ObjectiveTo observe the clinical efficacy of Gandou Fumu Granules （GDFMG） combined with sodium dimercaptosulphonate （DMPS） on liver fibrosis in Wilson disease （WD） patients with the syndrome of phlegm and blood stasis， evaluate its effect on cuproptosis-related indicators， and explore the possible mechanisms of cuproptosis in WD-related liver fibrosis. MethodsSixty WD patients diagnosed with the syndrome of phlegm and blood stasis between January 2023 and December 2023 were randomly divided into a control group and an observation group， with 30 patients in each group. The control group received the copper chelator DMPS for the first 6 days， followed by calcium gluconate injection for the next 2 days， completing an 8-day treatment cycle. The observation group received GDFMG in addition to the treatment regimen of the control group， with both groups treated for 21 cycles. A Beckman fully automated biochemical analyzer was used to detect levels of type Ⅳ collagen （CⅣ）， hyaluronic acid （HA）， laminin （LN）， N-terminal propeptide of type Ⅲ procollagen （PⅢ-NP）， and serum copper （SCu） before and after treatment in both groups. Enzyme-linked immunosorbent assay （ELISA） was used to measure levels of ferredoxin 1 （FDX1）， lipoic acid synthetase （LIAS）， and dihydrolipoamide S-acetyltransferase （DLAT）. Atomic absorption spectroscopy measured 24-hour urine copper levels before treatment and after the 7， 14， and 21 treatment cycles in both groups. An Fibro Touch （FT） non-invasive liver fibrosis diagnostic device was used to measure liver stiffness （LSM） in both groups before and after treatment. Traditional Chinese medicine syndrome score （TCMSS） was evaluated at the same intervals. Clinical efficacy， adverse events， and safety indicators were also compared. ResultsAfter treatment， levels of CⅣ， HA， LN， and PⅢNP significantly decreased in both groups compared to pre-treatment levels （P<0.01）. The observation group showed a more pronounced reduction compared to the control group （P<0.05）. There were no statistically significant differences in SCu levels in both groups before and after treatment. After treatment， levels of FDX1，LIAS and DLAT significantly increased in both groups（P<0.01）. The observation group showed more notable improvements in these indicators than the control group （P<0.05）. After the 7， 14， 21 treatment cycles， 24-hour urine copper levels significantly increased in both groups compared to pre-treatment levels （P<0.01）. The observation group had a greater increase in 24-hour urine copper levels than the control group after treatment （P<0.05，P<0.01）， and although 24-hour urine copper levels increased after 7 cycles， a gradual decline was observed in subsequent cycles. After treatment， LSM levels significantly decreased in both groups compared to pre-treatment levels （P<0.01）， with the observation group showing a greater reduction than the control group （P<0.05）. Clinical efficacy was significantly better in the observation group than the control group （P<0.05）. No significant differences in the incidence of adverse events or safety indicators were observed between the two groups after treatment. ConclusionGDFMG combined with DMPS can reduce LSM in WD patients with liver fibrosis and the syndrome of phlegm and blood stasis， inhibit cuproptosis， and improve clinical efficacy.

Objective:To explore the risk factors of oral-mucosal pressure injury (OMPI) in patients with tracheal intubation in ICU and to establish a nomogram model.Methods:Using the convenient sampling method, a total of 640 patients with oral tracheal intubation admitted to ICU of the First Affiliated Hospital of Xinjiang Medical University from January to May 2023 were selected as the research objects. They were divided into the occurrence group ( n=286) and the non-occurrence group ( n=354) according to whether OMPI occurred or not. Binomial Logistic regression analysis was used to explore the risk factors for OMPI in patients with tracheal intubation in ICU. A risk nomogram model was created based on independent risk factors, and internal verification was conducted by Bootstrap repeated sampling method. Results:OMPI occurred in 286 of 640 ICU patients with tracheal intubation. Binomial Logistic regression analysis showed that high APACHEⅡ score, modified Beck oral score greater than or equal to 11 points, use of sedative drugs, prone ventilation, long retention time of tracheal catheter, low oxygenation index less than 200 mmHg (1 mmHg=0.133 kPa) and tracheal catheter fixation frequency of 1 time /24 h were the risk factors for OMPI in patients with tracheal intubation in ICU ( P<0.05). A risk nomogram model for OMPI in patients with tracheal intubation in ICU was established based on independent risk factors. The results showed that the predictive performance (area under the receiver operating characteristic curve of subjects was 0.918, 95% confidence interval was 0.897 to 0.938) and calibration (χ 2 value of 4.647, P=0.795) of the risk nomogram model for OMPI in patients with tracheal intubation in ICU were good. When the threshold probability was 0 to 1, the decision curve showed that the model had good clinical effectiveness. Conclusions:The OMPI risk nomogram model of tracheal intubation patients in ICU established in this study has good calibration and differentiation, which can be used as an effective tool for screening high-risk patients.

