Pediatric Cardiology Fellowship Standards for Training in Exercise Medicine and Curriculum Outline.

Over the past 2 decades, fundamentals of exercise medicine, including clinical exercise testing, assessment and promotion of physical activity, exercise prescription, and supervised exercise training/rehabilitation programming have demonstrated considerable clinical value in the management of children and adolescents with congenital and acquired heart disease. Although the principles of exercise medicine have become an integral component in pediatric cardiology, there are no standardized training recommendations for exercise physiology during pediatric cardiology fellowship at this time. Thus, the Pediatric Cardiology Exercise Medicine Curriculum Committee (PCEMCC) was formed to establish core and advanced exercise physiology training recommendations for pediatric cardiology trainees. The PCEMCC includes a diverse group of pediatric cardiologists, exercise physiologists, and fellowship program directors. The expert consensus training recommendations are by no means a mandate and are summarized herein, including suggestions for achieving the minimum knowledge and training needed for general pediatric cardiology practice.

[A multicenter study to test the reliability and validity of the frailty assessment scale for elderly patients with inguinal hernia and to evaluate the value of clinical application].

Objectives: To verify the reliability and validity of the frailty assessment scale for elderly patients with inguinal hernia and to evaluate the value of its clinical application. Methods: A convenience sampling method was used to collect 129 geriatric patients who underwent inguinal hernia surgery from January 2018 to January 2023 in nine hospitals in Liaoning Province. There were 120 males and 9 females, of whom 89 patients were 60 to <75 years old, 33 patients were 75 to <85 years old and 7 patients were ≥85 years old. The 129 patients included 11 elderly patients with inguinal hernia who had recovered from preoperative infection with COVID-19. Statistical methods such as Cronbach's coefficient, Kaiser-Meyer-Olkin test, Bartlett's test, Pearson's correlation analysis, etc. were calculated to verify the reliability indexes such as feasibility, content validity, structural validity, criterion-related validity, internal consistency reliability, and re-test reliability. Taking the 5-item modified frailty index (5-mFI) as the gold standard, the area under the curve was used to analyze the ability of the two scales to predict the occurrence of postoperative acute urinary retention, postoperative delirium, poor incision healing, operative hematoma seroma, and postoperative complications. Results: The frailty assessment scale for elderly patients with inguinal hernia showed good reliability and validity (valid completion rate of 99.2%; item content validity index of 1.000, and the scale content validity index of 1.000; exploratory factor analysis extracted a total of 1 principal component, and factor loadings of each item of 0.565 to 0.873; the AUC for frailty diagnosis using 5-mFI as the gold standard of 0.795 (P<0.01) Cronbach's coefficient of 0.916, retest reliability coefficient of 0.926), it could effectively predict postoperative acute urinary retention, delirium, hematoma seroma in the operative area and total complications (AUC of 0.746, 0.870, 0.806, and 0.738, respectively; all P<0.05), and prediction efficiency was higher than that of 5-mFI (AUC of 0.694, 0.838, 0.626 and 0.641, P<0.05 for delirium only), but both scales were inaccurate in predicting poor incision healing (AUC of 0.519, P=0.913 for the frailty assessment scale and 0.455, P=0.791 for the 5-mFI). Conclusions: The frailty assessment scale for elderly patients with inguinal hernia is reliable and significantly predicts the occurrence of postoperative adverse events in elderly inguinal hernia patients. The scale can also be used for preoperative frailty assessment in elderly patients with inguinal hernia after rehabilitation from COVID-19 infection.

First Measurement of High-Energy Reactor Antineutrinos at Daya Bay.

This Letter reports the first measurement of high-energy reactor antineutrinos at Daya Bay, with nearly 9000 inverse beta decay candidates in the prompt energy region of 8-12 MeV observed over 1958 days of data collection. A multivariate analysis is used to separate 2500 signal events from background statistically. The hypothesis of no reactor antineutrinos with neutrino energy above 10 MeV is rejected with a significance of 6.2 standard deviations. A 29% antineutrino flux deficit in the prompt energy region of 8-11 MeV is observed compared to a recent model prediction. We provide the unfolded antineutrino spectrum above 7 MeV as a data-based reference for other experiments. This result provides the first direct observation of the production of antineutrinos from several high-Q_{ß} isotopes in commercial reactors.

[Endovascular abdominal aortic aneurysm repair with a new stent graft:early results from a multicenter study].

