ObjectiveTo evaluate the clinical efficacy of Huayu Tongluo Formula （化瘀通络方， HTF） in patients with mid-stage diabetic kidney disease of blood stasis syndrome and explore its potential mechanisms. MethodsA multi-center， randomized， double-blind， placebo-controlled clinical trial was conducted. Ninety patients of mid-stage diabetic kidney disease of blood stasis syndrome were divided into a control group of 46 cases and a treatment group of 44 cases. Both groups received conventional western medicine treatment， the treatment group additionally taking HTF， while the control group taking a placebo of the formula. The treatment was administered once daily for 24 weeks. The primary outcomes included 24-hour urine total protein （24 h-UTP）， serum albumin （Alb）， glycated hemoglobin （HbA1c）， and serum creatinine （Scr）.The secondary outcomes included changes in levels of endothelin-1 （ET-1）， nitric oxide （NO）， vascular endothelial growth factor （VEGF）， and traditional Chinese medicine （TCM） syndrome scores before and after treatment. Clinical efficacy was evaluated based on TCM syndrome scores and overall disease outcomes. Adverse reactions and endpoint events were recorded. ResultsIn the treatment group after treatment， 24 h-UTP， ET-1， and VEGF levels significantly decreased （P＜0.05）， Alb and NO levels significantly increased （P＜0.05）； while the TCM syndrome scores for edema， lumbar pain， numbness of limbs， dark purple lips， dark purple tongue or purpura， and thin， rough pulse all significantly decreased （P＜0.05）. In the control group， no significant changes were observed in any of the indicators after treatment （P＞0.05）.Compared with the control group， the treatment group showed significant reductions in 24 h-UTP， ET-1， and VEGF levels， and increases in Alb and NO levels （P＜0.05）. The TCM syndrome scores for edema， lumbar pain， dark purple tongue or purpura， and thin， rough pulse were all lower in the treatment group than in the control group （P＜0.05）. The total effective rate of TCM syndrome in the treatment group was 59.09% （26/44）， and the overall clinical effective rate was 45.45% （20/44）. In the control group， these rates were 15.22% （7/46） and 8.7% （4/46）， respectively， with the treatment group showing significantly better outcomes （P＜0.05）. A total of 7 adverse events occurred across both groups， with no significant difference （P＞0.05）. No endpoint events occurred during the study. ConclusionOn the basis of conventional treatment of Western medicine， HTF can further reduce urinary protein levels and improve clinical symptoms in patients with mid-stage diabetic kidney disease of blood stasis syndrome. The mechanism may be related to its effects on endothelial function.

【Objective】 To statistically analyze the relationship between homologous recombination repair deficiency (HRD) score and clinicopathological characteristics, genomic mutations in patients with high-risk and metastatic hormone-sensitive prostate cancer (mHSPC) and the prognostic predictive value in mHSPC. 【Methods】 A total of 127 patients diagnosed with high-risk prostate cancer and mHSPC, treated at the Department of Urology of Chinese PLA General Hospital during Dec.2021 and Nov.2023 were enrolled.Homologous recombination repair (HRR) gene sequencing was performed, and the genomic scar score (GSS) algorithm were conducted to calculate the HRD score.The relationship between HRD scores and clinicopathological features, genomic alterations, and prognosis were analyzed. 【Results】 The median HRD score was 1.6(0.8, 5.2), 30(23.6%) patients’ HRD scores ≥10, and 11(8.7%) patients’ HRD scores ≥20.Clinicopathological features, including ISUP classification ≥4 (P=0.044) and metastatic status (P=0.008) were associated with high HRD score.Patients with mutations in the BRCA, TP53 and MYC systems had significantly higher HRD score than those with wild-type genes (P<0.05).In mHSPC, the risk of biochemical recurrence was 12.836 times higher in patients with HRD score ≥20 than in those with <20 [OR:12.836 (1.332-124.623), P=0.028]. 【Conclusion】 Baseline HRD score was lower in patients with high-risk prostate cancer and mHSPC.Patients with high HRD score may have higher histological grading (ISUP≥4) and later clinical stage.Further investigation is needed to determine the threshold of HRD scores as biochemical markers suggestive of a poor prognosis.

