[Association between different treatment timings and adverse neonatal outcomes in pregnant women with syphilis during pregnancy].

Objective: To analyze the association between different treatment timings and adverse neonatal outcomes (premature birth, death, congenital syphilis) in syphilis-infected pregnant women. Methods: The National Management Information System for Prevention of HIV, Syphilis and HBV Mother-to-Child Transmission was used to collect information on the detection and treatment of syphilis-infected pregnant women and their newborns in Guangdong Province from October 2011 to December 2021. According to the gestational weeks of syphilis-infected pregnant women receiving penicillin treatment for the first time, they were divided into four groups: treatment in the first trimester, treatment in the second trimester, treatment in the third trimester, and no treatment during pregnancy. Multivariate logistic regression was used to analyze the association between different treatment timings and adverse neonatal outcomes in syphilis-infected pregnant women. Results: A total of 22 483 syphilis-infected pregnant women were included. The number of pregnant women who started treatment in the first trimester, second trimester, and third trimester and did not receive treatment during pregnancy were 4 549 (20.23%), 8 719 (38.78%), 2 235 (9.94%) and 6 980 (31.05%), respectively. Compared with pregnant women who started treatment in the first trimester, pregnant women who did not receive anti-syphilis treatment during pregnancy had increased risks of neonatal preterm birth (OR=1.42, 95%CI: 1.24-1.62), death (OR=4.27, 95%CI: 1.64-14.69) and congenital syphilis (OR=12.26, 95%CI: 6.35-27.45). At the same time, the risk of congenital syphilis in the newborns of pregnant women who started anti-syphilis treatment in the second trimester (OR=2.68, 95%CI: 1.34-6.16) and third trimester (OR=6.27, 95%CI: 2.99-14.80) also increased. Conclusion: Early initiation of anti-syphilis treatment during pregnancy in patients with syphilis can improve neonatal outcomes.

[Changing trend of incidence and mortality of esophageal cancer during 2010-2016 in Henan Province, China].

Objective: To estimate the incidence and mortality of esophageal cancer in 2016 and their changing trend during 2010-2016 according to the cancer registration data in Henan province. Methods: The data quality including completeness, validity, and reliability of local registries which submitted the cancer registration data of 2016 were assessed according to the criteria of Guideline on Cancer Registration in China and IARC/IACR. Esophageal cancer cases (ICD10: C15) were extracted from the database, and the incidence and mortality stratified by gender, age, and areas (urban/rural) were calculated, the incidence and mortality of provincial cancer were estimated combined with provincial population data. China's 2000 census population and Segi's population were used to calculate the age-standardized rate. Joinpoint model was used to estimate the changing trend of age standardized incidence and mortality along with the calendar year. Results: Approximately 40.10 thousand new esophageal cancer cases were diagnosed in Henan in 2016, accounting for 13.46% of all new cancer cases, and it ranked the third among cancer of all sites. The crude incidence of esophageal cancer was 37.21/100 000 with an age-standardized incidence rate by China standard population (ASIRC) of 26.74/100 000 and an age-standardized incidence rate by world standard population (ASIRW) of 27.12/100 000. The incidence of esophageal cancer in males was higher than that in females, with the ASIRC of 34.53/100 000 and 19.19/100 000, respectively. It was higher in rural areas than that in urban areas, with the ASIRC of 28.13/100 000 and 20.90/100 000, respectively. About 29.30 thousand deaths of esophageal cancer in Henan in 2016, accounting for 15.61% of all cancer deaths in Henan, which ranked the third among cancer of all sites. The crude mortality rate was 27.14/100 000 with an age-standardized mortality rate by China standard population (ASMRC) of 18.74/100 000 and an age-standardized mortality rate by world standard population (ASMRW) of 18.78/100 000. The mortality in males was higher than that in females, with the ASMRC of 24.78/100 000 and 13.12/100 000, respectively. It was also higher in rural areas than that in urban areas, with the ASMRC of 19.48/100 000 and 15.73/100 000, respectively. The ASIRC and ASMRC were declining with annual percent change (APC) of 3.12% (APC=-3.12%; 95%CI: -5.30%, -0.90%; P=0.015) and 2.47% (APC=-2.47%; 95%CI: -4.70%, -0.20%; P=0.039) during 2010-2016. However, the significant declining trend was only observed in rural areas in Henan, and the changing trend was same between males and females. Conclusions: The incidence and mortality of esophageal cancer are declining since 2010, however, the disease burden remains large in Henan. Therefore, comprehensive prevention and control efforts should be strengthened according to its epidemic characteristics and risk factors.

[Changing trend of incidence and mortality of stomach cancer during 2010-2016 in Henan Province, China].