Objective: To examine the safety and effectiveness of a new stent graft system for endovascular repair of abdominal aortic aneurysm(AAA). Methods: This is a prospective,multi-center,single-arm clinical trial. The patients with AAA treated with a new stent graft system were enrolled at 21 centers from September 2018 to September 2019 in China. Follow-up was performed before discharge, and at 30, 180, 360 days after operation, respectively. The primary safety endpoint was the incidence of major adverse events(MAE) within 30 days. The primary efficacy endpoint was the success rate of AAA treatment at 360 days. Secondary safety endpoints were the incidence of perioperative access complications and acute lower limb ischemia,all-cause mortality, AAA related mortality and incidence of serious adverse events (SAE) at 180 and 360 days. Secondary efficacy endpoints were the incidence of type Ⅰ or Ⅲ endoleak,stent displacement,and conversion to open surgery or re-intervention at 180 and 360 days. Results: One hundred and fifty-six patients were enrolled,including 137 males and 19 females. The age was (68.9±6.9) years (range:48.2 to 84.6 years).Maximum aneurysm diameter was (50.8±11.2) mm (range:25.0 to 85.0 mm),diameter of proximal landing zone was (21.2±2.5) mm (range:17.0 to 29.5 mm),and length of proximal landing zone was (31.4±13.0) mm (range:11.0 to 75.0 mm).The incidence of MAE was 1.3% (2/156) at 30 days,both were all-cause death cases. The success rate of AAA treatment was 88.5% (138/156) at 360 days. No perioperative access complication and acute lower limb ischemia occurred. All-cause mortality was 2.0% (3/154) at 180 days and 2.6% (4/153) at 360 days,and there was no AAA related death. The incidence of SAE was 23.0%(35/152) at 180 days and 30.5%(46/151) at 360 days, and no device-related SAE occurred. The incidence of type Ⅰor Ⅲ endoleak was 3.4% (5/147) at 180 days and 3.5% (5/144) at 360 days. Conclusion: The new stent graft system is easy to operate,and early-term safety and effectiveness results are expected.

[Choices of emergency treatment and surgical method for ruptured abdominal aortic aneurysms].

Objective: To investigate the emergency management process of ruptured abdominal aortic aneurysm (RAAA), and analyze the perioperative mortality factors of different surgical methods. Methods: The emergency data and hospitalization data of 91 patients with ruptured abdominal aortic aneurysm in Xiangya Hospital of Central South University from June 2010 to June 2019 were retrospectively analyzed.Twelve of the patients died preoperatively due to excessive blood loss, and the remaining 79 patients were hospitalized for open surgery (OSR) or endovascular repair (EVAR).The differences in age, time to hospital arrival, emergency preparation time, first creatinine value, emergency infusion volume, preoperative drop in blood pressure, preoperative use of vasoactive drugs and iliac artery involvement were compared between preoperative death group (n=12) and preoperative survival group (n=79), OSR group (n=50) and EVAR group (n=29), postoperative death group (n=23) and postoperative survival group (n=56). Results: Seventy-nine patients received open surgery or endovascular repair, and 23 died after operation. Age, time to hospital arrival, first creatinine value and emergency infusion volume were (77±11) years, (18±5)h, (469±150) µmol/L, (4 140±1 743) ml in the preoperative death group and (70±10) years, (12±8) h, (228±174) µmol/L, (1 358±1 211) ml in the preoperative survival group, respectively, and the differences were statistically significant (all P<0.05). There were no significant differences in preoperative data, intraoperative treatment and postoperative perioperative mortality between the open surgery group and the endovascular repair group (all P>0.05). The intraoperative blood loss, operation time and aortic occlusion rate in the endovascular repair group were 100 (50, 175) ml, (3.2±0.9) h, 13.8%, respectively, which were better than that in the open surgery group 1700 (600, 3425) ml, (5.2±1.1) h, 100%. The differences were statistically significant (all P<0.05). Age, emergency preparation time, first creatinine value, emergency infusion volume, blood pressure decline rate and vasoactive drug utilization rate in the death group were (77±8) years, (4.1±1.7) h, (456±172) µmol/L, (2 024±1 687) ml, 100%, 100%, respectively, and (68±10) years, (2.7±2.2) h, (135±26) µmol/L, (1 085±825) ml, 21.4%, 12.5% in the survival group, respectively. The differences were statistically significant (all P<0.05). Conclusions: Age, emergency preparation time, first creatinine value, emergency infusion volume, decreased blood pressure and use of vasoactive drugs are all associated with perioperative death in patients with ruptured abdominal aortic aneurysm. EVAR surgery is a better choice if conditions exist.

[Comparison of the accuracy of intraocular lens power calculation formulas based on the new swept-source optical coherence tomography biometry].

