[Effectiveness, safety and cost of urinary follicle stimulating hormone in controlled ovarian stimulation in China: multi-center retrospective cohort study of 102 061 in vitro fertilization cycles].

Objective: To explore the effectiveness, safety and cost between urinary follicle stimulating hormone (uFSH) and recombinant follicle stimulating hormone (rFSH) in controlled ovarian stimulation (COS) in China. Methods: Data were collected from 16 reproductive centers in China covering oocytes collection time from May 1, 2015 to June 30, 2018. Eligible patients were over 18 years old, adopting COS with uFSH (uFSH group) or rFSH (rFSH group) as start gonadotropins (Gn), and using in vitro fertilization (IVF) and (or) intracytoplasmic sperm injection for fertilisation, excluding frozen embryo recovery cycle. Generalised estimating equation was used to address the violation of independency assumption between cycles due to multiple IVF cycles for one person and clustering nature of cycles carried out within one center. Controlling variables included age, body mass index, anti-Müllerian hormone level, cause of infertility, ovulation protocol, type of fertilisation, number of embryos transferred, number of days of Gn use. Results: Totally 102 061 cycles met eligibility criteria and were included in the analyses. In terms of effectiveness, after controlling relevant unbalanced baseline characteristics, compared with rFSH group, the high oocyte retrieval (>15 oocytes was considered high retrieval) rate of uFSH group significantly decreased in gonadotropin-releasing hormone agonist protocol (OR=0.642, P<0.01) and in gonadotropin-releasing hormone antagonist protocol (OR=0.556, P=0.001), but the clinical pregnancy rate per transfer cycle and the live birth rate per transfer cycle significantly increased (OR=1.179, OR=1.169, both P<0.01) in both agonist and antagonist protocols. For safety, multiple analysis result demonstrated that in the agonist protocol, compared with rFSH group, the incidence of moderate to severe ovarian hyperstimulation syndrome of uFSH group significantly decreased (OR=0.644, P=0.002). The differences in ectopic pregnancy rate and multiple pregnancy rate between the uFSH and rFSH groups were not significant (P=0.890, P=0.470) in all patients. In terms of cost, compared with rFSH group, the uFSH group had lower total Gn costs for each patient (P<0.01). Conclusion: For patients who underwent COS, uFSH has better safety, and economic profiles over rFSH in China.

CXCL-10/CXCR3 in macrophages regulates tissue repair by controlling the expression of Arg1, VEGFa and TNFα.

Macrophages have been reported to participate in inflammation, tissue homeostasis and tissue repair. The detailed mechanism of macrophage-mediated tissue repair is not clear. CXCL-10, secreted by monocytes, endothelial cells and fibroblasts, mediates immune response and angiogenesis by binding to CXCR3. In this study, the expression of CXCL-10 and CXCR3 in porcine lung injury induced by porcine reproductive and respiratory syndrome virus (PRRSV) infection was firstly examined. The results showed that the expression of both CXCL-10 and CXCR3 increased in the infected pig lungs. In addition, the increased expression of CXCL-10 and CXCR3 in macrophage treated by poly (I:C) was also observed, suggesting the autocrine system existed in macrophages. Furthermore, CXCL-10 treatment induced upregulation of Arg1 and VEGFa, and downregulation of TNFα in macrophage, and CXCR3 antagonist AMG487 treatment presented the contrary effects on the expression of Arg1, VEGFa, and TNFα. CXCL- 10-stimulated effects were dependent on PI3K/Akt signaling pathway. Wound-healing assay showed that CXCL-10 treatment macrophage conditioned medium promoted the healing process of endothelial cells. Our results suggested that CXCL-10/CXCR3 in macrophage may mediate tissue repair by regulating the macrophage expression of Arg1, VEGFa and TNFα. Modulation of CXCL-10/CXCR3 axis in macrophage may be a potential therapeutic strategy for tissue injury and repair.

