[Application and research progress of patient-derived organoids in the multimodality treatment of pancreatic cancer].

Pancreatic cancer is one of the most malignant tumors with a 5-year survival rate of 13%. Difficulty in early diagnosis,high tumor heterogeneity,high rate of drug resistance,and lack of effective new drugs are the main reasons for the poor therapeutic effect. Traditional cell line models cannot simulate the tumor environment in vitro and cannot reflect the heterogeneity of pancreatic cancer,while animal models have a long culture process and cannot be used for high-throughput screening. Pancreatic cancer organoids can be continuously expanded and cultured in vitro,which can realistically reflect the heterogeneity of pancreatic cancer and allow high-throughput drug screening,making it an ideal tool for individualized precision diagnosis and treatment of pancreatic cancer. According to recent studies on the evaluation of clinical drug efficacy using pancreatic cancer organoids,the drug sensitivity of pancreatic cancer organoids is highly consistent with the clinical efficacy,demonstrating the feasibility of drug sensitivity of pancreatic cancer organoids in guiding clinical therapy,comfirming the ability to discover potential therapeutic drugs through high-throughput drug screening of pancreatic cancer organoids. At the same time,this review reveals the importance of pancreatic cancer organoids as a model of the pancreatic cancer microenvironment for the development of new drugs and tumor microenvironment research. and the role of pancreatic cancer organoids as a model that can reflect the specific microenvironment of pancreatic cancer for new drug discovery and microenvironmental evaluation. Pancreatic cancer organoids and organ-on-chips are powerful tools for precision companion therapy and new drug discovery.

[Analysis of safety and factors influencing the surgical efficacy of benign biliary stenosis treated with autologous gastric flap repair with the vascular tip].

Objective: To investigate the complication rate and risk factors associated with using autologous gastric flap tissue with a vascular tip to treat benign biliary strictures. Methods: A retrospective analysis was conducted on clinical data of 92 patients with benign biliary stenosis who applied autologous gastric flap tissue to repair the stenosis at the PLA General Hospital from January 2006 to May 2022. Among them, there were 40 males and 52 females, aged from 25 to 79 (50.5±12.9) years. The perioperative clinical data of the patients were recorded(Body Mass Index、preoperative platelets et.), and a multivariate logistic regression model was used to analyze the factors influencing postoperative complications. Long-term follow-up was conducted to evaluate the long-term efficacy of autologous gastric flap tissue with vascular tissues for benign biliary stenosis surgery. Results: The incidence of recent postoperative complications in patients was 26.1%, and univariate analysis showed that preoperative bile-intestinal anastomosis, positive intraoperative bile bacterial culture, low preoperative hemoglobin, and low preoperative platelet count were significantly associated with the occurrence of postoperative complications after biliary stenosis repair with a vascularized gastric flap (P<0.05). Multifactorial analysis showed that low preoperative platelets (OR=0.990, 95%CI: 0.982-0.998, P=0.015), low preoperative hemoglobin (OR=4.953, 95%CI: 1.405-15.010, P=0.012) and positive intraoperative bile bacterial culture (OR=19.338, 95%CI: 3.618-103.360, P<0.001) were independent risk factors for the development of postoperative complications. The excellent long-term follow-up rate of patients was 92.0%. Conclusions: The procedure of repairing benign biliary stenosis with a vascularized gastric flap preserves the function of the sphincter of Oddi and reconstructs the normal physiological passage of the bile duct. This procedure is safe and feasible and provides a reliable option for the surgical treatment of bile duct injury and bile duct stenosis.

[The predictive values of platelet mitochondrial mass and quantity during the perioperative period in elderly patients on the occurrence of postoperative delirium].

Objective: To investigate the changes of platelet mitochondrial mass and quantity during perioperative period in elderly patients, and assess their predictive values on the occurrence of postoperative delirium (POD). Methods: In this prospective study, 162 elderly patients scheduled for abdominal surgery under general anesthesia were enrolled from November 2021 to January 2022 in Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School. Among them, 20 patients [10 males, 10 females, aged (71.4±6.8) years] developed POD within 3 days after surgery (POD group), and another 20 patients[12 males, 8 females, aged (67.7±5.3) years] who did not develope POD were selected as controls (control group) using propensity score matching method. Blood samples were collected preoperatively, at the end of surgery and on the first postoperative day. Platelets were extracted and mitochondrial mass was detected with flow cytometry. Transmission electron microscopy was used to determine mitochondrial quantity. The receiver operating characteristic (ROC) curve was drawn to analyze the value of mitochondrial mass and quantity in predicting the occurrence of POD. Results: The mean fluorescence intensities of platelet mitochondrial mass were 193±46, 236±61, 264±53 preoperatively, at the end of surgery and on the first postoperative day in the POD group, respectively. The corresponding values were 209±61, 191±67 and 201±56 in the control group. The platelet mitochondrial mass of patients in the POD group was significantly increased on the first postoperative day compared to preoperative levels (P<0.001). In contrast, there was no significant difference in the control group (P=0.410). Patients in the POD group had higher platelet mitochondrial mass than patients in the control group on the first postoperative day(P=0.002). Meanwhile, platelets from patients in the POD group showed significantly higher number of mitochondria than platelets from patients in the control group [3 (2, 4) vs 2 (1, 2), P<0.001]. According to the ROC curve of platelet on the first postoperative day, at a mitochondrial mass cut-off value of>275.35, the sensitivity, specificity and area under the ROC curve to detect the occurrence of POD were 55%, 90% and 0.800 (95%CI: 0.666-0.934, P<0.001). At a mitochondrial quantity cut-off value of>2, the sensitivity, specificity and area under the ROC curve to detect the occurrence of POD were 53%, 78% and 0.680 (95%CI: 0.584-0.776, P<0.001). Conclusions: Patients who developed POD show higher platelet mitochondrial mass after surgery compared to preoperative levels. The mitochondrial mass of platelets on the first postoperative day has good predictive value on the occurrence of POD.

