[Nomogram analysis of risk factors for diabetic neuropathy in primary type 2 diabetic mellitus patients in Zhejiang Province].

Objective: To investigate the risk factors of diabetic nephropathy (DN) in primary type 2 diabetes mellitus (T2DM) patients and to quantitatively analyze the risk of DN by nomogram modeling. Methods: A total of 1 588 primary T2DM patients from 17 townships and streets in Zhejiang Province were enrolled from June 2018 to August 2018 in this cross-sectional study, with an average age of (56.8±10.1) years (50.06% male) and a mean disease duration of 9 years. The clinical data, biochemical test results, and fundus photographs of all T2DM patients were collected, and logistic regression analysis was used to screen the risk factors of DN. Then, a nomogram model was used to quantitatively analyze the risk of DN. Results: DN occurred in 27.71% (440/1 588 cases) primary type 2 diabetes patients. Hemoglobin A1c (HbA1c) (OR=1.159, 95%CI 1.039-1.292), systolic blood pressure (OR=1.041, 95%CI 1.031-1.051), serum creatinine (Scr) (OR=1.011, 95%CI 1.004-1.017), serum globulin (GLOB) (OR=1.072, 95%CI 1.039-1.105), diabetic retinopathy (DR) (OR=1.463, 95%CI 1.073-1.996), education level of more than junior high school (OR=2.018, 95%CI 1.466-2.777), and moderate-intensity exercise (OR=0.751, 95%CI 0.586-0.961) were influencing factors of DN. Nomogram model analysis showed that the total score of each factor of DN ranged from 64-138 points, and the corresponding risk rate ranged from 0.1-0.9. The nomogram model also predicted a C-index value of 0.753 (95%CI 0.726-0.781) and an area under the receiver operating characteristic curve of DN of 0.753. Internal verification of the C-index reached 0.738. The model displayed medium predictive power and could be applied in clinical practice. Conclusions: HbA1c, systolic blood pressure, Scr, GLOB, DR, and more than a junior high school education are independent risk factors of DN. Nomogram modeling can more intuitively evaluate the risk of DN in primary T2DM patients.

[Expression and clinical significance of CXC chemokine ligand 10 in glioma].

Objective: To analyze the expression of CXC chemokine ligand 10 (CXCL10) in glioma and its clinical significance through bioinformatics. Methods: The expression level of CXCL10 in glioma, and its prognostic significance, gene ontology (GO) function annotation, Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment and the correlation of tumor cell purity were analyzed in TCGA, CGGA, MetaScape, TIMER databases. In addition, 34 clinical glioma tissues were collected for Western Blot and immunohistochemistry to further verify the correlation between CXCL10 and glioma. Results: CGGA and TCGA database analysis showed that with the increase of WHO grade, the expression of CXCL10 in gliomas increased (P<0.01). The overall survival rate of patients with high CXCL10 expression was significantly lower than that of patients with low expression (χ2 =148.1,P<0.05). Among patients with grade Ⅳ glioblastoma who received radiotherapy or chemotherapy, the patients with low CXCL10 expression were associated with good survival (χ2 =6.714,P<0.05;χ2 =5.618,P<0.05). Moreover, GO and KEGG analysis showed that genes co-expressed with CXCL10 were mainly enriched in the biological processes such as cytokine-mediated signaling pathways, regulating adaptive immune responses and inflammatory responses. Furthermore, TIMER database analysis showed that CXCL10 was negatively correlated with the purity of glioma cells (LGG: r=-0.129;GBM: r=-0.165;P<0.05). Similarly, clinical sample analysis also showed that the expression level of CXCL10 increased in glioma, and it increased with the grade of glioma (all P<0.05). Conclusion: The expression of CXCL10 is up-regulated in glioma as well as it increased with the malignant degree of glioma. At the same time, the high expression of CXCL10 in glioma is closely related to the poor prognosis of patients.

[Association between grip strength, rapid gait speed and cognition in people aged 50 and above in Shanghai during 2009-2010].

