Objective:To analyze the influencing factors and improvement paths of the cultivation of full-time doctoral scientific and technological innovation ability in large public hospitals, and propose countermeasures and suggestions.Methods:This studyed conducted a survey and analysis of 122 doctors from Linyi People′s Hospital in Shandong Province, and completed a current situation study based on the analysis results.Results:There was no significant difference between the two groups in gender, age, degree type, professional category, discipline level, Graduate School type, job type and other indicators. There were significant differences between the two groups in scientific research topic selection ability score, project design ability score, data analysis ability score, data interpretation ability score, project approval in recent 5 years, project level, number of SCI journal papers published in recent 5 years, cumulative impact factors of SCI journal papers, and annual number of academic activities ( P<0.05). Conclusions:The hospital can improve the scientific and technological innovation ability of full-time doctors by setting up a special cultivation plan, establishing an interdisciplinary team, optimizing scientific research management services, improving the evaluation and assessment system, and improving welfare protection.

OBJECTIVE To establish an HPLC method for investigating the stability of mandelonitrile in commonly used solvents and quantitation determination of mandelonitrile in Jian’er Qingjie mixture. METHODS The assay was performed on an Agilent TC-C18(250 mm×4.6 mm, 5 μm) column with a mobile phase consisting of acetonitrile-0.1% phosphoric acid(23∶27) pumped at a flow rate of 1.0 mL·min–1. The column temperature was 30 ℃ and the detection wavelength was set at 207 nm. The stability of the mandelonitrile solution prepared with solvents such as methanol, 95% ethanol, acetonitrile, water, phosphoric acid solution with pH 2.0−6.0, and acetonitrile solution containing 1.0% glacial acetic acid was investigated using the peak reduction rate as the indicator. RESULTS Mandelonitrile was labile in methanol, 95% ethanol or water and relatively stable in acetonitrile. The standard solutions of mandelonitrile prepared with phosphoric acid solutions at pH 2.0−3.5 or acetonitrile containing 1.0% glacial acetic acid were stable in 12 h. The linear range of mandelonitrile was 1.033−294.987 µg·mL–1(r=0.999 9) and the average recovery was 97.4% with RSD of 0.6%(n=9). The content range of mandelonitrile in 16 batches of Jian’er Qingjie mixture produced by 5 manufactures was 3.854−154.578 µg·mL–1. CONCLUSION The established method is simple and accurate. It can be used for the quality control of Jian’er Qingjie mixture. For almond aromatic water and its preparations, the influence of solvent on stability of mandelonitrile should be noticed.

Objective To investigate the action mechanism of Bufei Yiqi Tongluo formula in treating id-iopathic pulmonary fibrosis (IPF) based on the transforming growth factor-β1 (TGF-β1)/c-Jun N-terminal ki-nase (JNK) signaling pathway.Methods The key targets of network pharmacology conducted the enrichment analysis and the IPF rat model was constructed,which was divided into the blank control group,IPF model group and Bufei Yiqi Tongluo formula group.The pathological changes of lung tissue in various groups were observed,and the levels of white blood cells (WBC) in bronchoalveolar lavage fluid (BALF) were analyzed. The enzyme-linked immunosorbent assay (ELISA) was used to detect the protein expression levels of tumor necrosis factor-α (TNF-α),interleukin-6 (IL-6),phosphorylated JNK (p-JNK)/JNK,TGF-β1,tissue inhibitor of metalloproteinases-1 (TIMP-1) and matrix metalloproteinase-9 (MMP-9) in serum,BALF and lung tissue. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the mRNA expression levels of these proteins in serum,BALF and lung tissue.Results The network pharmacology enrichment analysis re-sults revealed that TGF-β1 and JNK signaling pathways were closely related with IPF.Compared with the IPF model group,the lung tissue orderliness in the Bufei Yiqi Tongluo formula group was increased,the consolida-tion range was decreased,the fibrotic tissue proliferation was significantly reduced,the WBC level and expres-sion levels of TNF-α and IL-6 in BALF were significantly decreased.Compared with the blank control group,the mRNA expression levels of TGF-β1,p-JNK/JNK,TIMP-1 and MMP-9 in serum,BALF and lung tissues in the IPF model group were increased with statistical difference (P<0.05).After the intervention on the model rats by the Bufei Yiqi Tongluo formula,except there was no difference in the expression level of MMP-9 pro-tein in serum,TGF-β1 in BALF,TIMP-1 in serum and MMP-9 mRNA in lung tissue,but the other indicators were decreased (P<0.05).Conclusion The therapeutic effect of Bufei Yiqi Tongluo formula in IPF may be related to its regulation on the TGF-β1/JNK signaling pathway.

