[Detection rate and clinical significance of regions of homozygosity in prenatal genetic diagnosis].

Objective: To detect the incidence and analyze the clinical significance of regions of homozygosity (ROH) through the single nucleotide polymorphism array (SNP array). Methods: The SNP array detection results of 5 116 pregnant women in the Third Affiliated Hospital of Guangzhou Medical University from January 2016 to December 2020 were retrospectively analyzed. The pregnant women with ROH (5 Mb as the threshold) were followed up to analyze the relationship between ROH and abnormal fetal phenotype. Whole exon sequencing was performed in 4 cases of consanguineous marriage to detect potential recessive causative genes in the ROH region. Results: (1) A total of 39 cases of ROH were detected, with a positive rate of 0.76% (39/5 116). Among them, 25 cases (64%, 25/39) were detected only on single chromosome, and chromosome 11 had the highest detection rate, suggesting the risk of uniparental disomy; fourteen cases (36%,14/39) were detected on multiple chromosomes, most commonly on chromosomes 11, 1, 3, 4 and 8. (2) The number of cases and detection rate of ROH detected by different prenatal diagnosis indicators were as follows: 12 cases (1.78%, 12/676) in pregnant women with abnormal non-invasive prenatal testing result, 12 cases (0.37%, 12/3 284) in pregnant women with ultrasound abnormality, 4 cases (4/4) in pregnant women with consanguineous marriage, 3 cases (0.92%, 3/326) in pregnant women with previous adverse pregnancy, 2 cases (1.15%, 2/174) in pregnant women with high risk of serology in screening, 2 cases (4.00%, 2/50) in pregnant women with abnormal fetal chromosomal karyotype, 2 cases (0.79%, 2/253) in pregnant women with advanced maternal age, 1 case (0.56%, 1/178) in pregnant women with related parental genetic factors and 1 case (0.58%, 1/171) in pregnant women with the other factors. (3) The follow-up results of 39 cases of prenatal ROH showed that there were 16 cases of term birth, 15 cases of termination of pregnancy, 2 cases of preterm births, 1 case of fetal death and 5 cases lost to follow-up. Conclusions: Chromosomal ROH phenomenon is not rare. By analyzing the detection rate of ROH in prenatal diagnosis, combined with the results of fetal phenotype and postpartum follow-up, the clinical characteristics of ROH are discussed, so as to better understand the relationship between ROH and its phenotype.

[Autopsies and placental examinations of perinatal fetal deaths: a clinicopathological analysis of 105 cases].

Objective: To summarize the clinicopathological factors related to perinatal fetal death and to evaluate importance of fetal autopsy and placental pathology. Methods: The clinicopathological data of 105 perinatal fetal deaths in Beijing Haidian Maternal and Child Health Hospital from November 2012 to December 2020 were retrospectively analyzed. Relevant literature was also reviewed. Results: The maternal age of the deceased fetuses ranged from 22 to 43 years with the average (31.35±4.04 years), and the gestational weeks were 28-40+6 weeks. Among them, 101 were singleton cases and 4 twin cases. 103 fetuses died in uterus and 2 died during delivery. Relevant factors analysis of the 105 perinatal fetal deaths showed that 86 cases (81.9%, 86/105) were related to umbilical cord/placental abnormality, 10 cases (9.5%, 10/105) uterine infection, 6 cases (5.7%, 6/105) fetal factors, 1 case was fetal maternal blood transfusion syndrome, 1 case twin blood transfusion syndrome, and 1 case died of complete uterine rupture. Among the 86 cases related to umbilical cord/placental abnormality, the diagnosis was most often based on the gross examination of placenta. The most common cause of death was umbilical cord torsion with thin root, followed by placental abruption, tight umbilical cord winding, vascular rupture and umbilical cord true knot. The morphology of placenta revealed mainly functional changes. Among the 10 cases related to intrauterine infections, the placenta generally showed lobular placental edema. The morphological characteristics of ascending infection were mainly acute chorioamnionitis, and the morphological characteristics of blood-borne infection were mainly acute or chronic villitis, as well as villous interstitial inflammation. Identification of viral inclusions suggested viral etiology, while the final diagnosis was relied on laboratory testing. Among the 6 cases related to fetal abnormality, the diagnostic value of placenta was limited and the diagnosis could be made with fetal autopsy. Conclusion: The causes of perinatal fetal death are complex, diverse, and often the synergistic result of multiple factors. Fetal autopsy and placental pathology are the key technical means to identify the cause of death and deserve more attention and utilization.