Objective: To compare the accuracy of 6 intraocular lens power calculation formulas based on the new swept-source optical coherence tomography biometry and to analyze the prediction error. Methods: Retrospective case series study. Clinical data were collected from 599 patients (599 eyes) who had underwent uncomplicated phacoemulsification and the IOLMaster 700 examination at the Eye Hospital of Wenzhou Medical University between November 2018 and November 2019. Among the patients, there were 208 males and 391 females with an age of (69±10) years. According to the axial length (AL), eyes were divided into the short AL group (≤22.5 mm, n=100), the normal AL group (>22.5 mm and<25.5 mm, n=375); and the long AL group (≥25.5 mm, n=124). Eyes were also grouped based on the mean keratometry (Km) as flat (≤42.00 D, n=47), normal (>42.00 D to<46.00 D, n=461), and steep (≥46.00 D, n=91), and by anterior chamber depth (ACD) as shallow (≤2.5 mm, n=71), normal (>2.5 mm to<3.5 mm, n=436), and deep (≥3.5 mm, n=92). The median absolute errors (MedAEs) of the Barrett Universal Ⅱ, Haigis, Hoffer Q, Holladay Ⅰ, Holladay Ⅱ, and SRK/T formulas in different AL, Km, and ACD groups were compared using the Friedman test. Results: The differences in MedAE among the 6 formulas of 599 patients (599 eyes) were statistically significant (χ²=120.549, P<0.001). The MedAE of the Barrett Universal Ⅱ formula was smallest (0.35 D), followed by the SRK/T formula (0.36 D). There was no significant difference between the MedAEs of the Barrett universal Ⅱ and Haigis, SRK/T formula (all P=1.000), but there were statistically significant differences among the other formulas (all P<0.01). In different AL groups, the MedAE of each formula was statistically different (χ²=38.307, 38.779, 112.997; all P<0.01).The Barrett Universal Ⅱ formula resulted in the lowest MedAE in the short AL group (0.40 D) and the long AL group (0.31 D). The MedAE of the SRK/T in the normal AL group was lowest (0.35 D). The 6 formulas showed significant differences in MedAE values in different Km groups (χ²=12.284, 90.924, 39.387; all P<0.05).The Haigis formula achieved the lowest MedAE in the flat Km group (0.26 D) and the steep Km group (0.34 D). The Barrett UniversalⅡ formula achieved the lowest MedAE in the normal Km group (0.33 D). The differences in MedAE values of the 6 formulas in different ACD groups were statistically significant (χ²=37.389, 57.643, 52.845; all P<0.01), and the MedAE values of the Barrett Universal Ⅱ in different ACD groups were smallest (0.46, 0.33, 0.31 D). Conclusions: The Barrett Universal Ⅱ formula perform the best over the entire AL range, followed by the Haigis and SRK/T formulas. The Barrett Universal Ⅱ formula result in the lowest prediction error in the short AL group, the long AL group, and all ACD groups. The Haigis formula may be more accurate when the Km was ≤42.00 D or ≥46.00 D. (Chin J Ophthalmol, 2021, 57: 502-511).

Biological Characteristics and Genetic Diversity of Phomopsis asparagi, Causal Agent of Asparagus Stem Blight.

Asparagus stem blight is a regional disease. In the present study, we compared strains of Phomopsis asparagi from six different provinces to determine their biological characteristics and genetic diversity, differences in the pycnidium and conidium production, pathogenicity, and growth rate. Considerable differences were established in the pycnidium and conidium production among the P. asparagi strains from the six studied provinces. The largest pycnidium and conidium production had the strains from Fujian, followed by those from Hainan. The virulence of P. asparagi strains was significantly different but without a correlation with the geographical source of the strain. FJ2 had the highest virulence, followed by HN2, SD4, and SD5, whereas SD5 had the lowest virulence. The colony diameter and dry weight of the strains of asparagus stem blight fungus from the six provinces were substantially different. The colonies of HN1-5 had the largest diameters, whereas those of XT1-5, LT1-3, FJ1-5, and SX6 had smaller diameters. Four primers with good repeatability and strong specificity were selected from 100 intersimple sequence repeat (ISSR) primers. ISSR-PCR amplification was performed on 36 strains of asparagus stem blight fungus, and a large number of repeatable DNA fingerprints were obtained. Most of the amplified fragments were within 300 to 500 bp. In all, 69 total points, 64 multiple points, and 92.75% polymorphism points were established. The number of ISSR gene sites detected by four primers ranged from 14 to 20, with an average of 16 multiple sites. The copolymerization was divided into three groups: XT1-5, LT1-3, and FJ1-5, which were clustered into the first group; SD1-6, SX1-6, and HB1-6, clustered into the second group; and HN1-5 in the third group. The results of the cluster analysis revealed that the strains of the neighboring provinces had a nearer phylogenetic relationship than that between distant ones. Therefore, the system evolution of P. asparagi is related to the geographical distribution of its strains.

