Observation of room-temperature polar skyrmions.

Complex topological configurations are fertile ground for exploring emergent phenomena and exotic phases in condensed-matter physics. For example, the recent discovery of polarization vortices and their associated complex-phase coexistence and response under applied electric fields in superlattices of (PbTiO3)n/(SrTiO3)n suggests the presence of a complex, multi-dimensional system capable of interesting physical responses, such as chirality, negative capacitance and large piezo-electric responses1-3. Here, by varying epitaxial constraints, we discover room-temperature polar-skyrmion bubbles in a lead titanate layer confined by strontium titanate layers, which are imaged by atomic-resolution scanning transmission electron microscopy. Phase-field modelling and second-principles calculations reveal that the polar-skyrmion bubbles have a skyrmion number of +1, and resonant soft-X-ray diffraction experiments show circular dichroism, confirming chirality. Such nanometre-scale polar-skyrmion bubbles are the electric analogues of magnetic skyrmions, and could contribute to the advancement of ferroelectrics towards functionalities incorporating emergent chirality and electrically controllable negative capacitance.

[Epidemiological investigation and risk factors of diabetic retinopathy in Yunnan Province].

To investigate the prevalence and epidemiological characteristics of diabetic retinopathy (DR) in Yunnan Province, explore its risk factors, and provide a basis for the prevention and treatment of chronic complications of diabetes mellitus (DM). This is a large cross-sectional study, in all, 1 524 DM patients in 16 communities and villages of Yunnan Province who were registered in health service centers were included in this study from August to November 2019. All patients completed a uniform questionnaire, anthropometric measurements, biochemical measurements, and auxiliary examinations. Logistic regression analysis was used to screen the risk factors of DR. The prevalence rates of DR, mild non-proliferative DR (mild-NPDR), and referable DR (RDR) were 16.0% (244/1 524), 4.5% (69/1 524), and 11.5% (175/1 524), respectively. Glycated hemoglobin A1c (HbA1c)≥7.0% was the risk factor of mild-NPDR (OR=1.872, 95%CI 1.055-3.323) and RDR (OR=4.821, 95%CI 2.917-7.969). Blood pressure≥130/80 mmHg (1 mmHg=0.133 kPa) was the risk factor of mild-NPDR (OR=1.933, 95%CI 1.112-3.358) and RDR (OR=1.505, 95%CI 1.063-2.130). In Yunnan Province, 16.0% DM patients had accompanying DR, wherein about 71.7% of them required an ophthalmology referral, and the high incidence of RDR in DM patients was associated with poor control of blood glucose and blood pressure.

[Prognostic nutritional index application value for acute-on-chronic liver failure co-infection].

Objective: To explore the predictive value of the prognostic nutritional index (PNI) in concurrently infected patients with acute-on-chronic liver failure (ACLF). Methods: 220 cases with ACLF diagnosed and treated at the First Affiliated Hospital of Xi'an Jiaotong University from January 2011 to December 2016 were selected. Patients were divided into an infection and non-infection group according to whether they had co-infections during the course of the disease. Clinical data differences were compared between the two groups of patients. Binary logistic regression analysis was used to screen out influencing factors related to co-infection. The receiver operating characteristic curve was used to evaluate the predictive value of PNI for ACLF co-infection. The measurement data between groups were compared using the independent sample t-test and the Mann-Whitney U rank sum test. The enumeration data were analyzed using the Fisher exact probability test or the Pearson χ(2) test. The Pearson method was performed for correlation analysis. The independent risk factors for liver failure associated with co-infection were analyzed by multivariate logistic analysis. Results: There were statistically significant differences in ascites, hepatorenal syndrome, PNI score, and albumin between the infection and the non-infection group (P < 0.05). Among the 220 ACLF cases, 158 (71.82%) were infected with the hepatitis B virus (HBV). The incidence rate of infection during hospitalization was 69.09% (152/220). The common sites of infection were intraabdominal (57.07%) and pulmonary infection (29.29%). Pearson correlation analysis showed that PNI and MELD-Na were negatively correlated (r = -0.150, P < 0.05). Multivariate logistic analysis results showed that low PNI score (OR=0.916, 95%CI: 0.865~0.970), ascites (OR=4.243, 95%CI: 2.237~8.047), and hepatorenal syndrome (OR=4.082, 95%CI : 1.106~15.067) were risk factors for ACLF co-infection (P < 0.05). The ROC results showed that the PNI curve area (0.648) was higher than the MELD-Na score curve area (0.610, P < 0.05). The effectiveness of predicting infection risk when PNI was combined with ascites and hepatorenal syndrome complications was raised. Patients with co-infections had a good predictive effect when PNI ≤ 40.625. The sensitivity and specificity were 84.2% and 41.2%, respectively. Conclusion: Low PNI score and ACLF co-infection have a close correlation. Therefore, PNI has a certain appraisal value for ACLF co-infection.

[The impact of uncertainty resection on the prognosis of non-small cell lung cancer].

