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Immune checkpoint blockade (ICB) targeting PD-1/PD-L1 has been used for the treatment of head and neck squamous cell carcinoma (HNSCC). However, the overall response rate to ICB therapy for HNSCC remains less than 20%. It has recently been reported that the appearance of tertiary lymphoid structures (TLSs) in tumor tissue is correlated with better prognosis and response to ICB treatment. Here, we demonstrated an immune classification for the tumor microenvironment (TME) of HNSCC by analyzing The Cancer Genome Atlas (TCGA)–HNSCC data set and found that immunotype D with TLS enrichment had a better prognosis and response to ICB treatment. Furthermore, we observed that TLSs were present in a part of tumor samples of human papillomavirus (HPV) infection negative HNSCC (HPV− HNSCC) and were associated with the densities of dendritic cell (DC)–LAMP+ DCs, CD4+ T cells, CD8+ T cells, and progenitor T cells in TME. We established an HPV− HNSCC mouse model with TLS-enriched TME by overexpressing LIGHT in a mouse HNSCC cell line. We found that the induction of TLS formation enhanced the response to PD-1 blockade treatment in the HPV− HNSCC mouse model, accompanied by increases in DCs and progenitor exhausted CD8+ T cells in the TME. Elimination of CD20+ B cells attenuated the therapeutic effect of PD-1 pathway blockade in TLS+ HPV− HNSCC mouse models. These results indicate that TLSs contribute to the favorable prognosis and antitumor immunity of HPV− HNSCC. Inducing TLS formation in HPV− HNSCC tumors is a potential therapeutic method for improving the ICB response rate in patients with HPV− HNSCC. [ABSTRACT FROM AUTHOR]

Most species of the family Cupressaceae are widely distributed throughout China, but Sabina przewalskii f. pendula and Juniperus przewalskii are endemic to the Qinghai-Tibet Plateau region. Therefore, they are of great significance to the plateau ecosystem. Sabina przewalskii and J. przewalskii have similar characteristics, but they be distinguished by the presence or absence of drooping branchlets. However, this feature can be difficult to distinguish with the naked eye. In this study, the complete chloroplast (CP) genomes of S. przewalskii and J. przewalskii were determined by highthroughput sequencing, aiming to unveil their differences at the molecular level. The sizes of the CP genomes of J. przewalskii and S. przewalskii are 128,748 bp and 127,315 bp, respectively, sharing the typical structure of conifer species. The GC content of the S. przewalskii plastome is 35.08%, encoding 84 proteins, 32 tRNAs and 4 rRNAs. The GC content of the J. przewalskii CP genome is 34.98%, and one additional rpl32 gene was detected. Phylogenetic analysis proved that J. przewalskii showed a close relationship to Juniperus tibetica and S. przewalskii, both of which belong to the family Cupressaceae. Our results of the plastome of J. przewalskii and S. przewalskii further clarify the evolution of Cupressaceae species. The divergent regions and the repetitive sequences identified could be developed as molecular markers that would benefit breeding and species discrimination. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To explore the effect of polyethylene glycol loxenatide (long-acting GLP-1R agonist) on the lipid, glucose levels, and weight in type 2 diabetes mellitus patients with obesity. PATIENTS AND METHODS: A total of 40 obese patients with type 2 diabetes mellitus in our hospital from July 2019 to June 2020 were randomly divided into a control group and a study group. The study group was treated with metformin and polyethylene glycol loxenatide injection, while the control group was treated with metformin. RESULTS: Before treatment, there was no significant difference in FPG (Fasting Blood Glucose) and PPG (Post Prandial Glycaemia) levels between the study group and the control group (p>0.05). After a treatment period, the FPG and PPG levels in the study group were significantly lower than those in the control group (p<0.05). With the longer treatment time, the patient's weight and BMI were lower (p<0.05). The weight and BMI of patients changed the least after one month of treatment, and the weight and BMI changed the most after more than seven months of treatment. After a period of treatment, the levels of FPG and PPG in the blood of male patients in the study group were significantly lower than those of female patients (p<0.05). After treatment, the TG level of the study group was significantly lower than that of the control group (p<0.05). In comparison, the HDL-C level was significantly higher than that of the control group (p<0.05). CONCLUSIONS: Lipid and glucose levels of type 2 diabetes mellitus patients with obesity have decreased after 12 weeks of polyethylene glycol loxanatide use. The weight of type 2 diabetes mellitus patients with obesity has changed after using polyethylene glycol loxenatide for a period of treatment. Among them, there is a certain relationship between body weight and treatment time, gender, and original body weight, which is worthy of further research and promotion in clinical practice. [ABSTRACT FROM AUTHOR]

