Objective Differentially expressed genes in oral squamous cell carcinoma (OSCC) were subjected to bioinformatic and Mendelian randomization analyses to elucidate their prognostic significance in OSCC. Methods The TCGA database and dataset GSE138206 were used to screen the common differential genes of OSCC, and their relationship was analyzed by using Mendelian randomization. The prognostic value of differential genes was further analyzed by Cox risk regression. The biological function of genes with high prognostic value was further evaluated by single gene differential analysis. Results A total of 147 common differential genes were screened from the two databases. Results of two-sample Mendelian randomization showed that GREM2 was associated with the increased risk of OSCC. In addition, SH3BGRL2 was associated with a decreased risk of OSCC, and DKK1, CCL11, and HOXC6 were considered as independent prognostic markers of OSCC. The predicted results of DKK1 were consistent with the actual results. KEGG enrichment analysis indicated the potential involvement of DKK1 in arachidonic acid and linoleic acid metabolism. Furthermore, DKK1 showed positive correlations with Tgd and Th2 cells, while displaying negative associations with PDC, Cytotoxic cells, Mast cells, CD8 T cells, TFH cells, B cells, T cells, and Th17 cells. Conclusion GREM2 is associated with an increased risk of OSCC. DKK1 is highly expressed in OSCC and associated with poor prognosis, which may be involved in regulating the metabolism of arachidonic acid and linoleic acid and immune cell invasion in OSCC.

BACKGROUND: Temozolomide (TMZ) resistance is a significant challenge in treating glioblastoma (GBM). Collagen remodeling has been shown to be a critical factor for therapy resistance in other cancers. This study aimed to investigate the mechanism of TMZ chemoresistance by GBM cells reprogramming collagens. METHODS: Key extracellular matrix components, including collagens, were examined in paired primary and recurrent GBM samples as well as in TMZ-treated spontaneous and grafted GBM murine models. Human GBM cell lines (U251, TS667) and mouse primary GBM cells were used for in vitro studies. RNA-sequencing analysis, chromatin immunoprecipitation, immunoprecipitation-mass spectrometry, and co-immunoprecipitation assays were conducted to explore the mechanisms involved in collagen accumulation. A series of in vitro and in vivo experiments were designed to assess the role of the collagen regulators prolyl 4-hydroxylase subunit alpha 1 (P4HA1) and yes-associated protein (YAP) in sensitizing GBM cells to TMZ. RESULTS: This study revealed that TMZ exposure significantly elevated collagen type I (COL I) expression in both GBM patients and murine models. Collagen accumulation sustained GBM cell survival under TMZ-induced stress, contributing to enhanced TMZ resistance. Mechanistically, P4HA1 directly binded to and hydroxylated YAP, preventing ubiquitination-mediated YAP degradation. Stabilized YAP robustly drove collagen type I alpha 1 ( COL1A1) transcription, leading to increased collagen deposition. Disruption of the P4HA1-YAP axis effectively reduced COL I deposition, sensitized GBM cells to TMZ, and significantly improved mouse survival. CONCLUSION P4HA1 maintained YAP-mediated COL1A1 transcription, leading to collagen accumulation and promoting chemoresistance in GBM.
Temozolomide ; Humans ; Glioblastoma/drug therapy* ; Animals ; Mice ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics* ; YAP-Signaling Proteins ; Hydroxylation ; Dacarbazine/pharmacology* ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Collagen/biosynthesis* ; Collagen Type I/metabolism* ; Prolyl Hydroxylases/metabolism* ; Antineoplastic Agents, Alkylating/therapeutic use*