Objective: To investigate the association between grip strength, rapid gait speed and cognition in people aged 50 and above in Shanghai. Methods: Cross-sectional data was collected from the World Health Organization (WHO) study on global ageing and adult health (SAGE) wave 1 (2009-2010). A questionnaire survey was conducted among 8 643 participants aged 50 years old and above selected by using multistage random cluster sampling strategies in Shanghai. Factor analysis was applied to evaluate and generate cognitive function overall score.Association between grip strength, rapid gait speed and cognition was examined by a two-level hierarchical linear model. Results: A total of 8 175 participants were included in this study, who were (62.9±9.7) years old, including 3 782 (46.3%) males. The average grip strength and rapid gait speed of participants were (27.46±12.01) kg and (1.44±0.43) m/s respectively. The average scores of verbal recall (VR), verbal fluency (VF), forward digit span (FDS), backward digit span (BDS) and total cognitive scores were (5.72±0.09), (12.67±0.35), (6.84±0.10), (4.32±0.14) and (60.50±0.95) respectively. Grip strength was positively associated with VR, VF, FDS, BDS and overall cognition (standardized ß=0.036, 0.079, 0.042, 0.046 and 0.043 respectively, P<0.05), and rapid gait speed was also positively associated with VR, VF and overall cognition (standardized ß=0.040, 0.031, 0.039 respectively, P<0.05) after adjusted for age, sex, residence, education level, marital status, household income, co-morbidity of chronic conditions, BMI, drinking, smoking, fruits, vegetables intake and physical activities. Conclusion: Grip strength and rapid gait speed are both positively associated with cognitive function of people aged 50 and above, which would be indicators to evaluate their cognition.

Salient space detection algorithm for signal extraction from contaminated and distorted spectrum.

An algorithm for signal extraction from a contaminated and distorted spectrum is proposed. First, this algorithm combines the salient space of the spectrum and the statistical characteristics of the noise to detect signal regions at different scales. Second, it extracts signals by subtracting the baseline from the spectrum in the signal regions. The baseline is fitted by segmented polynomial functions. This algorithm has been applied to simulated and experimental data, and the results show that this algorithm can accurately and automatically extract signals with varying widths from a contaminated spectrum. This method minimizes the influence of baseline distortion and exhibits good anti-noise capability and high real-time performance.

The clinical implications of mean platelet volume and mean platelet volume/platelet count ratio in locally advanced esophageal squamous cell carcinoma.

As a hallmark of platelet activation, mean platelet volume (MPV) has been identified to be associated with various malignancies. However, the correlation between MPV, mean platelet volume/platelet count ratio (MPR), and esophageal squamous cell carcinoma (ESCC) remains unclear. The aim of this study is to clarify the relevance of MPV and MPR in patients with locally advanced ESCC. Four hundred and fifty-seven cases with newly diagnosed locally advanced ESCC followed by radical surgery and 240 healthy subjects matched for age and gender were included in this study. We retrospectively compared various hematological variables between groups and analyzed the correlation between MPV, MPR, and patients' clinicopathologic characteristics. Preoperative MPV and MPR were found to be significantly decreased in locally advanced ESCC when compared to healthy controls, they were (8.14 ± 1.09 fL vs. 10.23 ± 0.78 fL, P < 0.0001) and (0.03875 ± 0.02645 vs. 0.04463 ± 0.00972, P = 0.001), respectively. In addition, patients with advanced tumor length (≥4 cm) tended to have lower MPV levels (8.03 ± 1.11 fL versus 8.33 ± 1.21 fL, P = 0.005), while there was no difference between other subgroups. Moreover, decreased MPR was significantly correlated with advanced tumor length (P < 0.001) when divided at a median of 0.03420. Decreased MPV and MPR were significantly associated with locally advanced ESCC. Thus, they might be helpful in screening and risk stratification for locally advanced ESCC in combination with other approaches.

[Clinicopatholigic features of renal cell carcinoma associated with chromosome X inversion harboring gene fusions involving TFE3].

