Wilson disease （WD） is an autosomal recessive disorder of copper metabolism， and decoppering therapy and symptomatic treatment are the main Western medicine therapies for WD. This article systematically reviews the understanding of the etiology and pathogenesis of WD in traditional Chinese medicine （TCM） and points out that abnormal natural endowment is the core etiology and pathogenesis of WD， with internal accumulation of copper toxicity as the manifestation， liver/spleen/kidney dysfunction as the root cause， and intermingled “toxin， stasis， phlegm， and deficiency” as the key pathogenesis. Literature research and clinical observation are conducted to summarize the common TCM syndromes of WD， including stagnation of liver Qi， internal retention of damp-heat， phlegm-stasis-heat accumulation syndrome， liver-kidney Yin deficiency syndrome， spleen-kidney Yang deficiency， and syndrome of deficiency damage and phlegm stasis. This article proposes the corresponding therapies and representative prescriptions for each syndrome and discusses the advantages of treatment by stage and integrated traditional Chinese and Western medicine therapy. This article aims to provide a systematic reference for the syndrome differentiation-based treatment of WD in clinical practice of TCM， thereby giving full play to the advantages of TCM in the treatment of this disease.

OBJECTIVE To investigate the effects of metformin （Met） on liver injury in non-alcoholic steatohepatitis （NASH） rats by regulating the PI3K/AKT/PDGF signaling pathway. METHODS NASH model was constructed by feeding rats with a high- glucose and high-fat diet， and assigned into Model group， Met low-dose group （Met-L group， 100 mg/kg）， Met medium-dose group （Met-M group， 200 mg/kg）， Met high-dose group （Met-H group， 400 mg/kg）， and high dose of Met+PI3K activator group （Met-H+740 Y-P group， 400 mg/kg Met+50 mg/kg 740 Y-P）， with 12 rats in each group. Another 12 rats were regarded as the Control group. Each group of rats was orally administered/injected with the corresponding medication once a day for 6 consecutive weeks. The changes in body weight and liver index of rats were recorded and analyzed. The pathological damage [evaluation of non-alcoholic fatty liver disease activity score （NAS）]， lipid deposition （calculation of the proportion of oil red O-positive staining area）， and fibrosis （calculation of collagen deposition score） were observed in liver tissue of rats. The levels of inflammatory factors [interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α）] in serum and liver tissue， the levels of serum lipid metabolism indicators [total cholesterol （TC）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C）] and liver function indicators [aspartate aminotransferase （AST） and alanine Δ 基金项目 武汉市知识创新专项项目（No.2022020801010588）； aminotransferase （ALT）] were measured. The expression levels of PI3K/AKT/PDGF signaling pathway-related proteins and Caspase-3 in liver tissue of rats were determined. RESULTS Compared with the Control group， body weight， liver index， the levels of serum lipid metabolism indicators and liver function indicators， the levels of IL-6 and TNF-α in serum and liver tissue， the NAS， the proportion of oil red O-positive staining area， the collagen deposition fraction， and the levels of phosphorylated PI3K and AKT proteins， as well as the expression levels of PDGF and Caspase-3 proteins in liver tissue， were all significantly increased （P＜0.05）. The liver tissue showed severe pathological damage， characterized by an abundance of lipid droplets and pronounced collagen deposition. After the intervention with Met， the aforementioned quantitative indicators and pathological changes in rats were significantly improved in a dose- dependent manner （P＜0.05）. 740 Y-P could reverse the improvement effects of high dose of Met on the above indexes of rats （P＜ 0.05）. CONCLUSIONS Met can improve liver damage， and alleviate inflammatory reactions and liver fibrosis of NASH rats， the mechanism of which may be associated with inhibiting PI3K/AKT/PDGF signaling pathway.

