[Characteristics and diagnostic value of serum bile acids profile in pregnant women with intrahepatic cholestasis of pregnancy and asymptomatic hypercholanemia of pregnancy].

Objective: To analyze serum bile acid profiles in pregnant women with normal pregnancy, intrahepatic cholestasis of pregnancy (ICP) and asymptomatic hypercholanemia of pregnancy (AHP), and to evaluate the application value of serum bile acid profiles in the diagnosis of ICP and AHP. Methods: The clinical data of 122 pregnant women who underwent prenatal examination in Xuzhou Maternal and Child Health Care Hospital from June 2022 to May 2023 were collected, including 54 cases of normal pregnancy group, 28 cases of ICP group and 40 cases of AHP group. Ultraperformance liquid chromatography-tandem mass spectrometry was used to measure the levels of 15 serum bile acids in each group, including cholic acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), lithocholic acid (LCA), ursodeoxycholic acid (UDCA), glycolcholic acid (GCA), glycochenodeoxycholic acid (GCDCA), glycodeoxycholic acid (GDCA), glycolithocholic acid (GLCA), glycoursodeoxycholic acid (GUDCA), taurocholic acid (TCA), taurochenodeoxycholic acid (TCDCA), taurodeoxycholic acid (TDCA), taurolithocholic acid (TLCA) and tauroursodeoxycholic acid (TUDCA). Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to screen differential bile acids. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of differential bile acids and combined indicators between groups. Results: (1) Compared with normal pregnancy group, the serum levels of LCA, GCA, GCDCA, GDCA, GLCA, UDCA, TCA, TCDCA, TDCA, TLCA, GUDCA and TUDCA in ICP group were significantly different (all P<0.05), while the levels of LCA, DCA, GCA, GCDCA, GDCA, GLCA, TCA, TCDCA, TDCA, TLCA, GUDCA and TUDCA in AHP group were significantly different (all P<0.05). Compared with ICP group, the serum levels of CDCA, DCA, UDCA, TDCA, GUDCA and TUDCA in AHP group were significantly different (all P<0.05). (2) In the OPLS-DA model, the differential bile acids between ICP group and AHP group were TUDCA, TCA, UDCA, GUDCA and GCA, and their variable importance in projection (VIP) were 1.489, 1.345, 1.344, 1.184 and 1.111, respectively. TCA, GCDCA, GCA, TDCA, GDCA and TCDCA were the differentially expressed bile acids between AHP group and normal pregnancy group, and their VIP values were 1.236, 1.229, 1.197, 1.145, 1.139 and 1.138, respectively. (3) ROC analysis showed that the area under the curve (AUC) of TUDCA, TCA, UDCA, GUDCA and GCA in the differential diagnosis of ICP and AHP was 0.860, and the sensitivity and specificity were 67.9% and 95.0%, respectively. The AUC of TCA, GCDCA, GCA, TDCA, GDCA and TCDCA in the diagnosis of AHP was 0.964, and the sensitivity and specificity were 95.0% and 93.1%, respectively. Conclusions: There are differences in serum bile acid profiles among normal pregnant women, ICP and AHP. The serum bile acid profiles of pregnant women have potential application value in the differential diagnosis of ICP and AHP and the diagnosis of AHP.

[The value of quantitative flow ratio in the hemodynamic evaluation of myocardial bridge].