[The study of the effects of occupational aluminum exposure on TNFR1 expression and cognitive function].

Objective: To analyze the relationship between cognitive function and tumor necrosis factor receptor 1 (TNFR1) expression of occupational exposed workers to aluminum and provide the basis for the diagnosis of cognitive impairment. Methods: 140 cases Shanxi aluminum plant workers were collected in 2016 as the research object, including 70 potroom workers for exposure group, 70 non-electrolytic aluminum plant workers in the control group, respectively. Using mini mental status examination (MMSE), digit span test (DST), fuld object memory examination(FOME) and simple reaction time test(SRTT) evaluate the cognitive function of objects. Using graphite furnace atomic absorption method for the determination of plasma aluminum levels as an indicator of aluminum contact exposure of workers. Using RT-PCR method for detection of tumor necrosis factor receptor 1 (TNFR1) mRNA expression levels. And comparison group differences in cognitive and TNFR1 mRNA expression levels. Results: The plasma aluminum content of exposed group (77.12±27.18) µg/L higher than the control group (55.6±28.69)µg/L (P=0.000); Compared to control group, FOME and MMSE score was significantly increased in the exposed group (P=0.000, P=0.000), SRTT scores significantly higher in the exposed group (P=0.001), DST no significant difference in the control group (P=0.893). Compared to control group, The mRNA expression of TNFR1 was significantly higher in the exposed group(P=0.002); Compared to control group, The protein expression of TNFR1 was significantly higher in the exposed group (P=0.002). By correlation analysis in exposure group, plasma aluminum content was negatively correlated with MMSE and the DST (r=-0.284, r=-0.331, P<0.05) and positively correlated with the SRTT, TNFR1 (mRNA) and TNFR1(protein)(r=0.255, r=0.333, r=0.987, P<0.01), MMSE was negatively related to TNFR1 (mRNA) and TNFR1 (protein) (r=-0.268, r=-0.255, P<0.05); DST was negatively correlated with the SRTT and TNFR1 (protein)(r=-0.267, r=-0.330, P<0.05); SRTT was positively correlated with TNFR1 (protein)(r=0.243, P<0.05); TNFR1 (mRNA) was positively correlated with TNFR1 (protein)(r= 0.340, P<0.01). Conclusion: Cognitive function change of occupational exposed workers to aluminum was related to the increase of TNFR1 expression.

[Correlation between mismatch repair proteins status and clinicopathological characteristics in sporadic colorectal cancer patients].

Objective: To explore the expression of mismatch repair (MMR) proteins in sporadic colorectal cancer (SCRC) patients, and its association with clinicopathological characteristics of SCRC. Methods: Patients with histologically confirmed colorectal cancer were consecutively recruited between December 2011 and June 2015 at Sun Yat-sen University Cancer Center. The exclusion criteria included multiple primary colorectal tumors, hereditary colorectal cancer (including Lynch syndrome, familial adenomatous polyposis), and the patients without the MMR proteins status tested. A total of 2 684 patients were included. Correlations of MMR proteins status and patients' demographics (including gender, age), tumor characteristics (site and differentiation) and TNM staging (excluding 315 SCRC patients receiving neoadjuvant therapy) were investigated. Results: The percentage of deficient MMR (dMMR) in these SCRC patients was 10.2%, and that of proficient MMR (pMMR) was 89.8%. The dMMR was more likely to be detected in younger (≤59 old years) SCRC patients compared to the elderly (>59 years) [12.7%(179/1 406)vs 7.5%(96/1 278), P<0.001]. The dMMR rate in right colon cancer was significantly higher than that in left colon cancer and rectal cancer [22.7%(151/664)vs 7.2%(69/956)vs 5.2%(55/1 064), P<0.001]. Among the various pathological types of SCRC, mucinous adenocarcinoma showed the highest rate of dMMR (24.4%), and neuroendocrine carcinoma the lowest rate of dMMR (0) (P<0.001). In addition, the proportions of dMMR in stage Ⅰ, stage Ⅱ, stage Ⅲ and stage Ⅳ SCRC were 9.7%, 16.5%, 8.5%, and 3.9%, respectively (P<0.001). There is no significant difference in the proportion of dMMR between male and female (11.0% vs 9.1%, P=0.114). Conclusion: dMMR status may be most likely to exist in younger (≤59 years) patients with stage Ⅱ right colon mucinous adenocarcinoma among SCRC.