Objective To investigate the liver disease phenotypes and clinical features of patients with different genotypes of Wilson's disease(WD).Methods A retrospective analysis was performed for 163 patients with WD who were diagnosed and underwent genetic testing in The Fifth Medical Center of Chinese PLA General Hospital from August 2008 to June 2023,and clinical manifestations,laboratory examination,pathological examination,imaging examination,and ATP7B genetic testing results were collected.According to ATP7B gene mutation,the patients were divided into groups as follows:R778L mutation group and non-R778L mutation group;P992L mutation group and non-P992L mutation group;truncation mutation group and non-truncation mutation group.Liver disease phenotypes and clinical features were analyzed for the patients with c.2333G>T/p.R778L mutation(R778L mutation),c.2975C>T/p.P992L mutation(P992L mutation),and truncation mutation of the ATP7B gene.The Mann-Whitney U test or the Kruskal-Wallis H test was used for comparison of continuous data between groups,and the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups.Results The 163 patients with WD had varying severities of liver disease phenotypes,among whom 121(74.23%)were diagnosed with chronic liver disease,36(22.09%)were diagnosed with decompensated cirrhosis,and 6(3.68%)were diagnosed with fulminant WD,and in addition,there were 5 patients(2 with chronic liver disease and 3 with decompensated cirrhosis)with neurological abnormalities.For the 163 patients with WD,R778L mutation(with an allele frequency of 28.2%)was the most common mutation in the ATP7B gene,followed by P992L mutation(with an allele frequency of 12.6%),and truncation mutation showed an allele frequency of 11.0%.There was no significant difference in the distribution of the three mutations across different liver disease phenotypes(P>0.05).The R778L mutation group had a significantly lower level of ceruloplasmin(CP)than the non-R778L mutation group[0.04(0.02-0.08)g/L vs 0.08(0.03-0.13)g/L,Z=-2.889,P=0.004].Compared with the non-P992L mutation group,the P992L mutation group had significantly higher levels of alanine aminotransferase[135.0(80.5-237.0)U/L vs 80.5(36.0-173.3)U/L,Z=2.684,P=0.007]and aspartate aminotransferase[121.4(77.0-195.0)U/L vs 84.0(39.0-123.3)U/L,Z=3.388,P<0.001].Compared with the non-truncation mutation group,the truncation mutation group had significantly lower levels of CP[0.03(0.02-0.08)g/L vs 0.06(0.03-0.11)g/L,Z=-3.136,P=0.002]and serum copper[3.20(2.15-5.00)mg/L vs 4.20(2.60-7.50)mg/L,Z=-2.296,P=0.025].Conclusion R778L mutation,P992L mutation and truncation mutation are not associated with liver disease phenotype in WD patients;however,R778L mutation is associated with a lower level of CP,P992L mutation is associated with higher levels of ALT and AST,and truncation mutation is associated with lower levels of CP and serum copper.

Objective To identify the key genes differentially expressed in Wilms tumor and analyze their potential impacts on prognosis and immune responses of the patients. Methods High-throughput RNA sequencing was used to identify the differentially expressed mRNAs in clinical samples of Wilms tumor and paired normal tissues, and their biological functions were analyzed using GO, KEGG and GSEA enrichment analyses. The hub genes were identified using STRING database, based on which a prognostic model was constructed using LASSO regression. The mutations of the key hub genes were analyzed and their impacts on immunotherapy efficacy was predicted using the cBioPortal platform. RT-qPCR was used to verify the differential expressions of the key hub genes in Wilms tumor. Results Of the 1612 differentially expressed genes identified in Wilms tumor, 1030 were up-regulated and 582 were down-regulated, involving mainly cell cycle processes and immune responses. Ten hub genes were identified, among which 4 genes (TP53, MED1, CCNB1 and EGF) were closely related to the survival of children with Wilms tumor. A 3-gene prognostic signature was constructed through LASSO regression analysis, and the patients stratified into with high- and low-risk groups based on this signature had significantly different survival outcomes (HR=1.814, log-rank P=0.002). The AUCs of the 3-, 5-and 7-year survival ROC curves of this model were all greater than 0.7. The overall mutations in the key hub genes or the individual mutations in TP53/CCNB1 were strongly correlated with a lower survival rates, and a high TP53 expression was correlated with a poor immunotherapy efficacy. RT-qPCR confirmed that the key hub genes had significant differential expressions in Wilms tumor tissues and cells. Conclusion TP53 gene plays an important role in the Wilms tumor and may potentially serve as a new immunotherapeutic biomarker as well as a therapeutic target.