Objective: To explore the application value of quantitative flow ratio (QFR) in the hemodynamic evaluation of myocardial bridge and to preliminarily evaluate the correlation and related influencing factors between deformation quantitative flow ratio (D-QFR) and QFR. Methods: This is a cross-sectional study. Patients with CAG-confirmed simple myocardial bridge of the middle anterior descending coronary artery from June 2012 to June 2022 at the Air Force Medical Center were retrospectively included in this study. Systolic stenosis of mural coronary arteries (MCA) and myocardial bridge length were measured using quantitative coronary angiography. The patients were divided into mild stenosis group (<50% systolic stenosis) and moderate-to-severe stenosis group (≥50% systolic stenosis) according to the Nobel grading criteria. At different time periods (systolic and diastolic), the QFR values were measured at 3 locations (1 to 2 cm before the MCA entrance, the middle segment of the MCA, and 1 to 2 cm after the MCA exit), denoted as QFRa, QFRb, and QFRc, respectively, and the D-QFR values, incorporating vessel deformation information, were recorded. The MCA distal QFR≤0.8 in either stage was defined as an abnormal QFR value. QFR values were compared between the two groups at different locations and within each group. Factors associated with abnormal QFR values were analysed using multifactorial logistic regression. Spearman rank correlation analysis was used to examine the correlation between D-QFR values and systolic and diastolic QFR values.Multiple linear regression was used to analyse the factors associated with D-QFR. Results: A total of 83 patients were enrolled, including 58 males, aged (57.1±13.1) years. There were 48 cases in the mild stenosis group and 35 cases in the moderate-to-severe stenosis group, and the differences in systolic and diastolic QFRb and QFRc values between the two groups were statistically significant (all P<0.05). Within-group comparisons showed the values of QFRb and QFRc in the systolic phase were lower than those in the diastolic phase; QFRb and QFRc were both lower than QFRa during the same period (all P<0.05). Multifactorial logistic regression analysis showed that MCA systolic stenosis (OR=1.225, 95%CI 1.093-1.372, P<0.001) was an influential factor for abnormal QFR. D-QFR values were positively correlated with both systolic and diastolic QFR values (correlation coefficients were 0.849 and 0.675, respectively, both P<0.01). Multiple linear regression analysis showed that D-QFR values were negatively correlated with age (ß=-0.208, P=0.029), systolic stenosis (ß=-0.500, P<0.001), and myocardial bridge length (ß=-0.211, P=0.036). Conclusions: The QFR values in middle and distal of myocardial bridge decrease. The systolic stenosis rate of myocardial bridge is an important factor affecting QFR value. D-QFR is positively correlated with both systolic and diastolic QFR values. Age, myocardial bridge systolic stenosis rate and length are factors influencing the D-QFR values.

The age-dependent association of risk factors with pancreatic cancer.

BACKGROUND: Pancreatic cancer presents as advanced disease in >80% of patients; yet, appropriate ages to consider prevention and early detection strategies are poorly defined. We investigated age-specific associations and attributable risks of pancreatic cancer for established modifiable and non-modifiable risk factors. PATIENTS AND METHODS: We included 167 483 participants from two prospective US cohort studies with 1190 incident cases of pancreatic cancer during >30 years of follow-up; 5107 pancreatic cancer cases and 8845 control participants of European ancestry from a completed multicenter genome-wide association study (GWAS); and 248 893 pancreatic cancer cases documented in the US Surveillance, Epidemiology, and End Results (SEER) Program. Across different age categories, we investigated cigarette smoking, obesity, diabetes, height, and non-O blood group in the prospective cohorts; weighted polygenic risk score of 22 previously identified single nucleotide polymorphisms in the GWAS; and male sex and black race in the SEER Program. RESULTS: In the prospective cohorts, all five risk factors were more strongly associated with pancreatic cancer risk among younger participants, with associations attenuated among those aged >70 years. The hazard ratios comparing participants with three to five risk factors with those with no risk factors were 9.24 [95% confidence interval (CI) 4.11-20.77] among those aged ≤60 years, 3.00 (95% CI 1.85-4.86) among those aged 61-70 years, and 1.46 (95% CI 1.10-1.94) among those aged >70 years (Pheterogeneity = 3×10-5). These factors together were related to 65.6%, 49.7%, and 17.2% of incident pancreatic cancers in these age groups, respectively. In the GWAS and the SEER Program, the associations with the polygenic risk score, male sex, and black race were all stronger among younger individuals (Pheterogeneity ≤0.01). CONCLUSIONS: Established risk factors are more strongly associated with earlier-onset pancreatic cancer, emphasizing the importance of age at initiation for cancer prevention and control programs targeting this highly lethal malignancy.

[Study on parameters of robot-assisted ultrasonic drilling on bovine vertebral body].