Objective:To identify the pathogenic characteristics of a suspected gonadal mosaicism Becker muscular dystrophy (BMD) family, and provide provide basis for pregnancy selection of similar families.Methods:A BMD family admitted to Hunan Jiahui Genetics Hospital from June 2012 to September 2019 was systematically reviewed. The medical history and family history of the proband were checked, and multiplex ligation-dependent probe amplification was used to detect the deletion/duplication of 79 exons of the Duchenne muscular dystrophy (DMD) gene in the proband, fetuses, and parents. Moreover, potential variants were verified by combining PCR amplification, short tandom repeat polymorphic linkage analysis, and real-time fluorescence quantitative PCR. High-quality embryos are screened for transplantation after preimplantation genetic testing for monogenic (PGT-M). And amniotic fluid was collected in the second trimester for prenatal diagnostic verification.Results:According to the phenotype analysis of the proband, the initial clinical diagnosis was BMD, and the exon 45-50 deletion in DMD gene was detected. The mutation was not detected in the mother′s peripheral blood, but when she was pregnant again, the prenatal diagnosis showed that the fetus had the same deletion mutation as the proband. Neither of two vitro embryos tested by PGT-M has the deletion mutation, then single embryo transfer was performed nor was pregnancy successful. After confirmation of prenatal diagnosis during pregnancy, a normal baby girl was born by full-term cesarean section.Conclusions:This BMD family was a family with two consecutive BMD homodeletion mutations, and the mutation of the DMD gene was not detected in the peripheral blood of the proband′s mother and two embryonic cells, suggesting that the mother may be a gonad chimeric carrier of this deletion mutation. The combined application of prenatal diagnosis and PGT-M provides a reference approach to effectively avoid the birth of similar children.

Objective:To explore the effect of the enriched environment(EE)on pyroptosis in rats with cerebral ischemia-reperfusion injury(CIRI).Methods:45 male Sprague-Dawley rats were randomly divided into three groups: a sham surgery(Sham)group, a cerebral ischemia-reperfusion(CIR)group and an enriched environment(EE)group, with 15 rats in each group.Except for the Sham group, the right middle cerebral artery occlusion model was established in the other two groups.After surgery, the EE group was fed in EE, and the other two groups were fed in standard environment.All the rats were assessed using the modified neurological severity score(mNSS)before modeling and on the 1st day, 7th day and 14th day following surgery.On the 14th day after surgery, 2, 3, 5-triphenyltetrazolium chloride(TTC)staining was used to evaluate the infarct volume, hematoxylin and eosin(HE)staining was used to examine pathomorphological changes of the hippocampal CA1 region on the ischemic side of the rats in each group, immunohistochemical assay was used to detect the expression of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)and cysteinyl aspartate specific proteinase-1(caspase-1)proteins in the CA1 region, and ultrastructural changes in neurons in the CA1 region were observed under transmission electron microscopy.Results:Compared with the Sham group, the mNSS scores of the CIR group and the EE group were significantly higher on the 1st day and 7th day after surgery( P<0.05), but there was no significant difference between the CIR and EE groups( P>0.05). On the 14th day after surgery, compared with the CIR group, the EE group showed a decrease in the mNSS score and the cerebral infarct volume( P<0.05), alleviated pathomorphological changes, decreased expression of NLRP3 and caspase-1 proteins( P<0.05), and alleviated pathological changes of pyroptosis in the ultrastructure of neurons. Conclusions:EE can reduce the damage of neurological function, reduce the cerebral infarct volume, and play a protective role for the brain in CIRI rats.The mechanism may be related to the down-regulation of the expression of NLRP3 and caspase-1 proteins related to the classical pyroptosis pathway, leading to the inhibition of pyroptosis.