Background Some studies have shown that PM_2.5 exposure is closely related to central nervous system diseases that lead to cognitive dysfunction and change the composition of intestinal flora. However, there are few studies on the role of intestinal flora in PM_2.5-induced depression- and anxiety-like behaviors in mice. Objective To observe the effects of PM_2.5 exposure on depression- and anxiety-like behaviors and the composition of intestinal flora in mice, and to explore the role of intestinal flora in regulating 5-hydroxytryptamine (5-HT) in depression- and anxiety-like behaviors in mice exposed to PM_2.5. Methods Eight-week-old male SPF C57BL/6J mice were randomly divided into control group (NS group), probiotic group (LGG group), PM_2.5 group (PM group), and combined exposure group (PML group), 6 mice in each group. Mice in the PM group and the PML group were exposed to PM_2.5 in a dynamic exposure cabinet for 6 h per day, 6 d a week for 7 consecutive weeks, and the PM_2.5 concentrations were approximately 8 times higher than the outdoor concentration. The LGG group and the PML group were orally administered with Lactobacillus rhamnosus while the NS group and the PM group were orally administered with the same amount of saline. Elevated plus maze test and open field test were used to detect depression and anxiety in mice. Fecal samples of mice were collected to evaluate intestinal flora abundance, diversity, and structure between groups using high-throughput sequencing of 16S rRNA. ELISA was employed to detect the levels of 5-HT in serum and hippocampus. Spearman correlation was used to analyze the correlations of differential intestinal flora with 5-HT level in hippocampus and depression- and anxiety-like behavior indicators in mice. Results The percentage of open-arm entry [M(P₂₅, P₇₅)] in the PM group was 0.0% (0.0%, 33.3%), lower than those in the NS group [47.7% (25.0%, 50.8%) ] and the PML group [46.9% (40.0%, 50.0%)], and the differences were statistically significant (P<0.05). The total travelled distance and the time spent in central area (\begin{document}$\bar x \pm s $\end{document}) in the PM group were (2.01±0.90) m and (10.31±1.99) s respectively, shorter than those of the NS group [(3.80±0.89) m, (14.47±3.07) s], the total travelled distance in the PML group [(2.73±1.12) m] was shorter than those of the NS group and the LGG group [(4.21±1.08) m], and the differences were statistically significant (P<0.05). Compared to the NS group, the Simpson index of the PM group significantly increased (P<0.05). Compared to the LGG group, the Simpson index of the PML group significantly decreased (P<0.05). The results of Beta diversity analysis showed that there were differences in the composition of intestinal flora among the four groups of mice. Compared with the NS group and the LGG group, the abundances of Erysipelotrichaceae and Dubosiella in the PM group and the PML group increased, while the abundances of Prevotellaceae_UCG-001 decreased, and the differences were statistically significant (P<0.05). In hippocampus, the level of 5-HT in the PM group [(135.02±10.31) μg·g⁻¹] was lower than those in the NS group [(178.77±43.15) μg·g⁻¹] and the LGG group [(224.85±22.98) μg·g⁻¹], and the level of 5-HT in the PML group [(161.27±15.81) μg·g⁻¹] was lower than that in the LGG group (P<0.05). 5-HT level in hippocampus was significantly positively correlated with the relative abundance of Prevotellaceae_UCG-001 (r=0.6090, P=0.012). The percentage of open-arm entry was significantly negatively correlated with the relative abundance of Dubosiella (r=−0.4630, P=0.023). Conclusion Atmospheric PM_2.5 exposure may cause depression- and anxiety-like behaviors in mice. The observed behavior dysfunction may be associated with the changes in diversity and relative abundance of intestinal flora as well as the decrease of 5-HT level. Such depression- and anxiety-like behaviors are alleviated after adding probiotics.