Objective: To estimate stomach cancer incidence and mortality in Henan, 2016 and analyze the trend of stomach cancer incidence and mortality from 2010 to 2016. Methods: Stomach cancer related data in 2016 was extracted from Henan cancer registration and follow-up system. All data were qualified in validity, reliability and completeness according to the Guideline on Cancer Registration in China and International Agency for Research on Cancer (IARC/IACR). The incidence and mortality of stomach cancer were estimated by areas, gender and age based on the quality data and the registered population data of Henan province in 2016. The epidemic trend of stomach cancer was also been evaluated based on the age-standardized incidence and mortality by Chinese population (ASR China) from 2010 to 2016. Results: In 2016, the estimated incident cases of stomach cancer were 44 311. The incidence was 41.07/100 000, ASR China was 30.17/100 000, ASR by world population (ASR world) was 30.36/100 000, and the cumulative incidence rate was 3.84%. The incidences of male and female were 55.65/100 000 and 25.35/100 000, respectively. Meanwhile, 32 927 people died of stomach cancer in Henan. The mortality was 30.52/100 000, ASR China was 21.45/100 000, ASR world was 21.54/100 000, and the cumulative mortality was 2.53%. From 2010 to 2016, both the ASR China for incidence and mortality of stomach cancer in Henan showed a steady downward trend. In rural, the ASR China for incidence and mortality decreased rapidly, while the stable trend was observed in urban. Nevertheless, the incidence and mortality of stomach cancer in rural were still higher than those in urban. Conclusions: The incidence and mortality of stomach cancer in Henan province showed steadily declining trend from 2010 to 2016, and the geographical distribution difference between rural and urban areas was gradually narrowing. However, the disease burden was still high in 2016.

[Noninvasive assessment of the risk of esophageal variceal bleeding from noncirrhotic portal hypertension].

Objective: To verify Baveno VI criteria, Expanded-Baveno VI criteria, liver stiffness×spleen diameter-to-platelet ratio risk score (LSPS), and platelet count/spleen diameter ratio (PSR) in evaluating the severity value of esophageal varices (EV) in patients with non-cirrhotic portal hypertension (NCPH). Methods: 111 cases of NCPH and 204 cases of hepatitis B cirrhosis who met the diagnostic criteria were included in the study. NCPH included 70 cases of idiopathic non-cirrhotic portal hypertension (INCPH) and 41 cases of nontumoral portal vein thrombosis (PVT). According to the severity of EV on endoscopy, they were divided into the low-bleeding-risk group (no/mild EV) and the high-bleeding-risk group (moderate/severe EV). The diagnostic value of Baveno VI and Expanded-Baveno VI criteria was verified to evaluate the value of LSPS and PSR for EV bleeding risk severity in NCPH patients. The t-test or Mann-Whitney U test was used to compare the measurement data between groups. Comparisons between counting data groups were performed using either the χ2 test or the Fisher exact probability method. Results: Considering endoscopy was the gold standard for diagnosis, the missed diagnosis rates of low/high bleeding risk EVs in INCPH/PVT patients with Baveno VI and Expanded-Baveno VI criteria were 50.0%/30.0% and 53.8%/50.0%, respectively. There were no statistically significant differences in platelet count (PLT), spleen diameter, liver stiffness (LSM), LSPS, and PSR between low-bleeding-risk and high-bleeding-risk groups in INCPH patients, and the area under the receiver operating characteristic curve (AUC) of LSPS and PSR was 0.564 and 0.592, respectively (P=0.372 and 0.202, respectively). There were statistically significant differences in PLT, spleen diameter, LSPS, and PSR between the low and high-bleeding risk groups in PVT patients, and the AUCs of LSPS and PSR were 0.796 and 0.833 (P=0.003 and 0.001, respectively). In patients with hepatitis B cirrhosis, the Baveno VI and Expanded-Baveno VI criteria were used to verify the low bleeding risk EV, and the missed diagnosis rates were 0 and 5.4%, respectively. There were statistically significant differences in PLT, spleen diameter, LSM, LSPS and PSR between the low-bleeding-risk and high-bleeding-risk groups (P<0.001). LSPS and PSR AUC were 0.867 and 0.789, respectively (P<0.05). Conclusion: Baveno VI and Expanded-Baveno VI criteria have a high missed diagnosis rate for EVs with low bleeding risk in patients with INPCH and PVT, while LSPS and PSR have certain value in evaluating EV bleeding risk in PVT patients, which requires further clinical research.

[Acceptance evaluation of urine self-sampling, vaginal self-sampling and physician sampling in cervical cancer screening].