[Efficacy observation and compliance analysis of pollen allergen drops in seasonal allergic rhinitis].

To study the efficacy and compliance analysis of pollen allergen drops in the treatment of allergic rhinitis. The method of single-center controlled was used to analyze the dates' results. From July 2021 to September 2021, 80 patients with seasonal allergic rhinitis were referred to the clinic of otorhinolaryngology in First Hospital of Shanxi Medical University.40 patients received sublingual immunotherapy (SLIT group), and the other 40 patients received symptomatic drug treatment as the control group. The total rhinoconjunctivitis symptom score (TRSS), the visual analogue scale(VAS), total medication score (TMS) and combined scores of medication and rhinoconjunctivitis symptoms (CSMRS) of the patient before the start of the treatment and after the first year of the treatment were compared to assess the efficacy of sublingual immunotherapy of Artemisia pollen. Follow the shedding during the study, the safety of the drug and the causes for compliance analysis were analyzed and recorded. The results of comparison with TRSS, VAS, TMS and CSMRS in two groups in the period of pretherapy were as follows: TRSS(12.393±3.023, 12.450±3.029, t=-0.077, P=0.939), VAS(8.357±1.026, 8.400±0.982, t=-0.173, P=0.862), TMS(3.214±0.568, 3.175±0.501, t=0.301, P=0.764), CSMRS (5.286±0.680, 5.253±0.677, t=0.199, P=0.843), there was no significant difference (P>0.05); lower observed symptom scores were got in the post-treatment pollen peak SLIT group compared to the control group, TRSS(3.964±1.551, 7.750±2.169, t=-7.918, P<0.05), VAS(2.893±0.956, 5.175±1.481, t=-8.286, P<0.05), TMS (1.821±0.863, 3.175±0.501, t=-8.163, P<0.05), CSMRS (2.489±0.921, 4.468±0.601, t=-10.723, P<0.05), and the differences between the groups were statistically significant (P<0.05); the SLIT group significantly reduced all symptom scores at the first peak compared to the starting, TRSS(12.393±3.023, 3.964±1.551, t=20.576, P<0.05), VAS (8.357±1.026, 2.893±0.956, t=30.070, P<0.05), TMS (3.214±0.568, 1.821±0.863, t=7.151, P<0.05), CSMRS(5.286±0.680, 2.489±0.921, t=14.533, P<0.05) and there was statistical difference (P<0.05). No significant adverse reactions occured during medication in the SLIT group. A total of 12 cases were shed in the SLIT group, so the compliance rate was 70%. The four reasons were that patients considered the course was long (4 cases, 33%); the drugs were expensive (3 cases, 25%); patients were busy with their work and life (3 cases, 25%); patients were affected by the outbreak (2 cases, 17%). In summary, Artemisia pollen sublingual drops may improve the symptoms of the patients who got allergic rhinitis caused by Artemisia pollen after the treatment for one year. However, due to the lack of sufficient understanding of immunotherapy or the difficulty in adhering to standardized medication, the compliance with sublingual immunotherapy is still poor, the compliance with sublingual immunotherapy needs to be further improved through patient education.

[Distribution and reference intervals of daytime intraocular pressure in the eye health screening population of Handan].