Objective: To investigate the effect of ultrasonic parameter settings on maximum temperatures in the drilling site and penetration time and determine the most suitable parameters for efficient and safe robot-based ultrasonic bone drilling in spinal surgery. Methods: Five adult bovine thoracic and lumbar vertebrae specimens (T10-L6) were cut into 10 mm thick slices. A total of 50 slices were obtained. Among them, 30 and 20 slices were used for cancellous bone experiments and cortical bone experiments, respectively. In the cancellous bone experiment, the slices were randomly divided into three groups, corresponding to different feed rates of 0.8 mm/s, 1.6 mm/s, and 2.4 mm/s, respectively, with 10 slices in each group. The cancellous part of each slice was drilled 9 times with different output powers from 20% (48 W) to 100% (120 W). In the cortical bone experiment, the slices were randomly assigned into two groups, corresponding to a different feed rate (0.8 mm/s and 1.6 mm/s). Drilling was performed on the cortical part of each slice 4 times with different output power, which increased from 70% (84W) to 100% (120 W). All experiments were conducted at room temperature of 25 ℃. Maximum temperature and penetration time were recorded. The maximum grinding temperature and penetration time of cancellous bone and cortical bone under different output power and feed rate were compared. Results: At the same feed rate, the maximum temperature of the cancellous bone decreased as output power increased. There were statistically significant differences in the maximum temperature between the output powers of 120 W and 24 W under different feed rates(61.2 ℃±9.4 ℃ vs 70.9 ℃±5.7 ℃, 59.2 ℃±7.1 ℃ vs 69.5 ℃±10.7 ℃, 55.5 ℃±5.5 ℃ vs 69.2 ℃±9.3 ℃, all P<0.05). At the premise of the same output power, there was no significant difference in the maximum temperature among different feed rates (all P>0.05). At the feed rate of 0.8 mm/s, the maximum temperature of cortical bone decreased as the output power increased. The maximum temperature at the output power of 120 W was significantly lower than that of 84 W (P=0.048). However, at the feed rate of 1.6 mm/s, the maximum temperature could not be significantly lowered by the increase in output power (P>0.05). Under the same output power, the maximum temperature at the feed rate of 1.6 mm/s were all significantly lower than those of 0.8 mm/s (all P<0.05). The penetration time of cancellous bone did not decrease significantly with the increase in the output power (all P>0.05) while it decreased significantly as the feed rate increased (all P<0.05). Regarding cortical bone at the feed rate of 0.8 mm/s, the increase in output power could not shorten the penetration time (P>0.05); at the feed rate of 1.6 mm/s, the penetration time at the output power of 120 W was significantly shorter than that of 96 W (P=0.008). With the same output power, the penetration time at the feed rate of 1.6 mm/s were significantly shorter than those at 0.8 mm/s (all P<0.05). There was no statistical difference in the penetration failure rate among different feed rates with the same output power (all P>0.05). The penetration failure rate was 0 when the output power of cancellous bone was 48 W and above and the output power of cortical bone were 108 W and 120 W. Conclusions: The maximum temperature of vertebral cancellous bone and the cortical bone is primarily influenced by the output power and the feed rate, respectively; the penetration time of cancellous bone and the cortical bone is affected by the feed rate and both of feed rate and output power, respectively. The most suitable parameters are output power of 120 W and feed rate of 2.4 mm/s for cancellous bone and output power of 120 W and feed rate of 1.6 mm/s for cortical bone.

[Risk assessment of Cronobacter sakazakii in infant formula powder].

Objective: To assess the risk of foodborne diseases caused by Cronobacter sakazakii in infant formula powder from retail to feeding and provide formulate suggestions for safe feeding of infants at home. Methods: This study used the special monitoring and risk monitoring data of infant formula powder in Heilongjiang Province and combined data at home and abroad. The @RISK software was used to evaluate the disease risk caused by Cronobacter sakazakii in the process of infant formula powder from retail to feeding. Results: According to the results of this quantitative risk assessment, the risk of foodborne diseases caused by Cronobacter sakazakii at the current consumption pattern in Heilongjiang Province was 5.158×10-5 persons/million (40.0 ℃ and 50.0 ℃), 1.072×10-7 persons/million (60.0 ℃), 5.544×10-14 persons/million (70.0 ℃). When the feeding time of infant formula powder was adjusted to 0-2 h and 2-3 h respectively, the above prediction results did not change. When it was adjusted to 3-4 h, the risk increased. If it was adjusted to 4-24 h, the number of Cronobacter sakazakii increased by 14-24 orders of magnitude at room temperature. If the initial pollution concentration (after flushing) was adjusted to 1 MPN/ml, the average disease risk per meal was 805.7 persons/million (40.0 ℃ and 50.0 ℃), 1.7 persons/million (60.0 ℃) and 9.1 × 10-7 persons/million (70.0 ℃). The results of sensitivity analysis showed that the water temperature (70.0 ℃), initial pollution concentration, room storage time and temperature were important factors of risk. Conclusion: Controlling the contamination level of Cronobacter sakazakii in infant formula powder, controlling the feeding time within 3 h, storing in refrigerator and mixing with water with temperature not lower than 70.0 ℃ are effective measures to prevent infants from eating infant formula powder infected by Cronobacter sakazakii.

[A 10-year follow-up study of indications for artificial cervical disc replacement].