Objective:To investigate the changes of pathogenic bacteria distribution and immune response of urinary tract infection(UTI)after pyeloureteroplasty in children.Methods:A total of 150 children with obstructive hydronephroplasty who received pyeloureteroplasty in Qinghai Women and Children's Hospital from February 2020 to June 2023 were selected as the study objects.The postoperative urine of the children was collected,the pathogens were identified by automatic bacterial analyzer,and the patients were divided into infected group and uninfected group according to the infection status.The detection of pathogenic bacteria in children with UTI was analyzed.The clinical data of the two groups were compared,and the influencing factors of postoperative UTI were screened by Logistic regression analysis,and the prediction model was established and verified.The changes of immune response were compared between the two groups.Results:UTI occurred in 56 cases(37.33%)of 150 children who underwent pyeloureteroplasty.There were 58 strains of gram-negative bacteria,29 strains of gram-positive bacteria and 2 strains of fungi isolated.The main pathogenic bacteria was Escherichia coli.Multivariate Logistic regression analysis showed that serum creatinine(SCr)and hydronephrosis volume/renal volume(HV/RV)levels increased,urinary catheter retention time,urinary bag replacement time and hospital stay were risk factors for UTI after pyeloureteroplasty in children,increased age and elevated albumin(Alb)were protective factors(P<0.05).Through Bootstrap self-sampling,the prediction model had good differentiation and accuracy.There was no significant difference in the levels of CD4+,CD8+and IgM between the two groups before surgery(P>0.05),and the levels of CD4+,CD8+and IgM were signi-ficantly improved between the two groups after surgery,and the improvement degree of the uninfected group was significantly better than that of the infected group(P<0.05).Conclusion:The pathogens of UTI in children after pyeloureteroplasty are mainly gram-nega-tive bacteria,and the immune function is increased 7 days after the operation.

Objective:To investigate whether lncRNA SOX2-OT inhibits the proliferation and migration of colorectal cancer(CRC)HCT-116 cells by regulating the miR-215-5p/NIN/RPN12 binding protein 1 homolog(NOB1)signaling pathway.Methods:Cancerous and paired adjacent tissue samples from 29 CRC patients treated at Wuhan Jinyintan Hospital from June 2022 to May 2024 were collected,along with CRC cell lines(SW480,HCT-116,HP116,and LoVo)and normal human colon epithelial HCoApiC cells.The mRNA expression levels of SOX2-OT,miR-215-5p,and NOB1 in CRC tissues and cells were measured using qPCR method.HCT-116 cells were transfected with SOX2-OT knockdown or overexpression plasmids and corresponding negative control plasmids using RNA interference technology,dividing the cells into control group,si-NC group,si-SOX2-OT group,si-SOX2-OT+inhibitor(Inh)NC group,si-SOX2-OT+miR-215-5p Inh group,si-SOX2-OT+oe-NC group,and si-SOX2-OT+oe-NOB1 group.The mRNA expression levels of SOX2-OT,miR-215-5p,and NOB1 in each group of cells were detected using qPCR method.MTT assay,scratch wound healing assay,Transwell chamber assay,and flow cytometry were used to measure cell proliferation,migration,invasion,and apoptosis,respectively.Western blot was applied to detect protein expression levels of E-cadherin,N-cadherin,vimentin,Bcl-2,BAX,PCNA,MMP-9,and NOB1.The targeting relationship between miR-215-5p and SOX2-OT or NOB1 was validated using dual-luciferase reporter gene assays.Results:SOX2-OT and NOB1 mRNA were significantly upregulated,while miR-215-5p was downregulated in both CRC tissues and cells(all P<0.05).In HCT-116 cells with SOX2-OT knockdown,the expression of SOX2-OT and NOB1 mRNA,cell proliferation,wound healing rate,invasive cell number,and protein levels of N-cadherin,vimentin,Bcl-2,NOB1,PCNA,and MMP-9 were significantly reduced(all P<0.05),while miR-215-5p expression,apoptosis rate,and protein levels of E-cadherin and BAX were significantly increased(all P<0.05).Both miR-215-5p knockdown and NOB1 overexpression reversed the inhibitory effects of SOX2-OT knockdown on HCT-116 cells(both P<0.05).miR-215-5p was validated to target SOX2-OT and NOB1.Conclusion:SOX2-OT knockdown upregulates miR-215-5p expression and downregulates NOB1 expression,further inhibiting the proliferation,migration,and invasion of HCT-116 cells and promoting apoptosis.