Objective: To describe the distribution and establish reference intervals (RI) of daytime intraocular pressure (IOP) in the eye health screening population of Handan. Methods: This cross-sectional study included subjects who participated in eye health screening at the Physical Examination Center of Handan First Hospital from May 2021 to June 2022. A complete general and ocular examination was performed, including measurements of visual acuity and IOP (using Goldmann tonometry), slit lamp microscopy, fundus photography, and anterior and posterior segment optical coherence tomography. Subjects with factors that could cause significant changes in IOP or affect the accuracy of IOP measurement, or with an inability to measure IOP were excluded. Simple random sampling was used to select participants, who were grouped by gender and age (18 to <30, 30 to <40, 40 to <50, 50 to <60, 60 to <70, and ≥70 years). Central corneal thickness and IOP at 8 to 11 o'clock in one eye of each participant were recorded. The independent sample t test and ANOVA were used for statistical analysis, and the RI of IOP values was calculated by x¯±1.96s. Results: A total of 9 310 subjects had their IOP measured, and 3 491 participants (3 491 eyes) were randomly selected from 7 886 healthy subjects. The age of the participants was (47.74±14.47) years old, ranging from 18 to 90 years old. There were 1 694 males and 1 797 females. The central corneal thickness of all participants was (525.56±49.39) µm. The daytime IOP of all participants was (15.40±2.54) mmHg (1 mmHg=0.133 kPa), and the RI was 10.42 to 20.39 mmHg. The IOP was (15.49±2.58) mmHg for males and (15.29±2.49) mmHg for females, and the gender difference was statistically significant (P<0.05). The RI of daytime IOP values was 10.43 to 20.54 mmHg for males and 10.41 to 20.18 mmHg for females. There were significant differences in daytime IOP [(15.13±2.58), (15.33±2.53), (15.49±2.50), (15.53±2.55), (15.39±2.62), and (15.28±2.52) mmHg] among 6 age groups (P<0.05). Conclusions: The distribution of daytime IOP in different gender and age groups in the eye health screening population of Handan and the RIs derived from the distribution were roughly the same as the international normal IOP RI (10 to 21 mmHg). It is recommended to refer to the RI of daytime IOP values of different genders and ages for clinical decision.

Genomic selection for meat quality traits in Pekin duck.

Genomic selection uses genome-wide molecular marker data to predict an animal's genetic value in the breeding program. This study's objective was to present heritability estimates and accuracy of genomic prediction using different methods for meat quality traits in Pekin duck. There were two kinds of ducks in the genomic selection training population: 639 fat-type ducks and 540 lean-type ducks. A single-trait animal model was used to estimate heritability and adjust the phenotype. GBLUP and BayesR methods were performed to estimate the SNP effects. The accuracy of genomic prediction was calculated using 5-fold cross-validation. The accuracy varied from 0.235 to 0.501 with the lowest accuracy estimated for traits associated with abdominal fat weight in the combined population and the most remarkable accuracy observed for abdominal fat percentage traits in the lean-type duck population. Overall, BayesR can achieve the highest prediction accuracy, while the combined population strategy could be used to increase the accuracy of prediction only when the two populations have the same breeding aim for a certain trait.

[Casticin inhibits the proliferation, migration and invasion of bladder cancer cells by inhibition of TM7SF4 expression].

Objective: To explore the effect and mechanism of Casticin (CAS) on the proliferation, migration and invasion of bladder cancer T24 cells. Methods: T24 cells were cultured in vitro and divided into control group, 5, 10, 20 µmol/L CAS groups, si-NC group, si-TM7SF4 group, CAS+ pcDNA group and CAS+ pcDNA-TM7SF4 group. Cell counting kit-8 (CCK-8) was used to detect cell proliferation; Transwell was used to detect cell migration and invasion; western blot was used to detect the protein expressions of cyclin D1, p21, MMP-2, MMP-9 and TM7SF4, and real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to detect the expression of TM7SF4 mRNA. Results: The inhibition rates of T24 cells in the 5, 10, 20 µmol/L CAS groups were (17.68±1.41)%, (33.54±3.16)% and (61.44±5.50)%, respectively, higher than (0.00±0.00)% of the control group (P<0.001), but the numbers of migration and invasion were 72.83±5.66, 59.13±4.27, 41.25±3.22 and 55.83±5.15, 42.19±3.06, 31.13±3.22, respectively, lower than 86.11±5.16 and 68.82±5.29 of the control group (P<0.001). The protein expression levels of cyclin D1, MMP-2, MMP-9, TM7SF4 and the expression levels of TM7SF4 mRNA in the 5, 10, and 20 µmol/L CAS groups were lower than the control group (P<0.001). However, the protein expression levels of p21 were 0.37±0.03, 0.51±0.04, and 0.66±0.06, respectively, higher than 0.25±0.03 in the control group (P<0.001). The inhibition rate of T24 cells in the si-TM7SF4 group was (50.35±4.67)%, higher than (6.31±0.58)% in the si-NC group (P<0.001), but the numbers of migration and invasion were 53.51±4.18 and 42.92±3.81, lower than 85.26±4.99 and 67.93±4.64 of the si-NC group (P<0.001). The protein expression levels of TM7SF4, CyclinD1, MMP-2, MMP-9 in the si-TM7SF4 group were lower than the si-NC group (P<0.001). However, the protein expression level of p21 in the si-TM7SF4 group was higher than the si-NC group (P<0.001). The inhibitory rate of T24 cells in the CAS+ pcDNA-TM7SF4 group was (21.45±2.46)%, lower than (64.06±4.49)% of the CAS+ pcDNA group (P<0.001), but the number of migration and invasion in the CAS+ pcDNA-TM7SF4 group were 75.66±6.57 and 59.35±5.40, higher than 40.43±3.85 and 30.25±3.32 in the CAS+ pcDNA group (P<0.001). The protein expression levels of TM7SF4, CyclinD1, MMP-2 and MMP-9 in the CAS+ pcDNA-TM7SF4 group were higher than the CAS+ pcDNA group (P<0.001), but the protein expression level of p21 was lower than the CAS+ pcDNA group (P<0.001). Conclusion: CAS may suppress the proliferation, migration and invasion of bladder cancer T24 cells by inhibiting the expression of TM7SF4.