[Pepsin and bile acids detection in saliva for the diagnosis of gastroesophageal reflux disease].

Objective: To identify the value of the detection of pepsin and bile acids in saliva for the diagnosis of gastroesophageal reflux disease(GERD). Methods: From January 2018 to June 2019, 104 GERD patients and 43 healthy people in Guangdong Provincial People's Hospital were recruited. The 104 patients of GERD group were divided into four sub-groups, including esophageal symptoms GERD group, extraesophageal symptoms GERD group, anxiety or depression group, non-anxiety and non-depression group. Saliva was collected on waking in morning and 2 h after finishing lunch. The concentration of the total pepsin(TPP) and total bile acids(TBA) from saliva was detected by ELISA method. Receiver operating characteristics analysis was used to identify the sensitivity and specificity of the saliva pepsin and bile acids detection. Results: The concentration of TPP in morning waking samples and postprandial samples in the GERD group was 27.1(9.7,50.3) µg/L and 32.4(14.0,58.7) µg/L, the concentration of TBA in postprandial samples was (18.4±2.3)µmol/L, and these levels were significantly higher than that of the control group [7.0(5.1, 9.1) µg/L, 7.4(5.2, 9.4) µg/L, (12.6±5.0)µmol/L](P<0.01). The concentration of TBA in morning waking samples had no significant difference between these two groups(P>0.05). The concentration of TPP and TBA had no significant difference among the four GERD sub-groups(P>0.05).Pepsin in postprandial saliva samples had moderate diagnostic value for GERD, when the saliva pepsin concentration in postprandial samples was higher than 41.33 µg/L, it had a sensitivity of 82.8% and a specificity of 73.3%. The bile acids in saliva had no significant diagnostic value for GERD. Conclusions: Pepsin detection in saliva has a high level of sensitivity and specificity for diagnosing GERD. However, bile acids in saliva has no significant diagnostic value for GERD.

[Expression and significance of chemokine CXCL12 and receptor CXCR4 in adenomyosis].

Objective: To observe the expression, correlation and significance of chemokine (C-X-C motif) ligand 12 (CXCL12) and chemokine (C-X-C motif) receptor 4 (CXCR4) in endometrium and myometrium of adenomyosis. Methods: Totally 38 patients were selected in this study, who underwent hysterectomy for adenomyosis at Beijing Obstetrics and Gynecology Hospital from October 2017 to December 2018 as the adenomyosis group, and, in the same period, selected 31 patients with cervical intraepithelial neoplasia Ⅲ or cervical cancer undergoing hysterectomy served as control group. The expression levels of mRNA and protein for CXCL12, CXCR4 in the endometrium and myometrium of the two groups were detected by immunohistochemistry and real-time PCR. Results: (1) The protein levels of CXCL12 and CXCR4 in endometrium in uterus with adenomyosis (0.229±0.025 and 0.226±0.016) were significantly higher than those in endometrium in uterus without adenomyosis (0.153±0.018 and 0.178±0.026); compared with each other, the differences were statistically significant (all P<0.05). And the expressions of CXCL12 and CXCR4 proteins in uterine myometrium of adenomyosis were 0.222±0.045 and 0.126±0.058, respectively, which were higher than those in the control group (0.091±0.029 and 0.099±0.020); compared with each other, the differences were statistically significant (all P<0.05). (2) The expression levels of CXCL12 and CXCR4 mRNA in endometrium of patients with adenomyosis were 6.31±0.12 and 8.49±0.21, respectively, which were higher than those in the control group (1.23±0.10 and 1.36±0.13); compared with each other, the differences were statistically significant (all P<0.05). Moreover, the expression levels of CXCL12 and CXCR4 mRNA in myometrium of patients with adenomyosis were 9.11±0.12 and 8.45±0.16, respectively, which were higher than those in the control group (1.18±0.08 and 1.46±0.13); compared with each other, the differences were statistically significant (all P<0.05). (3) In endometrium and myometrium of uterus with adenomyosis, CXCL12 and CXCR4 mRNA expression levels were positively associated (r=0.478, 0.542, all P<0.05). Conclusions: The levels of CXCL12 and CXCR4 in the endometrium and myometrium of adenomyosis are increased and positively correlated. The two chemokine may be involved in the development of adenomyosis.