Objective: To investigate the influence of the preoperative factors on the segmental range of motion (ROM) during long-term follow-up after artificial cervical disc replacement (ACDR), so as to further improve the selection of surgical indications for ACDR. Methods: Retrospective analysis was performed on 71 patients with cervical degenerative diseases who underwent single-segment Bryan ACDR in Beijing Jishuitan Hosptial from December 2003 to December 2008, and a 10-year clinical follow-up was conducted. Among the patients, 44 were males and 27 were females, with a mean age of (45±8) years at operation. The mean follow-up time was (129±14) months. Preoperative and follow-up imaging evaluation including measurement of the segmental range of motion (ROM) by cervical X-ray, and preoperative height of intervertebral space was measured by cervical lateral X-ray. According to CT and coronal reconstruction, the grade of paravertebral ossification (PO) was assessed. Clinical symptoms assessment including the Japanese Orthopaedic Association scoring (JOA), the Neck Disability Index (NDI) evaluation was performed preoperatively. Multivariate logistic regression analysis was used to analyze the influencing factors of the range of motion of the surgical segment during follow-up. The best cut-off value was calculated by receiver operating characteristic (ROC) curve. Results: The preoperative and follow-up ROM at the operated segment was 9.7°±4.5° and 8.7°±5.4°, respectively (P>0.05). Univariate analysis revealed that the postoperative segmental ROM was not significantly correlated with the factors including the surgical level, gender, age, and preoperative clinical diagnosis (1: Radiculopathy; 2: Myelopathy; 3: Mixed type), preoperative segmental ROM, preoperative JOA score and preoperative NDI score (all P>0.05), and was significantly correlated with imaging diagnosis (1: cervical disc herniation; 2: degenerative cervical stenosis), preoperative PO grade (both P<0.05). The multi-factor analysis showed that preoperative segmental ROM (OR=1.228, 95%CI:1.012-1.489, P<0.05) and PO grade (OR=0.190, 95%CI: 0.085-0.424, P<0.05) had significance in the overall test, but imaging diagnosis had no significance in the overall test (P>0.05). The optimal cutoff value of preoperative segmental ROM and PO grade was 9.185° and grade 2.5 assessed by ROC curve, and the area under the ROC curve was 0.86 and 0.72, respectively. Conclusions: ACDR surgery can achieve satisfactory long-term effects for patients with nerve root type, spinal cord type and mixed type cervical degenerative diseases, and effectively retain the overall ROM of the cervical spine and the ROM of replacement segments. Patients with good preoperative segmental ROM and lower PO levels have a greater chance of obtaining good segmental ROM in the long-term postoperatively.

[Clinical characteristics of severe pre-eclampsia in a single tertiary referral center].

Objective: To explore the feasibility and key point of improvement in preventing and postponing the onset of severe pre-eclampsia (SPE) and its severe complications in the tertiary referral system by analyzing the clinical characteristics of SPE in a single tertiary referral center. Methods: The clinical data of 217 patients with SPE who were hospitalized and terminated pregnancy in Peking University Third Hospital from January 2020 to December 2020 were retrospectively analyzed. The risk factors, clinical characteristics and severe complications of SPE between the patients referred from primary hospitals (referral group) and the patients received regular prenatal care in the tertiary referral center (central group) were compared, as well as the influence of the referral timing on the characteristics and perinatal outcome. Results: (1) Clinical characteristics: among the 217 cases of SPE, 84 cases were in the referral group and 133 cases were in the central group. The gestational ages at SPE clinical diagnosis [31.5 weeks (28.1-34.6 weeks) vs 35.6 weeks (33.3-37.2 weeks); Z=-6.547, P<0.01], termination of pregnancy [32.3 weeks (29.5- 35.1 weeks) vs 36.3 weeks (34.4-37.5 weeks); Z=-6.554, P<0.01] and onset of SPE severe complications [30.6 weeks (26.4-32.7 weeks) vs 34.9 weeks (32.7-36.5 weeks); Z=-4.040, P<0.01] in the referral group were significantly earlier than those in the central group, the rates of ICU [10.7% (9/84) vs 3.8% (5/133); χ²=4.126, P=0.042] and neonatal ICU hospitalization [72.9% (51/70) vs 54.7% (70/128); χ²=6.286, P=0.012] were higher than those in the central group, while the live birth rate [83.3% (70/84) vs 96.2% (128/133); χ²=10.736, P=0.001] was lower than that of the central group. (2) Analysis of risk factors: for the patient whose risk factors were obesity, advanced age or pre-eclampsia history, the gestational ages at SPE clinical diagnosis and termination of pregnancy in the referral group were significantly earlier than those in the central group (P<0.05). For those with chronic hypertension, the gestational ages at severe complications onset in the referral group were significantly later than those in the central group (P<0.05). For those without obvious risk factors, the gestational ages at SPE clinical diagnosis, termination of pregnancy and onset of SPE severe complications in the referral group were earlier than those in the central group (P<0.05). (3) Analysis of severe complications: the top three severe complications in the referral group and the central group were hypertensive encephalopathy/cerebrovascular accident [20.2% (17/84) vs 7.5% (10/133)], HELLP syndrome [7.1% (6/84) vs 8.3% (11/133)] and placental abruption [8.3% (7/84) vs 7.5% (10/133)]. The rate of hypertensive encephalopathy/cerebrovascular accident in the referral group was significantly higher than that in the central group (χ²=7.645,P=0.006). (4) Analysis of referral timings: the timings included referral after onset of SPE severe complications (8.3%, 7/84), referral after onset of SPE (67.9%, 57/84), referral after detection of SPE early warning signs (14.3%, 12/84) and referral after detection of SPE risk factors in the 2nd and 3rd trimester (9.5%, 8/84). The earlier the referral, the longer the interval from clinical diagnosis to onset of severe complications, from referral to termination of pregnancy, and from referral to severe complications onset (P<0.05). The earlier the referral, the lower the NICU hospitalization rates, the higher the live birth rates. The ICU hospitalization rate of referrals after severe complications onset was significantly higher than those of the other three referral timing groups (P<0.05). Conclusions: SPE occurs in hospitals of different levels. Although tertiary referral center may postpone the onset of SPE and its severe complications, reduce the severity of SPE and prolong the gestational age, its awareness of prevention and control still needs to be further improved. Early identification of the risk of SPE and timely referral are important parts of improving SPE adverse outcomes in primary medical institutions. The significance and value of referral system need to be brought into full play.