OBJECTIVE To sort out drug prophylaxis regimens for venous thromboembolism （VTE） in adult patients after artificial joint replacement， and provide a basis for clinic. METHODS Databases and related official websites were searched according to the “6S” model， including the National Institute for Health and Clinical Excellence （NICE）， the Scottish Intercollegiate Guidelines Network （SIGN）， the Guidelines International Network （GIN）， the National Guidelines Clearinghouse （NGC）， PubMed， Embase， CNKI， Wanfang database and SinoMed， to search for guidelines， expert consensuses， systematic evaluations， randomized controlled trials， and cohort studies about preventing VTE in adult patients after artificial joint replacement from the inception until December 2023. Literature that met the inclusion criteria were selected， and the quality evaluation of the literature was completed by 2 researchers independently； the evidence rating was performed by using the Joanna Briggs Institute （JBI） evidence pre-classification and evidence rank system （2014 edition）. RESULTS A total of 36 articles were included in the study， which were categorized into 9 areas of risk assessment， post-assessment prophylaxis， medication selection， medication method， duration of medication prophylaxis， medication prophylaxis observation points， contraindications to drug prophylaxis， response to bleeding， and health education， which were summarized to form 37 pieces of evidence on the pharmacological prophylaxis for postoperative VTE in patients who underwent artificial joint replacement. CONCLUSIONS The evidence of drug prophylaxis for postoperative VTE in patients who underwent artificial joint replacement summarized in this study is comprehensive， with certain scientific reference and practicality， which can provide clinical pharmacists with a scientific evidence-based basis for perioperative VTE prophylaxis management.

Objective:To investigate the clinical manifestations, pathological, and gene mutation characteristics of ABCB4 gene variant-associated cholestatic liver disease in adults. Methods:Eight adult cases of ABCB4 gene variant-associated cholestatic liver disease who were hospitalized in the Department of Hepatology, Fifth Medical Center of the People's Liberation Army General Hospital from May 2010 to December 2022 were enrolled in this study. The clinical manifestations, pathological features, gene variant features, and prognostic conditions were analyzed. Patient gene testing and biological information analysis were performed using whole-exome next-generation sequencing. SPSS 19.0 software was used to conduct descriptive analysis. Results:Among the eight adult cases of the ABCB4 gene variant, there were three males and five females, with a median age of onset of 24 (20, 37) years. There were three cases with a compound heterozygous variant in ABCB4, and the clinical phenotypes included two cases of progressive familial intrahepatic cholestasis type 3 and one case of intrahepatic cholestasis of pregnancy overlapping with low-phospholipid-associated cholelithiasis syndrome. There were five cases with a single heterozygous variant in ABCB4, and the clinical phenotypes included two cases of intrahepatic cholestasis of pregnancy overlapping with drug-induced liver injury and three cases of low-phospholipid-associated cholelithiasis syndrome. Imaging of all eight cases showed liver fibrosis, and six cases already had cirrhosis. All patients underwent liver histopathological examination, which mainly showed cholestasis and portal fibrosis in eight cases, small bile duct hyperplasia in seven cases, copper deposition in three cases, and cirrhosis in five cases. ABCB4 screening revealed 11 different mutations, including eight new mutations. The pathogenicity assessment showed that c.2394+82C>T (intron) was a benign mutation, and the rest were deleterious mutations. Ursodeoxycholic acid was the treatment for all patients, with a follow-up time of 7.5 (0.5, 12.7) years. One case died of end-stage liver disease, two cases developed cholestatic cirrhosis, and five cases were in stable condition. Conclusion:The adult ABCB4 gene variant-associated cholestatic liver disease are mostly single heterozygous mutations, the clinical phenotypes are diverse and overlapping, the disease is more severe in those who carried non-functional mutations.

Objective To explore the relationship between the expression of Toll like receptor 4(TLR4)and Janus protein tyrosine kinase 3(JAK3)genes and the imbalance of helper T cell 17(Th17)/regulatory T cells(Treg)in peripheral blood mononuclear cells(PBMCs)of patients with ankylosing spondylitis(AS).Methods A total of 101 AS patients were selected as the AS group.According to the AS Disease Activity Index(BASDAI)score,patients were divided into the AS stable phase(ASS)group(＜4 points,42 cases)and the AS active phase(ASA)group(≥4 points,59 cases).Additionally,50 healthy volunteers who underwent physical examinations at our hospital during the same period were selected as the control group(health group).Real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)was used to determine the mRNA expression of TLR4 and JAK3 in PBMCs,and the proportion of serum Th17 and Treg was measured and Th17/Treg levels were calculated.Results The levels of TLR4 mRNA and JAK3 mRNA in PBMCs of peripheral blood were higher in the AS group than those in the health group(P＜0.05).The levels of Th17,proportion and Th17/Treg in peripheral blood were higher in the AS group than those of the health group(P＜0.05).Higher levels of TLR4 mRNA,JAK3 mRNA,Th17,and Th17/Treg were risk factors for AS,while higher level of Treg was protective factors for AS.TLR4 mRNA and JAK3 mRNA in AS patients were positively correlated with Th17 ratio and Th17/Treg ratio,and negatively correlated with Treg ratio(P＜0.05).Conclusion TLR4 and JAK3 genes are highly expressed and Th17/Treg is unbalanced in PBMC of AS patients.The high expression of TLR4 and JAK3 genes is closely related to Th17/Treg imbalance in AS patients.