Objective:To analyze the gastroscopy treatment technology in a Children′s Medical Center based on the diagnosis-related groups(DRG) and put forward suggestions for resource optimization.Methods:The data of the front pages of medical records of 22 medical institutions in a Children′s Medical Center in 2018 were divided into DRG groups. The patients in gastroscope treatment operation group(GK3)were selected, and the disease diagnosis, operation and payment methods of the patients in this group were analyzed.Results:Of the 22 medical institutions, 16 had GK3 group cases, and the number of cases was significantly different, ranging from 2 to 917. Among them, the institution with code M was characterized by multiple endoscopic treatment of esophageal stricture, but most other institutions rarely carried out the treatment of esophageal stricture. In GK3 group, the main payment method of children in Institution M with the highest constituent ratio was at one′s own expense, followed by non-local medical insurance. The main payment type of O and P institutions with the second and third constituent ratio was local medical insurance.Conclusions:The gap of the technology of gastroscopy in the treatment of esophageal stricture is large in all institutions. The high-quality medical resources can be sunk through the construction of pediatric medical alliance, and the gap between the regional medical technology can be continuously leveled.

Objective:To explore the application value of heparin binding protein (HBP) in the diagnosis of severe infection in patients with silicosis.Methods:A prospective study was conducted on 150 patients with silicosis in the pneumoconiosis department of the General Hospital of Xuzhou Mining Group from January 2017 to March 2018. Among them, 100 were severely infected with silicosis and 50 were non-infected with silicosis. 30 patients were selected in the same period of physical examination as the control group. HBP, C-reactive protein (CRP) , procalcitonin(PCT) , white blood cell count (WBC) , neutrophil percentage, and absolute neutrophil count(ANC) were detected in all participants. Using the receiver operating characteristic curve(ROC) to analyze the diagnostic value of indicator above in patients with different stages of severe silicosis infection.Results:Plasma HBP levels in patients with severely infected silicosis group[(50.39±35.64) ng/ml] were higher than those in the non-infected group[(10.71±1.47) ng/ml] and the control group[(9.24±1.83) ng/ml] ( P<0.05) , and with the increase of silicosis stages, there is an increasing trend ( P<0.05). The ROC curve showed that the AUC of HBP in the patients with severe silicosis in the first, second, and third stages were 0.932, 0.977, and 0.964, which were higher than those of WBC, CRP, and PCT. Correlation analysis showed that HBP was positively correlated with WBC, CRP and PCT ( r=0.711, 0.359, 0.729, P<0.01). Conclusion:HBP has high diagnostic efficacy in the diagnosis of severe infections in patients with silicosis, which may become a clinical screening indicator for severe infections in patients with silicosis and an auxiliary examination indicator for the stage of silicosis patients.

Objective:To explore the application value of heparin binding protein (HBP) in the diagnosis of severe infection in patients with silicosis.Methods:A prospective study was conducted on 150 patients with silicosis in the pneumoconiosis department of the General Hospital of Xuzhou Mining Group from January 2017 to March 2018. Among them, 100 were severely infected with silicosis and 50 were non-infected with silicosis. 30 patients were selected in the same period of physical examination as the control group. HBP, C-reactive protein (CRP) , procalcitonin(PCT) , white blood cell count (WBC) , neutrophil percentage, and absolute neutrophil count(ANC) were detected in all participants. Using the receiver operating characteristic curve(ROC) to analyze the diagnostic value of indicator above in patients with different stages of severe silicosis infection.Results:Plasma HBP levels in patients with severely infected silicosis group[(50.39±35.64) ng/ml] were higher than those in the non-infected group[(10.71±1.47) ng/ml] and the control group[(9.24±1.83) ng/ml] ( P<0.05) , and with the increase of silicosis stages, there is an increasing trend ( P<0.05). The ROC curve showed that the AUC of HBP in the patients with severe silicosis in the first, second, and third stages were 0.932, 0.977, and 0.964, which were higher than those of WBC, CRP, and PCT. Correlation analysis showed that HBP was positively correlated with WBC, CRP and PCT ( r=0.711, 0.359, 0.729, P<0.01). Conclusion:HBP has high diagnostic efficacy in the diagnosis of severe infections in patients with silicosis, which may become a clinical screening indicator for severe infections in patients with silicosis and an auxiliary examination indicator for the stage of silicosis patients.