[Homology analysis and clinical infection characteristics of hypervirulent Klebsiella pneumonia].

Objective: The hvKP phenotype strains were screened from the sensitive and multi-drug resistant Klebsiella pneumoniae, and the distribution and homology of their clinical infection characteristics were compared. Methods: A total of 158 Klebsiella pneumoniae strains isolated from clinical infection specimens in the Third Affiliated Hospital of Sun Yat-sen University from 2014 to 2018 were retrospectively collected. The string test (ST) was used to screen the hvKP infection, and a total of 65 were screened. The number of patients included 51 males and 14 females, with an average age of 56 years. The composition ratio of Klebsiella pneumoniae was analyzed for clinical infection related information. Matrix assisted laser desorption-ionization time of flight mass spectrometry (MALDI-TOF MS) was used to identify the hypervirulent Klebsiella pneumoniae and establish a new database, and bio-tree cluster analysis and principal component analysis were carried out for all strains that met the experimental conditions by using analysis software and the homology of protein level was obtained. Results: A total of 65 strains hvKP were screened, 62 of which were susceptible strains and 3 were multi-drug resistant strains. The main diseases of infected patients were diagnosed as hepatobiliary disease, encephalopathy and liver abscess. The basic diseases of the population were mainly diabetes and hypertension. Dendrogram cluster analysis divided hvKP into 3 groups at a distance of 550 from the horizontal line; principal component analysis found that some strains were closely related, and the Kc group with the largest proportion was mainly related to hepatobiliary diseases. Ka group was mainly related to infection after surgery. Conclusions: HvKP was highly invasive and the clinical manifestations of infection were diverse. The infected patients were mostly elderly patients with weakened immunity. The rapid homology analysis of MALDI-TOF MS mass spectrometry has important clinical significance for the rapid screening of hvKP infection.

[The relationship between migration time and the prevalence of myopia of children and adolescents aged 6-18 years old in Shenzhen].

Objective: To analyze the relationship between migration time and the prevalence of myopia of children and adolescents aged between 6 and 18 years old in Shenzhen. Methods: From April to May 2019, 26 618 children and adolescents from 14 schools in six streets of Baoan District, including Fuyong, Shajing, Xin'an, Xixiang, Songgang and Shiyan, were included in the study by using random cluster sampling method. The demographic characteristics, migration status, self-reported myopia, screen time in the last seven days, outdoor activities in the last one month and other information were collected through the questionnaire. The differences of myopia among children and adolescents with different characteristics were compared by χ2 test, and the relationship between migration time and the prevalence of myopia was analyzed by multivariate unconditional logistic regression model. Results: The age of 26 618 study participants was (12.37±3.49) years old, and the overall prevalence of myopia was 49.4%. Multivariate logistic regression analysis showed that after controlling for relevant confounding factors, compared with migrant children and adolescents of migrant workers who migrated for 1-2 years, those of migrant workers who had migrated for more than 6 years had a higher risk of myopia [OR (95%CI): 1.48 (1.14-1.92)]. After being grouped by phase of school, in the lower grade group of primary school, the children and adolescents of migrant workers who had migrated for more than 6 years had a higher risk of myopia compared with those of migrant workers who migrated for 1-2 years [OR (95%CI): 1.96 (1.20-2.74)]. In the high school group, compared with the children and adolescents of migrant workers who migrated for 1-2 years, those of migrant workers who had migrated for 3-5 years and ≥6 years had a higher risk of myopia [OR (95%CI): 6.03 (1.29-28.15) and 6.52 (1.51-28.11), respectively]. Conclusion: The migration time is related to the prevalence of myopia of the children and adolescents of migrant workers.