Sialidosis is a rare lysosomal storage disease caused by NEU1 gene mutation at 6p21.33. It is characterized by myoclonic, ataxia, epilepsy, and decreased vision. A pair of twins with sialidosis type 1 are reported to enrich clinicians ′ understanding of the disease, so as to improve the diagnosis and treatment. The proband was a 16-year-old male. The main symptom was intermittent limb involuntary trembling for 2 years, with paroxysmal loss of consciousness. Fundus examination showed cherry-red spots. His twin brother had similar symptoms, but the overall performance was mild. Whole exome sequencing results showed that both patients carried compound heterozygous mutations of c.239C>T (p.P80L) and c.803A>G (p.Y268C) in NEU1 gene, which were from their normal phenotype mother and father.

Objective : To study the resistance pattern of streptomycin and ethambutol in Mycobacterium tuberculosis in Luoyang area , guide clinical medication and supplement epidemiological data on local drug⁃resistant tuberculosis . Methods : The positive results of high⁃resolution melting curve (HRM) in 2 941 cases in Luoyang area were analyzed to assess the risk factors associated with streptomycin and ethambutol resistance . Results : Of the 2 941 HRM⁃positive patients , 18 . 4% were resistant to streptomycin and 8. 0% were ethambutol . Both streptomycin and ethambutol and resistance rates were higher in men than those in women ( 19. 0% vs 16. 9% , P = 0. 129 ; 8. 0% vs 7. 9% , P = 0. 987) . The resistance rates to streptomycin and ethambutol were higher in urban than those in rural areas (21 . 3% vs 16. 6% , P = 0. 002 ; 9. 8% vs 6. 9% , P = 0. 004) . The resistance rate was much higher in previously treated patients than those newly diagnosed for MTB infection (25 . 8% vs 17. 3% , P < 0. 001 ; 12. 1% vs 7. 4% , P = 0. 002) . The resistance rates to streptomycin were higher in the < 51 years than those in the > 50 years group (21 . 1% vs 16. 1% , P < 0. 001) . According to age , the highest resistance rates to streptomycin and ethambutol occurred in the age range of 31 - 35 years and 56 - 60 years in men , respectively , while in the age range of 21 - 25 years and 56 - 60 years in women , respectively . In multivariate models , prior treatment history , age less than 51 years , and urban area were positively associated with streptomycin and ethambutol resistance after adjusting for smear results and year testing . Conclusion Men , prior treatment history , age less than 51 years , and urban residents are key monitoring targets for streptomycin and ethambutol resistant tuberculosis .

Silicosis is one of the most common forms of pneumoconiosis globally. Workers who engage in mining, construction, ceramics, and many other industries have a high risk of developing silicosis. Chronic and repeated inhalation of free silica (SiO₂) dust (<5 μm) during working can lead to inflammatory reactions, resulting in interstitial lung disease characterized by extensive nodular fibrosis in both lungs. Once silicosis occurs, it will develop progressively even when the workers are removed from the silica dust environment. The pathogenesis of silicosis is complex, especially the role of nod-like receptor family protein 3 (NLRP3) inflammasome in the pathogenesis and progression of silicosis remains to be further studied. NLRP3 inflammasome, a multi-protein complex composed of NLRP3, apoptosis-associated speck-like protein, and cysteinyl aspartate specific proteinase 1 is involved in oxidative stress, inflammatory response, apoptosis, and pyroptosis, and has become one of the hot spots in silicosis research. This review summarized the structure, function, and activation mechanism of NLRP3 inflammasome. Furthermore, the cellular and molecular mechanisms of NLRP3 in mediating oxidative stress, inflammatory response, apoptosis, and pyroptosis in the progression of silicosis were reviewed. Finally, the potential therapeutic drugs for silicosis based on NLRP3-associated mechanisms were outlined. More attention should be paid to the role of NLRP3 inflammasome in the pathogenesis and progression of silicosis in the future, which will provide new ideas for the prevention and treatment of silicosis.

Objective:To construct a "Five-in-one" blended teaching model in the course of fundamental nursing with ideological and political education as the core, integrated with online and offline, and complemented with theory and experiment, and to explore its application effect.Methods:Eight classes of nursing undergraduates in Batch 2019 were selected through convenience sampling method, and through random cluster sampling, Class 5 to 8 were divided into control group and Class 1 to 4 were divided into experimental group. The control group used the traditional teaching method, the experimental group used the "Five-in-one" mixed teaching model. After the course, the teaching effect was evaluated by the professional commitment scale, the recessive truancy scale for college students, the self-regulated learning ability scale and the examination results. SPSS 23.0 software was used for t test. Results:After teaching, the scores of professional commitment, self-adjustment in recessive truancy, autonomous learning ability and examination results of the experimental group were higher than those of the control group [(91.30±10.38) vs. (87.31±16.40), (23.30±4.50) vs. (21.23±4.51), (82.31±10.06) vs. (79.42±9.79), (72.31±10.13) vs. (70.14±9.67) and (87.93±4.60) vs. (86.50±4.67), respectively]. The scores of academic cognition, learning habit, classroom cognition and learning environment in recessive truancy of the experimental group were lower than those in control group, with statistical significance.Conclusion:The application of "Five-in-one" blended teaching model in the course of fundamental nursing can reduce students' recessive truancy and improve their professional commitment, autonomous learning ability and academic achievement.