Objective:To investigate the changes of pathogenic bacteria distribution and immune response of urinary tract infection(UTI)after pyeloureteroplasty in children.Methods:A total of 150 children with obstructive hydronephroplasty who received pyeloureteroplasty in Qinghai Women and Children's Hospital from February 2020 to June 2023 were selected as the study objects.The postoperative urine of the children was collected,the pathogens were identified by automatic bacterial analyzer,and the patients were divided into infected group and uninfected group according to the infection status.The detection of pathogenic bacteria in children with UTI was analyzed.The clinical data of the two groups were compared,and the influencing factors of postoperative UTI were screened by Logistic regression analysis,and the prediction model was established and verified.The changes of immune response were compared between the two groups.Results:UTI occurred in 56 cases(37.33%)of 150 children who underwent pyeloureteroplasty.There were 58 strains of gram-negative bacteria,29 strains of gram-positive bacteria and 2 strains of fungi isolated.The main pathogenic bacteria was Escherichia coli.Multivariate Logistic regression analysis showed that serum creatinine(SCr)and hydronephrosis volume/renal volume(HV/RV)levels increased,urinary catheter retention time,urinary bag replacement time and hospital stay were risk factors for UTI after pyeloureteroplasty in children,increased age and elevated albumin(Alb)were protective factors(P<0.05).Through Bootstrap self-sampling,the prediction model had good differentiation and accuracy.There was no significant difference in the levels of CD4+,CD8+and IgM between the two groups before surgery(P>0.05),and the levels of CD4+,CD8+and IgM were signi-ficantly improved between the two groups after surgery,and the improvement degree of the uninfected group was significantly better than that of the infected group(P<0.05).Conclusion:The pathogens of UTI in children after pyeloureteroplasty are mainly gram-nega-tive bacteria,and the immune function is increased 7 days after the operation.

Breast cancer is the most common cancer in women and one of the deadliest cancers worldwide.According to the distribution of tumor tissue,breast cancer can be divided into invasive and non-invasive forms.The cancer cells in invasive breast cancer pass through the breast and through the immune system or systemic circulation to different parts of the body,forming metastatic breast cancer.Drug resistance and distant metastasis are the main causes of death from breast cancer.Research on breast cancer has attracted extensive attention from researchers.In vitro construction of tumor models by tissue engineering methods is a common tool for studying cancer mechanisms and anticancer drug screening.The tumor microenvironment consists of cancer cells and various types of stromal cells,including fibroblasts,endothelial cells,mesenchymal cells,and immune cells embedded in the extracellular matrix.The extracellular matrix contains fibrin proteins(such as types Ⅰ,Ⅱ,Ⅲ,Ⅳ,Ⅵ,and Ⅹcollagen and elastin)and glycoproteins(such as proteoglycan,laminin,and fibronectin),which are involved in cell signaling and binding of growth factors.The current traditional two-dimensional(2D)tumor models are limited by the growth environment and often cannot accurately reproduce the heterogeneity and complexity of tumor tissues in vivo.Therefore,in recent years,research on three-dimensional(3D)tumor models has gradually increased,especially 3D bioprinting models with high precision and repeatability.Compared with a 2D model,the 3D environment can better simulate the complex extracellular matrix components and structures in the tumor microenvironment.Three-dimensional models are often used as a bridge between 2D cellular level experiments and animal experiments.Acellular matrix,gelatin,sodium alginate,and other natural materials are widely used in the construction of tumor models because of their excellent biocompatibility and non-immune rejection.Here,we review various natural scaffold materials and construction methods involved in 3D tissue-engineered tumor models,as a reference for research in the field of breast cancer.

Objective:To design a tracheotomy cannula cuff filling device for hyperbaric oxygen therapy, which is convenient for clinical operation, improves work efficiency and reduces the incidence of aspiration pneumonia.Methods:This study was a randomized controlled trial. From July 2020 to June 2022, 90 patients with tracheotomy who were treated with hyperbaric oxygen in the First Hospital of Jiaxing were selected as the research objects. According to the random number table method, the patients were divided into the experimental group and the control group, with 45 cases in each group. In the experimental group, the cuff pressure was maintained by the tracheotomy cannula cuff filling device, and in the control group, the traditional water injection method was used to maintain the cuff pressure. The operation time, infection index and incidence of aspiration pneumonia were compared between the two groups.Results:The operation time in the experimental group was (6.33 ± 1.31) s lower than that in the control group (40.96 ± 3.70) s, and the difference was statistically significant ( t=-59.11, P<0.05). Body temperature, C-reactive protein and procalcitonin after treatment in the experimental group were (36.91 ± 0.83) ℃, (34.59 ± 16.25) mg/L, (1.57 ± 0.82) μg/L, respectively, lower than those in the control group (37.42 ± 0.72) ℃, (44.18 ± 18.10) mg/L, (2.45 ± 0.92) μg/L, the differences were statistically significant ( t=-3.09, -2.64, -4.73, all P<0.05). The difference of white blood cell count post-treatment between the two groups was not statistically significant ( P>0.05). The incidence of aspiration pneumonia in the experimental group was 11.11%(5/45) lower than 31.11%(14/45) in the control group, and the difference was statistically significant ( χ2=5.17, P<0.05). Conclusions:The application of tracheotomy cannula cuff filling device can simplify the operation process, reduce the incidence of infection and aspiration pneumonia, and optimize the clinical work.