[Clinical outcome of therapeutic cervical cerclage in short cervix syndrome].

Objective: To investigate the clinical effect of therapeutic cervical cerclage on short cervix syndrome for anti-premature birth in the second trimester. Methods: Totally 44 singleton pregnant patients were diagnosed as short cervix syndrome, which was cervical length ≤2.5 cm without cervical dilatation, and received treatment from January 2008 and July 2015 in Peking University Third Hospital were collected. Among them, 30 patients who received therapeutic cervical cerclage were defined as cerclage group and another 14 cases who received conservative treatment were defined as un-cerclage group. The days of conservative treatment, delivery rate of different gestational weeks, birth weight of newborns, neonatal survival rate within 7 days of birth were analyzed between the two groups. Results: There were no significant differences between the two groups in days of pregnancy conservative treatment [103 (84-141) vs 105 (85-114) days], delivery weeks [38.0 (35.5-39.4) vs 38.5 (37.3-39.5) weeks], birth weight of newborns [3 120 (2 750-3 400) vs 3 130 (2 760-3 545) g], and survival rate of newborns [100% (30/30) vs 13/14]. The fetuses of both groups were all delivered after 28 weeks. There was no significant difference in accumulated delivery rate between the two groups after 32 weeks, 34 weeks, and 37 weeks, respectively (all P>0.05) . Conclusions: The treatment of cervical cerclage is not superior to conservative means in single pregnancy of cervical length ≤2.5 cm without cervical dilatation. For such patients with short cervix syndrome, the treatment of cervical cerclage may not be necessary, but dynamic monitoring and search for the causing factors and prompt treatment are more important.

[Autophagy regulated by JWA influenced sensitivity of esophageal cancer to cisplatin].

Objective: To explore the effect of JWA on cisplatin sensitivity and its potential molecular mechanism in esophageal cancer. Methods: The siRNA was used to inhibit the JWA expression, then cisplatin sensitivity and LC3 (autophagy related protein) expression levels were observed in TE1 cells.Further, the effect of autophagy inhibitor tamoxifen (3-MA) on above process was determined.Cisplatin sensitivity of 20 fresh esophageal cancer samples was evaluated by histoculture drug response assay (HDRA). Result: Silencing JWA gene increased the sensitivity of TE1 cells to cisplatin (P<0.05), and decreased the LC3-Ⅰ and LC3-Ⅱ proteins induced by cisplatin.Furthermore, combined with 3-MA increased the inhibition rate of cisplatin in JWA silencing group (P<0.05). Additionally, the inhibition rate of cisplatin on tissues with low JWA expression were higher than those with high expression (45.6% vs 25.6%, P=0.005). Conclusions: JWA could influence the cisplatin sensitivity by regulating autophagy in esophageal cancer.

A binary concrete crack self-healing system containing oxygen-releasing tablet and bacteria and its Ca2+-precipitation performance.

A strategy to supply molecular oxygen for microbial calcium precipitation was developed for the first time. Firstly, a controlled oxygen-releasing tablet (ORT) containing CaO2 and lactic acid with a suitable ratio of 9:1 was developed. It can provide a stable oxygen supply and maintain pH in the range of 9.5-11.0 for 45 days while contacting with water. In the presence of oxygen, a self-healing bacterium H4 spores germinated more effectively and maintained high metabolic activity. Furthermore, H4 vegetative cells induced 50 % more calcium precipitation than that obtained without oxygen supply. Finally, a binary self-healing system containing bacterial spores and ORT was established. The calcium precipitation experiments showed that H4 in the binary self-healing system precipitated 27.5 mM calcium with oxygen supply after 32 days and dissolved oxygen (DO) concentration of the solution decreased from 15 to 4 mg l-1, while only 6.9 mM calcium precipitation was obtained without oxygen supply. This work can disclose the effect of oxygen on microbial calcium precipitation and further lay a foundation for the establishment of ternary self-healing system containing bacteria, ORT, and nutrients, which will be promising for the self-healing of cracks deep inside the concrete structure.

Identification of hub genes and pathways associated with retinoblastoma based on co-expression network analysis.