Objective: To study the clinicopathologic features, immunophenotype, characteristic FISH pattern and prognosis of renal cell carcinoma (RCC) associated with chromosome X inversion harboring gene fusions involving TFE3. Methods: Ten cases of NONO-TFE3 RCC and four cases of RBM10-TFE3 RCC were investigated at Nanjing Jinling Hospital from 2009 to 2016 by clinicopathological findings, immunohistochemistry, and genetic analysis. Results: Morphologically, the distinct pattern of secretory endometrioid subnuclear vacuolization was overlapped with clear cell papillary RCC, and often accompanied by sheets of epithelial cells in NONO-TFE3 RCC. Most cases of RBM10-TFE3 RCC presented with the biphasic feature that acinar, tubular and papillary patterns of epithelioid cells combined with sheets of small cells with "pseudorosette-like" architectures. In addition, cytoplasmic vacuolization, nuclear groove, and psammoma bodies were also observed. Immunohistochemically, all NONO-TFE3 RCC cases were immunoreactive for TFE3, CD10, RCC markers, and PAX8, and negative for CK7, Cathepsin K, Melan A, HMB45, Ksp-cadherin, vimentin, and CD117. All 4 cases of RBM10-TFE3 RCC showed moderate to strong immunoreactivity for TFE3, Cathepsin K, CD10, Ksp-cadherin, E-cadherin, P504s, RCC marker, PAX8, and vimentin but negative for TFEB, HMB45 and CK7. CKpan and Melan A were at least focally expressed. The antibody to Ki-67 showed labeling of 3%-8% (mean 5%). There were some expression discrepancies of immunochemistry between different histological patterns. PAX8, CKpan, P504s, and Ksp-cadherin were expressed in epithelioid areas but not in small-cell areas. Ki-67 labeling index of epithelioid areas was higher than that in small-cell areas. In molecular analysis, NONO-TFE3 fusion transcripts were identified in 6 patients. The fusion points were between exon 7 of NONO and exon 6 of TFE3 in 5 patients and between exon 9 of NONO and exon 5 of TFE3 in one patient. All 4 cases of RBM10-TFE3 RCC demonstrated to have RBM10-TFE3 fusion transcripts and the fusion points were between exon 5 of TFE3 and exon 17 of RBM10. Using TFE3 break-apart FISH assay, all 10 cases of NONO-TFE3 RCC showed characteristic patterns of equivocal split signals with a distance of nearly 2 signal diameters. All 4 cases of RBM10-TFE3 RCC showed colocalized or subtle split signals with a distance of <1 signal diameter, which was considered as negative results. Long-term follow-up was available for 7 patients of NONO-TFE3 RCC and 4 patients of RBM10-TFE3 RCC. All patients were alive with no evidence of disease. Conclusions: Two rare genotypes, NONO-TFE3 RCC and RBM10-TFE3 RCC, are reported in this study. Both of these two tumors show specific morphology and good prognosis, along with the positive TFE3 staining and the equivocal or false-negative TFE3 FISH results, which could be missed. PCR detection or next-generation sequencing can determine the genotype.

Promoter identification and analysis of key glycosphingolipid biosynthesis-globo series pathway genes in piglets.

Glycosphingolipid biosynthesis-globo series pathway genes (FUT1, FUT2, ST3GAL1, HEXA, HEXB, B3GALNT1, and NAGA) play an important regulatory role in the defense against Escherichia coli F18 in piglets. In this study, we identified the transcription initiation site and promoter of this gene cluster by mined previous RNA-seq results using bioinformatics tools. The FUT1 transcription initiation region included five alternative splicing sites and two promoter regions, whereas each of the six other genes had one promoter. Dual luciferase reporter results revealed significantly higher transcriptional activity by FUT1 promoter 2, indicating that it played a more important role in transcription. The promoters of glycosphingolipid biosynthesis genes identified contained a CpG island within the first 500 bp, except for the B3GALNT1 promoter which included fewer CpG sites. These results provide a deeper insight into methylation and the regulatory mechanisms of glycosphingolipid biosynthesis-globo series pathway genes in piglets.

Expression of key glycosphingolipid biosynthesis-globo series pathway genes in Escherichia coli F18-resistant and Escherichia coli F18-sensitive piglets.