[Analysis on the concept and clinical practice of patient-controlled analgesia in the treatment of cancer pain by Chinese medical providers].

Objective: To investigated the concept and clinical practice of patient-controlled analgesia (PCA) in the treatment of cancer pain. Methods: Doctors, nurses, pharmacists from the oncology department, pain department, or hospice department were investigated using an electronic questionnaire from December 1 to December 31, 2021. In addition to the basic information, there were 26 questions were collected, including the current situation of cancer pain treatment, the concept of medical staff on PCA treatment of cancer pain and the clinical practice of PCA. Results: Questionnaires from 2 872 medical staff were collected from 993 hospitals in 30 provincial administrative units. Only 34.8% (955/2 748) of medical staff considered that the satisfaction rate of cancer pain control was over 75%, and 27.9% (548/1 968) of medical staff convinced that the satisfaction rate of breakthrough pain control was less than 50%. 97.1% (2 439/2 513) of medical staff considered that PCA could be effectively used for cancer pain treatment. The proportion of medical staff in secondary and tertiary hospitals who thought that PCA was applicable to cancer pain that could not be effectively alleviated by standardized non-invasive drug administration was 64.6% (319/494) and 69.1% (1 262/1 826) respectively, which was higher than that in primary hospitals [57.0% (110/193)] (P=0.002). In different occupations, the proportion of nurses who convinced PCA treatment of cancer pain increased the risk of addiction and drug overdose was 62.8% (431/686) and 76.1% (522/686), respectively, which was higher than doctors [39.2% (670/1709) and 58.2% (995/1709), respectively] and pharmacists [49.2% (58/118) and 65.3% (77/118), respectively] (all P<0.001). There was no significant difference in type of pump, route of administration, mode of infusion, protocol for PCA administration and selection of common medication in PCA treatment of cancer pain among different hospitals (all P>0.05). The calculation of continuous infusion dose and rescue dose of PCA was not uniform among different hospitals. After initiation of PCA, 71.7% (1 226/1 709) of hospitals had insufficient analgesia and most of them needed to be adjusted for 1-3 times to achieve satisfactory analgesia. Conclusion: Medical staff have insufficient cognition of PCA treatment of cancer pain and there is a lack of unified guidance in clinical practice. Therefore, it is an urgent need to develop an expert consensus on PCA treatment of cancer pain.

[The research progress of clinical features and pathogenesis of acute acquired concomitant esotropia].

Acute acquired concomitant esotropia (AACE) is a special type of esotropia that occurs suddenly and is accompanied by diplopia. In recent years, the number of patients with this eye disease has increased significantly. With differences in age and refractive status, children and adults have their own characteristics in terms of AACE classification, refractive status, eye position, and binocular visual function. However, the pathogenesis of AACE is still unclear. This article explores the pathogenesis and risk factors of AACE, including refractive error, convergence spasm, extraocular muscle, and visual cortex, that may be involved. The authors recommend that AACE, which is not related to intracranial and systemic diseases, should be classified according to the dominant mechanism of the disease.

Coordination of primary metabolism and virulence factors expression mediates the virulence of Vibrio parahaemolyticus towards cultured shrimp (Penaeus vannamei).

AIMS: Acute hepatopancreatic necrosis disease (AHPND) caused by Vibrio parahaemolyticus has emerged as a severe bacterial disease of cultured shrimp. To identify the key virulence factors, two AHPND-causing V. parahaemolyticus (VpAHPND ) strains (123 and 137) and two non-VpAHPND strains (HZ56 and ATCC 17082) were selected. METHODS AND RESULTS: Challenge tests showed that the four strains exhibited different virulence towards shrimp with cumulative mortalities at 48 h postinfection (hpi) ranging from 10 to 92%. The expression of pirABVP in strain 123 and 137 was not significantly different. Genomic analysis revealed that the two VpAHPND strains contain a plasmid with the PirABVP toxins (pirABVP ) flanked by the insertion sequence (ISVal1) that has been identified in various locations of chromosomes in VpAHPND strains. The two VpAHPND strains possessed almost identical virulence factors, while ISVal1 disrupted three genes related to flagellar motility in strain 137. Phenotype assay showed that strain 123 possessed the highest growth rate and swimming motility, followed by strain 137, suggesting that the disruption of essential genes mediated by ISVal1 significantly affected the virulence level. Transcriptome analysis of two VpAHPND strains (123 and 137) further suggested that virulence genes related to the capsule, flagella and primary metabolism were highly expressed in strain 123. CONCLUSIONS: Here for the first time, it is demonstrated that the virulence of VpAHPND is not only determined by the expression of pirABVP , but also is mediated by ISVal1 which affects the genes involved in flagellar motility and primary metabolism. SIGNIFICANCE AND IMPACT OF THE STUDY: The genomic and transcriptomic analysis of VpAHPND strains provides valuable information on the virulence factors affecting the pathogenicity of VpAHPND.

