OBJECTIVE To explore the intracellular expression changes of p38 and Erk1/2 under three phototoxic conditions, compare three detection methods, and further investigate their molecular mechanisms. METHODS The methods involved using three testing approaches to assess the phototoxicity of chlorpromazine(CPZ) and tiaprofenic acid(TA). Subsequently, whole-cell lysates from the biological samples used in the three testing methods were collected, and the changes in the expression levels of intracellular p38 and Erk1/2 were evaluated using Western blotting. RESULTS All three testing methods accurately identified CPZ and TA as phototoxic compounds. In the 3T3 NRU phototoxicity assay, compared to the control group, the expression of p38 significantly increased under phototoxic doses of TA and CPZ(P<0.05), a phenomenon not observed in other testing methods. In phototoxicity assays using guinea pig and artificial skin models, similar expression pattern changes were observed for p38 and Erk1/2. CONCLUSION p38 and Erk1/2 have obvious dose dependence and high sensitivity in the 3T3 NRU phototoxicity test, and can be considered as potential molecular markers for evaluating the phototoxicity of 3T3 NRU. However, they have not been feasible in guinea pig tests and EpiKutis artificial skin tests. Guinea pigs and EpiKutis artificial skin exhibit more similar changes in p38 and Erk1/2 expression, suggesting that the EpiKutis artificial skin model test method may be a better alternative to animal testing than the 3T3 NRU method.

Objective:To investigate the construction effects of the graduate biochemistry technology courses based on the outcome-based education (OBE) concept, analyze the technical needs of graduate students, and further integrate and optimize the teaching methods.Methods:A self-compiled questionnaire with good reliability and validity was used to conduct an overall sampling survey on the graduate students who took the elective courses in Batch 2021 in a medical college in Shanghai. Excel and GraphPad Prism software were used for data analysis.Results:According to this survey, the courses gain good effects in terms of teaching framework, course facilities, teaching forms, teaching contents and comprehensive evaluation of teaching. A total of 112 students (95.2%) thought that the course was very helpful to the expansion of experimental technology and experimental operation ability. However, there were still some teaching needs, such as expanding the types of experiments and increasing experimental operations.Conclusions:Under the guidance of OBE concept, the construction of the graduate biochemistry technology courses has gradually achieved good results. Later, the online-offline hybrid teaching form will be further improved and the curriculum teaching arrangement will be optimized further.

Objectives To explore the establishment and effects of a multilevel and inter-disciplinary management scheme for specialist nurses.Methods The multilevel and inter-disciplinary management scheme included establishing the pyramid hierarchical training model,exploring superimposed training mechanism for specialist nurses with horizontal expansion,vertical extension,and deep development,and constructing stereoscopic clinical evaluation and quantitative assessment system.Four hundred-forty two specialized nurses have been recruited to join the multilevel and inter-disciplinary management scheme from July 2021 to August 2023.The core competencies of specialized nurses were compared before and after the implementation of management scheme.Results The quality development of specialized nursing have been improved,and the total scores and the scores of 3 dimensions(research innovation,management,and professional development)in core competencies of specialized nurses after the intervention of multilevel and inter-disciplinary management scheme were higher than those before(P＜0.05).Conclusion The multilevel and inter-disciplinary management scheme can effectively improve the core competencies of specialized nurses,and promote the high-quality development of specialized nursing.

Objective To investigate and analyze the level of homocysteine(Hcy)in Tibet and to analyze the differences of Hcy level in different altitude regions,genders and ages,and thus to provide the prevalence profile of hyperhomocysteine and the differences in relevant tests between HHcy(hyperhomocysteinemia)and non-HHcy pop-ulations.Methods Totally 1 615(male n＝585)subjects were selected from Ngari,Lhasa,Shigatse and Nyingchi plat-eau areas of Tibet by stratified cluster sampling.Serum Hcy level was analyzed and the difference of Hcy level in pop-ulations located at different altitude plateau areas,gender groups were found.The prevalence of hyperhomocysteine and related test were analyzed.Kruskal Wallis test was used to compare Hcy levels in different altitudes,genders and age groups,and Pearson Chi-square test was used to compare HHcy prevalence.Variance analysis was used for the differences of different test indicators between non-HHcy and HHcy populations.Results The level of Hcy in differ-ent regions and different genders were statistically significant,which was higher in males than that in females,and higher in Lhasa and Shigatse than in Nyingchi and Ngari.There was difference in serum HHcy prevalence among dif-ferent genders,regions and age groups.Males showed a higher level than females,people from Lhasa and Shigatse showed a higher level than those from Nyingchi and Ngari.Conclusions The incidence of hyperhomocysteinemia in Tibet is statistically significant in different areas,different genders and different age groups.So this study provides a scientific basis for the rational use of Hcy as an indicator in clinical practice of prevention and treatment of related diseases in plateau areas.

