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.

ObjectiveTo explore the role of cuproptosis and identify cuproptosis-related genes in Wilson disease （WD） through bioinformatics analysis and clinical validation，providing implications and directions for the diagnosis and treatment of WD. Methods（1） Screening of target genes： The differentially expressed genes （DEGs） between WD and healthy control were obtained from GeneCards，and the cuproptosis-related genes were obtained from Gene Expression Omnibus （GEO） and published literature.The cuproptosis-related genes in WD were obtained by intersection.Through gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses，the specific biological process，functions or metabolic pathways of cuproptosis-related genes in WD were predicted.Molecular docking and PyMOL visualization were then performed to analyze and verify the potential regulatory mechanism of Gandou Fumu Decoction for cuproptosis.（2）Validation of target genes： The blood samples of 15 WD patients treated in the department of encephalopathy and 15 healthy volunteers undergoing physical examinations in the health management center were randomly collected from the First Affiliated Hospital of Anhui University of Chinese Medicine.The expression levels of target genes were determined by Western blot and real-time PCR. Results（1） A total of 3 607 DEGs in WD were obtained from GSE107323 in GEO，and 68 cuproptosis-related genes were obtained from GeneCards and published literature.Twelve common target genes were obtained by intersection，including three up-related genes（SQSTM1，MIF1，and TAX1BP1） and nine down-regulated genes（CP，SERPINE1，AOC3，GPX4，SLC27A5，VEGF-A，PDHB，PDK1，and ATP7B）.The common target genes were mainly enriched in monocarboxylic acid metabolism，oxidoreductase activity，negative regulation of molecular functions，which mainly involved HIF-1，ferroptosis and other signaling pathways.Molecular docking and PyMOL visualization results showed Gandou Fumu Decoction had good binding ability with the cuproptosis-related genes PDK1，SERPINE1，VEGFA，and AOC3 in WD.（2）A total of 30 blood samples were collected，including 15 WD patients and 15 health volunteers.Western blot results showed that expression levels of target genes were consistent with the results obtained by bioinformatics analysis.RT-qPCR results showed that compared with healthy volunteers，WD patients had down-regulated mRNA levels of SERPINE1，GPX4，SLC27A5，and VEGF-A and up-regulated mRNA levels of SQSTM1 and MIF1（P<0.05）. ConclusionThe expression levels of cuproptosis-related genes in WD patients are consistent with the results predicted by bioinformatics analysis.The characteristic preparation Gandou Fumu Decoction of Xin'an Medicine showed good binding abilities with the cuproptosis-related genes in WD.Cuproptosis may play a key role in the pathophysiological mechanism of WD，which can provide a new target for the diagnosis and treatment of WD.

Lipid metabolism disorders is a prevalent clinical symptom observed in patients with fatty liver type hepatolenticular degeneration.According to TCM,the key pathogenesis of this disease is deficiency of spleen yang.The method of warming yang and dissipating qi is the basic method to treat this disease.This article explored the pathological foundation of fatty liver type hepatolenticular degeneration based on the"spleen rules transformation".It elucidated that lipid metabolism disorder is a significant characteristic of this disease,considering both TCM and Western medicine perspectives.It also examined the treatment of fatty liver type hepatolenticular degeneration by regulating lipid metabolism through the method of warming yang and dissipating qi,with the purpose to guide the treatment of the disease.

The passing of ethical review is a necessary conditions and prerequisite for the development of life science and medical research involving humans. At present, some medical and health institutions have no or insufficient ethical review capabilities. The lack of ethical review ability has become a bottleneck restricting the development of life science and medical research involving humans. According to documents such as Opinions on Deepening the Reform of the Review and Approval System and Encouraging the Innovation of Pharmaceutical and Medical Devices, Opinions on Strengthening the Ethical Governance of Science and Technology, institutions can entrust competent institutional ethics review committees or regional ethics review committees in writing to conduct ethical review. Entrustment ethical review provides a viable solution for institutions that need to carry out life science and medical research involving humans but do not have an ethics (review) committee or the ethics (review) committee is not competent to review. To conduct the entrustment ethical review, the entrustment between the principal and the trustee is required. According to The Measures for Ethical Review of Life Sciences and Medical Research Involving Humans, if medical and health institutions and their ethical review committees do not accept the formal entrustment to provide the ethical review opinions for other institutions, the local health authorities at or above the county level will impose administrative penalties and sanctions on the relevant institutions and personnel in accordance with the law. Signing the entrustment ethical review contract, implementing legal compliance entrusted ethical review to protect the rights and interests of the trustee and the principal, and protect the research participants.

Objective To explore the effects of nasogastric tube nutrition and jejunal nutrition on the complications and mortality in severe neurological diseases during hospitalization.Methods The clinical data of patients with severe neurological diseases admitted to Department of Intensive Care Unit,Wuhan Fourth Hospital from June 2020 to June 2022 were analyzed retrospectively.Patients were di-vided into nasogastric tube nutrition group and jejunal nutrition group according to enteral nutrition methods.The propensity score matc-hing(PSM)was used to equalize the baseline data of the two groups,and the differences in complications,mortality,hospitalization costs,and mean length of stay between two groups were compared.Results There were no significant differences in baseline data be-tween the two groups after PSM(P>0.05).There were also no significant differences in complication rate and mortality between the na-sogastric tube nutrition group and the jejunal nutrition group(P>0.05).Further univariate and multivariate regression Logistic analysis showed that age(OR =1.135,P =0.001),acute physiology and chronic health evaluation Ⅱscore(APACHEⅡ score,OR =1.147,P<0.001)and blood urea nitrogen level(OR = 1.135,P = 0.001)might be the key factors affecting the prognosis of patients with severe neurological diseases.Conclusion Enteral nutrition had no significant effect on the incidence of complications and mortality during hos-pitalization in patients with severe neurocritical diseases,elderly patients,higher levels of APACHE Ⅱ score and blood urea nitrogen were independent risk factors for mortality patients with severe neurological diseases.