The objective of this paper was to identify hub genes and pathways associated with retinoblastoma using centrality analysis of the co-expression network and pathway-enrichment analysis. The co-expression network of retinoblastoma was constructed by weighted gene co-expression network analysis (WGCNA) based on differentially expressed (DE) genes, and clusters were obtained through the molecular complex detection (MCODE) algorithm. Degree centrality analysis of the co-expression network was performed to explore hub genes present in retinoblastoma. Pathway-enrichment analysis was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Validation of hub gene expression in retinoblastoma was performed by reverse transcription-polymerase chain reaction (RT-PCR) analysis. The co-expression network based on 221 DE genes between retinoblastoma and normal controls consisted of 210 nodes and 3965 edges, and 5 clusters of the network were evaluated. By assessing the centrality analysis of the co-expression network, 21 hub genes were identified, such as SNORD115-41, RASSF2, and SNORD115-44. According to RT-PCR analysis, 16 of the 21 hub genes were differently expressed, including RASSF2 and CDCA7, and 5 were not differently expressed in retinoblastoma compared to normal controls. Pathway analysis showed that genes in 2 clusters were enriched in 3 pathways: purine metabolism, p53 signaling pathway, and melanogenesis. In this study, we successfully identified 16 hub genes and 3 pathways associated with retinoblastoma, which may be potential biomarkers for early detection and therapy for retinoblastoma.

Emerging Yr26-Virulent Races of Puccinia striiformis f. tritici Are Threatening Wheat Production in the Sichuan Basin, China.

Stripe rust, caused by Puccinia striiformis f. tritici, is one of the most destructive diseases of wheat in the world. The Sichuan Basin is one of the most important regions of wheat production and stripe rust epidemics in China. Stripe rust resistance gene Yr26 (the same gene as Yr24) has been widely used in wheat breeding programs and in many cultivars grown in this region since the gene was discovered in the early 1990s. Virulence to Yr26 has increased in frequency since its first detection in 2008. The objective of this study was to assess the vulnerability of the wheat cultivars and breeding lines in the Sichuan Basin to Yr26-virulent races. In total, 85 wheat accessions were tested with Yr26-avirulent races CYR32, CYR33, and Su11-4 and two Yr26-virulent races, V26/CM42 and V26/Gui22. DNA markers for Yr26 were used to determine the presence and absence of Yr26 in the wheat accessions. Of the 85 wheat accessions, only 5 were resistant and 19 susceptible to all races tested, and the remaining 61 were resistant to at least one or more races tested in seedling stage. In all, 65 (76.5%) accessions were susceptible to the emerging Yr26-virulent race V26/Gui22. In field tests, susceptible accessions increased from 31.8% in a nursery inoculated with predominant and Yr26-avirulent races to 61.2% in the nursery inoculated with the predominant races mixed with V26/Gui22. Based on the results of the molecular marker and race tests, 33 (38.8%) accessions were determined to have Yr26, showing that the Yr26 virulence is a major threat to wheat production in the Sichuan Basin and potentially in other regions of China.

Characterization and molecular mapping of stripe rust resistance gene Yr61 in winter wheat cultivar Pindong 34.

KEY MESSAGE: We report a new stripe rust resistance gene on chromosome 7AS in wheat and molecular markers useful for transferring it to other wheat genotypes. Several new races of the stripe rust pathogen have established throughout the wheat growing regions of China in recent years. These new races are virulent to most of the designated seedling resistance genes limiting the resistance sources. It is necessary to identify new genes for diversification and for pyramiding different resistance genes in order to achieve more durable resistance. We report here the identification of a new resistance gene, designated as Yr61, in Chinese wheat cultivar Pindong 34. A mapping population of 208 F2 plants and 128 derived F2:3 lines in a cross between Mingxian 169 and Pindong 34 was evaluated for seedling stripe rust response. A genetic map consisting of eight resistance gene analog polymorphism (RGAP), two sequence-tagged site (STS) and four simple sequence repeat (SSR) markers was constructed. Yr61 was located on the short arm of chromosome 7A and flanked by RGAP markers Xwgp5467 and Xwgp5765 about 1.9 and 3.9 cM in distance, which were successfully converted into STS markers STS5467 and STS5765b, respectively. The flanking STS markers could be used for marker-assisted selection of Yr61 in breeding programs.

QTL verification of grain protein content and its correlation with oil content by using connected RIL populations of high-oil maize.