The aim of this study was to observe the effects of remifentanil on organ damage and energy metabolism in lipopolysaccharide (LPS)-induced septic rats. A total of 45 clean-grade male Wistar rats (weight 270-320 g) were randomly divided into three groups: a control group, an LPS group, and an LPS with remifentanil treatment (LPS+REM) group. After 6 hours of modeling, the levels of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) in lung and kidney tissues of rats in each group were detected by ELISA. The activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in lung and kidney tissues were determined, and the content of lactic acid, pyruvate and epinephrine in heart and kidney tissues were detected. Reverse transcription polymerase chain reaction and the Western blot test were used to detect the expression of pyruvate dehydrogenase kinase 4 (PDK4) in the myocardial tissue. We found that remifentanil treatment inhibited the levels of IL-6, TNF-α, and MDA in the lung and kidneys 6 h after the administration of LPS and increased the level of SOD activity. Treatment with remifentanil reduced the expression of lactic acid, pyruvate, and epinephrine in the heart and kidney tissues and attenuated the expression of PDK4 messenger RNA and PDK4 protein in the myocardial tissue. We concluded that remifentanil mignt inhibit the release of tissue inflammatory factors, regulate the body's energy metabolism, and ultimately protect the sepsis tissue damage caused by LPS. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Diabetes mellitus is a chronic metabolic disease which has an adverse impact on the quality of patient's life, so patients often need to receive treatment for a long time. Selection of medications with high therapeutics effects and low cost is very important for patients to take medicine for a longer period of time. Sitagliptin is a drug which is widely used in clinics and can effectively control blood glucose level. This article explores the pharmacoeconomic value of Sitagliptin in the treatment of diabetes mellitus. PATIENTS AND METHODS: A total of 100 patients with diabetes mellitus treated were recruited in this study. The patients were randomly divided into 4 groups with 25 cases in each group. Patients in group A were treated with pioglitazone, group B with Sitagliptin, group C with metformin and group D with glimepiride. The cost of the drugs, the treatment results and adverse effects were compared. RESULTS: Compared with group A, C and D, the cost-effectiveness ratio of group B was low (p<0.05), and the therapeutic effect was high (p<0.05). In addition, the incidence of adverse reactions in group B was lower than that in group A, C and D (p<0.05). There was no significant difference in the levels of FPG, 2hPG and HbAlc in patients among the four groups before treatment (p>0.05). After treatment, the levels of FPG, 2hPG and HbAlc in group B were significantly lower than those in groups A, C and D (p<0.05). Finally, there was no significant difference in waist circumference and BMI among the four groups before treatment (p>0.05). After treatment, the waist circumference and BMI in group B were lower than those in groups A, C and D (p<0.05). CONCLUSIONS: The application of Sitagliptin in the treatment of diabetic patients can effectively enhance the therapeutic effect. The cost effectiveness is satisfactory, and the blood glucose level can be maintained at a stable state. [ABSTRACT FROM AUTHOR]

To evaluate the impacts of guanidinoacetic acid (GAA) and coated folic acid (CFA) on growth performance, nutrient digestion and hepatic gene expression, fifty-two Angus bulls were assigned to four groups in a 2 × 2 factor experimental design. The CFA of 0 or 6 mg/kg dietary DM folic acid was supplemented in diets with GAA of 0 (GAA−) or 0·6 g/kg DM (GAA+), respectively. Average daily gain (ADG), feed efficiency and hepatic creatine concentration increased with GAA or CFA addition, and the increased magnitude of these parameters was greater for addition of CFA in GAA− diets than in GAA+ diets. Blood creatine concentration increased with GAA or CFA addition, and greater increase was observed when CFA was supplemented in GAA+ diets than in GAA− diets. DM intake was unchanged, but rumen total SCFA concentration and digestibilities of DM, crude protein, neutral-detergent fibre and acid-detergent fibre increased with the addition of GAA or CFA. Acetate:propionate ratio was unaffected by GAA, but increased for CFA addition. Increase in blood concentrations of albumin, total protein and insulin-like growth factor-1 (IGF-1) was observed for GAA or CFA addition. Blood folate concentration was decreased by GAA, but increased with CFA addition. Hepatic expressions of IGF-1, phosphoinositide 3-kinase, protein kinase B, mammalian target of rapamycin and ribosomal protein S6 kinase increased with GAA or CFA addition. Results indicated that the combined supplementation of GAA and CFA could not cause ADG increase more when compared with GAA or CFA addition alone. [ABSTRACT FROM AUTHOR]