[Preliminary study of the antibody level in confirmed patients with COVID-19 after discharge].

Objective: To analyze the antibody levels and dynamic changes in patients infected with 2019-novel coronavirus(2019-nCoV). Methods: The average age of 72 corona virus disease 2019 (COVID-19) patients was (45.53±16.74)years(median age:47 year), including (44.88±17.09) years(median age:46 year) for 38 males and (46.32±16.52)years (median age:46 year) for 34 females in Loudi City, Hunan Province. There is no significant difference in genders between the severe and mild groups (χ²=0.916, P>0.05). There is a significant difference in the age between the severe and mild groups (F=3.315, P<0.05). The blood samples of 72 discharged patients were collected and the consistence of IgM and IgG antibodies were detected by chemiluminescence method. SPSS25.0 was used for gender, age, case type and antibody analysis of variance, χ2 test and other analysis. Results: The average time of the serum samples collection of 72 patients was (34.89±9.02)days (median time: 34 days) from onset of COVID-19, and (14.53±8.35) days (median time: 14 days) from discharge. The positive rate of IgM or IgG was 97.22% (70/72), and the positive rate of IgM and IgG was 48.61% (35/72) and 97.22% (70/72) respectively. Serum COVID-19 antibodies were detected in 72 patients from 1st to 40th days after discharge. The average concentration of IgM in 1-7 days, 8-14 days, 15-21 days, 22-28 days, above 29 days were 21.91(7.07-52.84)AU/ml, 14.16(6.19-32.88)AU/ml, 11.36(6.65-42.15)AU/ml, 8.15(3.66-30.12)AU/ml, 2.98(0.46-6.37)AU/ml. There was no significant difference in the time of IgM antibody concentration (H= 8.439, P>0.05). The average concentrations of IgG in 1-7 days, 8-14 days, 15-21 days, 22-28 days, 29 days and above were 169.90 (92.06-190.91) AU/ml, 163.89 (91.19-208.02) AU/ml, 173.31 (95.06-191.28) AU/ml, 122.84 (103.19-188.34) AU/ml, 101.98 (43.75-175.30) AU/ml, respectively, (H=2.232, P>0.05). The IgM becomes negative after the 3rd week of discharge and decreases rapidly with time. The IgG concentration higher than IgM during the same period, and keep at high level without any change, and decrease in the fourth week. Among them, 5 cases developed "re-infection" within 1-3 weeks after discharge, and the rate of "re-infection" was 6.94% (5/72 cases). Conclusions: After the COVID-19 patients are discharged from the hospital, the level of antibodies produced varies greatly among individuals, but the overall changes in antibodies have a certain pattern. It is recommended to strengthen the antibody monitoring during hospitalization and after discharge from the hospital to reduce the "re-infection" rate and potential risk of infection.

[Post-marketing multi-center safety surveillance of inactivated enterovirus A71 vaccine (Vero cell)].

Objective: To evaluate the post-marketing safety profiles of the inactivated enterovirus type 71 (EV-A71) vaccine (Vero cell) after routine inoculation. Methods: Eleven cities of Zhejiang Province, Fengtai district of Beijing, Qinnan district, two counties as Pingle and Pingguo of Guangxi Zhuang Autonomous Region, and Dongtai city of Jiangsu Province were selected as the field sites. A total of 45 239 subjects were enrolled in this study from children who seeked the vaccination of EV-A71 vaccine during the period from July, 2016 to June, 2018. Different sampling method were adopted in different sites. All vaccinated children were invited to participate in the study in Fengtai and Dongtai, however, systematic sampling method were adopted in other sites. Active surveillance was conducted and information about adverse reactions (ARs) occurred in 30 min, 3 d and 30 d following each dose of EV-A71 immunization was collected by field observation, phone-call or face-to-face interview. The incidence of ARs in different types, symptoms and grades were described. Results: In total, there were 45 239 children who received 71 243 doses EV-A71 vaccine. The overall incidence of ARs was 1.079% (769 doses), with the highest incidence of 1.182% (177/14 973) in 5-11 month group and the lowest incidence of 0.849% (18/2 119) in ≥ 36 month group among different age groups. There was a higher incidence in solicited ARs, which was 1.047% (746 doses). The incidences of grade 1 and grade 2 ARs were also higher, which were 0.404% (288 doses) and 0.554% (395 doses), respectively. No grade 4 ARs occurred. The doses of the first and the second vaccination was 40 736 and 30 507, respectively, and the incidences of ARs were 1.281% (522 doses) and 0.810% (247 doses). Also, the incidences of ARs were 0.091% (37 doses) and 0.043% (13 doses) in local, and 1.168% (476 doses) and 0.760% (232 doses) in system. The symptoms of ARs after the two doses of vaccination were basically the same. Redness at the injection site was the most common local ARs after each dose vaccination, with doses of 24 and 11, while fever was the most common systemic ARs, with doses of 362 and 190. Moreover, ARs mainly occurred in 30 min to 3 d after each dose vaccination, with incidence of 1.016% (414 doses) and 0.698% (213 doses) in the first and second dose, respectively. Conclusion: The ARs had a low incidence after vaccination in children and most were mild or moderate. EV-A71 vaccine with good safety is suitable for inoculation in a large scale.