A pioneering study showed that the glycosphingolipid biosynthesis-globo series pathway genes (FUT1, FUT2, ST3GAL1, HEXA, HEXB, B3GALNT1 and NAGA) may play an important regulatory role in resistance to Escherichia coli F18 in piglets. Therefore, we analysed differential gene expression in 11 tissues of two populations of piglets sensitive and resistant respectively to E. coli F18 and the correlation of differential gene expression in duodenal and jejunal tissues. We found that the mRNA expression of the seven genes was relatively high in spleen, liver, lung, kidney, stomach and intestinal tract; the levels in thymus and lymph nodes were lower, with the lowest levels in heart and muscle. FUT2 gene expression in the duodenum and jejunum of the resistant population was significantly lower than that in the sensitive group (P < 0.01). ST3GAL1 gene expression was also significantly lower in the duodenum of the resistant population than in the sensitive group (P < 0.05). No significant differences were observed among the remaining genes. The expression level of FUT1 was extremely significantly positively correlated with FUT2 and B3GALNT1 expression (P < 0.01) and also had a significant positive correlation with NAGA expression (P < 0.05). The expression level of FUT2 had extremely significant positive correlations with FUT1, ST3GAL1 and B3GALNT1 (P < 0.01). These results suggest that FUT2 plays an important role in E. coli F18 resistance in piglets. FUT1, ST3GAL1, B3GALNT1 and NAGA may also participate in the mechanism of resistance to E. coli F18.

[Efficiency and adverse effects of the effective therapy applying etoposide + cisplatin and its subsequent maintenance therapy with different durations in patients with small cell lung cancer].

OBJECTIVE: To explore the efficiency and adverse effects of the effective EP (etoposide + cisplatin) therapy and its subsequent maintenance therapy with different durations in patients with small cell lung cancer (SCLC). METHODS: Clinical data of 104 SCLC patients diagnosed and treated at the Jilin Province Cancer Hospital between September 2010 and December 2013 were retrospectively analyzed.Among them, 35 patients were subsequently treated with a 4-week maintenance therapy following the original therapeutic regimen after the effective EP therapy (4-week maintenance therapy group), 35 patients were treated with a subsequent 6-week maintenance therapy (6-week maintenance therapy group), and 34 patients were treated without maintenance therapy (control group).52 patients were in limited stage, and 52 patients were in extensive stage. The progression-free survival (PFS), overall survival (OS) and adverse effects in the 4-week maintenance therapy group, 6-week maintenance therapy group and control group were analyzed. RESULTS: The median PFS in the control group, 4-week maintenance therapy group and 6-week maintenance therapy group was 4.0, 3.5, and 4.0 months, respectively, and the median OS was 9.0, 10.0 and 12.0 months, respectively, showing no significant difference among the groups (P>0.05 for all). The median PFS was prolonged by 2 months as compared with the control group after the 4-week maintenance therapy in the patients with complete remission in first-line chemotherapy (P=0.041), while the median OS was not improved (P=0.131). Neither the median PFS nor median OS showed statistically significant difference between each two groups in the patients with partial remission in first-line chemotherapy (P>0.05 for all). In the limited stage, the median PFS in the control group, 4-week maintenance therapy group, and 6-week maintenance therapy group was 5.0, 6.5, and 4.0 months, respectively, and median OS was 11.0, 13.5, and 13.0 months, respectively, the differences showed no statistical significance (P>0.05 for all). In the extensive stage, the median PFS in the control group, 4-week maintenance therapy group, and 6-week maintenance therapy group was 3.0, 3.0, and 3.5 months, respectively, showing significant differences (P=0.015); the median OS was 6.5, 8.0, and 8.0 months, respectively, presenting no statistically significant differences (P=0.096). In addition, the PFS in the 6-week maintenance therapy group was significantly improved as compared with that in the control group (P=0.016). Compared with the control group, the incidence rates of nausea (grade 3-4), vomiting, hypodynamia, leukopenia, neutropenia, and thrombocytopenia in the 4-week maintenance therapy group and 6-week maintenance therapy group were increased significantly (P<0.05 for all), however, the side effects were tolerable. CONCLUSION: Prolonging the treatment cycle of EP therapy can improve the PFS in SCLC patients in first-line CR chemotherapy and extensive stage.

Differential expression of Toll-like receptor 4 signaling pathway genes in Escherichia coli F18-resistant and - sensitive Meishan piglets.