Coated copper sulphate (CCS) could be used as a Cu supplement in cows. To investigate the influences of copper sulphate (CS) and CCS on milk performance, nutrient digestion and rumen fermentation, fifty Holstein dairy cows were arranged in a randomised block design to five groups: control, CS addition (7·5 mg Cu/kg DM from CS) or CCS addition (5, 7·5 and 10 mg Cu/kg DM from CCS, respectively). When comparing Cu source at equal inclusion rates (7·5 mg/kg DM), cows receiving CCS addition had higher yields of fat-corrected milk, milk fat and protein; digestibility of DM, organic matter (OM) and neutral-detergent fibre (NDF); ruminal total volatile fatty acid (VFA) concentration; activities of carboxymethyl cellulase, cellobiase, pectinase and α-amylase; populations of Ruminococcus albus, Ruminococcus flavefaciens and Fibrobacter succinogenes; and liver Cu content than cows receiving CS addition. Increasing CCS addition, DM intake was unchanged, yields of milk, milk fat and protein; feed efficiency; digestibility of DM, OM, NDF and acid-detergent fibre; ruminal total VFA concentration; acetate:propionate ratio; activity of cellulolytic enzyme; populations of total bacteria, protozoa and dominant cellulolytic bacteria; and concentrations of Cu in serum and liver increased linearly, but ruminal propionate percentage, ammonia-N concentration, α-amylase activity and populations of Prevotella ruminicola and Ruminobacter amylophilus decreased linearly. The results indicated that supplement of CS could be substituted with CCS and addition of CCS improved milk performance and nutrient digestion in dairy cows. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the effects of orthokeratology on biological parameters and visual quality of adolescents with low-grade corneal astigmatism myopia. PATIENTS AND METHODS: In this study, a total of 41 myopic adolescents were prescribed with orthokeratology glasses in our hospital from February 2018 to March 2019 and voluntarily cooperated with relevant examinations before and after wearing orthokeratology lenses. Patients' uncorrected distant visual acuity (UC-VA-D), uncorrected near visual acuity (UCVA-N) and naked eye near stereoacuity before wearing glasses, 1 month, and 3 months after wearing glasses were observed. The corneal astigmatism of patients was observed. The corneal endothelial cell density was observed. The dynamic adjustment function (NP, AF, NRA, PRA) values of patients were observed. The comparison of biological indexes in different time periods was observed. The changes of corneal curvature before wearing orthokeratology lens, 1 month and 3 months after wearing orthokeratology lens were observed. RESULTS: There were significant changes of patients 1 month after wearing orthokeratology lenses (p < 0.05), while there was no significant difference between 3 months after wearing the orthokeratology lenses and 1 month after wearing the orthokeratology lenses (p < 0.05). Patients' NCAV-D and UCVA-N were recorded by a conversion method of 5 points. There were differences in the NCVA-D, NCVA-N, naked eye near stereoacuity before, 1 month, and 3 months after wearing glasses (p < 0.05). By observing patients' biological indicators and dynamic adjustment, it was found that there were statistically significant differences in NP, AF, BRA and PRA before wearing the glasses, 1 month and 3 months after wearing the glasses (p < 0.05). CONCLUSIONS: The use of orthokeratology can greatly correct myopia patients' vision, improve their stereoscopic vision, control the progression of myopia, and improve their eye regulation, which is of high safety and great short-term effect. [ABSTRACT FROM AUTHOR]

The combined addition of branched-chain volatile fatty acids (BCVFAs) and folic acid (FA) could improve growth performance and nutrient utilization by stimulating ruminal microbial growth and enzyme activity. This study was conducted to evaluate the effects of BCVFA and FA addition on growth performance, ruminal fermentation, nutrient digestibility, microbial enzyme activity, microflora and excretion of urinary purine derivatives (PDs) in calves. Thirty-six Chinese Holstein weaned calves (60 ± 5.4 days of age and 107 ± 4.7 kg of BW) were assigned to one of four groups in a randomized block design. Treatments were control (without additives), FA (with 10 mg FA/kg dietary DM), BCVFA (with 5 g BCVFA/kg dietary DM) and the combined addition of FA and BCVFA (10 mg/kg DM of FA and 5 g/kg DM of BCVFA). Supplements were hand-mixed into the top one-third of total mixed ration. Dietary concentrate to maize silage ratio was 50 : 50 on a DM basis. Dietary BCVFA or FA addition did not affect dry matter intake but increased average daily gain (ADG) and feed conversion efficiency. Ruminal pH and ammonia N were lower, and total volatile fatty acids (VFAs) concentration was higher for BCVFA or FA addition than for control. Dietary BCVFA or FA addition did not affect