[Singleton placentas with abnormal shape: a clinicopathological analysis of 130 cases].

Objective: To investigate the pathological characteristics of singleton placenta with abnormal shape and its influence on the outcome of maternal-fetal pregnancy. Methods: The clinicopathological data of singleton placentas with abnormal shape from January 2014 to December 2020 in the Department of Pathology, Haidian Maternal and Children Health Hospital were analyzed retrospectively. Results: There were 130 singleton placentas with abnormal shape in this cohort, including 48 succenturiate placentas, 12 bilobed placentas, 50 marginate placentas, 13 circumvallate placentas, 3 annular placentas, 2 membranous placentas and 2 fenestrated placentas. Gestational age ranged from 29+5 to 40+4 weeks. There were 51 cases of premature rupture of membranes, 11 cases of placenta previa, 5 cases of placental abruption, 15 cases of placental adhesion/implantation and 27 cases of postpartum hemorrhage. There were 46 preterm fetuses,28 fetuses with fetal growth restriction, 22 fetuses with intrauterine distress, and 1 fetus with intrauterine death. Grossly, the placental lobules of succenturiate placentas had apparent size difference, while two lobules of bilobate placenta were more consistent. The chorionic plate size was smaller than the bottom plate of circumvallate placenta, the folded fetal membrane in the rim of placenta was thickened (termed marginate placenta if there was no thickening). The membranous placenta was characterized by a thin, large membrane-like shape. Annular placenta showed characteristic hollow cylinder, ring or horseshoe-shape. Fenestrated placenta was characterized by tissue defects near central area. Microscopically, functional/morphologic changes were the main manifestations of inadequate maternal-fetal perfusion, including villous infarction, distal villous dysplasia and excessive villous maturation. Conclusions: The abnormal shaped singleton placentas showed variable extent of inadequate maternal-fetal perfusion, which may lead to adverse pregnancy outcomes such as premature delivery, fetal growth restriction, intrauterine distress or fetal death.

[Analysis of pathogenic bacteria in cirrhotic patients complicated with bacterial infection in a tertiary hospital in Xinjiang].

Objective: To understand the species, distribution, and extent of drug resistance of pathogenic bacteria in patients with liver cirrhosis combined with bacterial infection in a tertiary hospital in Xinjiang. Methods: 1 271 cases with liver cirrhosis combined with infection were analyzed retrospectively for pathogenic bacterial species and drug resistance condition in different bacterial strain. Results: Among the 1 271 cases with liver cirrhosis, 480 were combined with infection, and the infection rate was 37.8%. The majority of infected patients had decompensated cirrhosis (438 cases). Peritoneum (327 cases, 60.8%) was the common infection site, followed by lungs (16.9%). 343 strains of pathogens were isolated from 480 infected cases, of which 289 strains were among the top 10 common distinct bacteria, accounting for 76.5% and 23.5% of Gram-negative and positive bacteria. The first top three strains were Escherichia coli. (33.2%), Klebsiella pneumoniae (11.4%), and Enterococcus faecium (11.1%), and there were differences in the drug resistance rates of each strain. Conclusion: In a tertiary hospital in Xinjiang, patients with decompensated cirrhosis have a high rate of bacterial infection. The pathogenic bacteria are diverse, mainly Gram-negative bacteria; however, the infection rate of Gram-positive bacteria such as Enterococcus is gradually increasing. Additionally, according to the bacterial properties, they are divided into four categories: Enterobacter, Enterococcus, glucose non-fermenting bacteria and Staphylococcus, and it is found that even the same species of bacteria have different drug resistance rates.

[Clinical and prognostic analysis of acute pulmonary thromboembolism in the elderly].