Serotonin receptor 1A promoter polymorphism, rs6295, modulates human anxiety levels via altering parasympathetic nervous activity.

OBJECTIVE: The G-allele of the -1019C/G (rs6295) promoter polymorphism of the serotonin receptor 1A (HTR1A) gene has been implicated in anxiety; however, the underlying neurophysiological processes are still not fully understood. Recent evidence indicates that low parasympathetic (vagal) tone is predictive of anxiety. We thus conducted a structural equation model (SEM) to examine whether the HTR1A rs6295 variant can affect anxiety by altering parasympathetic nervous activity. METHOD: A sample of 1141 drug-free healthy Han Chinese was recruited for HTR1A genotyping. Autonomic nervous function was assessed by short-term spectral analysis of heart rate variability (HRV). Anxiety and stress levels were evaluated by the Beck Anxiety Inventory (BAI) and the Perceived Stress Scale (PSS) respectively. RESULTS: The number of the HTR1A G allele was inversely correlated with high-frequency power (HF), a parasympathetic index of HRV. The HF index was negatively associated with BAI scores. Furthermore, the good-fitting SEM, adjusting for confounding variables (e.g., age and PSS levels), revealed a significant pathway linking rs6295 variant to BAI scores via HF index modulation. CONCLUSION: These results are the first to show that HTR1A -1019C/G polymorphism influences anxiety levels by modulating parasympathetic tone, providing a neurophysiological insight into the role of HTR1A in human anxiety.

Metabolic profiles of neratinib in rat by using ultra-high-performance liquid chromatography coupled with diode array detector and Q-Exactive Orbitrap tandem mass spectrometry.

Neratinib is a tyrosine kinase inhibitor that has been approved by the US Food and Drug Administration for the treatment of breast cancer. However, its metabolism remains unknown. This study was carried out to investigate the in vitro and in vivo metabolism of neratinib using an UHPLC-DAD-Q Exactive Orbitrap-MS instrument with dd-MS2 on-line data acquisition mode. The post-acquisition data was processed using MetWorks software. Under the current conditions, a total of 12 metabolites were detected and structurally identified based on their accurate masses, fragment ions and chromatographic retention times. Among these metabolites, M3, M10 and M12 were unambiguously identified using chemically synthesized reference standards. M6 and M7 (GSH conjugates) were the major metabolites. The metabolic pathways of neratinib were proposed accordingly. Our findings suggested that neratinib was mainly metabolized via O-dealkylation (M3), oxygenation (M8), N-demethylation (M10), N-oxygenation (M12), GSH conjugation (M1, M2, M4, M5, M6 and M7) and N-acetylcysteine conjugation (M9 and M11). The α,ß-unsaturated ketone was the major metabolic site and GSH conjugation was the predominant metabolic pathway. In conclusion, this study provided valuable metabolic data and would benefit the assessment of the contributions to the overall activity or toxicity from the key metabolites.

Fabrication of flexible thin polyurethane membrane for tissue engineering applications.

Thin and flexible polymeric membranes play a critical role in tissue engineering applications for example organs-on-a-chip. These flexible membranes can enable mechanical stretch of the engineered tissue to mimic organ-specific biophysical features, such as breathing. In this work, we report the fabrication of thin (<20 µm), stretchable, and biocompatible polyurethane (PU) membranes. The membranes were fabricated using spin coating technique on silicon substrates and were mounted on a frame for ease of device integration and handling. The membranes were characterized for their optical and elastic properties and compatibility with cell/tissue culture. It was possible to apply up to 10 kilopascal (kPa) pressure to perform cyclic stretch on 4 mm-diameter membranes for a period of 2 weeks at 0.2 hertz (Hz) frequency without mechanical failure. Adenocarcinomic human alveolar basal epithelial (A549) cells were cultured on the apical side of the PU membrane. The morphology and viability of the cells were comparable to those of cells cultured on standard tissue culture plates. Our experiments suggest that the stretchable PU membrane will be broadly useful for various tissue engineering applications in vitro.

