and the serum levels of IL-4, IL-5 and OVA-sIgE were significantly higher in Group C than in groups A, B and C (P < 0.05), while the serum IL-10 and TGF-ß levels were significantly greater in Group D than in Group C (P < 0.05). Microscopy showed apparent loss of nasal mucosa cilia, increased number and enlargement of goblet cells, interstitial edema and submucous vascular dilation in Group C, while the pathological changes of nasal mucosa were alleviated in Group D relative to Group C. CONCLUSIONS: E. granulosus HCFP has a protective activity against OVA-induced allergic rhinitis in mice.

[Stereotactic body radiation therapy for patients with lung and liver oligometastases from colorectal cancer: a phase â ¡ trial].

Objective: To explore the safety and effectiveness of stereotactic body radiation therapy (SBRT) for oligometastases from colorectal cancer (CRC). Methods: This is a prospective, single-arm phase Ⅱ trial. Patients who had histologically proven CRC, 1 to 5 detectable liver or lung metastatic lesions with maximum diameter of any metastases ≤5 cm were eligible. SBRT was delivered to all lesions. The primary endpoint was 3-year local control (LC). The secondary endpoints were treatment-related acute toxicities of grade 3 and above, 1-year and 3-year overall survival (OS) and progression free survival (PFS). Survival analysis was performed using the Kaplan-Meier method and Log rank test. Results: Petients from 2016 to 2019 who were treated in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Forty-eight patients with 60 lesions were enrolled, including 37 liver lesions and 23 lung lesions. Forty-six patients had 1 or 2 lesions, with median diameter of 1.3 cm, the median biologically effective dose (BED(10)) was 100.0 Gy. The median follow-up was 19.5 months for all lesions. Twenty-five lesions developed local failure, the median local progression free survival was 15 months. The 1-year LC, OS and PFS was 70.2% (95% CI, 63.7%~76.7%), 89.0% (95% CI, 84.3%~93.7%) and 40.4% (95%CI, 33.0%~47.8%). The univariate analysis revealed that planning target volume (PTV) and total dose were independent prognostic factors of LC (P<0.05). For liver and lung lesions, the 1-year LC, OS and PFS was 58.7% and 89.4% (P=0.015), 89.3% and 86.5% (P=0.732), 30.5% and 65.6% (P=0.024), respectively. No patients developed acute toxicity of grade 3 and above. Conclusion: SBRT is safe and effective treatment method for oligometastases from CRC under precise respiratory motion management and robust quality assurance.

Recovery patterns in patients undergoing revision surgery of the primary knee prosthesis.

PURPOSE: Despite good survival rates of revised knee prostheses, little is known about recovery trajectories within the first 12 months after surgery. This retrospective observational study explored recovery trajectories in terms of pain, function and quality of life in patients after revision knee arthroplasty over 12 months. METHODS: Eighty-eight revision knee arthroplasty patients rated changes in daily physical functioning using the anchor question (0: very much worsened; 7: very much improved). Patient reported outcome measures (PROMs) of pain (range 0-10), function (Oxford Knee Score) and quality of life (EQ-5D-3L) were assessed preoperatively, at 3 and 12 months postoperatively. Four recovery trajectories were identified using the anchor question at 3 and 12 months postoperatively: no improvement, late improvement, early improvement, and prolonged improvement. Repeated measures ANOVA was conducted with recovery trajectories as dependent variable and PROM assessments as independent variables. RESULTS: Sixty percent reported improvement in daily physical functioning at 12 months postoperatively. Age and reason for revision differed between groups. Pain, function and EQ-5D-3L differed between groups over time. Late and prolonged improvement groups improved on all PROMs at 12 months. The early improvement group did not report improvement in daily physical functioning at 12 months, while improvements in function and pain during activity were observed. CONCLUSIONS: Different recovery trajectories seem to exist and mostly match PROMs scores over time. Not all patients may experience beneficial outcome of revision knee arthroplasty. These findings are of importance to provide appropriate information on possible recovery trajectories after revision knee arthroplasty to patients. LEVEL OF EVIDENCE: III.

[Analysis of components of proteins from Echinococcus granulosus cyst fluid].