One hundred ten patients with Parkinson′s disease(PD)and 110 age-matched healthy controls were enrolled in the study.The non-motor symptoms(NMS)were assessed with Non-motor symptoms of Parkinson′s disease questionnaire(PDNMSQ30).The PD patients were classified as gait abnormality posture type(PIGD, n=73)and tremor type(TD, n=37).The non-motor symptoms were compared between two groups.Results showed that the NMS in PD patients was higher than that in healthy controls[(35.2 ±3.0)vs.(6.0 ±2.0)symptoms, t=6.43, P=0.01].The NMS score of PIGD group was higher than that of TD group[(28.9 ±1.1)vs.(6.2 ±0.7)symptoms, t=2.73, P<0.01]; Mini-mental state examination(MMSE)and Montreal cognitive assessment scale(MoCA)scores of TD group were significantly higher than those of PIGD group(t=11.52,P<0.01; t=8.79,P<0.01).The results indicate that for PD patients with different motor types,their NMS are different,and PD patients with PIGD have more axial involvement,and more NMS.

Objective To construct a grading nursing care system at public hospitals based on the severity of illness and activities of daily living ( ADL). Methods Multi-center stratified random sampling was used to investigate the general adult patients hospitalized in 12 wards of six tertiary-level hospitals in the eastern, central and western parts of China from January to December of 2016. The Barthel index and simple clinical score ( SCS) were used to evaluate their ADL and severity of illness, while a customized direct nursing hour scale was applied to record the direct nursing time needed by patients in 24 hours. Nursing grades were defined according to different conditions and ADL and to the difference of patient needs of 24 h direct nursing hours. Results 7 200 patients were investigated in total, and 7 073 effective questionnaires were collected (98. 24% ). Seven new grades of nursing care were defined based on patients′ severity of illness, ADL and different 24 h direct nursing time. These grades match the existing four grading nursing care levels to become refined sub-levels. Conclusions Patients can be graded according to their conditions, ADL and the 24 h direct nursing time needed. Such a new method is more objective, specific and quantitative than before, conducive to upgrading fine management level of nursing.

The genome, replication mode and nosogenesis of duck hepatitis B virus are similar to those of human hepatitis B virus. In addition, the natural host of duck hepatitis B virus is readily available, cheap and has a high success rate of infection. Therefore, duck hepatitis B virus-infected models have been widely used for drug screening, pharmacological and pathological studies. For drug screening, the model is easy to obtain with high infection success rate and good stability. In the pharmacological research, the model can maintain high levels of viral DNA replication in the hepatocytes and exhibit significant damaged liver phenotypes which can reflect the pharmacological effects of drugs with different mechanisms. Also in the pathologic mechanisms research, the model has entire virus life cycle and maintains a pool of covalent closed-loop DNA in the hepatocytes, which can help scientific researchers better understand human hepatitis B virus. This article reviews the applications of duck hepatitis B animal model in drug screening, pharmacological and pathological studies, also outlooks the application prospect of this model.

The purpose of this study was to investigate the formation thermodynamics of baicalein(BE)-nicotinamide(NCT)cocrystals in three solvents including ethyl acetate, acetone and trichloromethane. The solubilities of BE, NCT and BE-NCT in the above solvents at 25 °C were measured. Ternary phase diagrams(TPDs)of the BE-NCT-solvent systems were established. The non-linear fitting equation according to 1 ∶1 complexation mechanism of BE-NCT cocrystals demonstrated a good correlation between calculated and experiment data. ΔG0< 0 suggested that BE-NCT cocrystal formation was a spontaneous process. Among the organic solvents studied, the absolute value of ΔG0 in trichloromethane was significantly lower than that in the other two solvents. In addition, the cocrystallization zone in trichloromethane was far away from stoichiometric line. This study provides a theoretical foundation for solvent selection and preparation-condition optimization of BE-NCT cocrystals.