Objective:To explore the pathogenic genes, clinical characteristics and treatment follow-up of children with congenital long QT syndrome (LQTS).Methods:Clinical data of 20 cases diagnosed with congenital LQTS and underwent gene testing from April 15, 2011 to April 15, 2021 in Department of Pediatric Cardiology, Shandong Provincial Hospital Affiliated to Shandong University were retrospectively collected and analyzed using independent sample t-test and Fisher′ s exact probability method. Results:LQTS-related gene mutations were detected in all the 20 cases, and pathogenic or suspected pathogenic mutations were identified in 18 cases (90.0%). Five LQTS mutation genes were discovered, including KCNQ1, KCNH2, SCN5A, CACNA1C and AKAP9.Eighteen cases (90.0%) had positive symptoms, and 13 cases (65.0%) had definite inducements.The inducement of symptoms in children with LQTS type 1(LQT1) was related to exercise, the causes of syncope in LQT1 and Jervell-Lange-Nielsen syndrome type 1 (JLNS1) with complex heterozygous mutations were exercise or emotional agitation; the causes of syncope in LQTS type 2 (LQT2) were unrelated to exercise; severe exercise in LQTS type 3 (LQT3) resulted in symptoms; and seizure in LQTS type 8 (LQT8) was non-induced.The corrected QT(QTc) interval of 20 cases was (553.1±66.6) ms, with a range of 460-707 ms, among which 17 cases showed QTc≥480 ms.The electrocardiogram(ECG) manifestations of children with various types of LQTS were different.There was no significant difference in QTc between different genders, or between children with syncope and those without syncope (all P>0.05). The follow-up time was (3.4±2.3) years, ranging from 0 to 8.3 years.Seventeen children received treatment[beta blockers and implantable cardiovertor-defibrillator(ICD)] and 3 cases did not.By the end of the follow-up, 1 child died, 19 cases survived, and 2 cases of the surviving children lost consciousness. Conclusions:There is a high consistency between genetic diagnosis and clinical diagnosis of congenital LQTS.The positive rate of gene detection is 90.0%.The clinical manifestations and ECG characteristics vary with genotypes.Beta blockers are protective.ICD therapy can prevent sudden cardiac death when oral medication does not respond.

Group A Streptococcus (GAS) is a very important pathogen, especially for children.On a global scale, GAS is an important cause of morbidity and mortality.But the burden of disease caused by GAS is still unknown in China and also has not obtained enough attention.For this purpose, the expert consensus is comprehensively described in diagnosis, treatment and prevention of GAS diseases in children, covering related aspects of pneumology, infectiology, immunology, microbiology, cardiology, nephrology, critical care medicine and preventive medicine.Accordingly, the consensus document was intended to improve management strategies of GAS disease in Chinese children.

Objective To investigate the clinical effect of tenofovir alafenamide fumarate (TAF) on chronic hepatitis B (CHB) patients with low-level viremia (LLV) after entecavir (ETV) treatment. Methods A total of 160 CHB patients who received ETV antiviral therapy in Wuhan Jinyintan Hospital from March 2019 to October 2020 were enrolled and divided into experimental group and control group by propensity score matching, with 80 patients in each group. The patients in the experimental group were given TAF antiviral therapy, and those in the control group were given ETV treatment; the course of treatment was 24 weeks for both groups. The two groups were compared in terms of HBV-DNA clearance rate, HBeAg clearance rate, alanine aminotransferase (ALT) level, estimated glomerular filtration rate (eGFR), FIB-4 value, liver stiffness measurement, and adverse drug reactions after treatment. The t -test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. Results After 24 weeks of treatment, compared with the control group, the experimental group had significantly higher HBV DNA clearance rate (96.25% vs 16.25%, χ 2 =104.03, P < 0.001) and HBeAg clearance rate (34.78% vs 11.90%, χ 2 =6.32, P < 0.05). Compared with the control group, the experimental group had varying degrees of improvement in ALT, eGFR, FIB-4, and liver stiffness measurement ( t =5.77, 4.21, 8.45, and 4.58, all P < 0.05), and there was no significant difference in the incidence rate of adverse drug reactions between the control group and the experimental group during treatment (7.50% vs 8.75%, P > 0.05). Conclusion For CHB patients with LLV after ETV treatment, the change to TAF antiviral therapy can effectively increase their HBV DNA clearance rate and HBeAg clearance rate, improve liver and renal function, and reduce the degree of liver fibrosis, with good safety.