OBJECTIVE: To analyze the components of proteins from Echinococcus granulosus cyst fluid using the shotgun method, and to identify the active components with potential regulatory effects for immune dysregulation diseases. METHODS: The E. granulosus cyst fluid was collected aseptically from the hepatic cysts of patients with cystic echinococcosis, and characterized by liquid chromatography (LC) tandem mass spectrometry (MS/MS) following digestion with trypsin. The protein data were searched using the software MaxQuant version 1.6.1.0 and the cellular components, molecular functions, and biological processes of the identified proteins were analyzed using the Gene Ontology (GO) method. RESULTS: The E. granulosus cyst fluid separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) had a relative molecular mass of 25 to 70 kDa. LS-MS/MS analysis identified 37 proteins, including 32 known proteins and 5 unknown proteins. At least 4 proteins were preliminarily found to exhibit potential regulatory effects for immune dysregulation diseases, including antigen B, glutathione-S-transferase (GST), thioredoxin peroxidase (TPX) and malate dehydrogenase (MDH). GO enrichment analysis showed that the identified proteins had 149 molecular functions and were involved in 341 biological processes. CONCLUSIONS: E. granulosus cyst fluid has a variety of protein components, and four known proteins are preliminarily identified to be associated with immune dysregulation diseases.

[Comparison of preoperative chemotherapy with concurrent chemoradiotherapy combined with TME for 305 patients with locally advanced rectal cancer].

Objective: To retrospectively analyze the long-term efficacy and prognostic factors of preoperative chemotherapy (PCT) or chemoradiotherapy (PCRT) combined with total mesorectal excision in locally advanced rectal cancer. Methods: Clinical pathology data of 305 patients with localized advanced rectal cancer admitted to the Cancer Hospital, Chinese Academy of Medical Sciences from 2006 to 2018 were collected, of whom 246 patients received PCRT (PCRT group), 59 patients received PCT (PCT group). Kaplan-Meier and Log rank test were used for the survival analysis, Cox regression model was used for multivariate analysis, and the prognosis of two groups of patients were compared by the propensity score matching (PSM). Results: In the whole group of 305 patients, 20 cases of tumors located in the upper part of the rectum and at the junction of rectum and colon, 96 cases in the middle of the rectum and 189 cases in the lower part of the rectum. PCRT group included 38 cases of cT2-3 phase, 11 cases of cT4a stage, 10 cases of cT4b stage, while the cases in PCT group were 184, 0 and 62 cases, respectively, the difference is statistically significant (P<0.05). The R0 excision rates of PCRT group and PCT group were 100% (246/246) and 96.6% (57/59), respectively, and the total pathological remission rates were 13.4% and 3.3%, respectively (P<0.05). After PSM, the 3-year survival rates of PCRT group and the PCT group were 86.6% and 89.9% (P>0.05), respectively, and the progression-free survival rates were 74.6% and 77.2% (P>0.05), local recurring free survival rates were 100% and 92.3% (P>0.05), distant metastasis free survival rate were 75.6% and 77.3% (P>0.05). Pre-treatment N-positive, N-degeneration and MRF-positive were all associated with total survival (P<0.05). Conclusion: In the PCRT group, with a higher proportion of patients with stage T4b and lower rectal cancer, the long-term efficacy of PCRT was similar to that of PCT, and higher R0 excision rate and pathological complete response rate could be obtained.

[Analysis of the efficacy and prognostic factors of 1 637 esophageal cancer patients treated with intensity-modulated radiotherapy].

Objective: To summarize survival outcomes and prognostic factors in esophageal cancer (EC) patients treated with intensity-modulated radiotherapy (IMRT). Methods: A retrospective analysis was performed on the clinical and follow-up data of 1 637 patients with EC who were admitted to our hospital from January 2005 to December 2017 and met the inclusion criteria.The 5-year overall survival (OS), progression-free survival (PFS) and pattern of recurrence were analyzed. The Kaplan-Meier method was used to calculate survival rates, Log-rank test for univariate analysis and Cox method for multivariate analysis were used to detect survival difference. Results: 1-year, 3-year and 5-year OS and PFS of the entire group were 65.9% and 45.8%, 34.2% and 25.0%, 27.0% and 18.5%, respectively. Median OS and PFS were 19.4 months (95% CI=18.0-20.7 months) and 10.4 months (95% CI=9.3-11.3 months), respectively. Univariate analysis showed that the sex, KPS, tumor location, T stage, N stage, M stage, TNM stage, radiation dose and treatment modality were prognostic factors for 5-year OS and PFS of EC patients (P<0.05). Multivariate analysis indicated that the sex, KPS, TNM stage, radiation dose and treatment modality were independent prognostic factors for 5-year OS and PFS (P<0.05). Conclusions: EC patients treated with IMRT can obtain a promising survival. The sex, KPS, TNM stage, radiation dose and treatment modality are independent prognostic factors for prognosis.