[Clinical abservations of pulmonary surfactant' s autologous transfusion in massive lung lavage].

Objective: Investigate the pulmonary surfactant autotransfusion effect on the recovery of respiratory function in patients with whole lung lavage, to provide theoretical basis for the clinical application. Methods: We taken 30 patients of pneumoconiosis treated by whole lung lavage as the subjects. We extracted the pulmonary surfactant from lavage fluid, after single postoperative lung lavage for the first time; after one weeks when the second times of lung lavage were performed to the other side of the lung of patients, we put PS into the right side. We taken the patients the second times of lung lavage who were put PS into the right side as returning group, the first times of lung lavage who were not put PS into as on returning group. We observed indi-cators, such as expiratory resistance, respiratory work, lung compliance, airway pressure, PO(2), the pulmonary function recovery time and other indicators, comparing with the changes of pulmonary function before lung la-vage for the first time and at 0、60、90、120 min after the pulmonary surfactant autotransfusion. Results: Com-pared with the no returning group, the expiratory resistance of the returning group decreased significantly at 90 min、120 min after the pulmonary surfactant autotransfusion; the respiratory work and airway pressure of the re-turning group decreased significantly at 60、90、120 min after the pulmonary surfactant autotransfusion, there was statistically significant in the difference between different groups (P<0.05, P<0.01). Compared with the no returning group, the lung compliance and the PO(2) of the returning group increased significantly at 60 min、90 min、120 min after the pulmonary surfactant autotransfusion, there was statistically significant in the difference between different groups (P<0.05, P<0.01). The lung function recovery time of returning group was (155.7 ± 35.2) min, the lung function recovery time of no returning group was (183.71±41.81) min, there was statistical-ly significant in the difference between different groups (P<0.05). Compared with the no returning, there were not statistically significant in the difference of the Heart rate、the systolic blood pressure and the diastolic blood pressure about the returning at 60、90、120 min after the pulmonary surfactant autotransfusion.There was no ad-verse reactions such as pulmonary infection, pulmonary infection and so on. Conclusion: The pulmonary surfac-tant autotransfusion may reduce expiratory resistance, work of breathing, airway pressure; improve lung compliance, alveolar ventilation function; increase oxygen partial pressure and decrease the surgery recovery time in patients with pneumoconiosis.

A multicentre, randomized, single-blind comparison of topical clindamycin 1%/benzoyl peroxide 5% once-daily gel versus clindamycin 1% twice-daily gel in the treatment of mild to moderate acne vulgaris in Chinese patients.

BACKGROUND: Acne vulgaris affects up to 54% of Chinese adolescents. Combination therapy has become the recommended standard of care for acne. OBJECTIVE: The aim of this study was to compare the efficacy and safety of clindamycin (1%) and benzoyl peroxide (5%) (CDP/BPO) gel once daily vs. clindamycin (1%) (CDP) monotherapy gel twice daily in Chinese patients with mild to moderate acne. METHODS: 1020 patients (aged 12-45 years) with mild to moderate acne were randomized (1 : 1); 1016 patients were treated with CDP/BPO (n = 500) or CDP (n = 516) for a 12-week treatment period. Efficacy assessments were performed at baseline, and at weeks 1, 2, 4, 8 and 12; and primarily included change in total lesion count (inflammatory and non-inflammatory lesions), and proportion of patients with a minimum 2-grade improvement in Investigator's Static Global Assessment (ISGA) score. Patient safety and local tolerability were also evaluated. RESULTS: Patients in CDP/BPO group showed a greater per cent reduction in total lesion count compared with patients in CDP group at week 12 (delta = -0.05; 95% CI = -0.09, -0.02; P = 0.003); statistically significant reduction in lesion count was noted as early as week 1 and continued through week 12. A greater proportion of patients in CDP/BPO group showed a ≥2-grade improvement in ISGA score at week 12 compared with CDP group (30.2% vs. 22.7%; P = 0.018). Overall, the incidence of adverse events (AEs) was higher in the CDP/BPO group (14.4%) than in the CDP group (7.9%); the most commonly reported events were generally related to application site reactions (erythema, pruritus and swelling). Incidence of drug-related AEs was 8.6% in CDP/BPO group and 1.2% in CDP group. Both groups showed trends towards reduction in investigator and subject rated local tolerability scores. CONCLUSION: CDP/BPO gel demonstrated superior efficacy over CDP gel along with acceptable safety and tolerability in Chinese patients with mild to moderate acne. GOV NUMBER: NCT01915732.

[Phenotypic characteristics of LAP(+) CD4(+) T lymphocytes in colorectal cancer tissues].