Objective: To analyse the clinical characteristics and to explore the prognostic factors of acute pulmonary thromboembolism in the elderly. Methods: The medical records of inpatients with acute pulmonary thromboembolism discharged from Peking Union Medical College Hospital from January 1, 2012, to February 1, 2019 were retrospectively reviewed. The eligible patients were divided into elderly group (≥ 60 years old) and non-elderly group (<60 years old). The clinical symptoms, complications, laboratory results, pulmonary embolism severity index (PESI) and mortality were compared between the two groups. Mortality was further compared among elderly patients of different age groups. Cox regression analysis was used to analyze the risk factors of 7-day and 30-day death in elderly patients with pulmonary embolism. Results: A total of 503 patients with acute pulmonary embolism were included, including 279 cases in the elderly group and 224 cases in the non-elderly group. The incidence of cardiac arrest was higher in the elderly group compared with non-elderly group, while the incidence of chest pain and hemoptysis was less common in the elderly group. The proportions of comorbidities, including diabetes, hypertension, and coronary heart disease were higher in the elderly group while the proportion of autoimmune diseases was higher in the non-elderly group. In terms of prognosis, the PESI score and 7-day and 30-day mortality in the elderly group were higher than those in the non-elderly group. The mortality of elderly patients increased with age. Cox univariate regression analysis showed that infection, hypoalbuminemia, hypocalcemia, elevated cardiac troponin(cTnI), elevated N-terminal prohormone of brain natriuretic pepride(NT-proBNP) and PESI grade were associated with 30-day death. Multivariate Cox regression analysis showed that PESI grade and decreased serum calcium concentration were independent risk factors for 7-day death of pulmonary embolism in elderly patients. PESI grade, decreased serum calcium concentration and infection were independent risk factors for 30-day death. Conclusions: The mortality of elderly patients with pulmonary embolism was higher than that of non-elderly patients, and the mortality increased gradually with age. PESI grade, decreased serum calcium concentration and infection were independent risk factors for 30-day death of pulmonary embolism in elderly patients.

Oligoasthenoteratospermia and sperm tail bending in PPP4C-deficient mice.

Protein phosphatase 4 (PPP4) is a protein phosphatase that, although highly expressed in the testis, currently has an unclear physiological role in this tissue. Here, we show that deletion of PPP4 catalytic subunit gene Ppp4c in the mouse causes male-specific infertility. Loss of PPP4C, when assessed by light microscopy, did not obviously affect many aspects of the morphology of spermatogenesis, including acrosome formation, nuclear condensation and elongation, mitochondrial sheaths arrangement and '9 + 2' flagellar structure assembly. However, the PPP4C mutant had sperm tail bending defects (head-bent-back), low sperm count, poor sperm motility and had cytoplasmic remnants attached to the middle piece of the tail. The cytoplasmic remnants were further investigated by transmission electron microscopy to reveal that a defect in cytoplasm removal appeared to play a significant role in the observed spermiogenesis failure and resulting male infertility. A lack of PPP4 during spermatogenesis causes defects that are reminiscent of oligoasthenoteratospermia (OAT), which is a common cause of male infertility in humans. Like the lack of functional PPP4 in the mouse model, OAT is characterized by abnormal sperm morphology, low sperm count and poor sperm motility. Although the causes of OAT are probably heterogeneous, including mutation of various genes and environmentally induced defects, the detailed molecular mechanism(s) has remained unclear. Our discovery that the PPP4C-deficient mouse model shares features with human OAT might offer a useful model for further studies of this currently poorly understood disorder.

[Establishment of a preoperative prediction model for axillary lymph node burden in patients with early breast cancer].