[Preliminary study of the relationship between novel coronavirus pneumonia and liver function damage: a multicenter study].

Objective: To analyze the clinical characteristics of cases of novel coronavirus pneumonia and a preliminary study to explore the relationship between different clinical classification and liver damage. Methods: Consecutively confirmed novel coronavirus infection cases admitted to seven designated hospitals during January 23, 2020 to February 8, 2020 were included. Clinical classification (mild, moderate, severe, and critical) was carried out according to the diagnosis and treatment program of novel coronavirus pneumonia (Trial Fifth Edition) issued by the National Health Commission. The research data were analyzed using SPSS19.0 statistical software. Quantitative data were expressed as median (interquartile range), and qualitative data were expressed as frequency and rate. Results: 32 confirmed cases that met the inclusion criteria were included. 28 cases were of mild or moderate type (87.50%), and four cases (12.50%) of severe or critical type. Four cases (12.5%) were combined with one underlying disease (bronchial asthma, coronary heart disease, malignant tumor, chronic kidney disease), and one case (3.13%) was simultaneously combined with high blood pressure and malignant tumor. The results of laboratory examination showed that the alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), and total bilirubin (TBil) for entire cohort were 26.98 (16.88 ~ 46.09) U/L and 24.75 (18.71 ~ 31.79) U/L, 39.00 (36.20 ~ 44.20) g/L and 16.40 (11.34 ~ 21.15) µmol/L, respectively. ALT, AST, ALB and TBil of the mild or moderate subgroups were 22.75 (16.31 ~ 37.25) U/L, 23.63 (18.71 ~ 26.50) U/L, 39.70 (36.50 ~ 46.10) g/L, and 15.95 (11.34 ~ 20.83) µmol/L, respectively. ALT, AST, ALB and TBil of the severe or critical subgroups were 60.25 (40.88 ~ 68.90) U/L, 37.00 (20.88 ~ 64.45) U/L, 35.75 (28.68 ~ 42.00) g/L, and 20.50 (11.28 ~ 25.00) µmol/L, respectively. Conclusion: The results of this multicenter retrospective study suggests that novel coronavirus pneumonia combined with liver damage is more likely to be caused by adverse drug reactions and systemic inflammation in severe patients receiving medical treatment. Therefore, liver function monitoring and evaluation should be strengthened during the treatment of such patients.

PNPLA3 polymorphism influences the association between high-normal TSH level and NASH in euthyroid adults with biopsy-proven NAFLD.

AIM: We aimed to evaluate the association between serum thyroid stimulating hormone (TSH) levels, within the reference range, and the histological severity of nonalcoholic fatty liver disease (NAFLD), and whether this association was modulated by the patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 polymorphism. MATERIALS AND METHODS: We enrolled 327 euthyroid individuals with biopsy-proven NAFLD, who were subdivided into two groups, i.e., a 'strict-normal' TSH group (TSH level 0.4 to 2.5mIU/L; n=283) and a 'high-normal' TSH group (TSH level 2.5 to 5.3mIU/L with normal thyroid hormones; n=44). Logistic regression analyses were performed to assess the association between TSH status and presence of nonalcoholic steatohepatitis (NASH) after stratifying subjects by PNPLA3 genotypes. RESULTS: Compared to strict-normal TSH group, patients with high-normal TSH levels were younger and had a greater prevalence of NASH and higher histologic NAFLD activity score. After stratifying by PNPLA3 genotypes, the significant association between high-normal TSH levels and presence of NASH was restricted only to carriers of the PNPLA3 G risk allele and remained significant even after adjustment for potential confounding factors (adjusted-odds ratio: 3.279; 95% CI: 1.298-8.284; P=0.012). CONCLUSION: In euthyroid individuals with biopsy-proven NAFLD, we found a significant association between high-normal TSH levels and NASH. After stratifying by PNPLA3 rs738409 genotypes, this association was observed only among carriers of the PNPLA3 G risk allele.