Objective: To explore the impact of uncertain resection on postoperative survival in non-small cell lung cancer. Methods: This is a retrospective cohort study. A retrospective analysis was conducted on the data of 477 patients with non-small cell lung cancer who underwent lobectomy in the Department of Thoracic Surgery, the Fourth Hospital of Hebei Medical University from December 2012 to December 2013. There were 302 males and 175 females, aged (59±8) years (range: 27 to 79 years). According to the surgical resection criteria issued by the International Association for the Study of Lung Cancer, the patients were divided into the intact resection group (R0 group, 286 cases) and the uncertain resection group (R (un) group, 191 cases). Clinical data between the two groups were compared using χ2 test, and propensity score matching (PSM) was performed on patients using the R language, with matching variables including gender, age, smoking history, adjuvant therapy, TNM stage, pathological type, and tumor site. The nearest-neighbor method was used for 1∶3 matching and the caliper value was 0.02. The survival curve was plotted using the Kaplan-Meier method and compared using the Log-rank test. The Cox proportional hazards regression model was used to identify risk factors in overall survival (OS). Subgroup analysis was based on TNM staging and mediastinal lymph node metastasis status. Results: In the R (un) group, 68 patients had positive lymph in the highest group and 129 patients did not undergo complete dissection of the mediastinal lymph nodes. The baseline data for the R0 group and the R (un) group were corrected using PSM, and a total of 369 patients were successfully matched, including 227 cases in the R0 group and 142 cases in the R (un) group. After PSM, the 5-year survival rates of the R0 group and the R (un) group were 64.3% and 52.1%, respectively (P=0.021). The 5-year survival rates of stage Ⅰ, Ⅱ, and Ⅲ patients were 85.2%, 65.9%, and 34.8%, respectively (P<0.01). TNM stage (χ2=46.913, P<0.01), pathological classification of adenosquamous cell carcinoma (HR=5.970, 95% CI: 3.117 to 11.431, P<0.01) and R (un) resection (HR=1.512, 95% CI: 1.065 to 2.147, P=0.021) were prognostic factors for postoperative survival. Subgroup analysis showed that in stage Ⅲ patients, 5-year survival rates of the R0 group and the R (un) group after resection were 45.8% and 9.5%, respectively (P=0.002). Among patients with mediastinal lymph node metastasis, 5-year survival rates of the R0 group and the R (un) group were 50.6% and 7.1%, respectively (P<0.01). Conclusions: TNM staging, pathological type, and R (un) resection are prognostic factors for overall postoperative survival in non-small cell lung cancer. In stage Ⅰ and Ⅱ patients, R (un) is not a prognostic factor for postoperative survival of non-small cell lung cancer. In patients with stage Ⅲ and mediastinal lymph node metastasis, R (un) is a prognostic factor for non-small cell lung cancer after surgery.

[Effect of recombinant human thrombin for hemostasis in liver resection: a randomized controlled phase â ¢ clinical trial].

Objective: To evaluate the hemostatic efficacy, safety and immunogenicity of recombinant human thrombin in the treatment of liver wounds that still ooze after conventional surgical hemostasis. Methods: A multicenter, stratified randomized, double-blind, placebo-controlled phase Ⅲ trial with a planned enrollment of 510 subjects at 33 centers, with a 2∶1 randomization to the thrombin group versus the placebo group. An interim analysis will be conducted after approximately 70% of the subjects have completed the observation period. The primary efficacy endpoint was the rate of hemostasis within 6 minutes at the point of bleeding that could be evaluated. Safety analysis was performed one month after surgery, and the positive rates of anti-drug antibody (ADA) and neutralizing antibody were evaluated. Results: At the interim analysis, a total of 348 subjects had been randomized and received the study drug (215 were male and 133 were female). They were aged 19-69 (52.9±10.9)years. Among them, 232 were in the thrombin group and 116 were in the placebo group, with balanced and comparable demographics and baseline characteristics between the two groups. The hemostasis rate at 6 minutes was 71.6% (95%CI:65.75%-77.36%) in the thrombin group and 44.0% (95%CI: 34.93%-53.00%) in the placebo group, respectively (P<0.001). No grade≥3 drug-related adverse events and no drug-related deaths were reported from the study.No recombinant human thrombin-induced immunologically-enhanced ADA or immunologically-induced ADA was detected after topical use in subjects. Conclusion: Recombinant human thrombin has shown significant hemostatic efficacy and good safety in controlling bleeding during liver resection surgery, while also demonstrating low immunogenicity characteristics.

[Pay attention to the imaging research in marathon-related musculoskeletal injuries].

Marathon-related musculoskeletal injuries are very common. The imaging research of musculoskeletal injuries may provide scientific support for the health protection of marathon athletes. Unfortunately, imaging studies on musculoskeletal system injury are relatively lacking, large sample studies are almost blank, and neither imaging methods nor study populations are comprehensive enough. The imaging study of marathon-related musculoskeletal injuries remains to be further studied. As a country with a large number of marathon participants, China should strengthen relevant imaging studies to provide more health protection for marathon enthusiasts and professional athletes.