Objective: A model was built by neural network analysis to study the relationship between different degrees of vitamin B12 and folic acid deficiency and malnutrition-induced stomatitis. Methods: Data from 30 healthy volunteers and 30 patients with malnutrition-induced stomatitis were collected. The distribution of lesions, the number of affected sites and clinical manifestations were recorded, and the severity was scored. The levels of vitamin B12 and folic acid in the peripheral blood of the two groups were simultaneously measured. The SPSS software was used to analyze the correlation between vitamin B12 and folic acid levels in the peripheral blood of patients with malnutrition-induced stomatitis and healthy volunteers, and the MATLAB software package was used to analyze the data via a neural network. Results: The levels of vitamin B12 and folic acid significantly correlated with the grade of malnutrition-induced stomatitis. Simultaneous B12 and folic acid deficiency linearly correlated with the occurrence and severity of malnutrition-induced stomatitis. Based on this correlation, a thermogram model of malnutrition-induced stomatitis was constructed. Conclusion Malnutrition-induced stomatitis is closely related to vitamin B12 and folic acid deficiency. Their synergistic effect may promote the occurrence and development of malnutrition-induced stomatitis. The construction of the malnutrition-induced stomatitis model aids the targeted etiological treatment of patients with moderate and severe deficiency to prevent malnutrition-induced stomatitis.

Objective: To investigate the classification of atrophic glossitis and to study the correlation between the classification and changes of VitB12, folic acid (FOL) and blood cell parameters Methods: A total of 70 patients with atrophic glossitis (AG) were divided into complex type and simple type according to whether they had ulcer or erosion on the tongue mucosa or not. Another 65 healthy subjects during the same period were collected as the control group. The levels of vitamin B12, FOL and blood cell parameters were statistically analyzed using SPSS 25.0 software package. Results: The levels of vitamin B12, red blood cell count (RBC) (3.52 ± 0.69) × 1012·L-1, hemoglobin (HGB)(11.97 ± 1.70) g·dL-1, white blood cell count (WBC) (4.85 ± 1.16) × 109·L-1, neutrophil count (NEUT) (2.76 ± 0.99) × 109·L-1, lymphocyte count (LYMPH) (1.48 ± 0.44) × 109·L-1 in complex type AG group were lower than those in simple type AG group (P<0.05). The levels of mean red blood cell volume (MCV) (104.90 ± 11.13) fL, mean corpuscular hemoglobin (MCH) (34.83 ± 4.56) pg, mean corpuscular hemoglobin concentration (MCHC) (331.09 ± 13.60) g·L-1 were higher than those in the simple type AG group (P<0.05). There was no significant difference in FOL content between these two groups (P>0.05). The levels of VitB12, MCV, MCH, MCHC, WBC, lymph and neut were correlated with the classification of atrophic glossitis (P < 0.05). Conclusion VitB12 deficiency was more apparent in complex AG, especially in large cell anemia, which correlated with the levels of WBC, NEUT, and LYMPH.

Objective: To investigate the clinicopathological features, treatment and prognosis of oralmucosal malignant melanoma to provide a reference for clinical practice. Methods: Data from 19 patients with oralmucosal malignant melanoma were collected, and their clinical manifestations, treatment methods and follow-up results were retrospectively analyzed. Results: Among the 19 patients, 11 cases (58%) had lesions in the gingiva, 7 cases (37%) had lesions in the palate, and 1 case (5%) had lesions in the tongue, the difference was statistically significant (P<0.05). Eight patients had regional lymph node metastasis with a metastasis rate of 42%, of which 4 cases had multiple site metastasis, and the total number of regional lymph node metastasis sites was 15. Among the 19 patients, 3 cases received only surgery, 4 cases received cryotherapy, and 12 cases received combined surgery, cryotherapy and biological immunotherapy. Pathological examination showed malignant melanoma. The positive rates of S-100, HMB-45 and Melan-A were 95%, 89% and 84%, respectively. Kaplan-Meier survival analysis showed that patients with lesions less than 5 cm2 had a higher survival rate (P < 0.05). Conclusions Oral malignant melanomas usually present as black lesions in the oral mucosa, which are prone to metastasis in early stage. The area of lesions may affect the prognosis of the disease. Therefore, the large range of black lesions or masses should be the alert for the clinicians. Oral malignant melanoma patients are usually treated with combined treatment with surgery, cryotherapy and biological immunotherapy.