[The analysis of structural magnetic resonance imaging manifestation of hippocampus based on voxel and spherical harmonic surface morphometry in mesial temporal lobe epilepsy].

Objective: To compare the hippocampal volume and local surface morphology changes in patients with mesial temporal lobe (mTLE) using the voxel-based morphometry and spherical harmonic methods respectively. Methods: A total of 66 patients (31 males and 35 females, age range from 17 to 48 (28±8) years) with mTLE and 80 age-and gender-matched controls (38 males and 42 females, age range from 19 to 46 (27±7) years) were retrospectively collected from July 2009 to February 2019 at Jinling hospital.. High resolution structural MRI of the whole brain, three-dimensional T1-weighted data(3DT1) were acquired from each subject. The changes of hippocampal volume and surface morphology were evaluated between mTLE groups and controls for observing the hippocampal atrophy pattern by using voxel-based morphometry and spherical harmonic shape descriptions point distribution model respectively. Pearson correlation analysis was conducted for observing the relationship between the morphological changes of hippocampus and disease duration. Results: Compared with the controls, hippocampal volume on the affected side in patients with mTLE was significantly reduced (Z-score:-1.55±0.57 vs 0.38±0.58, P<0.001) and negatively correlated with disease duration (r=-0.297, P=0.016). Furthermore, surface morphology analysis subtly showed that the atrophy of the affected hippocampus in patients with mTLE mainly located in the head, mesial lateral part and posterior tail of the hippocampus. Their displacement values were negatively correlated with disease duration (r=-0.336, P=0.006) and positively associated with the hippocampal grey matter volume (r=0.336, P=0.006). Conclusions: Voxel-based morphometry analysis reveals a global reduction in hippocampal volume, while the morphological measurement method based on surface shape can describe the local morphological changes of hippocampal atrophy.

[A cohort study of maternal pregnancy-related anxiety at different trimesters and infants' neurobehavioral development].

Objective: To investigate the influence and critical period of pregnancy-related anxiety during pregnancy on the neurobehavioral development of infants. Methods: The subjects of this study were derived from the Ma'anshan Birth Corhot. From May 2013 to September 2014, a total of 3 474 pregnant women who registered in Ma 'anshan Maternal and Child Health Care Center were enrolled in the study. A total of 2 242 mother-infant pairs who completed three times assessments of maternal anxiety and at least once assessment of infants' neurobehavioral development were included in the final analysis. Maternal pregnancy-related anxiety was assessed by the Pregnancy-Related Anxiety Questionnaire during the first, second and third trimesters of pregnancy. When their children were at 6 and 18 months, their neurobehavioral development was evaluated using the Ages & Stages Questionnaire-China. The influence of maternal pregnancy-related anxiety on the neurobehavioral development of infants was analyzed by bi-nominal logistic regression. Results: The age of 2 242 pregnant women was (26.62±3.65) years, and the proportion of boys, low birth weight and exclusive breastfeeding for 6 months was 50% (1 120/2 242), 1.7% (38/2 242) and 11.5% (252/2 191), respectively. The detection rates of pregnancy-related anxiety during the first, second and third trimester were 24.9% (558), 28.6% (642) and 30.3% (674), respectively. After controlling confounding variables and other two trimester's anxiety, only pregnancy-related anxiety during the third trimester (not first or second trimester) significantly increased the risk of developmental delay in the domain of communication (relative risk, RR = 3.52, 95% confidence interval, CI: 1.89-6.58) and personal-social (RR=2.46, 95%CI: 1.10-5.49) at the 6 months of age, as well as in the domain of fine motor (RR=2.07, 95%CI: 1.11-3.85), problem-solving domains (RR=2.31, 95%CI: 1.24-4.31). Conclusion: Maternal pregnancy-related anxiety was associated with the risk of neurobehavioral development of infants, and the third trimester may be the critical period.

[Effect of tenofovir disoproxil fumarate antiviral therapy on virus-specific CD8+T Cells function in patients with chronic hepatitis B].