[Predictive value of mismatch negativity and P3a combined with electroencephalogram reactivity for the prognosis of comatose patients after severe brain injury].

Objective: To explore the clinical value of mismatch negativity and P3a combined with electroencephalogram (EEG) reactivity to predict the prognosis of patients after severe brain injury. Methods: The clinical data of patients with severe brain injury who were admitted to the neurosurgical intensive care unit of Xiangya Hospital of Central South University from October 2019 to July 2020 were retrospectively analyzed. All patients underwent evaluation of auditory mismatch negativity (MMN), P3a, and EEG reactivity (EEG-R) within 28 days after the onset of coma. Patients were divided into two groups using the 3-month Glasgow Outcome Scale (GOS) after coma onset, a GOS score of 3-5 was defined as a favorable outcome, and GOS grades 1-2 were defined as an unfavorable outcome. The correlation between clinical indicators and prognosis was analyzed, and the predictive values of statistically significant indicators and the cut-off values were determined using the receiver operating characteristic (ROC) curve. Results: A total of 48 patients were enrolled in the study, including 35 males and 13 females (age range:18-68 years old). Twenty-nine of the patients had a favorable outcome and 19 had an unfavorable outcome. The Glasgow Coma Scale (GCS), EEG-R, absolute amplitude of MMN at Fz (FzMMNA), and amplitude of P3a at Cz (CzP3aA) were significantly correlated with the prognosis of comatose patients (P<0.001). Multivariate logistic regression analysis revealed that only EEG-R, FzMMNA, and CzP3aA were independent predictors for the prognosis of comatose patients after severe brain injury (all P<0.05), with the area under the curve (AUC) of 0.757 (0.613-0.900), 0.912 (0.830-0.994) and 0.887 (0.793-0.981), respectively. The combination of FzMMNA and CzP3aA and the combinationof EEG-R, FzMMNA and CzP3aA increased the value of AUC to 0.942 (0.879-1.000) and 0.964 (0.920-1.000), respectively. Moreover, a cut-off value of 1.27 µV and 2.64 µV for FzMMNA and CzP3aA, respectively, yielded the best sensitivity and specificity for the prognosis prediction of patients with severe brain injury [FzMMNA: 89.66%(26/29) and 84.21%(16/19); CzP3aA:82.76%(24/29) and 84.21%(16/19)]. Conclusion: This study indicates that the combination of EEG-R, FzMMNA, and CzP3aA may serve as a favorable prognostic indicator for comatose patients after severe brain injury.

[Assessment of folate status among women of childbearing age from 2000 to 2020].

Objective: To analyze the folate status among women of childbearing age worldwide from 2000 to 2020, and explore the impact of socioeconomic factors on folate status, so as to provide support for the formulation of relevant supplementary policies in China in the future. Methods: The "folate" "folic acid" "deficiency" "status" "women" "childbearing" and "reproductive" were used as Chinese and English keywords to systematically search CNKI and PubMed database. Global Health Data Exchange database (GDHx), Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia datasets (BRINDA) and Ground Work publications were systematically searched with "micronutrients" and "nutrition" as keywords. The retrieval time was from January 1, 2000 to August 31, 2020, and the language was restricted to English and Chinese. After title, abstract and full-text screening, a total of 45 literatures were included. The folate status of women of childbearing age in the eligible literature was analyzed, and the income and folate status were tested by Kruskal Wallis H test and Nemenyi test. Results: The M (Q1, Q3) of serum folate deficiency rate and erythrocyte folate insufficiency rate in women of childbearing age were 15.0% (3.5%, 37.0%) and 49.0% (22.0%, 83.0%). There were great differences in serum folate status and serum folate deficiency rate among women of childbearing age in different income countries. The serum folate deficiency rate of women of childbearing age in low-income countries was significantly higher than that in middle and high-income countries. Conclusion: The folate status of women of childbearing age in most countries has not reached the ideal state from 2000 to 2020. More studies on folate supplementation programs should be carried out.

[The effect of maternal HBV DNA levels on HBV intrauterine transmission and fetal distress].

Aim: To identify the key risk factors of intrauterine hepatitis B virus transmission (HBV) and its effect on the placenta and fetus. Methods: 425 infants born to hepatitis B surface antigen (HBsAg)-positive pregnant women who received combined immunization with hepatitis B immunoglobulin and hepatitis B vaccine between 2009 to 2015 were prospectively enrolled in this study. The intrauterine transmission situation was assessed by dynamic monitoring of infants HBV DNA load and quantitative HBsAg. Univariate and multivariate regression analysis was used to determine the high risk factors for intrauterine transmission. Stratified analysis was used to determine the relationship between maternal HBV DNA load and fetal distress. Transmission electron microscopy was used to observe HBV Effects on placental tissue. Results: HBV intrauterine infection rate was 2.6% (11/425). Multivariate analysis result showed that the maternal HBV DNA load was an independent risk factor for intrauterine infection among infants (P=0.011). Intrauterine infection and distress rate was significantly higher in infants with with maternal HBV DNA>106 IU/ml than those with HBV DNA <106 IU/ml (12.2% vs. 1.8%; χ2=11.275, P=0.006), and (24.4% vs. 16.0%, χ2=3.993, P=0.046). Transmission electron microscopy showed that mitochondrial edema, endoplasmic reticulum expansion and thicker basement membrane were apparent when the maternal HBV DNA>106 IU/ml than that of maternal HBV DNA<106 IU/ml (960 nm vs. 214 nm, Z=-2.782, P=0.005) in the placental tissue. Conclusion: Maternal HBV DNA>106 IU/ml is associated not only with intrauterine infection, but also with increased incidence of intrauterine distress and placental sub-microstructural changes, providing strong clinical and histological evidence for pregnancy avoidance and treatment in this population.