OBJECTIVE: To analyze the phenotypic characteristics of LAP(+) CD4(+) T lymphocytes and investigate their molecular mechanisms in colorectal cancer (CRC) microenvironment. METHODS: Fifty colorectal cancer patients treated in our two hospitals from January 2014 to May 2014 were included in this study. Their tumor tissues and adjacent normal tissues, peripheral blood samples, and peripheral blood samples of 25 healthy donors (HD) were collected to isolate the lymphocytes. The different expressions of CCR7, CD45RA, Foxp3, CTLA-4, CCR4 and CCR5 in LAP(+) CD4(+) T and LAP(-)CD4(+) T lymphocytes were analyzed by flow cytometry (FCM). RESULTS: The FCM assay detected that the percentage of LAP(+) CD4(+) T cells in peripheral blood of the CRC patients were significantly higher than that of HD [(9.44±3.18)% versus (1.49±1.00)%, P<0.001]. In addition, significantly more LAP(+) CD4(+) T cells were also recruited into tumor tissue than those in the tumor-adjacent normal tissue [(11.76±3.74)% versus (3.87±1.64)%, P<0.001]. LAP(+) CD4(+) T cells in the tumor-adjacent normal tissue and peripheral blood of both HDs and CRC patients mainly displayed a central memory phenotype. However, effector memory lymphocytes were predominant in the tumor tissue.In the tumor tissue, the expression of Foxp3 in the LAP(+) CD4(+) T cells was (3.87±1.12)%, significantly lower than that in the LAP(-)CD4(+) T cells (16.70±2.61)%, (P<0.001); the expression of CTLA-4 in the LAP(+) CD4(+) T cells was (36.36±19.14)%, significantly higher than the (19.60±8.91)% in the LAP(-)CD4(+) T cells (P<0.001); the expression of CCR4 in the LAP(+) CD4(+) T cells was (37.72±11.14)%, significantly higher than the (30.06±9.14)% in the LAP(-)CD4(+) T cells (P<0.001); and the expression of CCR5 in the LAP(+) CD4(+) T cells was (18.86±7.10)%, significantly higher than the (13.92±3.31)% in the LAP(-)CD4(+) T cells (P<0.001). CONCLUSIONS: LAP(+) CD4(+) T cells with low expression of Foxp3 and high expressions of CTLA-4, CCR4 and CCR5 are tend to be enriched and accumulated in the tumor tissue. The unique phenotypic characteristics make these cells a distinct subset of lymphocytes, apparently different from the traditional CD4(+) CD25(+) Treg cells.

[Clinical application of multi-electrode synchronous radiofrequency ablation via switching controller for treating large hepatocellular carcinoma].

Objective: To explore the preliminary clinical efficacy and safety of multi-electrode synchronous radiofrequency ablation via switching controller for treating large hepatocellular carcinoma. Methods: A total of 20 patients with large hepatocellular carcinoma from minimally invasive Interventional department of Sun Yat-sen University Cancer Center were enrolled in this retrospective study from December 2013 to December 2014.The procedures were conducted with multi-electrode synchronous radiofrequency ablation via switching controller under CT guidance.The necrosis rate of tumor was assessed by the following imaging examination.The single factor analysis of variance (ANOVA) was employed to compare the total bilirubin, albumin, renal function, blood coagulation function before and after ablation, to evaluate the safety of treatment. Result: Twenty patients with a total of 31 lesions accepted 23 times ablation procedures using multi-electrode synchronous radiofrequency ablation via switching controller.The recent evaluation after treatment was as followed: complete necrosis rate 51.6% (16/31), nearly complete necrosis rate 22.6% (7/31), partial necrosis rate 9.7% (3/31), treatment effectiveness rate (necrosis rate > 50%) 83.9%.The necrosis rate which was less than half volume of the tumor was only seen in 5 cases with huge hepatocellular carcinoma (16.1%). No dead cases appeared after ablation procedures.The patients' total bilirubin elevated moderately after ablation procedures and reversed to normal level after liver function protection treatment.There were no statistical differences of renal function and blood coagulation function before and after ablation.After ablation procedures, 5 cases (21.7%, 5/23) appeared fever, 6 cases (26.1%) with vomiting, only 3 cases (13.0%, 3/23) with moderately severe pain in 3 days after ablation and remitted after taking oral analgesics in one week. Conclusion: The clinical efficacy of multi-electrode synchronous radiofrequency ablation via switching controller for large hepatocellular carcinoma is satisfactory with guaranteed security, which can be a choice for treating large hepatocellular carcinoma.