Age distribution of human papillomavirus infection and neutralizing antibodies in healthy Chinese women aged 18-45 years enrolled in a clinical trial.

OBJECTIVES: Data from clinical trials of human papillomavirus (HPV) vaccines showed that women naïve (negative for both type-specific antibodies and DNA) to vaccine types would derive benefit from vaccination; therefore, an understanding of the proportion of naïve women in different age groups is important for developing HPV vaccination strategies. METHODS: From November 2012 to April 2013, a total of 7372 healthy women aged 18-45 years were recruited in five provinces in China. Cervical specimens and serum samples were collected for each woman at entry. Cervical specimens were first tested by the HPV DNA enzyme immunoassay method; if positive, the specimens were then tested by reverse hybridization line probe assay and HPV-16 and HPV-18 specific polymerase chain reactions. Neutralizing antibodies against HPV-16 or HPV-18 were tested with a pseudovirion-based neutralization assay. RESULTS: The overall prevalence of high-risk HPV DNA was 14.8% (1088/7367, 95% CI 14.0-15.6), and the seroprevalence of neutralizing antibodies against HPV-16 and HPV-18 was 12.6% (925/7367) and 4.9% (364/7367), respectively. In younger women (18-26 years) and middle-aged women (27-45 years), 83.8% (3116/3719) and 81.4% (2968/3648) were naïve to both HPV-16 and HPV-18 (both neutralizing antibodies and DNA were negative), respectively. In addition, 98.5% (3664/3719) and 98.0% (3575/3648) of the younger or middle-aged women were naïve to at least one HPV type (HPV-16 or HPV-18). DISCUSSION: This study revealed that the majority of Chinese women aged 18-26 years and 27-45 years were naïve to both HPV-16 and HPV-18 and would thus derive full benefit from bivalent HPV vaccination.

Timing of anterior cruciate ligament reconstruction and preoperative pain are important predictors for postoperative kinesiophobia.

PURPOSE: Fear of movement (kinesiophobia) is a major limiting factor in the return to pre-injury sport level after anterior cruciate ligament reconstruction (ACLR). The aim of this study was to gain insight into the prevalence of kinesiophobia pre-ACLR, 3 months post-ACLR and 12 months post-ACLR. Furthermore, the preoperative predictability of kinesiophobia at 3 months post-ACLR was addressed. METHODS: A retrospective study with data, which were prospectively collected as part of standard care, was conducted to evaluate patients who underwent ACLR between January 2017 and December 2018 in an orthopaedic outpatient clinic. Patient characteristics (age, sex, body mass index), injury-to-surgery time, preoperative pain level (KOOS pain subscale) and preoperative knee function (IKDC-2000) were used as potential predictor variables for kinesiophobia (TSK-17) at 3 months post-ACLR in linear regression analysis. RESULTS: The number of patients with a high level of kinesiophobia (TSK > 37) reduced from 92 patients (69.2%) preoperatively to 44 patients (43.1%) 3 months postoperatively and 36 patients (30.8%) 12 months postoperatively. The prediction model, based on a multivariable regression analysis, showed a positive correlation between four predictor variables (prolonged injury-to-surgery time, high preoperative pain level, male sex and low body mass index) and a high level of kinesiophobia at 3 months postoperatively (R2 = 0.384, p = 0.02). CONCLUSION: The prevalence of kinesiophobia decreases during postoperative rehabilitation, but high kinesiophobia is still present in a large portion of the patients after ACLR. Timing of reconstruction seems to be the strongest predictor for high kinesiophobia 3 months post-ACLR. This study is the first step in the development of a screening tool to detect patients with kinesiophobia after ACLR. Identifying patients preoperatively opens the possibility to treat patients and thereby potentially increase the return to pre-injury sport level rate after ACLR. LEVEL OF EVIDENCE: III.