Serum YKL-40 levels are associated with type 2 diabetes mellitus in patients with obstructive sleep apnea syndrome.

Patients with obstructive sleep apnea syndrome (OSAS) have an increased risk for type 2 diabetes mellitus (T2DM). It has been recently demonstrated that serum YKL-40 levels, also named as human cartilage glycoprotein 39, are elevated in T2DM patients. The aim of this study was to determine whether serum YKL-40 levels are associated with T2DM in patients with OSAS. This study consisted of 432 patients with OSAS (234 and 198 patients with and without T2DM, respectively). Serum YKL-40 levels were examined using the enzyme-linked immunosorbent assay method. OSAS patients with T2DM had significantly elevated serum YKL-40 levels compared to those without T2DM [205.02 (146.16-272.70) vs 135.72 (114.06-163.38)]. According to the multivariable logistic regression analysis, serum YKL-40 levels were an independent determinant of T2DM in patients with OSAS. Furthermore, based on the linear regression analysis, serum YKL-40 levels were positively associated with the body mass index, systolic blood pressure, serum triglyceride levels, homeostasis model assessment of insulin resistance, and levels of C-reactive protein, fasting plasma glucose, 2-h postprandial plasma glucose, and HbA1c in patients with OSAS. Elevated serum YKL-40 levels may serve as a new biomarker to predict T2DM in patients with OSAS.

Association of GSTP1 and XRCC1 gene polymorphisms with clinical outcomes of patients with advanced non-small cell lung cancer.

We investigated the association between the polymorphisms GSTP1 rs1695 and XRCC1 rs1799782 and rs25487 and the clinical outcome of patients with non-small cell lung cancer (NSCLC) receiving cisplatin-based chemotherapy. Genotyping of GSTP1 rs1695 and XRCC1 rs1799782, and rs25487 was conducted by polymerase chain reaction-restriction fragment length polymorphism analysis. By conditional logistic regression analysis, patients carrying the GG genotype of GSTP1 rs1695 and the AA genotype of XRCC1 rs25487 were found to be more highly associated with response to chemotherapy than were those carrying the AA genotype; the ORs (95%CIs) were 0.13 (0.04-0.37) and 3.37 (1.44-8.53), respectively. Presence of the GG genotype of GSTP1 rs1695 and the GA and AA genotypes of XRCC1 rs25487 was associated with overall survival of NSCLC, and the hazards ratios (95%CI) were 4.35 (1.40-17.92), 0.53 (0.31-0.91), and 0.39 (0.18-0.83), respectively. The results of our study suggest that the GSTP1 rs1695 and XRCC1 rs25487 polymorphisms might affect the clinical outcome of patients with advanced NSCLC receiving cisplatin-based chemotherapy.

[The value of high-definition intelligent endoscopy combined with stroboscopy in the diagnosis and treatment of vocal cord leukoplakia].