Langerhans cell histiocytosis (LCH) is a rare disease characterized by the proliferation of Langerhans cells and the destruction of local tissue. LCH large occurs in children, whilst incidence of the elderly population is extremely low, and there are few related studies. LCH lesions can involve multiple organs and systems, including bone tissue, lymph nodes, skin, liver, and spleen. However, it is rare that multiple soft tissues are implicated for eldly patients with LCH and present with soft tissue mass as the main manifestation. Here is a report on the clinical features, treatment and prognosis of an elderly LCH with multiple soft tissue masses as the main manifestation, in order to provide clinical reference.

Myeloproliferative neoplasms (MPN) are a group of clonal disorders of hematopoietic stem cells, and JAK2 V617F gene mutation is the main basis for the diagnosis of MPN. Previous studies have shown that BCR-ABL fusion gene and JAK2 V617F gene mutation are mutually exclusive in MPN patients, but in recent years, patients with a double mutation of both genes are often reported. The article synthesizes the relevant domestic and foreign literature in recent years, and reviews the BCR-ABL fusion gene and JAK2 V617F mutation double-positive MPN.

Objective:To investigate the function, mechanism and therapeutic potential of macrophages in non-alcoholic steatohepatitis (NASH).Methods:Eight-week-old male foz/ foz (Alms mutant) mice were fed with a high fat diet (HFD) for 6, 8 and 10 weeks and 8-week-old male C57BL/6 mice were fed with a methionine and choline-deficient (MCD) diet for 7 d, 3 weeks and 4 weeks to establish NASH models. The mice of control group were fed with normal diet or MCD control diet. The expression of F4/80 mRNA level in the livers of mice of NASH model group and control group was detected by fluorescence quantitative polymerase chain reaction. Macrophages in the livers of mice of NASH group and control group were determined by immunofluorescence staining. After transgenic lysM-Cre/DTR mice were fed with MCD diet for 5 weeks, they were divided into transgenic experimental group (ablation of macrophages induced by diphtheria-toxin (DTox) injection) and transgenic control group (phosphate buffer saline injection). The levels of triglyceride and lipid peroxide in the livers of transgenic experimental group and transgenic control group were detected, and the inflammation of the livers of the mice was scored. The mechanism of macrophages regulating inflammation in NASH was investigated by cytokine profiliny analysis and Western blotting. The interaction between hepatocytes and macrophages were determined by co-culturing the conditional medium of hepatocytes AML-12 and macrophages RAW264.7. Macrophages of mice of control group and NASH model group were depleted by liposomal clodronate to confirm its value in NASH prevention. Independent sample t-test was used for statistical analysis. Results:F4/80 mRNA level in the livers of NASH model foz/ foz mice fed with HFD for 6 weeks, 8 weeks and 10 weeks was higher than that of control group (1.49±0.19, 1.70±0.15 and 1.93±0.04 vs.1.05±0.22), and the differences were statistically significant ( t=3.06, 4.92 and 7.92, all P<0.05). The expression of F4/80 mRNA level of the livers of NASH model mice fed with MCD for 7 d and 3 weeks was higher than that of control group (2.70±0.99 and 3.08±1.71 vs.1.00±0.83), and the differences were statistically significant ( t=3.43 and 3.54, both P<0.01). The results of immunofluorescence demonstrated that compared with that of control group, the number of F4/80 + inducible nitric oxide synthase (iNOS) + M1 macrophages were significantly increased, while F4/80 + CD206 + M2 macrophages were significantly decreased in the livers of NASH model mice fed with MCD for 4 weeks. After macrophages depletion, the inflammation score, the levels of triglyceride and lipid peroxide in the liver of transgenic experimental mice were all lower than those of transgenic control mice (0.69±0.32 vs. 1.95±0.74, (43.97±13.24) g/mg vs. (63.09±14.85) g/mg, (24.84±6.21) nmol/mg vs.(37.91±8.91) nmol/mg), and the differences were statistically significant ( t =3.14, 2.72 and 2.41, all P<0.05). The results of cytokine profiling analysis showed that macrophage depletion could lower the levels of interleukin (IL)-12 and macrophages inflammatory protein-1α (the difference between multiples: -3.98, -2.74, both P<0.05). CCAAT/enhancer binding protein β was defected in the nuclear of transgenetic experimental mice. In vitro study showed that RAW264.7 macrophages conditional medium could promote lipid accumulation in AML-12 hepatocytes, while conditional medium from MCD medium-treated AML-12 hepatocytes could promote RAW264.7 macrophages to M1 polarization. After treated with liposomal clodronate, the levels of triglyceride and lipid peroxidation in the liver of control mice were both lower than those of MCD-induced NASH model mice((45.33±14.59) g/mg vs. (63.10±16.02) g/mg, (2.11±0.48) nmol/mg vs. (2.73±0.17) nmol/mg), and the differences were statistically significant ( t=2.84 and 2.73, both P<0.05). The results of Western blotting indicated that after treating with liposomal clodronate, the relative content of phosphorylated protein kinase R-like endoplasmic reticulum kinase, inositol requiring enzyme-1α, protein disulfide isomerase, glucose regulatory protein 78, phosphorylated eukaryotic initiation factor 2α in the liver of NASH model mice were all lower than those of NASH model mice without liposomal clodronate treatment (1.84±0.36 vs. 3.05±0.83, 1.50±0.84 vs. 6.65±1.47, 0.87±0.12 vs. 2.28±0.52, 1.68±0.43 vs. 4.76±1.13, 1.42±0.19 vs. 2.75±0.79), and the differences were statistically significant( t=2.32, 5.28, 4.56, 4.41 and 2.85, all P<0.05). Conclusions:Macrophages are polarized into M1 phenotype in NASH. M1 macrophages contributed to NASH progression by interacting with hepatocyets to promote the secretion of inflammatory cytokines, up-regulation of lipogenic factors, oxidative stress and endoplasmic reticulum stress, resulting in the progression of NASH. Macrophages depletion by liposomal clodronate is a potential noval approach for NASH prevention.