Hepcidin protects pulmonary artery hypertension in rats by activating NF-κB/TNF-α pathway.

OBJECTIVE: The pulmonary artery hypertension (PAH) model was established in rats in this study. Therefore, we aimed to elucidate the protective role of Hepcidin in PAH rats and its underlying mechanism. MATERIALS AND METHODS: 24 male Sprague Dawley (SD) rats were randomly divided into sham group, PAH group and Hepcidin group, with 8 rats in each group. After animal procedures, hemodynamic parameters and right ventricular hypertrophy indexes were determined in rats. Cytokines in serum samples of rats were detected by enzyme-linked immunosorbent assay (ELISA). Pathological lesions in lung tissues were observed by hematoxylin and eosin (H&E) staining. Finally, Western blot was conducted to detect the protein expressions of nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), vascular cell adhesion molecule 1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1), and monocyte chemotactic protein-1 (MCP-1) in lung tissues of rats. RESULTS: Compared with sham group, mean pulmonary artery pressure (mPAP) and right ventricular systolic pressure (RVSP) were significantly elevated in rats of PAH group (p<0.05). On the contrary, mPAP and RVSP in rats of Hepcidin group were both significantly lower than PAH group (p<0.05). Hepcidin treatment attenuated PAH-induced pathological lesions in lung tissues. ELISA results elucidated that Hepcidin treatment significantly decreased serum levels of TGF-ß, TNF-α, IL-1ß, and IL-6. In addition, Western blot results demonstrated that protein levels of NF-κB, TNF-α, IL-1ß, VCAM-1, ICAM-1, and MCP-1 in Hepcidin group were remarkably lower than those of PAH group. CONCLUSIONS: Hepcidin alleviates inflammatory response in PAH rats by inhibiting NF-kB/ TNF-α pathway.

[Screening of periodontal and salivary parameters in patients with frequent acute exacerbation of chronic obstructive pulmonary disease].

Objective: To screen the risk factors of patients with frequent acute exacerbation of chronic obstructive pulmonary disease (COPD) by detecting the clinical indicators of periodontitis and the level of bacterial and inflammatory markers in saliva. Methods: Thirty-eight COPD patients in their stable period were recruited and detected from Beijing Chao-Yang Hospital,Capital Medical University during December 2016 to May 2017. The periodontal index were recorded. The levels of inflammatory factors in saliva samples were examined by using enzyme linked immunosorbent assay (ELISA). The bacteria composition in the saliva samples were identified by using 16SrRNA gene pyrosequencing. All patients were followed up and monitored for acute exacerbation of COPD for 12 months. The patients were divided into frequent acute exacerbation group (≥2 times/year, n=10) and non frequent acute exacerbation group (<2 times/year, n=28). Results: In univariate analysis, the patients' average age of frequent acute exacerbation group (69.0±7.3) was significantly older than that of non-frequent acute exacerbation group (61.8±8.3) (P=0.02). The numbers of remaining teeth ≤26 [100% (10/10)] was significantly higher and plaque index ≤2.5 (2/10) in frequent acute exacerbation group was significantly lower compared with the remaining teeth ≤26 [43% (12/28)] and the plaque index ≤2.5 [71% (21/28)] in non-frequent acute exacerbation group (P=0.02, P=0.01). The proportions of salivary inflammatory factors interleukin-6 (IL-6) level ≤60 ng/L (10%),C-reactive protein (CRP) level ≤1 550 µg/L (30%), matrix metalloproteinase-8 (MMP-8) level ≤140 µg/L (30%) and fibrinogen level ≤90 mg/L (30%) in frequent acute exacerbation group were significantly lower compared with salivary inflammatory factors IL-6 level ≤60 ng/L (71%),CRP level ≤1 550 µg/L (71%), MMP-8 level ≤140 µg/L (86%) and fibrinogen level ≤90 mg/L (71%) in non-frequent acute exacerbation group (P<0.05). The differences of relative abundances of salivary bacteria,such as species of Chloroflexi, Anaerolineae, Anaeroales, Corynebacteriales, Anaerolineaceae, Tissierellaceae, Leptotrichiaceae, Corynebacteriaceae, Leptotrichia, Moryella, Lachnoanaerobaculum and Corynebacterium between frequent acute exacerbation group and non-frequent acute exacerbation group were significantly different (P<0.05). In multivariate logistics regression analysis,the level of IL-6 >60 ng/L and the relative abundance of Corynebacteriales >0.2 had significant difference (P<0.05). Conclusions: The level of IL-6 and the relative abundance of Corynebacteriales might be the markers of frequent acute exacerbation in COPD patients.