Objective: To explore the method of predicting high lymph node load in patients with early breast cancer to avoid unnecessary sentinel lymph node biopsy. Methods: The clinicopathological and thoracic multi-slice spiral CT (MSCT) data of 2620 patients with early (cT1~2N0M0) breast cancer treated in the Affiliated Cancer Hospital of Zhengzhou University from January 1, 2014 to August 1, 2018 were collected. According to the postoperative pathological results, the patients were divided into the group with axillaryhigh lymph node burden (HNB) and the non-HNB group. The influencing factors of axillary lymph node burden in patients with early breast cancer were determined by univariate and multivariate analysis, and the diagnostic model of MSCT to HNB was established. The best cutoff value for the diagnosis of HNB was determined through analyzing the receiver operative characteristic (ROC) curve, and the consistency between MSCT diagnosis and pathological diagnosis was evaluated by Kappa test. Results: Among the 2 620 patients, 168 were diagnosed of HNB. Univariate analysis showed that the tumor size, the status of human epidermal growth factor receptor 2 (HER-2), the number of abnormal lymph nodes showed in MSCT, the ratio of the length to the diameter of the maximum abnormal lymph node as shown in MSCT, the condition of the maximum abnormal lymph node door, and the parenchyma of the maximum abnormal lymph node were related to axillary lymph node burden in patients with early breast cancer (P<0.05). Multivariate analysis showed that the number of abnormal lymph nodes showed in MSCT was an independent influencing factor of axillary HNB in patients with early breast cancer. Compared with patients without abnormal lymph nodes, the OR values of patients with 1, 2, 3 or more abnormal lymph nodes displayed by MSCT and in axillary HNB status were 3.305, 9.379, 126.163 and 780.953, respectively. Using 3 or more abnormal lymph nodes detected by MSCT to predict the area under the ROC curve of axillary HNB in patients with early breast cancer, the area was 0.928, the sensitivity was 82.1%, the specificity was 95.4%, and the accuracy was 94.5%. Kappa test showed that the consistency between MSCT diagnosis and pathological diagnosis was relatively high (Kappa=0.629, P<0.001). Conclusions: The number of abnormal lymph nodes showed in MSCT is an independent influencing factor of axillary HNB in patients with early breast cancer. Taking 3 or more abnormal lymph nodes showed in MSCT as the threshold can help to predict the axillary HNB status of early breast cancer patients and exempt some of them from unnecessary sentinel lymph node biopsy.

[Treatment outcome of 100 patients with hepatoblastoma based on a new risk stratification].

Objective: To provide the risk stratification method of hepatoblastoma (HB) suitable for implementation in China and explore the new treatment method for high-risk HB patients. Methods: A total of 100 cases of children and adolescents under 18 years old with newly diagnosed HB in Sun Yat-sen University Cancer Center and Sun Yat-sen University First Affiliated Hospital from September 2014 to September 2018 were included. According to the clinical stage, AFP level, pathological subtype and other factors, patients were stratified into four groups: extremely low-, low-, intermediate- and high-risk. The patients at very low risk were treated with surgery only and followed-up. The patients at very low risk were treated with C5V(Cisplatin+ 5-Fluroracil+ Vincristine) regimen for 4 courses. The patients at intermediate risk were treated with C5VD(Cisplatin+ 5-Fluroracil+ Vincristine+ Doxorubicin)regimen before and after surgery for 6-8 courses. The patients at high risk were treated with C5VD and IIV (ifoshamide+ irinotecan+ vincristine) alternately before and after surgery for 8 courses. Results: One hundred patients were stratified into extremely low-risk, low-risk, medium-risk and high-risk groups for 2, 10, 51 and 37 cases, respectively. Eighty three cases had evaluable lesions before chemotherapy. Among them, 65 patients achieved partial remission, stable disease and progressive disease were observed in 10, and 8 cases, respectively, with a response rate of 78.3%. During a median follow-up of 20 months, 30 patients experienced tumor relapse or progression, and 27 of them died. The 2-years progression-free survival (PFS) and overall survival (OS) rates were 69.2% and 72.0%, respectively. The 2-years PFS rates of patients with extremely low risk, low risk, medium risk and high risk were 100%, 88.9%, 75.3% and 43.2%, respectively. The 2-years OS rates were 100%, 100%, 81.0% and 44.8%, respectively. Conclusions: The novel HB risk classification is simple and feasible. With active comprehensive treatment, patients at extremely low-, low- and medium-risk have excellent outcomes. The survival rate of high-risk HB patients remains to be improved, and new treatment strategies need to be explored.

[Clinical value of suspicious calcification in the diagnosis and surgical treatment of breast lesions using contrast-enhanced spectral mammography].