The Toll-like receptor 4 (TLR4) signaling pathway is an important inflammatory pathways associated with the progression of numerous diseases. The aim of the present study was to investigate the relationship between TLR4 signaling and resistance to Escherichia coli F18 in locally weaned Meishan piglets. Using a real-time PCR approach, expression profiles were determined for key TLR4 signaling pathway genes TLR4, MyD88, CD14, IFN-α, IL-1ß and TNF-α in the spleen, thymus, lymph nodes, duodenum and jejunum of E. coli F18-resistant and -sensitive animals. TLR4 signaling pathway genes were expressed in all the immune organs and intestinal tissues, and the expression was generally higher in the spleen and lymph nodes. TLR4 transcription was higher in the spleen of sensitive piglets (p<0.05), but there was no significant difference in TLR4 mRNA levels in other tissues. Similarly, CD14 transcription was higher in lymph nodes of sensitive animals (p<0.05) but not in other tissues. IL-1ß expression was higher in the spleen and in the duodenum of resistant piglets (p<0.05, p<0.01, respectively), and there were no significant differences in other tissues. There were also no significant differences in the expression of MyD88, TNF-α and IFN-α between sensitive and resistant piglets (p>0.05). These results further confirm the involvement of the TLR4 signaling pathway in resistance to E. coli F18 in Meishan weaned piglets. The resistance appeared to be mediated via downregulation of TLR4 and CD14, and upregulation of MyD88 that may promote the release of cytokines TNF-α, IL-1ß, IFN-α and other inflammatory mediators which help to fight against E. coli F18 infection.

Agrobacterium-mediated transformation of tomato (Solanum lycopersicum L.) using the expansin 10 (CsEXP10) gene.

The cucumber expansin 10 (CsEXP10) gene was previously cloned from young cucumber fruits but its role has not been defined. To determine the role of this gene in plant growth and development, a CsEXP10 gene transformation system was established. The open reading frame of the gene was inserted behind the CaMV35S promoter of vector pCAMBIA1301, and the construct was introduced into tomato plants by Agrobacterium-mediated transformation. In total, 19 kanamycin-positive lines were produced and nine independent transgenic lines were identified by ß-glucuronidase and polymerase chain reaction (PCR) analysis. Quantitative real-time PCR analysis showed that levels of the CsEXP10 transcript were higher in transgenic lines than in a non-transgenic line.

Identification of BPI protein produced in different expression system and its association with Escherichia coli F18 susceptibility.

The super antibiotic bactericidal/permeability-increasing (BPI) protein is a member of a new generation of proteins that have been implicated as endotoxin-neutralizing agents. In this study, recombinant porcine BPI protein was obtained by generating porcine BPI encoding prokaryotic, eukaryotic, and yeast expression vectors. Recombinant protein expression was detected in yeast GS115, Escherichia coli, and 293-6E cells by gel electrophoresis and Western blotting. Escherichia coli F18 is the primary Gram-negative bacteria in the gut and the main pathogen leading to diarrhea and edema dis-ease in weaning piglets. Therefore, E. coli F18-resistant and -sensitive Sutai piglets were used to test differential expression of BPI protein by Western blotting and to investigate the potential correlation between BPI protein expression and E. coli F18-susceptibility. Recombinant porcine BPI protein expression was not detected in the prokaryotic and yeast expression systems; however, soluble protein was detected in the eukaryotic expression system. These data indicate the strong bacterio-static action of the BPI protein and confirm the feasibility of obtaining large amounts of recombinant porcine BPI recombinant protein using this eukaryotic expression system. In addition, the BPI protein expres-sion levels in the E. coli F18-resistant group were significantly higher than those in the sensitive group, indicating that high BPI protein ex-pression is associated with resistance to E. coli F18. Our findings pro-vide a basis for further investigations into the development of a drug designed to confer resistance to E. coli F18 in weaning piglets.

Differential expression of porcine TAP1 gene in the populations of pigs.

Transporter associated with antigen processing (TAP) transports peptides from the cytosol into the endoplasmic reticulum (ER) for subsequent loading onto the major histocompatibility complex (MHC) class I molecules. TAP is consisted of two subunits: TAP and TAP2. Using Real-time PCR technology, this study detected tissue expression profile and analyzed the differential expression of TAP1 gene in Sutai Escherichia coli-resistant group, Yorkshire and Meishan pigs. Tissue expression profile revealed that TAP1 gene expressed in all tissues we detected, and the expression levels were high in lung, immune tissues and intestines. Through the comparation of gene expression differention in different populations, TAP1 expression level of Sutai E. coli-resistant group was significantly higher than that of Yorkshire and Meishan populations in liver, spleen, lung, kidney, thymus, lymph, duodenum and jejunum (P<0.05). Meanwhile TAP1 gene was more highly expressed in Sutai E. coli-resistant group than that of Meishan population in stomach (P<0.05). In conclusion, the upregulation of TAP1 expression level in E. coli-resistant group could be related to E. coli F18 infection. In addition, Chinese local pigs may have special immune response and genetic mechanism in resisting E. coli F18 infection which is differing from MHC I moleculars.