Maize with high grain protein and oil contents offers great advantages for human food and animal feed. In this study, grain protein contents of 282 and 263 F7:8 recombinant inbred lines (RILs) of 2 crosses were evaluated in 4 environments within and between populations. The RILs were developed from crosses between an inbred high-oil maize line and 2 normal dent inbred maize lines. A total of 16 single-population QTLs and 19 joint-population QTLs were identified for protein content, and 21 QTLs were detected for protein-oil in each of the 4 environments tested and in combination. Most of the QTLs for protein content were greatly influenced by variation among populations and environments. Seven QTLs showed generational consistency compared with QTLs detected in the 2 F2:3 populations. However, 7 and 6 QTLs were detected in only the RIL and F2:3 populations, respectively. Protein and protein-oil QTLs with the same parental effects were detected at bins 3.03-3.05, 5.04-5.06, 6.03-6.05, 8.03-8.04, and 8.04-8.06, demonstrating that tightly linked and/or pleiotropic QTLs are controlling both traits at these bins. Four single-population QTLs and 11 joint-population QTLs identified at bins 3.02-3.03, 3.05, 7.01, 8.02, 8.03, 8.04-8.05, 8.05, 9.03, and 9.05 with intervals <5 cM could be used in marker-assisted selection. Along with the previously detected QTLs qPRO1-8-1 and qPRO1-5-1 at bins 8.03-8.04 and 5.02-5.04, the QTLs detected herein could be used to develop near isogenic lines and chromosome segment substitution lines in future studies.

Effects of growth differentiation factor 9 and bone morphogenetic protein 15 on the in vitro maturation of porcine oocytes.

Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) are members of the transforming growth factor-ß (TGF-ß) family, and their roles in oocyte maturation and cumulus expansion are well known in the mouse and human, but not in the pig. We investigated GDF9 and BMP15 expressions in porcine oocytes during in vitro maturation. A significant increase in the mRNA levels of GDF9 and BMP15 was observed at germinal vesicle breakdown, with expression levels peaking at metaphase I (MI), but decreasing at metaphase II (MII). GDF9 and BMP15 protein localized to the oocyte cytoplasm. While treatment with GDF9 and BMP15 increased the expression of genes involved in both oocyte maturation (c-mos, cyclinb1 and cdc2) and cumulus expansion (has2, ptgs2, ptx3 and tnfaip6), SB431542 (a TGFß-GDF9 inhibitor) decreased meiotic maturation at MII. Following parthenogenetic activation, the percentage of blastocysts in SB431542 treatment was lower than in the control (41.3% and 74.4%, respectively). Treatment with GDF9 and BMP15 also increased the mRNA levels of maternal genes such as c-mos [a regulatory subunit of mitogen-activated protein kinase (MAPK)], and cyclinb1 and cdc2 [regulatory subunits of maturation/M-phase-promoting factor (MPF)]; however, SB431542 significantly decreased their mRNA levels. These data were supported by poly (A)-test PCR and protein activity analyses. Our results show that GDF9 and BMP15 participate in cumulus expansion and that they stimulate MPF and MAPK activities in porcine oocytes during in vitro maturation.

Bioinformatic analysis of endothelial progenitor cells exposed to folic acid in type 1 diabetes mellitus.

We investigated the effects of type 1 diabetes mellitus (T1DM) on endothelial progenitor cells (EPCs) at the molecular level and assessed the therapeutic potential of folic acid (FA) in DM. We downloaded the gene expression profile of the EPCs from T1DM patients before and after treatment with FA and from healthy controls. We identified the differentially expressed genes (DEGs) in the EPCs from T1DM patients before and after a four-week period of FA treatment and compared them with those obtained from the healthy subjects by using limma package in R language. Then, functional annotation of the DEGs was performed using the online tool Database for Annotation, Visualization and Integrated Discovery (DAVID) based on the Kyoto Encyclopedia of Genes and Genomes database. The expression of 696 genes was altered in the EPCs from T1DM patients compared to those from the healthy controls. These genes were mainly involved in the pathways associated with immune response. FA can normalize majority of the altered gene expression profiles of EPCs from T1DM patients to resemble those of healthy subjects, albeit with some side effects. FA can be a potential therapeutic agent for the treatment of T1DM. However, focused efforts are required to ensure that the dose of FA falls within the permissible pharmacological range.

Choice of microsatellite markers for identifying homozygosity of mitotic gynogenetic diploids in Japanese flounder Paralichthys olivaceus.

A set of 72 microsatellite markers distributed evenly among 24 linkage groups were selected from the published genetic linkage maps of Japanese flounder Paralichthys olivaceus. In two normal diploid full-sib families, the test for Mendelian inheritance showed that genotypic segregation deviations were not significant at all analysed loci. To estimate microsatellite-centromere map distances, four meiotic gynogenetic diploid lines were produced by the activation of eggs using UV irradiated sperm of red seabream Pagrus major and cold-shock treatment to block the extrusion of the second polar body. Under the assumption of complete interference, 21 markers were located in the centromeric region, 39 in the telomeric region and the rest in the intermediate region of linkage groups. A total of 192 mitotic gynogenetic diploids from one spawn were identified by these markers. Genotype analysis showed that the number of homozygous individuals decreased as microsatellite-centromere map distance increased on each linkage group.