Objective: To evaluate the clinical value of high-definition intelligent endoscopy (iSCAN) combined with stroboscopy in identifying vocal cord leukoplakia. Methods: Seventy-nine patients with vocal cord leukoplakia who underwent CO2 laser laryngeal microsurgery and diagnosed by histopathology were recruited between October 2020 to August 2021. The morphological features, microvascular morphology and mucosal waves were observed by stroboscope; SPSS 20.0 software was used for statistical analysis. Results: There were 79 patients with a total of 119 lesions (56 on left and 63 on right).Pathological examination showed that 51 sides of the vocal cords were malignant lesions (severe dysplasia, carcinoma in situ and invasive carcinoma), and 68 sides were benign lesions.Under stroboscopy, 69 sides of mucosal wave were normal or slightly decreased, and 50 sides were severely decreased or disappeared.The decrease degree of mucosal wave was positively correlated with malignant lesions (ρ=0.687, P<0.001).Under iSCAN endoscopy, there was a positive correlation between the morphological changes of microvessels at the lesion site (vertical) and the malignant lesion (ρ=0.687, P<0.001).Univariate analysis showed that lesion size, thickness, uneven color, granular elevation, peripheral erythema and asymmetry were positively correlated with malignant lesions (ρ=0.530, 0.401, 0.538, 0.315, 0.497, 0.281, P<0.05).Logistic regression analysis showed that the risk of pathological malignancy with large lesions was 5.437 times higher than those of small lesions, the vertical vascular changes under iSCAN were 8.711 times higher than that of normal vascular morphology, and the severe reduction or disappearance of mucosal waves was 9.12 times higher than that of normal or mild reduction of mucosal waves. Conclusion: ISCAN can be combined with staphyloscopy to comprehensively observe and evaluate the changes of vocal cord morphology, submucosal microvessels and mucosal wave of vocal cord in patients with vocal cord leukoplosis, thus improving the ability to distinguish benign and malignant lesions.

Phase II study of pre-operative radiotherapy with capecitabine and oxaliplatin for rectal cancer and carcinoembryonic antigen as a predictor of pathological tumour response.

This study investigated the efficacy and tolerability of pre-operative radiotherapy with concurrent capecitabine and oxaliplatin in patients with rectal cancer. Forty-seven patients with rectal adenocarcinoma (stages T3 - T4; node-positive) were enrolled and received radiotherapy (46 Gy in 23 fractions) in combination with capecitabine (1000 mg/m(2) twice daily on days 1 - 14 and 22 - 35) and oxaliplatin (130 mg/m(2) on days 1 and 22) (XELOX regimen). The main endpoints were safety and efficacy, as assessed by pathological complete response (pCR). All patients received pre-operative chemoradiotherapy (CRT) as planned. The most common severe toxicity was diarrhoea (12.8%); post-operative complications were rare (9.8%). The pCR rate was 20.9% in all patients and 34.8% in patients with normal pre-CRT serum carcinoembryonic antigen (CEA < or = 5 ng/ml) level, compared with 5.0% in the patients with elevated CEA (> 5 ng/ml). In conclusion, pre-operative radiotherapy with concurrent XELOX regimen in rectal cancer patients is feasible and effective. Serum CEA may be a suitable predictor of pCR.

[The effect of monrustet on the exhalation of nitric oxide and inflammatory cytokines in patients with asthma combined with OSAHS].

Objective:To study the effect of monrustet on fractional exhaled nitric oxide and inflammatory cytokines in the elderly with bronchial asthma combined obstructive sleep apnea hypopnea syndrome.Method:150 cases diagnosed as asthma were enrolled in this study. The patients were divided into bronchial asthma combined with OSAHS (n=72)and bronchial asthma (n=78). According to the different treatment methods , patients were divided into observation group and control group. Two groups were given common treatment with inhaled corticosteroids, and the observation group was taken orally montrast 10mg/night additionally. The fractional exhaled nitric oxide was detected before and after treatment. Serum were collected for detection of tumor necrosis factor alpha (TNR-α), Creactive protein (CRP) and interleukin 6 (IL-6), according to the sleep monitoring results, the sleep apnea low ventilation index (AHI) was calculated, and the changes of FeNO level,CRP,TNR-α,IL-6 and AHI were analyzed in the two groups.Result:Before treatment, the gender, age, degree of disease, FeNO level,TNR-α, CRP,IL-6 and AHI differences were not statistically significant in the two groups (P>0.05).After treatment, both groups of FeNO, TNR-α,CRP,IL-6 and AHI decreased before treatment (P < 0.05).The observation group was lower than the control group, and the difference was statistically significant (FeNO level, AHIP< 0.01,TNR-α, CRP,IL-6 P< 0.05).Conclusion::Montelukast can reduce the FeNO level, the expression of TNR-α, CRP, and IL-6 of patients of bronchial asthma combined with OSAHS. Further improvement of the patient's condition, and provide reference value for the clinical medicine of patients with asthma.