[Prognostic analysis of different comprehensive treatment models for locally advanced esophageal squamous cell carcinoma based on propensity score matching].

Objective: To compare the effects of preoperative neoadjuvant chemotherapy and postoperative adjuvant chemotherapy on the long-term survival of patients with radical resection for esophageal squamous cell carcinoma. Methods: Totally 1 082 patients with stage T3-4aN0-3M0 thoracic esophageal squamous cell carcinoma were recruited in this study who underwent radical resection at Department of Thoracic Surgery, Fourth Hospital, Hebei Medical University from January 2005 to January 2015. There were 798 males and 284 females, with a median age of 61 years (range: 37 to 86 years). There were 138 patients undergoing preoperative neoadjuvant chemotherapy, 392 patients postoperative adjuvant chemotherapy, and 552 patients surgery alone. The neoadjuvant chemotherapy group was used as the benchmark group to match the propensity score with the adjuvant chemotherapy group and the surgery-only group respectively at a ratio of 1∶3. A total of 7 covariates including tumor location, number of positive lymph nodes, tumor invasion depth, tumor differentiation degree, surgical procedure, vascular tumor thrombus and nerve invasion were included, and the caliper value was taken as 0.1. After matching, a total of 699 patients were included for the analysis, including 128 patients in the neoadjuvant chemotherapy group, 267 patients in the adjuvant chemotherapy group, and 304 patients in the surgery alone group. The Kaplan-Meier method was used to generate the survival curves which was tested by the Log-rank method for survival analysis. Results: After matching analysis, the 5-year overall survival rate was 41.5% in the neoadjuvant chemotherapy group with a median overall survival time of 43 months (95%CI: 27 to 59 months), 57.6% in the adjuvant chemotherapy group with a median overall survival time unreached, and 24.9% in the surgery alone group with a median overall survival time of 28 months (95%CI: 25 to 31 months) (χ²=60.475, P<0.01). For overall survival after matching, the adjuvant chemotherapy group was better than the neoadjuvant chemotherapy group (χ²=11.384, P=0.001), the neoadjuvant chemotherapy group was better than the surgery alone group (χ²=8.654, P=0.003), and the adjuvant chemotherapy group was better than surgery alone group (χ²=60.234, P<0.01). Conclusion: Both preoperative neoadjuvant chemotherapy and postoperative adjuvant chemotherapy can improve the long-term survival of patients with locally advanced esophageal squamous cell carcinoma undergoing radical resection, and the improvement effect of postoperative adjuvant chemotherapy is more obvious.

Correction: Protein kinase Mζ in medial prefrontal cortex mediates depressive-like behavior and antidepressant response.

Following publication of this article, the authors noted that the bands of Na-K ATPase in Figure S1B were mislabelled when selecting representative blots, and were erroneously duplicated from GluA2. However, the data analysis was still made with the correct immunoblots. The Supplementary Information file has now been updated to include the corrected Figure S1 with the correct western blot bands of Na-K ATPase.The authors would like to apologise for this error and the inconvenience this may have caused. This has been corrected in both the PDF and HTML versions of the article.

Analysis of a registry database for esophageal cancer from high-volume centers in China.

Esophageal cancer has a high incidence among malignancies in China, but a comprehensive picture of the status of its surgical management in China has hitherto not been available. A nationwide database has recently been established to address this issue. METHOD: A National Database was setup through a network platform, and data was collected from 70 high-volume centers (>100 esophagectomies/per year) across China. Data was entered between January 2009 and December 2014, and was analyzed in June 2015 after a minimal follow-up of 6 months for all patients. 8181 patients with complete data who received surgery for primary esophageal cancer on the Database were included in the analysis. RESULT: In this series, there were 6052 males and 2129 females, with a mean age of 60.5 years (range: 22-90 years). The pathology in 95.5% of patients was squamous cell carcinoma. The pathological stage distribution was 1.2% in stage 0, 2.5% in Ia, 11.5% in Ib, 14.8% in IIa, 36.1% in IIb, 19.3% in IIIa, 8.3% in IIIb, 6.2% in IIIc. 1800 patients (22.0%) with locally advanced disease received preoperative neoadjuvant therapy and 3592 patients (43.9%) underwent postoperative adjuvant chemotherapy and/or radiotherapy. The esophagectomies were performed through left thoracotomy approach in 5870 cases (72.6%), through right chest approach in 2215 cases (27.4%) including right thoracotomy (21.3%) and VATS (6.1%). The 30-day postoperative mortality rate was 0.6% (43 patients), and the overall postoperative complication rate was 11.6% (951 patients). The 1-, 3-, and 5-year overall survival rates were 82.6%, 61.6%, and 52.9%, respectively. CONCLUSION: This National Registry Database from high-volume centers provides a comprehensive picture of surgical management for esophageal cancer in China for the first time. Squamous cell carcinoma predominates, but there is heterogeneity with respect to the surgical approach and perioperative oncologic management. Overall, surgical mortality and morbidity rates are low, and good survival rates have been achieved due to improvement of surgical treatment technology in recent years.