Objective: To compare the acceptance of urine self-sampling, vaginal self-sampling and physician sampling in cervical cancer screening. Methods: Questionnaire surveys were conducted in women attending cervical cancer screening in Xiangyuan County and Yangcheng County in Shanxi Province from July to November 2015 and from October to December 2018. Both surveys included the following three parts: feelings and acceptance of women in urine self-sampling, vaginal self-sampling and physician sampling, and the ease evaluation of two self-samplings. Results: There were 3 485 questionnaires were collected finally. The proportions of women felt embarrassed in urine self-sampling, vaginal self-sampling and physician sampling were 2.3% (81/3 472), 7.1% (247/3 472) and 8.6% (299/3 472), and 1.3% (46/3 472), 9.7%(3 37/3 472) and 14.9% (518/3 472) of women felt uncomfortable, and 1.0% (35/3 469), 8.5% (295/3 469) and 15.3% (531/3 469) felt pain, and 98.3% (3 334/3 393), 96.3% (3 267/3 393) and 99.0% (3 360/3 393) thought that the sampling were conducted properly (P<0.05). Based on the feeling during sample collection, 61.2% (1 876/3 064), 39.1% (1 199/3 064) and 66.5% (2 037/3 064) women were willing to use the corresponded sampling methods in cervical cancer screening, respectively (P<0.05). If the accuracy was the same, there were 31.8% (1 109/3 485) women preferred self-sampling and 68.2% (2 376/3 485) preferred physician sampling for cervical cancer screening. Meanwhile, 23.5% (820/3 482) preferred vaginal self-sampling in comparison with 76.5% (2 662/3 482) for urine self-sampling in cervical cancer screening. 86.5% (3 007/3 478) of the women thought urine self-sampling was very easy, comparing 40.9% (1 423/3 478) for vaginal self-sampling. Conclusions: The bad feeling of women during urine self-sampling is less common and less serious than those during physician sampling and vaginal self-sampling, and the acceptance for physician sampling is highest, following by urine self-sampling and vaginal self-sampling. Urine self-sampling is much easier than vaginal self-sampling.

[The characteristics of digital subtraction angiography and the analysis of the therapeutic effect of interventional therapy on hemorrhage after partial nephrectomy].

Objective: To investigate the digital subtraction angiography (DSA) manifestations of hemorrhage after partial nephrectomy (PN) for renal tumors, and the safety and efficacy of interventional therapy. Methods: The clinical data, DSA images and interventional treatment of 15 patients undergoing emergency interventional therapy due to hemorrhage after PN in the Department of Interventional Therapy of Beijing University Cancer Hospital from January 2015 to January 2019 were retrospectively analyzed. The DSA manifestations, safety and prognosis of interventional therapy were summarized. Results: Among the 15 patients, 10 had abdominal hemorrhage, 2 had abdominal hemorrhage with hematuria, and 3 had hematuria, all of which occurred 6 hours to 7 days after the operation. The DSA manifestations included contrast medium overflow, local artery wall unevenness, local artery branch expansion, pseudoaneurysm formation and renal arteriovenous fistula. There were 14 survivors, followed up for 6-12 months, and further no bleeding occurred. The success rate of interventional therapy was 100% (14/14), and the success rate of hemostasis was 100% (14/14). One patient died of asphyxia due to intraoperative nausea and vomiting. The creatinine levels were (76.0±11.0), (80.0±9.0), (76.0±9.0) µmol/L before operation, 1 week after operation and 1 month after operation respectively. There was no significant difference in creatinine levels among the three groups (F=3.171, P=0.058). The levels of urea nitrogen before operation, 1 week after operation and 1 month after operation were (6.80±1.04), (7.13±0.89), (6.81±0.79) µmol/L respectively. There was significant difference among the three groups (F=4.322, P=0.024). The level of urea nitrogen at 1 month after operation was significantly lower than that at 1 week after operation (P=0.016), but there was no difference compared with that before operation (P=1.000). Conclusion: Contrast medium overflow, pseudoaneurysm formation and renal arteriovenous fistula were the main manifestations of DSA hemorrhage after PN. Interventional therapy was safe and effective and might be a priority in cases of hemorrhage after PN.

[Distribution of the anterior corneal astigmatism in over 140 000 patients with age-related cataract].