Objective:To observe any effect of intermittent theta burst stimulation (iTBS) of the cerebellum on swallowing dysfunction after cerebellar infarction, and to explore its mechanism.Methods:Sixty-two cerebellar stroke survivors with dysphagia were randomly divided into an observation group and a control group, each of 29. In addition to the routine swallowing rehabilitation training, the observation group was treated with iTBS, while the control group was given sham iTBS. The incubation and amplitude of the bilateral suprahyoid muscle motor evoked potential (MEP) were recorded before and after 4 weeks of treatment. The exponential approximate entropy (ApEn) of different brain regions was compared between the two groups during reflex and autonomous swallowing. Swallowing function was evaluated using the penetration-aspiration scale (PAS).Results:MEP incubation in the bilateral suprahyoid muscles had decreased significantly after 4 weeks of treatment in the observation group, and the MEP amplitude in the bilateral suprahyoid muscles of the two groups had increased significantly. The average improvement in the amplitude and incubation in the observation group was significantly greater than in the control group. The average ApEn at C3, C4, P3, P4, T5 and T6 had increased significantly in both groups during both reflex and spontaneous swallowing, with the improvement in the observation group significantly greater. Swallowing function had improved significantly in both groups, but the average PAS grade of the observation group was again significantly better.Conclusions:iTBS can improve the swallowing function of dysphagic cerebellar stroke survivors. This may be due to iTBS improving the excitability of the cerebral cortex and improving motor control of the swallowing muscles.