[Epidemiological characteristic and current status of surgical treatment for esophageal cancer by analysis of national registry database].

Objective: To investigate the epidemiological characteristics and current status of surgical management for esophageal cancer in China. Methods: A national database was setup through a network platform. The clinical data of esophageal cancer treated by surgery was collected from 70 major hospitals in China between January 2009 and December 2014. Results: Complete data of 8 181 cases of esophageal cancer patients who underwent surgery were recorded in the database and recruited in the analysis. Among them, 6 052 cases were male and 2 129 were female, the average age was 60.5 years.The epidemiological investigation results showed that 148 cases (1.8%) had history of psychological trauma, 7 527 cases (92.0%) were lower social economic status, 5 072 cases (62.0%) were short of fresh vegetables and fruits, 6 544 cases (80.0%) ate rough food frequently, 3 722 cases (45.5%) drank untreated water directly from lake or river or shallow well, 3 436 cases (42.0%) had a unhealthy eating habit, including habits of eating food fast (507 cases, 6.2%), eating hot food or drinking hot tea/soup (998 cases, 12.2%), eating fried food (1 939 cases, 23.7%), 4 410 cases (53.9%) had the habits of smoking cigarettes and 2 822 cases (34.5%) drank white wine frequently.The pathological results showed that 7 813 cases (95.5%) were squamous cell carcinoma, 267 cases were adenocarcinoma (3.3%), 25 cases were adenosquamous cell carcinoma (0.3%) and 50 cases were small cell carcinoma (0.6%). A total of 1 800 cases (22.0%) received preoperative neoadjuvant therapy due to locally advanced disease or difficulty of resection. The esophagectomies were performed through left thoracotomy approach in 5 870 cases (71.8%), through right chest approach in 2 215 cases (27.1%), and the remain 96 cases (1.2%) received surgery though other approaches.A total of 8 001 cases (97.8%) underwent radical resection, the other 180 cases (2.2%) received palliative resection. The 30-day postoperative mortality rate was 0.5%, the overall ≥ grade Ⅱ postoperative complication rate was 11.6% (951 cases). The 1-yr, 3-yr, and 5-yr overall actual survival rates were 82.6%, 61.6%, and 52.9%, respectively. Conclusions: The data analysis of the national database for esophageal cancer shows that bad eating habits or eating rough food without enough nutrients, lower social and economic status, drinking white wine and smoking cigarettes frequently may be correlated with tumorigenesis of esophageal cancer. However, strong evidences produced by prospective observation studies are needed. Overall, the long-term survival of esophageal cancer patients has been improved gradually due to the application of advanced surgical techniques and reasonable multimodality treatment.

[Relationship of plasma vitamin A levels between neonates and pregnant women in third trimester].

OBJECTIVE: To study the correlation of plasma vitamin A (VitA) levels between neonates and pregnant women in third trimester. METHODS: A total of 688 pregnant women were recruited in Yuanshi and Laoting counties of Hebei Province, from May to June 2009. Venous blood samples of women before delivery and cord blood samples of newborns were collected and measured for retinol (retinol concentration was used to reflect VitA level) using high performance liquid chromatography assay. According to venous blood plasma retinol concentration, maternal VitA nutritional status was divided into deficiency (<0.70 µmol/L), marginal deficiency (0.70-<1.05 µmol/L), and sufficiency (≥1.05 µmol/L). According to cord blood plasma retinol concentration, neonatal VitA nutritional status was divided into deficiency (<0.35 µmol/L), marginal deficiency (0.35-<0.70 µmol/L), and sufficiency (≥0.70 µmol/L); neonatal VitA relative deficiency was further defined as cord blood plasma retinol concentration lower than the 10th percentile. VitA placental transport ratio was defined as retinol concentration in the neonates divided by that in pregnant women. Multivariable fractional polynomials (MFP) model and Pearson correlation were used to study the dose-response relationship between maternal and neonatal plasma VitA levels, Logistic regression model to estimate the effect of maternal VitA nutritional status on neonatal VitA deficiency, and MFP model and Spearman correlation to describe the relationship between maternal VitA level and VitA placental transport ratio. RESULTS: The average retinol concentration of the pregnant women was (1.15±0.30) µmol/L, and the prevalence of VitA deficiency and marginal deficiency were 4.5% and 37.8%, respectively. Average retinol concentration of the neonates was (0.78±0.13) µmol/L, and no neonates were VitA deficiency, 28.2% of the neonates were marginal deficiency. After multivariable adjustment, the VitA level of the neonates was positively and linearly related to maternal VitA level (pm=1, P<0.05), with the corresponding Pearson correlation coefficient of 0.13 (P<0.01). As compared with the women with sufficient VitA, those with VitA deficiency (crude OR=2.20, 95%CI:1.04-4.66) and marginal deficiency (crude OR=1.43, 95%CI:1.01-2.02) had higher risks to deliver neonates with VitA marginal deficiency; while the risks turned to be non-significant after multivariable adjustment. The pregnant women with VitA deficiency had higher risk to deliver neonates with relative VitA deficiency before and after multivariable adjustment (crude OR=3.02, 95%CI:1.21-7.50; adjusted OR=2.76, 95%CI:1.05-7.22). The maternal VitA level was negatively and non-linearly correlated with placental transport ratio (pm= -0.5, P<0.05), with corresponding adjusted Spearman correlation coefficient of -0.82 (P<0.001). CONCLUSION: There was a positive linear dose-response relationship between VitA levels of newborns and pregnant women in third trimester, indicating that neonatal VitA storing levels at birth was affected by maternal VitA nutritional status.