Cell proliferation and apoptosis in the fetal and neonatal ovary of guinea pigs.

The guinea pig is an excellent animal model for studying reproductive biology of adult humans and most domestic animals. Yet, whether this animal might serve as a good model for embryonic stage investigations and determinations of signals affecting or directing ovary development remains unknown. These questions were addressed by examining morphological evolution and the expression of biomarkers of cell proliferation and apoptosis in the ovaries of fetal and neonatal guinea pigs in the present study. Embryonic and neonatal guinea pigs at 30, 40, 50, 60, and 68 days postcoitum (dpc) and at 1 day postpartum (dpp) were evaluated, and the dynamic changes in follicles between 30 dpc and 1 dpp were observed. Results also showed that a critical period of follicular development in guinea pig embryos occurred at 40 to 50 dpc. Moreover, the proliferating-cell nuclear antigen, a cell proliferation marker, immunohistochemically stained healthy follicles, while caspase-3, an apoptosis marker, was mainly observed in atretic follicles. Together, these results demonstrate that cell proliferation and apoptosis contribute to follicular formation, development, and atresia in fetal and neonatal guinea pig ovaries. Furthermore, this study confirmed that the guinea pig is also an excellent animal model for studying reproductive biology in human and domestic animal embryos.

[Association between dietary pattern and frailty among people aged 50 years and over in Shanghai].

Objective: To investigate dietary patterns of individuals aged ≥50 in Shanghai and analyze their association with frailty. Methods: Using data from the third wave of the Study on Global Ageing and Adult Health in Shanghai conducted between 2018 and 2019. We collected the frequency and average intake of food by the food frequency questionnaire. Factor analysis was used to extract dietary patterns, and a frailty index was constructed using the ratio of the cumulative total score of health deficits to 35 health-related variables considered. We used an ordinal multinomial logistic regression model to analyze the association between dietary patterns and frailty. Results: A total of 3 274 participants aged (67.9±9.2) years were included in the study, including 1 971 (60.2%) men and 1 303 (39.8%) women. We extracted four dietary patterns: high-protein-nuts pattern, potato-bean-vegetable-fruit pattern, poultry-meat pattern, and high-oil-salt pattern. After adjusting for confounding factors, the logistic regression analysis showed that compared with the high-oil-salt pattern, the high-protein-nuts pattern was negatively associated with the risk of higher frailty (OR=0.743, 95%CI: 0.580-0.951). We did not find an association between dietary patterns and frailty between the different gender groups. In the age group 50-64, the high-protein-nuts and potato-bean-vegetable-fruit patterns were negatively correlated with a higher degree of frailty than the high-oil-salt pattern. In the low-level physical activity group, the high-protein-nuts pattern was negatively correlated with a higher degree of frailty than the high-oil-salt pattern (OR=0.509, 95%CI: 0.361-0.720). However, we found no significant effect of the high-protein nuts pattern, potato-bean-vegetable-fruit pattern, and poultry-meat pattern on the risk of higher frailty compared to the high-oil-salt pattern in the moderate to high level of physical activity group. Conclusions: Compared to the high-oil-salt pattern, dietary patterns with a higher intake of high-protein nuts, potatoes, legumes, and fruits and vegetables might be associated with a lower risk of higher frailty in residents aged 50-64 years of age than with a high oil and salt pattern. At the same time, it may have a more significant protective effect in people with lower physical activity levels. It is suggested that a diet rich in high-protein foods, nuts, potatoes, beans, vegetables, and fruits may help reduce and delay the risk of frailty.

[Association between vitamin D level and grip strength in adults aged 50 and older in Shanghai].