Objective: To analyze the distribution characteristics of the anterior corneal astigmatism in 140 000 cataract patients from 18 hospitals in China. Methods: Retrospective study. A total of 143 889 patients (143 889 right eyes) over the age of 40 years with age-related catarac were admitted to 18 Aier eye hospitals in China from July 2015 to October 2018. The average values of the three measurements of the magnitude of anterior corneal astigmatism, the meridian of corneal astigmatism, anterior chamber depth, corneal refractive power, and axial length measured by IOLMaster 500 were obtained. The data acquisition method of each sub-center was to collect and analyze the electronic case data in accordance with the inclusion and exclusion criteria, and to provide them for the sponsor Wuhan Aier Eye Hospital. Non-normal distribution data are presented as M (P25, P75). Mann-Whitney test, Kruskal-Wallis test, Chi-square test were used to analyze the distribution differences of the magnitude of corneal astigmatism and the meridian of corneal astigmatism in gender, age, anterior chamber depth, corneal refractive power and axial length. Results: Among the 143 889 patients, 84 319 were females and 59 570 were males, the median age was 72 (65, 78) years old, the median corneal astigmatism was 0.84 (0.51, 1.33) D; the corneal astigmatism was ≥0.75 D in 80 895 patients (56.22%) and was ≥1.00 D in 57 304 patients (39.83%). The median corneal astigmatism was 0.87 (0.53, 1.37) D in women and 0.82 (0.50, 1.29) D in men; with statistical difference (U=-14.891; P<0.05). The proportion of with-the-rule (WTR) astigmatism was 33.26% (28 046/84 319) for women and 34.26% (20 408/59 570) for men; The proportion of against-the-rule (ATR) astigmatism was 49.08% (41 385/84 319) for women and 46.91% (27 945/59 570) for men, with statistical difference (χ²=70.913; P<0.05). With the increase of age, the magnitude of corneal astigmatism first decreased from 0.94 (0.57, 1.48) D to 0.75 (0.46, 1.18) D, and then increased to 1.19 (0.74, 1.79) D, with statistical difference (H=1 263.438; P<0.05), and the change was at 61 to 70 years old. With the increase of age, the proportion of WTR astigmatism decreased from 77.50% (396/511) to 12.50% (3/24), the proportion of ATR astigmatism increased from 11.15% (57/511) to 79.07% (34/43), and the proportion of oblique astigmatism changed little from 17.02% (16/94) to 19.92% (245/1 230), the distribution difference was significant (χ²=10 174.496; P<0.05). As the anterior chamber became shallow, the magnitude of corneal astigmatism significantly increased from 0.82 (0.51, 1.31) D to 1.05 (0.61, 1.56) D, and the proportion of ATR astigmatism increased from 47.32% (60 207/127 227) to 51.69% (184/356) (H=409.961, χ²=120.995, both P<0.05). With the corneal refractive power rising, the magnitude of corneal astigmatism increased from 0.80 (0.49, 1.33) D to 0.95 (0.58, 1.53) D, the proportion of ATR astigmatism decreased from 52.84% (4 963/9 392) to 39.97% (9 023/22 577); the difference was significant (H=808.562, χ²=752.147, both P<0.05). When the axial length was>25.00 mm, the magnitude of corneal astigmatism was highest [1.04 (0.62, 1.65) D], and the proportion of ATR astigmatism was also highest [49.00% (10 964/22 376)]; the difference was significant (H=2 071.198, χ²=131.130, all P<0.05). Conclusions: The meridian of corneal astigmatism in middle-aged and elderly cataract patients is mainly ATR astigmatism. With the increasing of age, the magnitude of corneal astigmatism decreases first and then increases. The turning point from the proportion of WTR astigmatism to the proportion of ATR astigmatism is 65 years old. The shallower the anterior chamber is, the more the magnitude of corneal astigmatism and the proportion of ATR astigmatism increase. When the axial length is>25.00 mm, both the magnitude of corneal astigmatism and the proportion of ATR astigmatism reach the peak. (Chin J Ophthalmol, 2021, 57: 56-62).

[Performance of high-risk HPV typing test in early diagnosis of cervical cancer].

Objective: To evaluate the performance of High-risk HPV typing detection in cervical cancer screening. Methods: A total of 3 231 women were recruited as the subjects of cervical cancer screening from Jiyuan city of Henan provinces from June to July 2017. All women underwent HPV DNA test. The women with cytological examination ≥ASCUS or cytological examination negative and HPV 16/18 positive underwent colposcopy biopsy and pathological examination. Pathological diagnosis was used as the gold standard. Sensitivity, specificity, positive predictive value (PPV), negative predictive value(NPV) as well as corresponding 95% confidence interval (CI) of HR-HPV and HPV 16/18 were calculated. Results: The mean age of 3 231 subjects selected in this study was 46.84±10.00 (21-64) years old. 524 subjects had the positive results of HR-HPV, including 91 of HPV16 and 15 of HPV18. Pathological test result CIN2+ was the gold standard. The sensitivity and specificity of HR-HPV for cervical precancer lesions screening were 93.75 (95%CI: 79.85-98.27) and 84.56% (95%CI: 83.26-85.77), respectively. To compared with HR-HPV, HPV16/18 had low sensitivity (65.63%, 95%CI: 48.31-79.59)and higher specificity (97.44%, 95%CI: 96.83-97.93). After age stratification by age 30 and 45, the sensitivity of HPV 16/18 was same with HR-HPV (100%, 95%CI: 34.24-100.00), the specificity of HPV 16/18 was higher than HR-HPV (98.71%, 95%CI: 96.27-99.56 vs 84.48%, 95%CI: 79.27-88.58) in<30 age group.The sensitivity of HR-HPVin 30-45 and ≥45 age group were higher than HPV16/18 (85.71%, 95%CI: 48.69-97.43 vs 71.43%, 95%CI: 35.89-91.78, 95.65%, 95%CI: 79.01-99.23 vs 60.87%, 95%CI: 40.79-77.84), but the specificity werelower than HPV16/18 (86.89%, 95%CI: 84.58-88.90 vs 98.51%, 95%CI: 97.51-99.11、83.49%, 95%CI: 81.81-85.04 vs 96.80%, 95%CI: 95.94-97.48). Conclusions: HR-HPV detection has relatively high sensitivity and specificity in cervical cancer screening. For >30 years old women, HR-HPV is more recommended in cervical cancer screening. Therefore, HR-HPV detection is an effective method for cervical cancer screening.