[Predicting the prognosis for severe brain injury patients: short-latency somatosensory evoked potential combined with electroencephalogram reactivity].

Objective: To explore the the effectiveness of using short-latency somatosensory evoked potential(SLSEP) combined with electroencephalogram(EEG) reactivity to predict the prognosis of severe brain injury(SBI) patients. Methods: Consecutive patients with SBI admitted in neurosurgery intensive care unit(NSICU) at Xiangya Hospital of Central South University from July 2018 to January 2019 were prospectively collected. SLSEP and EEG were recorded in these patients in NSICU within two weeks after injury onset. EEG reactivity(EEG-R) was tested during EEG signal stabilization. In addition, the concentrations of serum neuron-specific enolase (NSE) and S100 protein were also detected. All patients were evaluated with Glasgow Outcome Scale(GOS) during 12 months' follow-up. GOS grade 3 to 5 was defined as favorable group, and GOS grade 1 to 2 was defined as unfavorable group. The association of relevant predictors with patient's prognosis was assessed. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate each potential predictor. Results: Forty-three patients were included in the study, with 26 patients of favorable outcomes and 17 patients with unfavorable prognosis. Univariate analysis revealed that the Glasgow Coma Scale (GCS) score, the concentration of serum NSE, EEG-R, the amplitude of SLSEP were all associated with the prognosis after 12 months' follow-up. Moreover, the AUC for prediction of favorable prognosis by GCS, NSE, EEG-R, SLSEP was 0.661(95%CI: 0.493-0.829), 0.697(95%CI: 0.531-0.862), 0.718(95%CI: 0.557-0.879) and 0.758(95%CI: 0.609-0.907) respectively. However, there was no significant difference of age, gender, pupillary light reflex and S100 protein between the two groups. Furthermore, multiple logistic regression analysis showed that only SLSEP amplitude (OR=2.058, 95%CI: 0.867-4.888) and EEG-R(OR=3.748, 95%CI: 0.857-16.394) were independent predictors of favorable prognosis, and the prognostic model containing these two variables yielded an predictive performance with an AUC of 0.798. Conclusion: The higher amplitude of SLSEP and the existence of EEG-R are predictors of good prognosis in SBI patients, and the combined use of SLSEP and EEG-R in predicting the prognosis of SBI patients is more reliable.

[Continue to strengthen the study on diagnosis and surgical treatment of primary esophageal motility disorders and gastroesophageal reflux diseases].

The advent of high-resolution esophageal manometry in this century produced manometric types of esophageal achalasia, which was very important for the selection of treatment methods and the assessment of prognosis. The application of 24-hour esophageal pH monitoring combined with impedance played a decisive role in determination of gastroesophageal reflux and refluxant. Advanced technologies such as laparoscopic Heller myotomy and per-oral endoscopic myotomy were used for surgical treatment of achalasia, laparoscopic anti-reflux procedures and magnetic sphincter augmentation were applied to the treatment of gastroesophageal reflux diseases (GERD). These advanced procedures implied that the treatment of primary esophageal motility disorders (PEMD) and GERD came into the minimally invasive era. However, the diagnosis and treatment of PEMD and GERD are not popular enough in our country, the studies and high-level clinical evidences are insufficient on uncommon PEMD and complex GERD, which are the further directions of efforts.

[Efficacy of three-dimensional visualization technology in the precision diagnosis and treatment for primary liver cancer: a retrospective multicenter study of 1 665 cases in China].