In order to explore the effects of Coptis detoxification powder on immune suppression and inflammatory response caused by heat stress in animals,Bama pigs were used as experimental animals to establish an animal model of heat stress,and the effects of Coptis detoxification powder on transcriptional activation of TLRs mRNA in PBMC induced by heat stress and its mediated ex-pression of inflammatory factors were studied in vivo.The animal model of heat stress was estab-lished by artificial climate greenhouse,Chinese medicine"Coptis detoxification powder"was pre-pared,and its inhibitory effect on heat stress and inflammation was studied by preventive and therapeutic administration.Real-time fluorescence quantitative PCR was used to determine the transcriptional changes of HSP70,TLRs and IL-17 mRNA,and ELISA was used to determine the dynamic changes of serum IL-2,IL-6 and TNF-α.Western blot and indirect immunofluorescence(IFA)were used to determine the nuclear translocation and protein expression of p65 phosphoryl-ated protein in NF-κβ inflammatory factor pathway.The transcription of PBMC TLRs mRNA and its mediated inflammatory factor expression and function in Bama pigs under heat stress were sys-tematically analyzed.The results showed that the experimental animal model of Bama pigs under heat stress was successfully established,and heat stress significantly up-regulated the mRNA tran-scription levels of HSP70,TLR2,TLR4 and inflammatory factor IL-17,resulting in significantly enhanced expressions of serum inflammatory factors IL-2,IL-6 and TNF-α.The NF-κβ pathway significantly promoted the level of p65 nuclear phosphorylation and the expression of cytoplasmic protein.The Chinese medicine"Coptis detoxification powder"could significantly reduce the upreg-ulation effect of heat stress conditions on the transcription levels of HSP70 and TLRs mRNA,thus inhibiting the mRNA transcription of inflammatory factor IL-17 and the expression of IL-2,IL-6 and TNF-α in serum,and significantly antagonizing the transcriptional activity of NF-κβ caused by heat stress.It showed good anti-heat stress effect.The anti-inflammatory effects of Chinese veteri-nary medicine prescription"Coptis detoxification powder",its pathway of action and its effectors were investigated,the expression and secretion levels of the regulatory factors related to the path-way associated with TLRs mRNA inhibition were analyzed,and the functional effects and mecha-nism of its clinical anti-heat stress and anti-inflammatory effects were clarified,which laid a data foundation for the promotion and application of this prescription and related mechanism research.

Zi goose is a small local variety with high fecundity,good meat quality,roughage resist-ance,strong adaptability and excellent down quality.It is an excellent female parent for cross breeding among varieties.With the rapid development of goose industry,the variety of Zi goose has not been well protected,the variety is hybrid and degraded seriously,and the number of pure Zi goose is decreasing day by day.This paper reviewed the research progress on the breeding distribu-tion and preservation status of Zi goose and the variety characteristics of Zi goose,in order to pro-vide reference for the research,protection and utilization of germplasm resources of Zi goose and the stable development of goose industry.

Objective To identify the key genes differentially expressed in Wilms tumor and analyze their potential impacts on prognosis and immune responses of the patients. Methods High-throughput RNA sequencing was used to identify the differentially expressed mRNAs in clinical samples of Wilms tumor and paired normal tissues, and their biological functions were analyzed using GO, KEGG and GSEA enrichment analyses. The hub genes were identified using STRING database, based on which a prognostic model was constructed using LASSO regression. The mutations of the key hub genes were analyzed and their impacts on immunotherapy efficacy was predicted using the cBioPortal platform. RT-qPCR was used to verify the differential expressions of the key hub genes in Wilms tumor. Results Of the 1612 differentially expressed genes identified in Wilms tumor, 1030 were up-regulated and 582 were down-regulated, involving mainly cell cycle processes and immune responses. Ten hub genes were identified, among which 4 genes (TP53, MED1, CCNB1 and EGF) were closely related to the survival of children with Wilms tumor. A 3-gene prognostic signature was constructed through LASSO regression analysis, and the patients stratified into with high- and low-risk groups based on this signature had significantly different survival outcomes (HR=1.814, log-rank P=0.002). The AUCs of the 3-, 5-and 7-year survival ROC curves of this model were all greater than 0.7. The overall mutations in the key hub genes or the individual mutations in TP53/CCNB1 were strongly correlated with a lower survival rates, and a high TP53 expression was correlated with a poor immunotherapy efficacy. RT-qPCR confirmed that the key hub genes had significant differential expressions in Wilms tumor tissues and cells. Conclusion TP53 gene plays an important role in the Wilms tumor and may potentially serve as a new immunotherapeutic biomarker as well as a therapeutic target.