Activation of liver X receptor promotes fatty acid synthesis in goat mammary epithelial cells via modulation of SREBP1 expression.

In bovine mammary tissue and cells, liver X receptor (LXR) regulates lipid synthesis mainly via transactivation of the transcription factor sterol regulatory element binding protein 1 (SREBP1). In the present work, we investigated the role of LXR in controlling lipid synthesis via transactivation of SREBP1 in goat primary mammary cells (GMEC). The GMEC were treated with a synthetic agonist of LXR, T0901317, and transactivation and transcription of SREBP1, expression of lipogenic genes, and fatty acid profiling and triacylglycerol (TAG) content of the cells were measured. A mild increase in the mRNA expression level of LXRα (NR1H3) was observed following treatment with different concentrations of T0901317, and a dose-dependent increase in mRNA and transactivation of SREBP1 was detected. Activation of LXR resulted in a significant increase in the mRNA expression of most of the measured genes related to de novo synthesis, desaturation, and transport of fatty acids; TAG synthesis; and transcription regulators. Compared with the control, total content of cellular TAG increased by more than 20% with T0901317 treatment. Furthermore, addition of T0901317 increased the proportion of unsaturated fatty acids (e.g., C16:1, C18:1, C20:1, and C22:1), and decreased the proportion of saturated fatty acids (e.g., C16:0, C18:0, C20:0, and C22:0). These results provide evidence that LXR regulates the expression and activity of SREBP1. Our results indicated that LXR participate in regulating the transcription of genes involved in milk fat synthesis in GMEC in an SREBP1-dependent fashion.

Phylogenetic analysis of HA and NA genes of influenza H1N1 viruses from 1918 to 2017.

The 1918 "Spanish" pandemic is the earliest known influenza H1N1 virus. Since then H1N1 viruses circulated between humans and animals continuously. With the increased amount of samples of H1N1 viruses and technology development, researchers have been studying how the viruses evolved. Here, we analyzed HA and NA genes of H1N1 viruses from three aspects: host distribution, geographical distribution and phylogenetic analysis. The data showed hosts were predominantly human, swine and poultry, and other hosts were mainly cat, ferret, wild bear, canine, cheetah and seal. In terms of geographical distribution, the North America and Eurasia were the main H1N1 influenza pandemic areas. Of them, the United States, China, Japan, Canada, the United Kingdom, India and Singapore were the most affected. The phylogenetic analysis of surface genes of influenza H1N1 viruses from 1918 to 2017 worldwide revealed the distribution of all avian influenza viruses (AIVs) showed a clear geographical difference, mainly concentrated in Eurasia and America. American and Eurasian swine viruses might be the ancestors of the 2009 pandemic virus' HA and NA genes. Swine influenza viruses played an important role in the spread of influenza viruses across species. To our knowledge, this is the first large-scale phylogenetic analysis of HA and NA genes of influenza H1N1 viruses worldwide until now. Our findings further emphasize the importance of surveillance of the genetic diversity of influenza H1N1 viruses in different hosts and raised more concerns about the long-time monitoring. Keywords: influenza H1N1 viruses; HA genes; NA genes; phylogenetic analysis; evolution.

[The association between the characteristics of egocentric network and HIV prevalence among men who have sex with men].

Objective: This study aimed to analyze the association between the characteristics of egocentric network and HIV prevalence among men who have sex with men (MSM) through social network analysis. Methods: The study was conducted in Guangzhou city from November 2016 to June 2017 using convenient sampling method. Participants were recruited from 13 voluntary counseling and testing (VCT) locations. Data were collected by using nomination generation and nomination interpretation methods. Questionnaire includes two parts, the first part about the social tie, and the second one about social demography and behavioral characteristics of respondents and their nominees. The multivariate logistic regression was applied to quantify the association. Results: 8.67%(93/1 073) HIV antibody positive MSM had been detected in 1 073 respondents who nominated 4 301 partners in total. Compared to egocentric sexual network with a size of 1-2, the size of sexual network larger than 3 (OR=1.68, 95%CI: 1.07-2.65) were associated with HIV infection. Compared to egocentric risk sexual network with a size of 1-2, the size of risk sexual networks larger than 3 (OR=1.87, 95%CI: 1.06-3.31) were associated with HIV infection. There were no significant association between marital similarity of respondents and their nominees, the type of the relationship of sexual partners and HIV prevalence (P>0.05). Conclusion: The composition of social network in MSM is related to their susceptibility of HIV infection. MSM population with a large sexual network is more susceptible to HIV infection.

[The efficacy and safety of insulin degludec versus insulin glargine in insulin-naive subjects with type 2 diabetes: results of a Chinese cohort from a multinational randomized controlled trial].