[Effects of ketotifen on fractional exhaled nitric oxide in patients with combined allergic rhinitis and asthma syndrome].

Objective:To study effects of ketotifen on fractional exhaled nitric oxide in patients with combined allergic rhinitis and asthma syndrome.Method:One hundred and twelve patients with asthma were selected from department of respiration, Affiliated Hospital of North China University of science and technology from January 2016 to 2017 in March. Eighty-four patients with allergic rhinitis were selected as the subjects, Randomly divided into two groups,including observed group(n=42) and control group(n=42).The control group was treated with antitussive,expectorant and inhaled corticosteroids, while the observed group in the control group combined with ketotifen 1 mg 2/ day oral treatment,the changes of FeNO and IL-17 in the two groups were compared after one month treament.Result:Before treatment, two groups of patients in general IL-17 and fractional exhaled nitric oxide ware no significant difference(P> 0.05).After treatment, compared to the control group, the observed group was significantly more effective,the difference was statistically significant(P <0.05);fractional exhaled nitric oxide in treatment group were lower than those in control group, the difference was statistically significant(P<0.05,P< 0.01).And the observed group was lower than the control group, and the differences were statistically significant,t(P<0.05).Conclusion:Ketotifen significantly reduce the FeNO of allergic rhinitis and asthma syndrome, reduce airway inflammation.

Cytogenetic monitoring of petrochemical workers.

The frequencies of chromosomal aberrations and sister-chromatid exchanges (SCEs) in the peripheral blood lymphocytes of 360 persons, 180 workers in a petrochemical corporation and 180 appropriate controls, were studied. A significant increase in chromosomal aberrations and SCEs, compared to the control group, was observed in two sewage-treatment workshop workers; however, there were no significant differences between petrochemical workers from four workshops and a control group.

Prognostic factors in surgically managed gastrointestinal stromal tumours.

OBJECTIVE: To determine prognostic factors associated with survival in patients with surgically managed gastrointestinal stromal tumours (GISTs). METHODS: This retrospective study included 374 patients with pathologically confirmed GISTs. Medical records were reviewed and prognostic factors associated with adverse outcomes were determined. RESULTS: A total of 337 patients underwent complete resection with curative intent; 37 underwent incomplete resection. Overall mean survival time was 127.3 months; 5-year survival rate was 70.4%. Multivariate analyses determined that tumour size, risk status (of recurrence or metastasis) and surgical procedure were significant predictive factors for survival. There was a significant difference in the 5-year survival rate between patients who received adjuvant imatinib compared with those who did not (75.1% versus 13.8%). CONCLUSIONS: Patients with GISTs managed by surgical resection combined with targeted chemotherapy had a good prognosis. Clinical factors predictive of survival included tumour size, risk status and surgical procedure.

Circulating antibodies to carcinoembryonic antigen related to improved recurrence-free survival of patients with colorectal carcinoma.