Objective To explore the effect of seamless nursing mode under Six Sigma management on nosocomial infection,nursing quality,and overall rehabilitation of premature infants.Methods A total of 92 premature infants born in affiliated matemal and child health care hospital of nantong university from March 2019 to March 2022 were enrolled.According to the length of hospital stay,they were assigned to the control group or the study group,with 46 cases in each group.The control group was given routine nursing management,and the research group was given seamless nursing under Six Sigma management on the basis of routine nursing.The incidence of complications related to nosocomial infection,nursing quality,and neuropsychological development were compared between the two groups one month later.The weight and height of premature infants at 3 months,6 months,and 12 months after discharge were compared between the two groups.Results Before nursing,there were no significant differences in nursing quality,neuropsychological development,weight,or height between the two groups(P>0.05).After nursing,the total incidence of intestinal infection,septicemia,and other infections in the study group was significantly lower than that in the control group(P<0.05).The scores of ward management,basic nursing operation,nursing document record,nursing service attitude,risk management,and communication ability in the study group were significantly higher than those in the control group(P<0.05).The scores of gross and fine movements in the study group were significantly higher than those in the control group(P<0.05).The body weight and height of the study group were significantly higher than those of the control group at 3 months,6 months,and 12 months after discharge(P<0.05).Conclusion The seamless nursing under Six Sigma management is helpful to reduce the incidence of nosocomial infection-related complications of premature infants,improve the quality of nursing,promote neuropsychological development of premature infants,and increase their weight and height.

Objective:To study the inhibitory effect of overexpression of mitofusion 2 (Mfn2) protein on acute respiratory distress syndrome (ARDS) pulmonary fibrosis and its mechanism.Methods:Human embryo lung fibroblasts (HELF) were cultured in vitro, and digested and passaged when the adherent rate of HELF reached 80%, and then the cells in good condition were selected for experiment. The ARDS cell model was reproduced by 5 mg/L of lipopolysaccharide (LPS, LPS group); 75 mol/L adenovirus vector carrying mitofusion 2 (Adv-Mfn2) was transfected into HELF (Adv-Mfn2+LPS group); at the same time, blank control group (complete medium culture) and Adv-vector+LPS group were set as controls. The cell proliferation was observed by sulforhodamine B (SRB) method at 0, 12, 24, 36 and 48 hours. After Hoechst 33342 staining, the morphological changes were observed under confocal microscope. Western blotting was used to detect the protein expressions of Bcl-2 and caspase-3. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect the gene expressions of Bcl-2 and caspase-3. Results:After LPS stimulation for 12-48 hours, the cell proliferation rates in the LPS group increased gradually, which were significantly higher than those in the blank control group [12 hours: (10.75±1.51)% vs. (0.73±1.22)%, 24 hours: (20.09±1.71)% vs. (1.15±1.12)%, 36 hours: (20.58±1.55)% vs. (1.20±1.12)%, 48 hours: (21.30±1.51)% vs. (1.23±1.10)%, all P < 0.01]. There was no statistically significant difference in the cell proliferation rate between the LPS group and the Adv-vector+LPS group. After overexpression of Mfn2, the cell proliferation rates at 12, 24, 36, 48 hours in the Adv-Mfn2+LPS group were (8.93±1.14)%, (10.52±1.24)%, (10.72±1.30)%, and (10.91±1.20)%, which were significantly lower than those in the LPS group (all P < 0.05). Confocal microscopy showed that some cells in the blank control group had nuclei of different sizes, and some nuclei fragmented or shrank to form apoptotic bodies. The nuclei of the cells in the LPS and Adv-vector+LPS groups were round or oval in size, and only a few apoptotic cells appeared. When Mfn2 was overexpressed, there were more apoptotic cells in the visual field in the Adv-Mfn2+LPS group than LPS group. Western blotting and RT-qPCR results showed that Bcl-2 expressions increased significantly after LPS stimulation in the LPS group as compared with the blank control group [Bcl-2 protein (Bcl-2/GAPDH): 0.68±0.01 vs. 0.29±0.01, Bcl-2 mRNA (2 -ΔΔCT): 2.23±0.34 vs. 1.00±0.00, both P < 0.01], and caspase-3 expressions decreased significantly [caspase-3 protein (caspase-3/GAPDH): 0.37±0.02 vs. 0.66±0.02, caspase-3 mRNA (2 -ΔΔCT): 0.31±0.05 vs. 1.00±0.00, both P < 0.01]. Compared with LPS group, the expressions of Bcl-2 after overexpression of Mfn2 in the Adv-Mfn2+LPS group were down-regulated [Bcl-2 protein (Bcl-2/GAPDH): 0.46±0.01 vs. 0.68±0.01, Bcl-2 mRNA (2 -ΔΔCT): 1.45±0.14 vs. 2.23±0.34, both P < 0.01], and the expressions of caspase-3 were up-regulated [caspase-3 protein (caspase-3/GAPDH): 0.54±0.02 vs. 0.37±0.02, caspase-3 mRNA (2 -ΔΔCT): 0.88±0.10 vs. 0.31±0.05, both P < 0.01]. Conclusion:Mfn2 protein is involved in ARDS pulmonary fibrosis, which may be related to mitochondrial mediated inhibition of cell proliferation.