Objective: To compare the safety and efficacy of insulin degludec (IDeg) with those of insulin glargine (IGlar) in insulin-naive subjects with type 2 diabetes (T2DM). Methods: This was a 26-week, randomized, open-label, parallel-group, treat-to-target trial in 560 Chinese subjects with T2DM (men/women: 274/263, mean age 56 years, mean diabetes duration 7 years) inadequately controlled on oral antidiabetic drugs (OADs). Subjects were randomized 2∶1 to once-daily IDeg (373 subjects) or IGlar(187 subjects), both in combination with metformin. The primary endpoint was changes from baseline in glycosylated hemoglobin(HbA1c) after 26 weeks. Results: Mean HbA1c decreased from 8.2% in both groups to 6.9% in IDeg and 7.0% in IGlar, respectively. Estimated treatment difference (ETD) of IDeg-IGlar in change from baseline was -0.10% points (95%CI-0.25-0.05). The proportion of subjects achieving HbA1c<7.0% was 56.3%and 49.7% with IDeg and IGlar, respectively [estimated odds ratio of IDeg/IGlar: 1.26(95%CI 0.88-1.82)]. Numerically lower rateof overall confirmed hypoglycaemia and statistically significantly lower nocturnal confirmed hypoglycemia were associated with IDeg compared with IGlar, respectively [estimated rateratio of IDeg/IGlar 0.69(95%CI 0.46-1.03), and 0.43(95%CI 0.19-0.97)]. No differences in other safety parameters were found between the two groups. Conclusions: IDeg was non-inferior to IGlar in terms of glycaemic control, and was associated with a statistically significantly lower rate of nocturnal confirmed hypoglycaemia. IDeg is considered to be suitable for initiating insulin therapy in Chinese T2DM patients on OADs requiring intensified treatment. Clinical trail registration: Clinicaltrials.gov, NCT01849289.

[The surgical treatment of ovarian cancer metastasis between liver and diaphragm: a report of 83 cases].

Objective: To explore the safety and feasibility of associating diaphragm resection and liver-diaphragmatic metastasis lesions resection for patients with advanced ovarian cancer. Methods: Retrospectively analysis 83 cases(98 times) of advanced ovarian cancer with liver-diaphragmatic metastasis between January 2012 and December 2016 at Department of Liver Surgery, Peking Union Medical College Hospital.The patients were aged from 19 to 75 years.Surgical procedure included metastatic lesions resection(43 times) and stripping(55 times). Operation status, post-operative complications, pathology results and follow-up of the patients were analyzed. Results: Fifteen patients received twice surgical treatment and 68 patients received one time surgical treatment. Postoperative hemorrhage in chest and between liver and diaphragm was not occurred in all cases.Dyspnea and low oxygen saturation were occurred in two cases of stripping patients and 1 case of metastatic lesions resection patients.Results of CT examination indicated that there was medium to large amount of ascites in right chests.The symptoms were relieved after placing thoracic closed drainage.Other patients were recovered smoothly.All patients were diagnosed as ovarian cancer by pathological examination. Conclusion: Associating diaphragm resection is safe and feasible for liver-diaphragmatic metastasis lesions from ovarian cancer.

Short communication: Altered expression of specificity protein 1 impairs milk fat synthesis in goat mammary epithelial cells.

Specificity protein 1 (encoded by SP1) is a novel transcription factor important for the regulation of lipid metabolism and the normal function of various hormones in model organisms. Its potential role, if any, on ruminant milk fat is unknown. Despite the lower expression of the lipolysis-related gene ATGL (by 44 and 37% respectively), both the adenoviral overexpression and the silencing of SP1 [via short interfering (si)RNA] markedly reduced cellular triacylglycerol (TAG) content (by 28 and 25%, respectively), at least in part by decreasing the expression of DGAT1 (-36% in adenovirus treatment) and DGAT2 (-81 and -87%, respectively) that are involved in TAG synthesis. Consistent with the markedly lower expression of genes related to lipid droplet formation and secretion (TIP47 by 19 and 32%, and ADFP by 25 and 25%, respectively), cellular lipid droplet content was also decreased sharply, by 9 and 8.5%, respectively, after adenoviral overexpression of SP1 or its silencing via siRNA. Overall, the results underscored a potentially important role of SP1 in maintaining milk-fat droplet synthesis in goat mammary epithelial cells.

Overexpression of SREBP1 (sterol regulatory element binding protein 1) promotes de novo fatty acid synthesis and triacylglycerol accumulation in goat mammary epithelial cells.