This prospective study evaluated the prognostic value of antibodies to carcinoembryonic antigen (anti-CEA), detected by indirect immunosorbent assay, in the serum of colorectal carcinoma patients. Serum carcinoembryonic antigen (CEA) concentrations, measured by electrochemiluminescence immunoassay, were elevated in 26 (37.7%) of 69 patients with colorectal cancer and could not be detected among the 28 patients with benign intestinal conditions or 37 healthy individuals who comprised the control groups. Anti-CEA immuno globulin (Ig)G or IgM was detected by immunonephelometry in 44 (63.8%) patients with colorectal cancer, three (10.7%) with benign intestinal conditions and four (10.8%) healthy blood donors. Differences in antibody detection frequencies between the cancer patient group and the control groups were statistically significant. Titres of anti-CEA correlated significantly with CEA levels and Dukes' cancer stage. Antibody titre was an independent, significant, favourable predictor for 5-year recurrence-free survival. It is concluded that measurement of serum anti-CEA combined with CEA might be useful as a tumour marker and to assess prognosis. These results need to be confirmed in large, well-controlled, randomized clinical trials.

Relationship between the Kinetic Properties and the Small Subunit Composition of Nicotiana Ribulose-1, 5-bisphosphate Carboxylase.

Genetic variability in the large and small subunits of ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBPCase) in several Nicotiana species has been characterized by isoelectric focusing patterns. This heritable variation provides an opportunity to examine the functional role of each of these subunits. In this study, specifically designed RuBPCase enzymes composed of identical large subunits but different small subunits were constructed in vivo by interspecific hybridization between the species N. sylvestris, N. tabacum, N. glauca, N. glutinosa, N. plumbaginifolia, and N. tomentosiformis. Small subunit polypeptides were combined to form a sequence of one, two, three, and four polypeptides with the large subunit of N. sylvestris. Kinetic properties of these hybrid enzymes were compared. No differences in the specific activity of either carboxylation or oxygenation nor in K(m) values for ribulose 1,5-bisphosphate, CO(2), or O(2) were detected among the RuBPCase enzymes from the various interspecific hybrids. Likewise, the ratio of carboxylation to oxygenation was constant.

Sister chromatid exchange (SCE) frequencies differ between directly prepared cytotrophoblasts and cultured mesenchymal core cells.

Analysis of sister chromatid exchange (SCE) in chorionic villus cells may become useful in measuring the response of fetal tissues to clastogens or mutagens or for prenatal diagnosis of chromosome breakage syndromes such as Bloom syndrome. Previous studies have failed to analyze cytotrophoblastic cells and mesenchymal core cells, or have found no difference between SCE frequencies in directly prepared and cultured cells. Our data indicate significant differences in SCE frequencies between the two cell types: SCE frequency in directly prepared cytotrophoblasts was 6.73 SCE/cell +/- 1.6, whereas SCE frequency in cultured mesenchymal core cells was 10.31 SCE/cell +/- 0.49 (P less than 0.001). SCE analyses involving chorionic villi must take into account cell type.

Sister chromatid exchange frequency in directly prepared cytotrophoblasts: demonstration of in vivo deoxyribonucleic acid damage in pregnant women who smoke cigarettes.

Assessing frequency of sister chromatid exchange is a sensitive method of monitoring exposure to clastogens, mutagens, and other substances that induce deoxyribonucleic acid damage. Aware that cigarette smoke is associated with increased sister chromatid exchange in many cell types, we sought to determine whether an in vivo effect of cigarette smoke could be demonstrated by study of sister chromatid exchange in chorionic villus cells. Directly prepared cytotrophoblasts and cultured mesenchymal core cells were analyzed. Mean sister chromatid exchange frequency in cytotrophoblasts from smoking subjects (8.87 sister chromatid exchanges per cell) was significantly greater than in nonsmoking subjects (5.81 sister chromatid exchanges per cell; p less than 0.001); however, no significant difference in cultured mesenchymal core cells was found. Our results demonstrate that maternal exposure to cigarette smoke results in direct placental deoxyribonucleic damage, which in turn could explain deleterious effects of smoking on pregnancy. Increased sister chromatid exchange frequency was observed only in directly prepared cytotrophoblasts, showing the necessity of using this cell type to evaluate the effects of clastogens on placentas.