Objective: To understand the association between vitamin D level and grip strength in people aged ≥50 years in Shanghai. Methods: Data were obtained from the WHO's Study on Global Ageing and Adult Health in Shanghai during 2018-2019. Logistic regression model was used to analyze the association between vitamin D level and grip strength, and a stratified analysis was conducted for different gender, age and dairy product intake groups. Restricted cubic spline was used to evaluate the dose-response association between vitamin D level and low grip strength. Results: A total of 4 391 participants were included in the study, including 2 054 men (46.8%), with an average age of (67.02±8.81) years. And 1 421 individuals (32.4%) had low grip strength; 1 533 individuals (34.9%) had vitamin D deficiency, and 401 individuals (9.1%) had vitamin D deficiency. After adjusted for confounding factors, the logistic regression results analysis showed that individuals with vitamin D deficiency had a higher risk for low grip strength (OR=1.41, 95%CI: 1.09-1.83). In men, after adjusting for confounding factors, vitamin D deficiency was positively associated with the risk for low grip strength (OR=1.67, 95%CI: 1.12-2.50), but there was no significant association between vitamin D level and grip strength in women (OR=1.30, 95%CI: 0.97-1.74). In age group 60-69 years and ≥80 years, there was significant association between vitamin D deficiency and low grip strength after adjusting for confounding factors (OR=1.57, 95%CI: 1.05-2.35; OR=2.40, 95%CI: 1.08-5.31). In people who had daily intake of dairy product <250 ml, there was positive association between vitamin D deficiency and low grip strength, but there was no significant association in people who had daily dairy product ≥250 ml after adjusting for confounding factors. The restrictive cubic spline demonstrated that risk of low grip strength might decreased with the increase of vitamin D levels, however, the difference was not significant (P>0.05). Conclusions: This study demonstrated that there is association between vitamin D level and grip strength. People with vitamin D deficiency have higher risk for low grip strength.

Interspecies difference of luteolin and apigenin after oral administration of Chrysanthemum morifolium extract and prediction of human pharmacokinetics.

The aims of the present study were to study the interspecies difference in the pharmacokinetics of luteolin and apigenin occurring in Chrysanthemum morifolium extract (CME) among rats, beagle dogs, mini-pigs, and humans, and compared the human pharmacokinetic parameters with the data predicted from the above three animals. The plasma concentrations of luteolin and apigenin were determined with a RP-HPLC method. An interspecies difference of pharmacokinetics was found, especially between rats and other species, the plasma concentration of luteolin was much lower than that of apigenin in rats, although the content of luteolin in CME was higherthan that of apigenin, whereas the plasma concentration of luteolin was much higher than that of apigenin in dogs, mini-pigs and humans. Animal scale-up of some pharmacokinetic parameters of luteolin and apigenin were also performed after rats, beagle dogs, mini-pigs and humans were orally given CME at dosages of 400 mg/kg, 102 mg/kg, 90 mg/kg, and 20 mg/kg, respectively. Linear relationships were obtained between log mean retention time (MRT) and log species body weight (W) (kg), and log elimination half-life (t1/2) (h) and logW. The corresponding allometric equations were MRT=9.382W(0.1711) (R2 = 0.9999) and t1/2 = 4.811W(0.1093) (R2 = 0.9013) for luteolin, MRT = 12.53W(0.0356) (R2 = 0.9980) and t1/2 = 7.940W(0.0294) (R2 = 0.9258) for apigenin, respectively. The predicted human pharmacokinetic parameters (MRT and t1/2) by an allometric approach were 18.6 h and 7.46 h for luteolin, 14.3 h and 8.95 h for apigenin, respectively, which were close to the values obtained from humans (20 mg CME/kg) in the present study. The study has demonstrated the possibility to extrapolate the pharmacokinetic behavior of flavonoids from animals to humans.

Association between early vasopressor administration and in-hospital mortality in critically ill patients with acute pancreatitis: A cohort study from the MIMIC-IV database.