Objective: To evaluate the efficacy of three-dimensional(3D) visualization technology in the precision diagnosis and treatment for primary liver cancer. Methods: A total of 1 665 patients with primary liver cancer who admitted to seven medical centers in China between January 2009 to January 2019, diagnosed and treated by 3D visualization protocol were analyzed, and their clinical data were retrospectively reviewed. There were 1 255 males(75.4%) and 410 females(24.6%), with age of (52.9±11.9) years (range: 18 to 86 years). The acquisition of high-quality CT images with submillimeter spatial resolution were conducted using a quality control system. By means of homogenization methods, 3D reconstruction and 3D visualization analysis were performed. Postoperative observation: pathology reports, microvascular invasion, perioperative complications and follow-up. SPSS 25.0 statistical software was used for statistical description and analysis of clinical data. Kaplan-Meier curve was used to calculate overall survival and disease-free survival rate. Results: (1)In the sample of 1 265 patients, 3D reconstructed models clearly displayed as follows. tumor size: ≤2 cm in 155 cases (9.31%), >2 cm to 5 cm in 551 cases (33.09%), >5 cm to 10 cm in 636 cases (38.20%), >10 cm in 323 cases (19.40%). (2) Classification of hepatic blood vessels. Hepatic artery: type Ⅰ(normal type) in 1 494 cases(89.73%),variant hepatic artery in 171 cases (10.27%), including type Ⅱ in 35 cases, type Ⅲ in 38 cases, and other types in 98 cases. Hepatic vein: type Ⅰ (normal) in 1 195 cases (71.77%),variant hepatic veins in 470 cases(28.23%), including type Ⅱ in 376 cases and type Ⅲ in 94 cases. Portal vein:normal type in 1 315 cases (78.98%), variant portal veins in 350 cases (21.02%), including type Ⅰ in 189 cases, type Ⅱin 103 cases, type Ⅲ in 50 cases, type Ⅳ in 8 cases. Hepatic artery variation coexisting with portal vein variation in 24 cases (1.44%). Hepatic vein variation coexisting with portal vein variation in 113 cases (6.79%). Three types of vascular variation in 4 cases (0.24%), including coexistence of type Ⅱ hepatic artery variation or type Ⅰ portal vein variation with type Ⅲ hepatic vein variation in 2 cases,coexistence of type Ⅲ hepatic artery variation or type Ⅲ portal vein variation with type Ⅱ hepatic vein variation in 2 cases. (3) Preoperative liver volume calculation:1 499.3 (514.4)ml (range:641.7 to 6 637.0 ml) of total liver volume, including 479.1 (460.1) ml (range:10.5 to 2 086.8 ml) for liver resection and 959.9 (460.4)ml (range:306.1 to 5 638.0 ml) for residual function. (4)Operative methods: anatomical hepatectomy in 1 458 cases (87.57%); non-anatomic hepatectomy in 207 cases (12.43%). (5)the median operation time was 285(165)minutes (range: 40 to720 minutes). (6)The median intraoperative blood loss was 200(250)ml (range:10 to 4 200 ml) and 346 cases (20.78%) had intraoperative transfusion. (7)Pathology reports: hepatocellular carcinoma in 1 371 cases (82.34%), cholangiocarcinoma in 260 cases (15.62%) and mixed hepatocellular carcinoma in 34 cases (2.04%). Microvascular invasion: M0 in 199 cases, M1 in 64 cases, and M2 in 27 cases. (8)Postoperative complications in 207 cases (12.43%), including Clavien-Dindo grade Ⅰ or Ⅱ in 57 cases, grade Ⅲ or Ⅳ in 147 cases and grade Ⅴ in 3 cases.There were 13 cases (0.78%) of liver failure and 3 cases (0.18%) of perioperative death. (9) The follow-up time was 3.0 to 96.0 months, with a median time of 21.0(17.8) years. The overall 3-year survival and disease-free survival rates were 80.0% and 56.5%, respectively. The overall 5-year survival and disease-free survival rates were 59.7% and 30.0%, respectively. Conclusion: 3D visualization technology plays an important role in realizing accurate diagnosis of anatomical location and morphology of primary liver cancer, improving the success rate of surgery and reducing the incidence of complications.

Overall survival and updated progression-free survival outcomes in a randomized phase II study of combination cediranib and olaparib versus olaparib in relapsed platinum-sensitive ovarian cancer.