Objective:To investigate the correlation between basilar artery (BA) dolichosis and clinical outcome of patients with acute isolated pontine infarction.Methods:Consecutive patients with acute isolated pontine infarction within 7 d after onset admitted to the Department of Neurology, the Affiliated Hefei Hospital of Anhui Medical University were enrolled. The demographic, clinical and MRI data were collected. The modified Rankin Scale was used to evaluate the clinical outcome at 3 months after the onset. 0-2 was defined as good outcome, and >2 was defined as poor outcome. A binary multivariate logistic regression model was used to analyze the correlation between BA dolichosis and clinical outcome of the patients. Results:A total of 116 patients with acute isolated pontine infarction were enrolled. There were 69 (59.5%) males and 47 (40.5%) females, with a median age of 65 years (interquartile range: 57-76 years). There were 39 patients (33.6%) in BA dolichosis group and 77 (66.4%) in non-BA dolichosis group. The BA diameter ( P=0.021), theoretical length (basilar artery length, BAL) ( P<0.001), bending length (BL) ( P<0.001) and the proportion of patients with BA bending ( P<0.001) in the BA dolichosis group were significantly higher than those of the non-BA dolichosis group. There were 93 (80.2%) patients in good outcome group and 23 (19.8%) in poor outcome group. The baseline National Institute of Health stroke scale (NIHSS) score ( P<0.001), approximate length of BA ( P=0.007), BAL ( P=0.020), BL ( P=0.005) and the proportion of patients with BA dolichosis ( P=0.002) and bending ( P=0.008) in the poor outcome group were significantly higher than those in the good outcome group. Spearman correlation analysis showed that the approximate length of BA was significantly positively correlated with BL ( r=0.597, P<0001). Multivariate logistic regression analysis showed that BA dolichosis (odds ratio 5.441, 95% confidence interval 1.814-16.320; P=0.003) and the higher baseline NIHSS score (odds ratio 1.696, 95% confidence interval 1.291-2.228; P<0.001) were the independent risk factors for poor outcomes in patients with acute isolated pontine infarction. Conclusion:BA dolichosis is common in patients with acute isolated pontine infarction. BA dolichosis may be an independent risk factor for poor outcome in patients with acute isolated pontine infarction at 3 months after onset.

Objective: To explore the effect of Dahuang-Zhidan decoction on postoperative peripheral inflammatory factors and prognosis in patients with hypertensive cerebral hemorrhage. Methods: A total of 103 patients with hypertensive cerebral hemorrhage in our hospital from May 2015 to January 2017 were divided into two groups according to the randomly number tables method. The control group (n=51) were treated by conventional treatment of western medicine, and the observation group (n=52) were treated with Dahuang-Zhidan decoction based on the treatment of the control group.The inflammatory factors, including interleukin-6 (IL-6), tumor necrosis factor (TNF-α), highly sensitive C-reactive protein (hs-CRP), interleukin-1β (IL-1β) in hematoma lesions after treatment for 1st, 7th day between two groups were measured. The comparisons of awake rate after treatment for the 7th, 14th, 30th day between two groups was conducted. The National Institute of Health Stroke Scale (NIHSS) scores after treatment for 30th, 90th day between two groups was launched. The Glasgow Prognosis Score (GOS) between two groups was compared at the 90th day. Results: After treatment for 7 d,the postoperative peripheral inflammatory factors IL-6 (90.55 ± 18.89 pg/ml vs. 122.71 ± 19.62 pg/ml, t=-6.892), TNF-α (172.26 ± 29.85 pg/ml vs. 229.02 ± 30.34 pg/ml, t=-10.332), hs-CRP (137.55 ± 24.60 pg/ml vs. 162.14 ± 23.98 pg/ml, t=-8.615), IL-1β (95.57 ± 18.92 pg/ml vs. 110.65 ± 17.38 pg/ml, t=-3.594) in the observation group was significantly lower than those in the control group (P<0.05). After treatment for 7, 14, 30 d, the awake rate was 44.23% (23/52), 69.23% (36/52), 90.38% (47/52) in the observation group, which was significantly higher than those in the control group (χ²=3.977, 4.355, 4.499, P<0.05). After treatment for 30, 90 d, the NIHSS scores (12.24 ± 6.38 vs. 16.27 ± 7.69, t=-2.906), (5.39 ± 6.24 vs. 9.94 ± 8.11 , t=-3.198) in the observation group were significantly lower than those in the control group (P<0.05). After treatment for 90 d, the distribution of GOS scores in the observation group was significantly different from the control group (Z=-2.400, P=0.016). Conclusions The Dahuang-Zhidan decoction in the treatment of patients with hypertensive cerebral hemorrhage significantly inhibit postoperative the inflammatory response around hematoma lesions, and improve the neurological function, the awake rate and the qualify of life.