Objective: To evaluate clinical value of suspicious calcification in the diagnosis and surgical treatment of breast lesions using contrast-enhanced spectral mammography. Methods: Ninty-four patients who underwent CESM with suspicious calcification on the low-energy(LE) images in Third Affiliated Hospital of Soochow University from April 2017 to April 2019 were collected.All patients were female, with an average age of 51 years (26 to 89 years).All patients underwent biopsy or surgery to obtain pathological results. Two experienced radiologists provide BI-RADS classification for LE images and CESM. To assess pairwise agreement between BI-RADS classification on CESM and LE images among readers, kappa test were calculated. Using pathology results as the gold standard,the diagnostic efficacy of LE images and CESM were analyzed by receiver operating characteristic (ROC)curve, and Z test was used to compare the areas under the ROC curves (AUC) among them, calculated the sensitivity, specificity. The intraclass correlation coefficient (ICC) was used to analyze the consistency of the maximum image diameter and pathological diameter of malignant lesions. Two experienced radiologists provided the preferred surgical treatment (breast conservation therapy versus mastectomy) for all malignant cases according the imaging findings. McNemars test was used to compare the difference between surgical decision making and final surgical procedure. Results: One hundred and three lesions were found in 94 patients, in which 49 were benign and 54 were malignant.Overall agreement on BI-RADS classification between LE imaging and CESM among readers was substantial (0.74 vs 0.86), CESM was higher than LE images. The sensitivity of LE images and CESM were 80.4%, 96.2%, specificity was 75.0%, 94.0%, AUC were 0.810, 0.960 respectively. There was significant difference of the AUC between LE images and CESM (Z=3.66, P<0.01). The ICC of malignant lesions measured on LE images and CESM and histopathological results were 0.86 and 0.96, respectively. Based on LE images, 44.4%(24/54) of patients recommended BCT, 55.6%(30/54) of patients recommended mastectomy, the difference was statistically significant (P=0.008). Based on CESM, 27.8%(15/54) of patients recommended breast conservation therapy, 72.2%(39/54) of patients recommended mastectomy,there was no significant statistically difference with the final surgical procedure (P=0.125). Conclusion: CESM has a high diagnostic accuracy for suspicious calcification of breast. And its accuracy in assessing malignant lesion size is higher, which can provide a basis for preoperative surgical decision making.

[Clinical characteristics and related factors of acute tubular necrosis in patients with minimal change disease].

Objective: To investigate the clinical characteristics and related factors of acute tubular necrosis (ATN) in patients with minimal change disease (MCD). Methods: Patients from Chinese PLA General Hospital who were pathologically diagnosed with MCD and had clinical manifestations of nephrotic syndrome from January 1, 2013 to December 31, 2019 were included. The clinical and pathological data of patients were retrospectively analyzed. Meanwhile, the incidence and clinical characteristics of ATN in different age groups were compared. The risk factors for ATN were assessed using binary logistic regression. Results: A total of 525 patients were included, with a gender ratio of 1.56∶1 (male: female), aged 33 (21, 48) years old. ATN occurred in 49 (9.3%) of 525 patients, of which 34 were male and 15 were female. The incidence of ATN increased with age in MCD patients of different age groups (χ(2)=31.442, P<0.001). The incidence of ATN in groups of age≤20 years, 21-40 years, 41-60 years, and >60 years was 2.4% (3/123), 5.2% (10/192), 13.2% (20/152) and 27.6% (16/58), respectively. Elevations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transpeptidase (GGT) and serum IgE occurred in 92 patients (17.5%), 53 patients (10.1%), 99 patients (18.9%), and 303 patients (57.7%), respectively. There were significant differences in age, ALT, serum creatinine, serum urea nitrogen, history of diabetes and history of hypertension between non-ATN group and ATN group (all P<0.05). The results of logistic regression analysis showed that>40 years old (OR=6.283, 95% CI: 2.695-14.649, P<0.001) and serum albumin (OR=0.924, 95% CI: 0.857-0.997, P=0.040) was independently associated with ATN in MCD patients. Conclusion: Age>40 years is an independent risk factor and serum albumin is a protective factor for ATN in MCD patients.

[Mutational analysis of ATP7B gene of hepatolenticular degeneration in Xinjiang region].

Objective: To understand the mutational characteristics of ATP7B gene of hepatolenticular degeneration in Xinjiang region. Methods: 24 cases were diagnosed as hepatolenticular degeneration and the exon of ATP7B gene was detected in some of their siblings and parents. Results: A total of 45 ATP7B gene mutations (93.75%) were detected in 24 cases, of which 14 cases were homozygous mutations or compound heterozygous mutations, six cases were heterozygous mutations and four cases were no mutations. A total of 24 gene mutations and 14 SNPS were detected, including 8 new mutations: c.251C > A, c.121A > c, c.2945C > A, c.2194C > T, c.2947T > c, c.3626T > A, c.3662_3664del, c.3557G > T. The most common mutations were c.2621C > T (p.A874V) [16.7% (4/24)] and c.2333G > T (p.R778L) [12.5% ​​(3/24)]. A total of 4 cases were diagnosed as pre-symptomatic. Conclusion: In this study, the most common mutation in the ATP7B gene is A874V. The most common genetic mutations in Han and Uyghur patients were different. The most common mutation in Han and Uyghur patients is R778L and A874V. Exon 11 is the gene mutations hot spot for patients with hepatolenticular degeneration in Xinjiang region, and is one of the priority exons to be detected when screening patients with suspected hepatolenticular degeneration.