Objective To evaluate the effect of bone marrow mesenchymal stem cell (BMSC) on the expression of interleukin (IL)-10 and tumor necrosis factor (TNF)-α in mice with ischemia-reperfusion acute kidney injury (IR-AKI). Methods All mice were randomly divided into the sham operation group (control group), ischemia-reperfusion injury group (IRI group) and BMSC treatment group (BMSC group), with 6 mice in each group, respectively. The renal function and pathological changes of mice were detected. The cell apoptosis of renal tissues of mice was determined. The expression levels of serum IL-10 and TNF-α of mice were quantitatively measured. The mouse BMSC was randomly divided into the control and hypoxia-reoxygenation groups (IRI group), and the expression levels of IL-10 and TNF-α in cell supernatant were determined. Results The renal structure of mice was normal in the control group, severe damage was observed in the IRI group, and mild damage occurred in the BMSC group. Compared with the control group, the renal tissue injury scores were significantly higher in the IRI and BMSC groups (both P < 0.05). Compared with the IRI group, the renal tissue injury score was significantly lower in the BMSC group (P < 0.05). Compared with the control group, the levels of serum creatinine (Scr) and blood urea nitrogen (BUN) were remarkably up-regulated in the IRI group, and the level of BUN was significantly up-regulated in the BMSC group (all P < 0.05). Compared with the IRI group, the levels of Scr and BUN were significantly down-regulated in the BMSC group (both P < 0.05). In the IRI group, the quantity of apoptotic cells in the renal tissues was considerably higher than those in the BMSC and control groups, and the quantity of apoptotic cells in the BMSC group was significantly higher than that in the control group (all P < 0.05). Compared with the control group, the levels of serum IL-10 and TNF-α were significantly up-regulated in the IRI group, whereas the level of serum TNF-α was significantly down-regulated and the level of serum IL-10 was significantly up-regulated in the BMSC group (all P < 0.05). Compared with the IRI group, the levels of serum IL-10 and TNF-α were significantly down-regulated in the BMSC group (both P < 0.05). The levels of IL-10 and TNF-α in the cell supernatant did not significantly differ between the IRI and control groups (P=0.080、0.627). Conclusions BMSC infusion may reduce the incidence of renal IRI and inflammation, probably via the mechanism of down-regulating TNF-α expression rather than up-regulating IL-10 expression.

Objective To investigate the effect of ulinastatin (UTI) preconditioning combined with ischemic preconditioning (IPC) on hepatic ischemia-reperfusion (IR) injury in rats and possible mechanism of action.Methods A total of 50 male Sprague-Dawley rats were randomly divided into sham-operation group,IR group,IPC group,UTI group,and UTI-IPC group (UCI group).Blood samples were collected from the inferior vena cava after surgery and liver tissue samples were also collected.The serum levels of aspartate aminotransferase (AST),alanine aminotransferase (ALT),and tumor necrosis factor-o (TNF-α),the levels of myeloperoxidase (MPO) and nuclear factor-kappa B (NF-κB) in the liver tissue,and wet/dry weight ratio were determined,and pathomorphological changes of the liver tissue were observed under a light microscope.A one-way analysis of variance was used for comparison of continuous data between groups,and the LSD-t-test was used for further comparison between two groups.Results The IR,IPC,UTI,and UCI groups had significantly higher serum levels of ALT,AST,and TNF-α,levels of MPO and NF-κB in the liver tissue,and wet/dry weight ratio than the sham-operation group (all P ＜ 0.05);the IPC,UTI,and UCI groups had significantly lower levels than the IR group (all P ＜ 0.05),the UTI group had significantly lower levels than the IPC group (all P ＜ 0.05),and the UCI group had significantly lower levels than the IPC and UTI groups (all P ＜ 0.05).Liver pathological examination showed that compared with the sham-operation group,the IR,IPC,UTI,and UCI groups had significantly greater liver injury (all P ＜0.05),while the IPC,UTI,and UCI groups had a significantly lower degree of liver injury than the IR group (all P ＜ 0.05),the UTI group had significantly slighter liver injury than the IPC group (P ＜ 0.05),and the UCI group had significantly slighter liver injury than the IPC and UTI groups (both P ＜ 0.05).Conclusion Both UTI and UCI have a protective effect against hepatic IR injury,and the combination of UTI and UCI significantly enhances such protective effect,possibly by inhibiting the expression of NF-κB,reducing the release of TNF-α and MPO,and alleviating liver inflammatory response.