OBJECTIVE: This study aims to explore the association between early administration of vasopressors and in-hospital mortality in acute pancreatitis (AP) patients admitted to the ICU. PATIENTS AND METHODS: The MIMIC-IV database was used to identify AP patients who had and had not received vasopressors. Univariate and multivariate logistic regression, propensity score matching (PSM), and inverse probability of treatment weighting (IPTW) were used for statistical analysis. RESULTS: A total of 894 AP patients admitted to the ICU were included in the study. Among them, AP patients who received vasopressors were associated with an increased risk of in-hospital mortality in the unadjusted model (OR: 7.77, 95% CI 4.92-12.61, p<0.001), multivariable-adjusted model (OR: 2.51,95% CI 1.1-5.76, p<0.05), PSM model (OR: 2.58, 95% CI 1.03-6.85, p<0.05) and IPTW model (OR: 1.82, 95% CI 1.06-3.15, p<0.05) compared with patients who did not receive vasopressors. In the subgroup analysis, age (≥ 65 years old: OR: 2.5, 95% CI 0.82-7.91; <65 years old: OR: 4.63, 95% CI 0.84-26.41), male (OR: 1.19, 95% CI 0.35-4.03), ethnicity (white: OR: 2.49, 95% CI 0.81-7.62; non-white: OR: 4.28, 95% CI 0.85-23.7), usage of norepinephrine (OR: 2.29, 95% CI 0.91-5.78), and single-use of vasopressor (OR: 1.48, 95% CI 0.43-4.95) were not associated with in-hospital mortality in patients with AP, whereas vasopressin (OR: 4.27, 95% CI 1.24-15.13; p<0.05) and phenylephrine usage (OR: 4.75, 95% CI 1.66-13.95; p<0.05), combined vasopressor usage (OR: 4.41, 95% CI 1.55-12.96; p<0.01), and female usage (OR: 7.89, 95% CI 2.03-34.2; p<0.01) were associated with in-hospital mortality. CONCLUSIONS: Early vasopressor use is significantly associated with increased in-hospital mortality among critically ill AP patients. This association might be greater in females, vasopressin, phenylephrine, and combined vasopressor users. Our results may benefit clinicians as they can guide the rational use of vasopressors in critically ill AP patients admitted to the ICU.

[Research prospect of preclinical model construction and precision therapy in ameloblastoma].

Ameloblastoma (AM) is a benign odontogenic tumor with unknown etiology. It is prone to recurrence and has a potential for malignant transformation. Patients often show high rates of relapse after curettage, or suffer from structural and functional damage of jaw after partial resection. Whole-genome sequencing data revealed that BRAF mutations and SMO mutations were common and likely to be mutually exclusive in AM. It was also reported that BRAF inhibitors were effective in several patients carrying BRAFV600E mutation. However, reliable preclinical models are urgently needed for exploring targeted therapy as it's so difficult to conduct large clinical trials in this tumor. Patient-derived cell models in vitro and xenograft models in vivo are frequently used preclinical models. In fact, benign tumor cells generally showed a finite proliferative capacity in two-dimensional culture, and most likely, they could exhibit altered cellular phenotype after immortalization. Moreover, this benign tumor presented low chances of subcutaneous engraftment in nude mice. Accordingly, humanized mouse xenograft model needs more exploration. Yet, it is worth mentioning that a three-dimensional organoid model presents a high potential in culturing stem-cell-like epithelial cells in AM, and it would further be used in recapitulating corresponding tumors and developing targeted medicines. In this paper, we review research progress in preclinical models and the genetic variations of AM, and raise drug screening prospect of the current organoid models, which may pave the way for the possible personalized medicine in AM.

Nomograms for predicting survival in patients with gastric carcinoid or neuroendocrine carcinoma based on the SEER database.

OBJECTIVE: The aim of this study was to construct a competent model that can effectively predict the prognosis of patients with gastric carcinoid (GC) or neuroendocrine carcinoma (NEC). PATIENTS AND METHODS: Data of patients with GC or NEC were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database from 1975 to 2017. Univariable and multivariable Cox analysis was used to determine the independent factors for patients with GC or NEC. Nomograms were established based on the independent factors and the results were evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). RESULTS: A total of 214 patients with GC and 65 patients with gastric NEC were extracted from the SEER database. Independent prognostic factors for patients with GC were M stage, gender, age, and chemotherapy. Independent prognostic factors for patients with gastric NEC included age, M stage, and chemotherapy. ROC curves, calibration curves, and DCA confirmed that the nomograms can precisely predict the prognosis of patients with GC and NEC. CONCLUSIONS: The nomograms can effectively predict survival in patients with GC or NEC, which may assist the clinician in their decision-making and quantitatively judge the prognosis of individual patients.