Sterol regulatory element binding protein 1 (SREBP1; gene name SREBF1) is known to be the master regulator of lipid homeostasis in mammals, including milk fat synthesis. The major role of SREBP1 in controlling milk fat synthesis has been demonstrated in bovine mammary epithelial cells. Except for a demonstrated role in controlling the expression of FASN, a regulatory role of SREBP1 on milk fat synthesis is very likely, but has not yet been demonstrated in goat mammary epithelial cells (GMEC). To explore the regulatory function of SREBP1 on de novo fatty acids and triacylglycerol synthesis in GMEC, we overexpressed the mature form of SREBP1 (active NH2-terminal fragment) in GMEC using a recombinant adenovirus vector (Ad-nSREBP1), with Ad-GFP (recombinant adenovirus of green fluorescent protein) as control, and infected the GMEC for 48 h. In infected cells, we assessed the expression of 20 genes related to milk fat synthesis using real time-quantitative PCR, the protein abundance of SREBP1 and FASN by Western blot, the production of triacylglycerol, and the fatty acid profile. Expression of SREBF1 was modest in mammary compared with the other tissues in dairy goats but its expression increased approximately 30-fold from pregnancy to lactation. The overexpression of the mature form of SREBP1 was confirmed by >200-fold higher expression of SREBF1 in Ad-nSREBP1 compared with Ad-GFP. We observed no changes in amount of the precursor form of SREBP1 protein but a >10-fold increase of the mature form of SREBP1 protein with Ad-nSREBP1. Compared with Ad-GFP cells (control), Ad-nSREBP1 cells had a significant increase in expression of genes related to long-chain fatty acid activation (ACSL1), transport (FABP3), desaturation (SCD1), de novo synthesis of fatty acids (ACSS2, ACLY, IDH1, ACACA, FASN, and ELOVL6), and transcriptional factors (NR1H3 and PPARG). We observed a >10-fold increase in expression of INSIG1 but SCAP was downregulated by Ad-nSREBP1. Among genes related to milk fat synthesis and lipid droplet formation, only LPIN1 and DGAT1 were upregulated by Ad-nSREBP1. Compared with the Ad-GFP, the cellular triacylglycerol content was higher and the percentage of C16:0 and C18:1 increased, whereas that of C16:1, C18:0, and C18:2 decreased in Ad-nSREBP1 cells. Overall, the data provide strong support for a central role of SREBP1 in the regulation of milk fat synthesis in goat mammary cells.

Thyroid hormone responsive (THRSP) promotes the synthesis of medium-chain fatty acids in goat mammary epithelial cells.

In nonruminants, thyroid hormone responsive (THRSP) is a crucial protein for cellular de novo lipogenesis. However, the role of THRSP in regulating the synthesis of milk fatty acid composition in goat mammary gland remains unknown. In the present study, we compared gene expression of THRSP among different goat tissues. Results revealed that THRSP had the highest expression in subcutaneous fat, and expression was higher during lactation compared with the dry period. Overexpression of THRSP upregulated the expression of fatty acid synthase (FASN), stearoyl-coenzyme A desaturase 1 (SCD1), diacylglycerol acyltransferase 2 (DGAT2), and glycerol-3-phosphate acyltransferase (GPAM) in goat mammary epithelial cells. In contrast, overexpression of THRSP led to downregulation of thrombospondin receptor (CD36) and had no effect on the expression of acetyl-coenzyme A carboxylase α (ACACA) and sterol regulatory element binding transcription factor1 (SREBF1). In addition, overexpressing THRSP in vitro resulted in a significant increase in triacylglycerol (TAG) concentration and the concentrations of C12:0 and C14:0. Taken together, these results highlight an important role of THRSP in regulating lipogenesis in goat mammary epithelial cells.

Characterization of the liver X receptor-dependent regulatory mechanism of goat stearoyl-coenzyme A desaturase 1 gene by linoleic acid.

Stearoyl-coenzyme A desaturase 1 (SCD1) is a key enzyme in the biosynthesis of palmitoleic and oleic acid. Although the transcriptional regulatory mechanism of SCD1 via polyunsaturated fatty acids (PUFA) has been extensively explored in nonruminants, the existence of such mechanism in ruminant mammary gland remains unknown. In this study, we used goat genomic DNA to clone and sequence a 1,713-bp fragment of the SCD1 5' flanking region. Deletion assays revealed a core region of the promoter located between -415 and -109 bp upstream of the transcription start site, and contained the highly conserved PUFA response region. An intact PUFA response region was required for the basal transcriptional activity of SCD1. Linoleic acid reduced endogenous expression of SCD1 and sterol regulatory element binding factor-1 (SREBF1) in goat mammary epithelial cells. Further analysis indicated that both the sterol response element (SRE) and the nuclear factor Y (NF-Y) binding site in the SCD1 promoter were responsible for the inhibition effect by linoleic acid, whereas the effect was abrogated once NF-Y was deleted. In addition, SRE and NF-Y were partly responsible for the transcriptional activation induced via the liver X receptor agonist T 4506585 (Sigma-Aldrich, St. Louis, MO). When goat mammary epithelial cells were cultured with linoleic acid, addition of T 4506585 markedly increased SCD1 transcription in controls, but had no effect on cells with a deleted SRE promoter. These results demonstrated that linoleic acid can regulate SCD1 expression at the transcriptional level through SRE and NF-Y in a liver X receptor-dependent fashion in the goat mammary gland.