[The clinical features and prognosis of interstitial lung disease patients with positive anti-neutrophil cytoplasmic antibody].

Objective: To investigate the clinical features and prognosis of interstitial lung disease patients with positive anti-neutrophil cytoplasmic antibody. Methods: The patients with interstitial lung disease who visited Peking Union Medical College Hospital from March 2006 to March 2016 were divided into three groups: interstitial lung disease with ANCA-positive(ANCA-ILD), connective tissue disease associated interstitial lung disease and interstitial pneumonia with autoimmune features (CTD-ILD/IPAF) and idiopathic interstitial pneumonia (IIP). The three groups were analyzed in terms of clinical manifestations, serology, lung function, imaging, survival and recurrence. Results: Two hundred and seventy four patients were enrolled and 38 (14%) were ANCA-positive of whom 16 were male and 22 were female. The age of 38 ANCA-positive patients was (59±10) years and the follow-up time was (52±31) months. Seven among the 38 ANCA-positive patients died and the death rate is 18.42%. The ANCA-positive patients with interstitial lung disease have higher onset age (ANCA-ILD:59±10,CTD-ILD/IPAF:52±10,IIP:53±11,H=19.29, P<0.001), lower hemoglobin (ANCA-ILD: 129±21, CTD-ILD/IPAF: 138±15, IIP: 140±19, H=8.17, P=0.017), higher erythrocyte sedimentation rate (ANCA-ILD:45±35, CTD-ILD/IPAF:26±24,IIP:19±22,H=19.73, P<0.001), lower lung function improvement rate after treatment (ANCA-ILD:31%,CTD-ILD/IPAF:59%,IIP: 39%,χ(2)=11.74,P=0.003), lower absorption rate of CT lesion (ANCA-ILD:61%,CTD-ILD/IPAF:82%,IIP:67%, χ(2)=9.23,P=0.010) and higher death rate(ANCA-ILD:18%,CTD-ILD/IPAF:6%,IIP:12%, χ(2)=7.16,P=0.028). Conclusions: There are significant differences in clinical characteristics between ANCA-positive patients and other types of pulmonary interstitial disease. And both the treatment effect and the prognosis is poor for the ANCA-positive patients.

[Countermeasures and treatment for aortic acute syndrome with novel coronavirus pneumonia].

The novel coronavirus pneumonia (NCP) has cost a great loss to the health and economic property of Chines people. Under such a special circumstance, how to deal with such patients with acute aortic syndrome has become a serious challenge. Rapid diagnosis of concomitant NCP, safe and effective transportation, implementation of the interventional procedure, protection of vascular surgical team and postoperative management and follow-up of such patients have become urgent problems for us. Combined with the latest novel government documents, the literature and the experiences from Wuhan, we answered the above questions briefly and plainly. It also hopes to inspire the national vascular surgeons to manage critical emergencies in vascular surgery and even routine vascular diseases with NCP, as a final point to limit the severe epidemic situation, and minimize the damage of NCP.

[Countermeasures and treatment for aortic acute syndrome with 2019 coronavirus disease].

The 2019 coronavirus disease(COVID-19) has cost a great loss to the health and economic property of Chines people. Under such a special circumstance, how to deal with such patients with acute aortic syndrome has become a serious challenge. Rapid diagnosis of concomitant COVID-19, safe and effective transportation, implementation of the interventional procedure, protection of vascular surgical team and postoperative management and follow-up of such patients have become urgent problems for us. Combined with the latest novel government documents, the literature and the experiences from Wuhan, we answered the above questions briefly and plainly. We also hope to inspire the national vascular surgeons to manage critical emergencies in vascular surgery and even routine vascular diseases with COVID-19, as a final point to limit the severe epidemic situation, and minimize the damage of COVID-19.

Intratumoral Polymorphism of Peroxisome Proliferator-Activated Receptor Delta-87 T>C in Colorectal Cancer.