APC promoter methylation is correlated with development and progression of bladder cancer, but not linked to overall survival: a meta-analysis.

The clinical role of APC promoter methylation in patients with bladder cancer remains to be determined. The relevant databases (PubMed, EMBASE, EBSCO, Wangfang, CNKI and Cochrane Library) were searched to get eligible studies. The overall odds ratios (ORs) and the corresponding 95% confidence intervals (95% CIs) were calculated to assess the effects of APC promoter methylation on bladder cancer risk and clinicopathological features. 2214 patients with bladder cancer and 665 controls were identified. APC promoter methylation was significantly higher in bladder cancer than in nonmalignant tissue and urine samples (tissue: OR = 11.14, 95% CI = 4.29-28.91, P < 0.001; urine: OR = 24.31, 95% CI = 6.26-94.38, P < 0.001), but not in blood samples (P = 0.242). The relationship was observed between APC promoter methylation and gender (male vs. female: OR = 1.46, 95% CI = 0.96-2.22, P = 0.074), tumor stage (stage T2-T4 vs. Ta-T1: OR = 3.00, 95% CI = 1.66-5.42, P < 0.001), and tumor grade (grade 3-4 vs. grade 1-2: OR = 1.99, 95% CI = 1.15-3.42, P = 0.013). But no correlation was found between APC promoter methylation and age, lymph node status, and tumor number (P > 0.1). APC gene was not associated with overall survival of bladder cancer. Our findings indicate that APC promoter methylation may be associated with the development and progression of bladder cancer and may serve as a promising noninvasive biomarker using urine samples for the detection of bladder cancer.

Nicotinamide pretreatment alleviates mitochondrial stress and protects hypoxic myocardial cells via AMPK pathway.

OBJECTIVE: The aim of this study was to explore the protective effect of nicotinamide on hypoxic cardiomyocytes and to investigate its possible mechanism. MATERIALS AND METHODS: Primary cardiomyocytes were used as study subjects. They were divided into three groups, including the blank group, control group and nicotinamide pretreatment group. Cell counting kit-8 (CCK-8) was used to detect cell viability. Lactate dehydrogenase (LDH) was used to detect cytotoxicity and flow cytometry was used to detect cell apoptosis. Polymerase Chain Reaction (PCR) and Western blot were used to measure the expressions of genes in adenosine monophosphate-activated protein kinase (AMPK) pathway. JC-1 detected the levels of mitochondrial membrane potential and reactive oxygen species (ROS). NAD was used for nicotinamide adenine dinucleotide (NAD)+, and NAD phosphate (NADP)+ levels. Adenosine triphosphate (ATP) assay was performed for the detection of intracellular energy metabolism. RESULTS: In the absence of oxygen, nicotinamide had a protective effect on primary cardiomyocytes. Meanwhile, nicotinamide could markedly inhibit the increase of caspase3 mRNA in cardiomyocyte apoptosis pathway, and suppress the expression of apoptotic proteins. Furthermore, it could significantly induce the increase of intracellular ATP and activate the AMPK pathway. The detection of mitochondria indicated that nicotinamide alleviated hypoxic cardiomyocytes. In addition, the mitochondrial membrane potential disrupted and inhibited mitochondrial oxidative stress levels. CONCLUSIONS: Nicotinamide pretreatment protects hypoxic cardiomyocytes and reduces intracellular mitochondrial stress. This protection may be related to the induction of the AMPK pathway and the increase of intracellular energy production.

MiR-98-5p regulates myocardial differentiation of mesenchymal stem cells by targeting TBX5.