Objective: To observe the effect of tenofovir disoproxil fumarate (TDF) antiviral therapy on HBV-specific CD8(+)T cell function in peripheral blood of patients with HBeAg-positive chronic hepatitis B, and to assess its correlation with HBeAg sero-negativeness. Methods: Sixty-three cases with HLA-A02 restricted HBeAg-positive chronic hepatitis B who received TDF (300 mg/d) antiviral therapy were enrolled from October 2016 to July 2018. The peripheral blood CD8(+)T cells were separated at baseline and 48 weeks after treatment. The peripheral blood T cells count were detected by flow cytometry. The frequency of HBV-specific CD8(+)T cells secreting perforin, granzyme B, and interferon-γ (IFN-γ) were detected by enzyme-linked immunoblotting test. Direct and indirect contact co-culture system was established between HBV-specific CD8(+)T cells and HepG2.2.15 cells. HBV DNA was detected in the culture supernatant. Target cell mortality was calculated by lactate dehydrogenase level. Cytokines expression was detected by enzyme-linked immunosorbent assay. Virus-specific CD8(+)T cells cytokilling and non-cytokilling functions were evaluated. Measurement data of the two groups were compared by t-test or paired t-test. Results: Viral response, biochemical response, and HBeAg seroconversion rate at 48 weeks of TDF treatment were 100%, 90.48% (57/63), and 25.40% (16/63), respectively. There was no statistically significant difference in peripheral blood T cell count when compared with baseline and control group at 48 weeks of TDF treatment (P > 0.05). At 48 weeks of TDF treatment, the frequency of HBV-specific CD8(+)T cells secreting perforin, granzyme B, and IFN-γ in CHB patients was significantly higher than baseline (P < 0.001). Furthermore, the frequency of HBV-specific CD8(+)T cells secreting perforin, granzyme B, and IFN-γ was also significantly higher in CHB patients with HBeAg negative than that of non-negative (P < 0.05). HBV-specific CD8(+)T cells had induced significant down-regulation of HBV DNA in the supernatant of HepG2.2.15 cell culture (P < 0.001) and remarkable IFN-γ and interleukin-2 secretion (P < 0.05) at 48 weeks of TDF therapy in direct and indirect contact co-culture system. However, HepG2.2.15 cells death rate induced by virus-specific CD8(+)T cells was increased only in the direct contact co-culture system (21.7% ± 6.18% vs. 16.1% ± 4.15%, P < 0.001). Compared with HBeAg non-negative patients, HBeAg negative CHB patients with HBV-specific CD8(+)T cells had induced a strong decrease in HBV DNA (P < 0.001) and an increase in IFN-γ secretion level (P < 0.05). However, the target cell death proportion difference between HBeAg negative and non-negative patients was not statistically significant (P > 0.05). Conclusion: During TDF treatment, with the viral load reduction, virus-specific CD8(+)T cells cytokilling and non-cytokilling functions are significantly enhanced, and are closely related to HBeAg negative.

The significance of Siglec-15 expression in resectable non-small cell lung cancer.

Siglec-15 (S15) is another important mechanism of tumor immune escape besides the PD-L1/PD-1 pathway and represents a new kind of immune checkpoint inhibitor. However, the associations of tumor Siglec-15 expression with clinicopathological characteristics and outcomes of non-small cell lung cancer (NSCLC), and tumor-infiltrating lymphocytes (TILs) in a tumor microenvironment (TME) have so far been unclear. A total of 324 NSCLC surgical samples on tumor microarray were used in this study for investigating the association of S15 expression with clinicopathological characteristics and overall survival (OS) as well as correlation with TILs using multiplex immunofluorescence staining and PD-L1. Results showed that the expression of S15 in adenocarcinoma was significantly higher than that in squamous cell carcinoma. S15 expression was positively correlated with CD8+ T cell density in the stroma. The expression rate of PD-L1 in lung squamous cell carcinoma was higher than that in lung adenocarcinoma. S15 expression was not associated with the prognosis of early NSCLC. The pathological mechanism of the co-expression of S15 and PD-L1 in resectable NSCLC remains to be further studied.

Genome-wide association study reveals novel loci associated with fat-deposition and meat-quality traits in Pekin ducks.

Meat-quality traits play an essential role in meat poultry production. To determine the genetic mechanisms of meat quality in Pekin ducks, we performed a large-scale GWAS to identify quantitative trait loci affecting meat quality in Pekin ducks. We measured 10 traits in 542 Pekin ducks and genotyped each duck using genotyping-by-sequencing. The genetic parameters (genomic heritability, genetic correlation) for 10 meat-quality related traits were evaluated. Based on the large genotype-phenotype dataset, we performed GWASs for all of these traits. A total of 33 significant QTL (P < 3.03 × 10-5 ) across 13 chromosomes were identified by loci-based analysis. Some newly identified candidate genes were discovered for fat-deposition and meat-quality traits, including PAG1 for body weight and eviscerated weight, INTU and NUP35 for abdominal fat weight and ratio, NUP3 and ARHGDIB for skin fat weight and ratio, GOLGA5 for breast muscle toughness and breast tenderness, and CTDSPL and PKP1 for breast muscle thickness. The current study is the first systematic report regarding duck meat quality.

Culture of human ovarian tissue in xeno-free conditions using laminin components of the human ovarian extracellular matrix.