Peroxisome proliferator activated receptor delta (PPARD) is a nuclear receptor transcription factor whose single nucleotide polymorphism (SNP), especially PPARD-87 T>C (rs2016520), may play an important role in expression regulation of PPARD. But its expression patterns as well as contribution in colorectal cancer (CRC) are still controversial. In this study, whether the intratumoral heterogeneity of polymorphism of PPARD-87 T>C (rs2016520) existed and its influence in CRC were investigated. Tumor masses from primary CRC patients were collected during the operation of tumorectomy, specimens at the different sites of the same tumor mass were sampled and stored individually. The SNP of PPARD-87 T>C was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and the expression of PPARD in vivo was observed by immunohistochemistry. The correlation of PPARD -87 T>C intratumoral polymorphism and the clinicopathological parameters of patients was analyzed statistically. Tumor samples were collected from 106 CRC patients (70 males and 36 females) with an average age of 61.04±13.67 years. A total number of 808 samples (7.60±1.60 per patient) were mainly harvested at peripheral superficial (n=376), central superficial (n=163), invasive front (n=112) and mesenteric cancer foci (n=42) of tumor tissues as well as cancerous adjacent mucosa (n=104). PCR-RFLP analysis showed that T/T (n=460, 56.9%) and T/C (n=334, 41.3%) were the main genotypes of -87 T>C among these samples. Furthermore, intratumoral genotype of -87 T>C was homogeneous in 90 patients and heterogeneous in other 16 patients. The intratumoral heterogeneity was related to patients' age (P=0.016), tumor location (P=0.011) and the grade of differentiation (P=0.022). For patients with intratumoral heterogeneity, immunochemistry showed the expressions of PPARD were not influenced by T/T or T/C genotypes. Intratumoral heterogeneity of PPARD-87 T>C wildly existed in CRC, and associated with patients' age, tumor location and differentiation. However, the immunochemistry assay revealed that there's no significant link between heterogeneity and expression of PPARD.

[Effect of liraglutide on glucagon secretion in obese type 2 diabetic patients].

Objective: To investigate the effect of liraglutide on glucagon release in obese type 2 diabetes (T2DM). Methods: A multi-center, prospective, and self-comparison study was conducted in four hospitals in Qingdao. Twenty-four patients with T2DM were selected and treated with liraglutide for 12 weeks. Glucagon levels before and after treatment were detected before and 30 min, 60 min and 120 min after meals. Results: After 12 weeks of treatment, the overall level of glucagon decreased, in which the differences in glucagon levels at 30 min [(220±79) ng/L vs. (203±77) ng/L, P<0.05] and 60 min [(248±119) ng/L vs. (203±82)ng/L, P<0.05] reached significance, respectively, comparing to those before treatment. The area under the curve of glucagon after treatment was significantly lower than that before treatment (438±190 vs. 389±153, P<0.05). In contrast, after treatment, the overall level of C-peptide increased, especially the levels at 30 min [(1.53±1.02) nmol/L vs.(2.03±1.29) nmol/L], 60 min [(1.93±1.19) nmol/L vs. (2.48±1.75) nmol/L] and 120 min [(2.36±1.47) nmol/L vs. (2.96±1.84) nmol/L], all P<0.05. The area under C-peptide curve increased significantly (3.6±2.2 vs. 4.6±2.9, P<0.05). Fasting plasma glucose, postprandial 2 h plasma glucose and glycosylated hemoglobin A1c were all lower than before, and the differences were statistically significant (P<0.05). Waist circumference and body mass index were significantly lower than before (P<0.05). The amount of insulin used for the treatment decreased by approximately 55.1% compared with that before liraglutide, and the difference was statistically significant (P<0.05). Conclusions: Liraglutide inhibits glucagon secretion and lowers blood glucose. It can also reduce body weight, improve islet cell function and reduce insulin use in T2DM.

[Association of fibroblast growth factor 23 with age-related cardiac diastolic function subclinical state in a healthy Chinese population].