Liver X receptor α promotes the synthesis of monounsaturated fatty acids in goat mammary epithelial cells via the control of stearoyl-coenzyme A desaturase 1 in an SREBP-1-dependent manner.

Stearoyl-coenzyme A desaturase 1 (SCD1) is a pivotal enzyme in the biosynthesis of monounsaturated fatty acids (MUFA). It is tightly regulated by transcription factors that control lipogenesis. In nonruminants, liver X receptor α (LXRα) is a nuclear receptor and transcription factor that acts as a key sensor of cholesterol and lipid homeostasis. However, the mechanism whereby LXRα regulates the expression and transcriptional activity of SCD1 in ruminant mammary cells remains unknown. In this study with goat mammary epithelial cells (GMEC), the LXRα agonist T 4506585 (T09) markedly enhanced the mRNA expression of SCD1 and sterol regulatory element binding factor 1 (SREBF1). The concentrations of C16:1 and C18:1 and their desaturation indices also were increased by LXRα activation. However, knockdown of LXRα did not alter the mRNA expression of SCD1. Although SCD1 was repressed by SREBF1 knockdown, T09 significantly increased SCD1 expression. Further analysis revealed that the SCD1 promoter activity was activated by LXRα overexpression. The goat SCD1 promoter contains 2 LXR response elements (LXRE), 1 sterol response element (SRE), and 1 nuclear factor Y (NF-Y) binding site. Site-directed mutagenesis of LXRE1, LXRE2, or SRE alone did not eliminate the upregulation of SCD1 when LXRα was overexpressed. In contrast, when NF-Y alone or in combination with SRE was mutated simultaneously, the basal transcriptional activity of the SCD1 promoter was markedly decreased and did not respond to LXRα overexpression. Furthermore, when SREBF1 was knocked down, overexpression of LXRα did not affect the promoter activity of SCD1. Together, these data suggest that LXRα regulates the expression of SCD1 through increasing SREBP-1 abundance to promote interaction with SRE and NF-Y binding sites. The present study provides evidence that LXRα is involved in the synthesis of MUFA in the goat mammary gland through an indirect mechanism.

Sterol regulatory element binding protein-1 (SREBP-1)c promoter: Characterization and transcriptional regulation by mature SREBP-1 and liver X receptor α in goat mammary epithelial cells.

Sterol regulatory element binding protein-1 (SREBP-1) is a key transcription factor that regulates lipogenesis in rodent liver. Two isoforms (SREBP-1a and SREBP-1c) of SREBP-1 are transcribed by an alternative promoter on the same gene (SREBF1), and the isoforms differ only in their first exon. Although the regulatory effects of SREBP-1 on lipid and milk fat synthesis have received much attention in ruminants, SREBP-1c promoter and its regulatory mechanisms have not been characterized in the goat. In the present study, we cloned and sequenced a 2,012-bp fragment of the SREBP-1c 5'-flanking region from goat genomic DNA. A luciferase reporter assay revealed that SREBP-1c is transcriptionally activated by the liver X receptor α (LXRα) agonist T0901317, and is decreased by SREBP-1 small interfering (si)RNA. A 5' deletion analysis revealed a core promoter region located -395 to +1 bp upstream of the transcriptional start site (TSS). Site-directed mutagenesis of LXRα binding elements (LXRE1 and LXRE2) and sterol regulatory elements (SRE1 and SRE2) revealed that the full effects of T 4506585 require the presence of both LXRE and SRE. We also characterized a new SRE (SRE1) and demonstrated a direct role of SREBP-1 (auto-loop regulation) in maintaining its basal transcription activity. Results suggest that goat SREBP-1c gene is transcriptionally regulated by mature SREBP-1 (auto-loop circuit regulation) and LXRα in goat mammary epithelial cells.

Calorimetric Studies on Thermal Properties of Nano-Cryoprotectant Solutions during Vitrification.

BACKGROUND: Vitrification, the ice-free cryopreservation, develops rapidly and can become an ideal method for long-term preservation of cells and tissues. But up to now it is not practical for samples with large size because of the ultra-rapid cooling rate required. It has been reported that nanoparticles improve heat conductivity of solutions. MATERIALS AND METHODS: In this study, Hydroxyapatite (HA) nanoparticles（20, 40 or 60nm）at 0.1 %, 0.5 % or 1 % (w/w) were added into glycerol solutions. Glass transition temperature and devitrification temperature of aqueous glycerol solutions with/without HA nanoparticles were measured by a differential scanning calorimeter(DSC) at a cooling rate of 150 degree C/min and a warming rate of 10 degree C/ min. RESULTS AND CONCLUSION: Glass-transition temperatures and devitrification temperatures of glycerol aqueous solutions increased after the incorporation of HA nanoparticles. In the study using slow cooling rate of 10 degree C/min and warming rate of 5 degree C/min, the fraction of unfrozen water in the 50 % (w/w) glycerol solution increases steadily with the addition of HA nanoparticles. The findings have significant implications for biomaterial cryopreservation.