acetate proportion but decreased propionate proportion and increased acetate to propionate ratio. Total tract digestibility of DM, organic matter, CP and NDF was higher for BCVFA or FA addition than for control. Dietary BCVFA or FA addition increased activity of carboxymethyl cellulase and cellobiase, population of total bacteria, fungi, Ruminococcus albus, R. flavefaciens, Fibrobacter succinogenes and Prevotella ruminicola as well as total PD excretion. Ruminal xylanase, pectinase and protease activity and Butyrivibrio fibrisolvens population were increased by BCVFA addition, whereas population of protozoa and methanogens was increased by FA addition. The BCVFA × FA interaction was significant for acetate to propionate ratio, cellobiase activity and total PD excretion, and these variables increased more with FA addition in diet without BCVFA than in diet with BCVFA. The data indicated that supplementation with BCVFA or FA increased ADG, nutrient digestibility, ruminal total VFA concentration and microbial protein synthesis by stimulating ruminal microbial growth and enzyme activity in calves. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Recently, the role of long noncoding RNAs (lncRNAs) is vital in tumor progression. Our study aims to identify the role of SNHG16 in the metastasis of pancreatic carcinoma. PATIENTS AND METHODS: Real-Time quantitative Polymerase Chain Reaction (RT-qPCR) was used to measure SNHG16 expression in 56 pancreatic carcinoma patients' tissues. Function assays, including wound healing assay, and transwell assay, were conducted to detect the effect of SNHG16 on the metastasis of pancreatic carcinoma. Besides, the luciferase assay was performed to explore the underlying mechanism. RESULTS: The expression level of SNHG16 was upregulated in pancreatic carcinoma samples compared with adjacent tissues. Moreover, cell migration and cell invasion were repressed via the knockdown of SNHG16, while cell migration and cell invasion were promoted via the overexpression of SNHG16. Moreover, the expression of miR-200a-3p was upregulated via knockdown of SNHG16 while the expression of miR-200a-3p was downregulated via the upregulation of SNHG16 in vitro. Furthermore, it was discovered that SNHG16 acted as a competing endogenous RNA via sponging miR-200a-3p in pancreatic carcinoma. CONCLUSIONS: Our study suggests that SNHG16 acts as an oncogene in pancreatic carcinoma and promotes cell metastasis via sponging miR-200a-3p, which might be a novel therapeutic strategy in pancreatic carcinoma. [ABSTRACT FROM AUTHOR]

The aim of present paper is to study a constrained programming with generalized α-univex fuzzy mappings. In this paper we introduce the concepts of α-univex, α-preunivex, pseudo α-univex and α-unicave fuzzy mappings, and we discover that α-univex fuzzy mappings are more general than univex fuzzy mappings. Then, we discuss the relationships of generalized α-univex fuzzy mappings and get some properties. In the last, we derive necessary and sufficient Karush-Kuhn-Tucker conditions and its dual problems with generalized di erentiable α-univex fuzzy mappings for fuzzy constrained programming problem. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Age-related macular degeneration (AMD) is mainly characterized by dysfunction of retinal pigment epithelium (RPE) cells. This study aimed to investigate the protective effects of resveratrol on oxidative damaged RPE cells. MATERIALS AND METHODS: Human D407 cells were divided into normal control (NC), H2O2 treated (H2O2, treating with H2O2 at a final concentration of 200 mol/l) and resveratrol treatment groups (treating with resveratrol at a concentration of 12.5, 25, 50 and 100 mg/l). Malondialdehyde (MDA) and superoxide dismutase (SOD) activities were examined using enzyme-linked immunosorbent assay (ELISA). 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl- 2-H-tetrazolium bromide (MTT) and cell count kit-8 (CCK-8) were used to examine cell viability. Cell cycle phase distribution and apoptosis of D407 cells were evaluated using flow cytometry assay. B-cell lymphoma-2 (Bcl-2) and cleaved caspase 3 expression were detected using quantitative real- time PCR (qRT-PCR) and Western blot assay, respectively. RESULTS: Resveratrol significantly decreased inhibitive ratios of D407 cell growth compared to that of H2O2 group (p<0.05). Resveratrol significantly increased SOD activity compared to that of H2O2 group (p<0.05). Resveratrol significantly reduced MDA activity compared to that of H2O2 group (p<0.05). Resveratrol affected cell cycle phase distribution of D407 cells compared to that of H2O2 group (p<0.05). Resveratrol significantly decreased the early stage and late stage apoptosis rates compared to that of H2O2 group (p<0.05). Resveratrol significantly enhanced Bcl-2 levels and decreased cleaved caspase 3 levels compared to that of H2O2 group (p<0.05). CONCLUSIONS: Resveratrol protected against the oxidative damage of RPE cells by modulating SOD/MDA activity and activating Bcl-2 expression. [ABSTRACT FROM AUTHOR]