OBJECTIVE: This study aims to investigate whether miR-98-5p can participate in the myocardial differentiation of bone marrow mesenchymal stem cells (MSCs) by regulating TBX5. MATERIALS AND METHODS: In this study, we first identified the MSCs that were isolated from rat bone marrow samples. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to detect mRNA expressions of cardiac-related genes, including brain natriuretic peptide (BNP), α-actinin, and Islet-1. The binding site of miR-98-5p and TBX5 was detected by dual-luciferase report gene assay. In addition, co-transfection of miR-98-5p mimics and TBX5 overexpression plasmids was conducted to assess whether miR-98-5p could regulate myocardial differentiation by targeting TBX5. RESULTS: Overexpression of TBX5 or knockdown of miR-98-5p promoted myocardial differentiation of BMSCs. The mRNA expressions of α-actinin and Islet-1 were significantly increased after the miR-98-5p knockdown. Dual-luciferase report gene assay showed that miR-98-5p could bind to TBX5, which was further verified by qRT-PCR. Additionally, TBX5 overexpression reversed the inhibitory effect of miR-98-5p on regulating the mRNA expressions of α-actinin and Islet-1. CONCLUSIONS: MiR-98-5p can inhibit the differentiation of rat MSCs into cardiomyocytes through targeting TBX5.

S-1 chemotherapy and intensity-modulated radiotherapy after D1/D2 lymph node dissection in patients with node-positive gastric cancer: a phase I/II study.

BACKGROUND: This phase I/II clinical trial investigated S-1 administered with intensity-modulated radiotherapy (IMRT) as adjuvant therapy for node-positive gastric cancer. Patients had undergone radical resection and D1/D2 lymph node dissection. METHODS: In phase I, patients received adjuvant chemoradiotherapy of IMRT (45 Gy in 25 fractions) with concurrent S-1 administered on a dose-escalation schedule to determine the recommended dose (RD). In phase II, the safety and efficacy of the RD of S-1 combined with IMRT were assessed. RESULTS: We consecutively enrolled 73 patients (56 men; median age, 53 years; range, 29-73 years) and the phase I portion of the study included 27 patients. The RD of S-1 administered concomitantly with IMRT was 80 mg m-2 day-1 orally, twice daily. The phase II analysis included 52 patients (46 new patients plus 6 from phase I). 8 patients (15.4%) developed grade 3 or 4 toxicities. There were 21 recurrence events and 15 deaths (1 bowel obstruction, 14 gastric cancer). Three-year disease-free survival and overall survival were 62.2% (95% confidence interval (CI), 48.5-75.9) and 70.0% (95% CI, 56.3-83.7), respectively. The median time to recurrence was 17.5 months (range, 3.8-42.0). The median time from recurrence to death was 7.0 months (range, 1.5-28.7). CONCLUSIONS: S-1 combined with IMRT adjuvant chemoradiotherapy is safe and efficacious for advanced gastric cancer.

Methionine synthase A2756G polymorphism and lymphoma risk: a meta-analysis.

OBJECTIVE: The association between methionine synthase (MS) A2756G polymorphism and lymphoma risk was studied with conflicting results. The present meta-analysis aimed to investigate the overall association between MS A2756G polymorphism and lymphoma risk. MATERIALS AND METHODS: We searched PubMed and Embase databases until March 30, 2017, for articles that assessed the association between MS A2756G polymorphism and lymphoma risk. Statistical analyses were performed using the Revman 5.0 software. RESULTS: A total of 14 articles involving 4,156 cases and 6,407 controls were included in this meta-analysis. Combined analysis revealed no association between this polymorphism and lymphoma susceptibility (OR = 0.92, 95% CI: 0.74-1.16, p = 0.50 for GG vs. GA+AA). Subgroup analysis by ethnicity showed decreased lymphoma risk with the MS A2756G gene polymorphism among Caucasians in GG+GA vs. AA and G vs. A models, but not among Asians. Subgroup analysis by disease type suggested that GG homozygous and G alleles were not associated with risks of non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), the subtype of NHL including the diffuse large B-cell lymphoma and follicular lymphoma. CONCLUSIONS: The results in this meta-analysis suggest no association between the MS A2756G polymorphism and lymphoma risk; however, the GG homozygous and G alleles could decrease the lymphoma risk in Caucasians.