Objective: To determine the association of serum fibroblast growth factor-23 concentrations with age-related cardiac diastolic function subclinical state and whether this association differs by sex. Methods: Seven hundred sixteen healthy subjects (aged 35-89 years, 68.4% female) were selected from National Basic Research Program of China (973 Program-China Medical University subsection) between January 2014 and February 2015 and assigned into 4 groups according to sex and age:< 60 years old male and female group, ≥ 60 years old male and female group. Blood biochemical indicators and general clinical data of the subjects were measured. The glomerular filtration rate (eGFR) were estimated using the Modified Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI-ASIA) equation. The fibroblast factor 23 (FGF-23), C-reactive protein (CRP) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA). Cardiac structure and function parameters including left atrial diameter (LAD), inter-ventricular septum thickness (IVST), left ventricle posterior wall thickness (LVPWT), left ventricle mass index (LVMI),left atrial mass index (LAVI) and the ratio of peak velocity of early filling to the septal early peak diastolic mitral annulus velocity(E/e') were measured by echocardiography. Association between serum FGF-23 and aging-related diastolic function subclinical status was analyzed by binary Logistic regression analysis. Results: (1) Serum log-transformed FGF-23 levels were significantly higher in males than in females [(2.0±0.3) ng/L vs (1.9±0.4) ng/L, P<0.05]. (2) Cardiac diastolic function gradually decreased with age, and age related cardiac diastolic function decline of female was significantly higher than males[E/e':<60 years old male group (7.6±2.6), ≥ 60 years old male group (8.6±2.7), P<0.01;<60 years old female group (8.3±2.3), ≥ 60 years old female group (9.5±3.1), P<0.01; LAVI:<60 years old female group (14±5) ml/m(2), ≥ 60 years old female group (16±5) ml/m(2), P<0.01]. (3) Serum FGF-23 was significantly positively correlated with age (r=0.089, P<0.05) and LAVI (r=0.084, P<0.05) in total study population while with E/e' (r=0.149, P<0.05) only in males. There was no significant correlation between serum FGF-23 and cardiac diastolic function parameters in females. (4) Binary Logistic regression analysis showed that median and high FGF-23 were independently associated with age-related cardiac diastolic function decline (OR=2.831, 95% CI: 1.144-7.009, P=0.024; OR=2.548, 95% CI: 1.053-6.163, P=0.038) in males. Conclusions: Serum FGF-23 concentrations are associated with age-related cardiac diastolic function subclinical state in a healthy Chinese population. High levels of FGF-23 are independently associated with age-related cardiac diastolic function decline in males.

Tunable Quantum Spin Liquidity in the 1/6th-Filled Breathing Kagome Lattice.

We present measurements on a series of materials, Li_{2}In_{1-x}Sc_{x}Mo_{3}O_{8}, that can be described as a 1/6th-filled breathing kagome lattice. Substituting Sc for In generates chemical pressure which alters the breathing parameter nonmonotonically. Muon spin rotation experiments show that this chemical pressure tunes the system from antiferromagnetic long range order to a quantum spin liquid phase. A strong correlation with the breathing parameter implies that it is the dominant parameter controlling the level of magnetic frustration, with increased kagome symmetry generating the quantum spin liquid phase. Magnetic susceptibility measurements suggest that this is related to distinct types of charge order induced by changes in lattice symmetry, in line with the theory of Chen et al. [Phys. Rev. B 93, 245134 (2016)PRBMDO2469-995010.1103/PhysRevB.93.245134]. The specific heat for samples at intermediate Sc concentration, which have the minimum breathing parameter, show consistency with the predicted U(1) quantum spin liquid.

Field-Driven Quantum Criticality in the Spinel Magnet ZnCr_{2}Se_{4}.

We report detailed dc and ac magnetic susceptibilities, specific heat, and thermal conductivity measurements on the frustrated magnet ZnCr_{2}Se_{4}. At low temperatures, with an increasing magnetic field, this spinel material goes through a series of spin state transitions from the helix spin state to the spiral spin state and then to the fully polarized state. Our results indicate a direct quantum phase transition from the spiral spin state to the fully polarized state. As the system approaches the quantum criticality, we find strong quantum fluctuations of the spins with behaviors such as an unconventional T^{2}-dependent specific heat and temperature-independent mean free path for the thermal transport. We complete the full phase diagram of ZnCr_{2}Se_{4} under the external magnetic field and propose the possibility of frustrated quantum criticality with extended densities of critical modes to account for the unusual low-energy excitations in the vicinity of the criticality. Our results reveal that ZnCr_{2}Se_{4} is a rare example of a 3D magnet exhibiting a field-driven quantum criticality with unconventional properties.