BACKGROUND: Olaparib is a poly(ADP-ribose) polymerase inhibitor and cediranib is an oral anti-angiogenic. In the primary analysis of this phase II study, combination cediranib/olaparib improved progression-free survival (PFS) compared with olaparib alone in relapsed platinum-sensitive ovarian cancer. This updated analysis was conducted to characterize overall survival (OS) and update PFS outcomes. PATIENTS AND METHODS: Ninety patients were enrolled to this randomized, open-label, phase II study between October 2011 and June 2013 across nine United States-based academic centers. Data cut-off was 21 December 2016, with a median follow-up of 46 months. Participants had relapsed platinum-sensitive ovarian cancer of high-grade serous or endometrioid histology or had a deleterious germline BRCA1/2 mutation (gBRCAm). Participants were randomized to receive olaparib capsules 400 mg twice daily or cediranib 30 mg daily and olaparib capsules 200 mg twice daily until disease progression. RESULTS: In this updated analysis, median PFS remained significantly longer with cediranib/olaparib compared with olaparib alone (16.5 versus 8.2 months, hazard ratio 0.50; P = 0.007). Subset analyses within stratum defined by BRCA status demonstrated statistically significant improvement in PFS (23.7 versus 5.7 months, P = 0.002) and OS (37.8 versus 23.0 months, P = 0.047) in gBRCA wild-type/unknown patients, although OS was not statistically different in the overall study population (44.2 versus 33.3 months, hazard ratio 0.64; P = 0.11). PFS and OS appeared similar between the two arms in gBRCAm patients. The most common CTCAE grade 3/4 adverse events with cediranib/olaparib remained fatigue, diarrhea, and hypertension. CONCLUSIONS: Combination cediranib/olaparib significantly extends PFS compared with olaparib alone in relapsed platinum-sensitive ovarian cancer. Subset analyses suggest this margin of benefit is driven by PFS prolongation in patients without gBRCAm. OS was also significantly increased by the cediranib/olaparib combination in this subset of patients. Additional studies of this combination are ongoing and should incorporate analyses based upon BRCA status. TRIAL REGISTRATION: Clinicaltrials.gov Identifier NCT0111648.

Protein kinase Mζ in medial prefrontal cortex mediates depressive-like behavior and antidepressant response.

Neuronal atrophy and alterations of synaptic structure and function in the medial prefrontal cortex (mPFC) have been implicated in the pathogenesis of depression, but the underlying molecular mechanisms are largely unknown. The protein kinase Mζ (PKMζ), a brain-specific atypical protein kinase C isoform, is important for maintaining long-term potentiation and storing memory. In the present study, we explored the role of PKMζ in mPFC in two rat models of depression, chronic unpredictable stress (CUS) and learned helplessness. The involvement of PKMζ in the antidepressant effects of conventional antidepressants and ketamine were also investigated. We found that chronic stress decreased the expression of PKMζ in the mPFC and hippocampus but not in the orbitofrontal cortex. Overexpression of PKMζ in mPFC prevented the depressive-like and anxiety-like behaviors induced by CUS, and reversed helplessness behaviors. Inhibition of PKMζ in mPFC by expressing a PKMζ dominant-negative mutant induced depressive-like behaviors after subthreshold unpredictable stress and increased learned helplessness behavior. Furthermore, stress-induced deficits in synaptic proteins and decreases in dendritic density and the frequency of miniature excitatory postsynaptic currents in the mPFC were prevented by PKMζ overexpression and potentiated by PKMζ inhibition in subthreshold stress rats. The antidepressants fluoxetine, desipramine and ketamine increased PKMζ expression in mPFC and PKMζ mediated the antidepressant effects of ketamine. These findings identify PKMζ in mPFC as a critical mediator of depressive-like behavior and antidepressant response, providing a potential therapeutic target in developing novel antidepressants.

[In vitro fertilization-embryo transfer affects focal adhension kinase signaling pathway in early placenta].

OBJECTIVE: To study the effects of in vitro fertilization-embryo transfer (IVF-ET) technique on gene expression of focal adhension kinase (FAK) signaling pathway in early placental trophoblast cells, and to explore the effects of IVF-ET technology on the development and function of early placenta. METHODS: We collected 7-8 weeks of gestation placenta tissue as a study group by ultrasound guided reduction of fetal from double embryo transfer under IVF-ET technology. In the control group, placenta tissues were obtained from the spontaneous abortion of natural pregnancy twin 7-8 weeks. Microarray hybridization analysis was performed on the placenta tissue of the two groups using the Affymetrix HG-U133 Plus 2.0 gene chip. Eight differentially expressed genes were identified by real-time quantitative polymerase chain reaction (qRT-PCR), and unsupervised clustering analysis and functional bioinformatics analysis were performed for the differentially expressed genes. RESULTS: Twenty-eight cases of IVF-ET reduced fetal villi and 8 cases of spontaneous abortion villi were collected. A total of 8 placental villi were detected by the gene chip. Compared with the natural pregnancy control group, 32 differentially expressed genes in the placental FAK signaling pathway were expressed in IVF-ET. The differential expression was greater than or equal to 2 times, of which 12 genes were up-regulated and 20 were down-regulated. The qRT-PCR showed that the expression of the 8 genes in FAK signaling pathways of IVF-ET was significantly different from that in the placenta of natural pregnancy, which was consistent with the result of the gene chip detection. The FAK signal pathway gene localization showed that the FAK gene was mainly located in the upstream of the signal pathway in the placenta of IVF-ET. The placental trophoblast cells maintained the FAK signaling pathway function through gene expression compensation. CONCLUSION: There are gene expression differences in the FAK signaling pathway between the IVF-ET derived early placenta and the natural pregnancy placenta. The differentially expressed genes are involved in many key functions of the FAK signaling pathway and affect the early development and function of the IVF-ET placenta, while the placental trophoblast cells change gene expression for interference to compensate for IVF-ET technology itself, maintain normal function of the FAK signaling pathway, and satisfy the need for placental and fetal development.