Since its establishment 30 years ago, the discipline of metabolic engineering has developed rapidly based on its deep integration with molecular biology, systems biology and synthetic biology successively, which has greatly contributed to advancing and upgrading biotechnology industry. This review firstly analyzes the current status of academic research and China's competence in the area of metabolic engineering according to the data of papers published in SCI-indexed journals in the past 30 years. Subsequently, the article summarizes the development of systems biology methods and enabling technologies of synthetic biology and their applications in metabolic engineering in the past 10 years. Finally, the major challenges and future perspectives for the development of metabolic engineering are briefly discussed.
Biotechnology ; Industry ; Metabolic Engineering ; Synthetic Biology ; Systems Biology

Objective To avoid the accumulation of copper sulfide (CuS) nanoparticles, prepare and optimize CuS nanoparticles, analyze the factors affecting the particle size and evaluate their photothermal properties. Methods Based on the single factor study, central composite design-response surface methodology was used to optimize the CuS nanoparticle formulation process. The morphology, particle size stability, photothermal conversion efficiency, photothermal stability of optimized CuS nanoparticles were characterized. The toxicity of CuS nanoparticles on 4T1 breast cancer cells and HK2 kidney cells was evaluated by CCK-8 method. In vitro photothermal experiment was used to investigate the ability of CuS nanoparticles on killing 4T1 breast cancer cells. Results The average hydration dynamic diameter of optimized CuS nanoparticles was (10.53±1.63)nm, the actual particle size of CuS nanoparticles showed by TEM image was (3.10±0.81)nm. It had good particle size stability, good photothermal conversion efficiency and photothermal stability. Within the concentration range of 100 μg/ml and 150 μg/ml，it showed no significant toxicity on 4T1 breast cancer cells and HK2 kidney cells, indicating the good stability of CuS nanoparticles. In vitro photothermal therapy showed that CuS nanoparticles had good ability to kill 4T1 breast cancer cells by photothermal. Conclusion The prepared CuS nanoparticles have a small particle size (less than 6nm) and a good photothermal effect, which is expected to solve the problem of CuS nanoparticles accumulation in vivo and make it better for tumor treatment.

Objective To evaluate the effects of different solubilizing techniques on the in vitro dissolution and in vivo pharmacokinetics of Sirolimus (SRL). Methods Solid dispersions (SD), inclusion complex (IC), self-micro emulsifying drug delivery system (SMEDDS) and nano-structured lipid carrier (NLC) were selected as the solubilization technology for SRL. SRL-SMEDDS and SRL-NLC have obtained the optimal prescription in the previous studies. Additionally, the formulation process of SRL-SD and SRL-IC was screened by using inclusion rate and dissolution profiles as indicators. 0.4% SDS, water and buffer solutions with pH 1.2, 4.5, 6.8, 7.4 were used as dissolution media. The dissolution profile of the commercially available formulation Rapamune^® and the lab-made solubilized preparations were investigated. The in vivo absorption of the above preparations was examined using a pharmacokinetic test in Beagle dogs. Results In 0.4% SDS, the dissolution of each preparation exceeded 80% in 2 h. In the medium of pH 1.2, the dissolution of SRL-SD could not be measured while the dissolution of IC, SMEDDS and NLC increased first and then decreased. In other media, the dissolution of the SRL was reduced. The SRL-IC showed the best dissolution without a significant decrease. The relative bioavailability of APIs, SRL-SD, SRL-IC, SRL-NLC and SRL-SMEDDS were 9.1%, 18.7%, 33.2%, 78.0%, and 97.6% respectively in vivo pharmacokinetic tests. Conclusion SD, SMEDDS, NLC, and IC can improve the in vitro dissolution and in vivo absorption of SRL. Among them, SMEDDS has the most significant improvement in the bioavailability of SRL.

Objective: Through research on the geriatric nursing related literature in Chinese journals and medical care and elderly care combination related keywords from 1979 to 2017, this study provides the development trend of geriatric nursing research. Methods: Searching articles in Wanfang, CNKI, VIP database, selecting the keywords and published time of the paper. Employing descriptive statistics to describe literatures information such as publication time, quantity of keywords, word frequency of keywords, heat degree of keywords, character of keywords and so on. Results: Totally 134 791 articles were got and 58 031 articles were included in the analysis. The amount of literature growth was slow before 2005, The cumulative amount of literature in 1979-2005 was only 12.75% of the total amount of literature. After 2005, the amount of literature increased rapidly year by year. The number of literature published in 2017 has exceeded 12%. The amount of the geriatric nursing related literature was proportional to the number of people aged 65 and over in China. In the research of geriatric nursing, the content related to medical care and elderly care combination was quite dispersed, and it did not involve research at the level of Medical Association. The medical care and elderly care combination and Medical Association were new areas in the research of geriatric nursing. Conclusion The amount of the geriatric nursing related literature from 1979 to 2017 was proportional to the number of people aged 65 and over in China. There are few researches on how to carry out geriatric nursing under the policy of medical care and elderly care combination and Medical Association, which should be the focus of future research and exploration to actively respond to the challenge of aging population.