PURPOSE: Our purpose was to identify human ovarian extracellular matrix (ECM) components that would support in vitro culture of human ovarian tissue and be compatible with possible future clinical applications. We characterized ovarian expression of laminins and selected three laminin tripeptides for culture experiments to be compared with Matrigel, an undefined and animal-based mixture of ECM components. METHODS: Expression of the 12 laminin genes was determined on transcript and protein levels using cortical tissue samples (n = 6), commercial ovary RNA (n = 1), follicular fluid granulosa cells (n = 20), and single-cell RNA-sequencing data. Laminin 221 (LN221), LN521, LN511, and their mixture were chosen for a 7-day culture experiment along with Matrigel using tissue from 17 patients. At the end of the culture, follicles were evaluated by scoring and counting from serial tissue sections, apoptosis measured using in situ TUNEL assay, proliferation by Ki67 staining, and endocrine function by quantifying steroids in culture media using UPLC-MS/MS. RESULTS: Approximately half of the cells in ovarian cortex expressed at least one laminin gene. The overall most expressed laminin α-chains were LAMA2 and LAMA5, ß-chains LAMB1 and LAMB2, and γ-chain LAMC1. In culture experiments, LN221 enhanced follicular survival compared with Matrigel (p < 0.001), whereas tissue cultured on LN521 had higher proportion of secondary follicles (p < 0.001). LN511 and mixture of laminins did not support the cultures leading to lower follicle densities and higher apoptosis. All cultures produced steroids and contained proliferating cells. CONCLUSIONS: LN221 and LN521 show promise in providing xeno-free growth substrates for human ovarian tissue cultures, which may help in further development of folliculogenesis in vitro for clinical practices. The system could also be used for identification of adverse effects of chemicals in ovaries.

[Protective effect and mechanism of mild hypothermia on liver injury after cardiopulmonary resuscitation in pigs].

Objective: To investigate the effect of mild hypothermia therapy on liver after cardiopulmonary resuscitation. Methods: Thirty-three inbred Chinese Wuzhishan (WZS) minipigs, weighted (28±2) kg, were used to establish a ventricular fibrillation model. And 30 animals survived after cardiopulmonary resuscitation reached basic life support. The surviving animals were randomly divided into two groups: mild hypothermia group (group M, n=15) and conventional treatment group (group C, n=15). All the animals were observed for 24 hours. Blood samples were extracted at baseline, 0.5, 1, 2, 4, 6, 12 and 24 h after successful resuscitation. The concentrations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected at the time points. The enzyme-linked immunosorbent assay (ELISA) was used to detect the concentrations of interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α). The data were compared between the two groups, LSD test was used when the variance was homogeneous, and Tamhane T2 test was used when the variance was uneven. Results: Eleven pigs (73.3%) in the group M and 8(53.3%) in the group C survived at 24 h after successful resuscitation, with no statistically significant difference between the two groups (χ(2)=1.229, P=0.225). After successful resuscitation, the AST, ALT increased in both group but less in M group (all P<0.05). After successful resuscitation, the concentrations of TFN-α and IL-6 in the blood increased in both groups, reached the peak at 4h, and then decreased gradually. The concentrations of TFN-α in group M were lower than those in group C at 0.5, 2, 4 and 6 h after successful resuscitation (t=0.01, 0.01, 0.87, 0.86, all P<0.05). The concentrations of IL-6 in the group M were lower than those in group C at 0.5, 1, 2 and 4 h after successful resuscitation (t=0.23, 0.78, 0.11, 0.80, all P<0.05). Conclusions: After successful resuscitation, the release of inflammatory mediators, such as TNF-α and IL-6, and cell apoptosis may involve in liver ischemia reperfusion injury. After successful resuscitation, the liver undergoes ischemia-reperfusion injury, which may be related to the release of inflammatory mediators such as TNF-α and IL-6. Mild hypothermia therapy can prevent the release of TNF-α, IL-6 to reduce the degree of liver damage after resuscitation.

[Magnetic resonance imaging morphological study of the effects of juvenile febrile convulsions on the brain structure of medial temporal lobe epilepsy].

Objective: To investigate the effect of febrile convulsions on gray matter volume (GMV) in medial temporal lobe epilepsy (mTLE) and its correlation with disease duration. Methods: A retrospective study was conducted to collect 41 mTLE patients with a history of febrile convulsions (mTLE-FC), 42 mTLE patients with no initial precipitating injury (mTLE-noIPI), and 42 normal and age and sex matched normal controls. High-resolution T1-weighted (T(1)WI) whole brain MR scans were performed on all subjects. Voxel-based morphometry were used to obtain GMV brain maps, and the GMV differences between the three groups of subjects were compared (P<0.01, GRF corrected). Finally, Spearmen rank correlation analysis was used to explore the correlation between GMV changes and the course of disease. Results: Compared with the normal control subjects, each mTLE group showed extensive GMV reduction, mainly in the affected hippocampus, thalamus, temporal lobe, and bilateral cerebellum. Further analysis found that mTLE-FC group had more significant reductions in GMV than the mTLE-noIPI group in the affected hippocampus, amygdala, inferior temporal gyrus, contralateral hippocampus, para hippocampus, and inner cingulate gyrus. At the same time, the affected amygdala and hippocampal GMV in the mTLE-FC group was significantly negatively related to the course of disease (r=-0.381, P=0.014), while the mTLE-noIPI group had no downward trend (r=0.081, P=0.611). The atrophic trend of the affected amygdala and hippocampus in patients with mTLE-FC was significantly greater than that in patients with mTLE-noIPI (P=0.029, permutation test). Conclusions: There is extensive damage to the gray matter structure of bilateral cerebral hemispheres, mainly in the hippocampus, in mTLE patients. The brain damage of mTLE patients with a history of juvenile fever convulsions is more extensive and serious, and the trend of progressive exacerbation with the course of the disease is more obvious, suggesting mTLE associated with juvenile fever convulsions may have different pathophysiological mechanisms.

[Retrospective analysis of mechanical thrombectomy for distal branch occlusion of middle cerebral artery].

Objective: To explore the necessity, feasibility, technical points, operative complications and prognosis of mechanical thrombectomy for distal branch occlusion of middle cerebral artery. Methods: Mechanical thrombectomy was performed on 42patients (28 males,14 females; age ranged from 43 to 88 years, mean 65.48years)with distal branch occlusion of middle cerebral artery (M2, M3), between May 2017 to July 2019. Theclinical feature was retrospectively analyzed. The NIHSS score before operation, 24 hours after operation and 1 week after operation, the recanalization of occluded vessels during operation, the complications and the recovery after 3 months (3 months mRS score) were analyzed. Results: Of the 42 patients, 38 patients were successfully recanalized, and the recanalization rate was 90.48%. Postoperative hemorrhage in 6 cases and vasospasm in 17 cases. At 90 days after operation, the mRS score was 0 in 13 cases, 1 in 11 cases, 2 in 6 cases, and 0 cases died. Conclusions: Mechanical thrombotomy is safe and feasible for patients with distal branch occlusion of middle cerebral artery (M2, M3). However, the risks and benefits of patients should be fully considered.

[The relationship between maternal pregnancy-related anxiety and executive function in preschool children: a cohort study].

Objective: To investigate the relationship between pregnancy-related anxiety and executive function in preschool children. Methods: From October 2008 to October 2010, pregnant women and live births were enrolled in the study. The expectant pregnant women and their live singleton fetuses were recruited from the antenatal care clinic of Ma'anshan maternal and Child Health Care Hospital. The cohort was followed up from April 2014 to June 2015. A total of 3 556 pairs of maternal and child were included in the final analysis. The questionnaire was used to collect the relevant information of pregnant women and the follow-up data of children. Pregnancy-related anxiety was assessed by using the Pregnancy-Related Anxiety Questionnaire, and the executive function of preschool children was assessed by using the Behavior Rating Inventory of Executive Function-Preschool (BRIEF) (Parent Version). Bi-nominal logistic regression was used to analyze the effect of pregnancy-related anxiety on executive function in preschool children. Results: The average age of 3 556 pregnant women was (26.78±3.42) years old, and the average age of preschool children was (4.32±0.46) years old. The proportion of primipara, only child and urban children was 94.96% (3 375/3 556), 91.37% (3 249/3 556) and 88.98% (3 164/3 556), respectively. The prevalence of pregnancy-related anxiety in the 1(st) and 3(rd) trimester was 17.60% (626/3 556) and 6.30% (224/3 556) respectively. The prevalence of abnormal global executive composite was 8.54% (304/3 556). The prevalence of anxiety in both trimesters was 7.68% (273/3 556). After controlling for confounding factors such as monthly family income, education years of parents, maternal age, pre-pregnancy weight, previous adverse pregnant outcomes, number of pregnancy, pregnant complications, the main residence of the children in the past six months, and Z score of birth weight, compared with the group without pregnancy-related anxiety in either 1(st) or 3(rd) trimester, pregnancy-related anxiety in the 1(st) trimester increased the risk of preschool children's abnormality in inhibition, working memory, planning/organization and global executive composite, and the OR (95%CI) value was 1.52 (1.08-2.13), 1.41 (1.14-1.74), 1.62 (1.13-2.33), and 1.60 (1.18- 2.17), respectively. Anxiety in the 3(rd) trimester increased the risk of children's abnormality in inhibition and global executive composite, and the OR (95%CI) value was 1.90 (1.15-3.12) and 1.69(1.05-2.71). Pregnancy-related anxiety in both trimesters increased the risk of abnormality in inhibition, working memory, planning/organization, and global executive composite in preschool children, and the OR (95% CI) value was 2.41 (1.61-3.62), 2.19 (1.66-2.88), 1.80 (1.11-2.92), and 2.41 (1.65-3.52), respectively. Conclusion: The exposure to pregnancy-related anxiety during pregnancy increases the risk of executive dysfunction in preschool children.