OBJECTIVE To provide references for ensuring the safety of prescription preparation， dispensing， and use of parenteral nutrition solution， as well as for expanding the scope of pharmaceutical services provided by pharmacists in the Pharmacy Intravenous Admixture Services （PIVAS）. METHODS Under the guidance of PIVAS pharmacists， the rules for reviewing medical orders of parenteral nutrition in the PIVAS system and the information displayed on the infusion labels of finished parenteral nutrition solutions were refined. The process management of dispensing parenteral nutrition solution was strengthened， and detailed quality control and inspection rules were formulated. Additionally， Clinical Safety Monitoring Form for Finished Parenteral Nutrition Infusions was designed to conduct clinical monitoring and inspections for abnormalities in the finished infusions， infusion operations， and complications that may arise during the use of finished parenteral nutrition infusions. The implementation effects of the aforementioned optimization/inspection measures were evaluated by comparing data on the efficiency of medical order review for parenteral nutrition， the rate of irrational medical orders， the compliance rate of vascular access selection and infusion rate standardization， the rate of dispensing error， as well as the abnormalities occurring during clinical use， before and after the optimization/inspection initiatives were put into place. RESULTS The optimized prescription review system achieved automatic review of medical orders for parenteral nutrition， enhancing the efficiency of order review. The average time taken to review one parenteral nutrition medical order was reduced from approximately 1 minute to 10 seconds. The irrational rate of parenteral nutrition orders decreased by 31.87%. The dispensing error rate of parenteral nutrition decreased by 56.55%. The standard rate of vascular access selection and standard rate of infusion speed were increased by 13.29% and 3.54%， respectively. The PIVAS pharmacists identified and intervened in 5 abnormal cases out of 298 cases examined for use of parenteral nutrition solutions. CONCLUSIONS By optimizing the prescription review system， improving labeling information， and strengthening quality control inspections during both preparation and administration processes， PIVAS pharmacists have enhanced the safety of compounded parenteral nutrition solutions. This initiative has expanded the scope and depth of pharmaceutical care provided by dispensing pharmacists.

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.

BACKGROUND:Semen cuscutae has the effect of tonifying the liver and kidney system and benefiting the essence.The main pathogenesis of osteoarthritis is deficiency of the liver and kidneys.Therefore,it is hypothesized that there is a link between semen cuscutae and osteoarthritis. OBJECTIVE:To explore the potential relationship between osteoarthritis and semen cuscutae and validate the mechanism of semen cuscutae based on the network pharmacology and molecular docking analysis. METHODS:First,the active ingredients and targets of semen cuscutae were screened in TCMSP,and the genes related to osteoarthritis were collected in the disease databases GeneCard's,OMIM and TTD.The intersected genes were taken and then subjected to a series of analyses and screened for hub genes.Through the enrichment analysis of hub genes,the pathway of semen cuscutae acting on osteoarthritis was selected.The role of hub genes was verified by molecular docking.Therefore,the appropriate active ingredients of semen cuscutae were selected for experimental verification. RESULTS AND CONCLUSION:There were 11 active ingredients of semen cuscutae,66 intersection target genes of semen cuscutae and osteoarthritis,and 12 hub genes,including tumor necrosis factor,interleukin 1B,TP53,RAC-alpha serine/threonine protein kinase(AKT1),vascular endothelial growth factor A,matrix metalloproteinase 9,prostaglandin peroxidase 2,cystatinase 3,epidermal growth factor,peroxisome proliferator-activated receptor gamma,interleukin 10,vascular cell adhesion factor 1.After the enrichment analysis of the hub genes,the classical inflammatory pathway,nuclear factor-κB signaling pathway,was selected for subsequent validation of semen cuscutae to alleviate osteoarthritic inflammation.Through the results obtained after molecular docking of each active ingredient and the hub gene of the pathway prostaglandin peroxidase 2,sesamin with the highest affinity was selected for subsequent cell experiments,and the experimental results confirmed that sesamin,the active ingredient of semen cuscutae,could reduce the expression of cyclooxygenase 2 by inhibiting the nuclear factor-κB signaling pathway induced by interleukin-1β.To conclude,sesamin,the active ingredient of semen cuscutae,reduces the expression of cyclooxygenase 2 by inhibiting the nuclear factor-κB signaling pathway induced by interleukin-1β,thereby improving inflammation in osteoarthritis and expanding the therapeutic effect of semen cuscutae in osteoarthritis.

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 analyze the clinical manifestations, pathology, and gene variant characteristics in children with progressive familial intrahepatic cholestasis type 3 (PFIC3).Methods:This retrospective study assessed the clinical manifestations, pathological features, gene variants, and prognosis data of 11 children with PFIC3 hospitalized in the Department of Hepatology, Fifth Medical Center, PLA General Hospital, from January 2015 to December 2022. Panel or whole exome sequencing was performed on the probands, followed by Sanger sequencing for verification within the family. Detected pathogenic variants were compared with known disease databases. Additionally, the new variants were predicted the deleteriousness and protein structure using relevant software to evaluate their pathogenicity.Results:Among the 11 PFIC3 children, 8 were boys and 3 were girls. The age of onset was 3.1 (0.2, 15.6) years. The main complaint of onset was different in the 11 patients;5 of them were abnormal liver function, 3 of them were liver and spleen enlargement, 2 of them were abdominal distension, and 1 of them was jaundice. Alanine aminotransferase, asparate aminotransferase and γ-glutamyltransferase increased in all the patients, which were(113±40), (150±44) and (270±156) U/L respectively. Moreover, direct bilirubin increased in 9 patients, and cholestasis was showed in 8 patients. All patients showed liver fibrosis on imaging, and 8 patients had cirrhosis. The pathological features of 8 cases by liver biopsy were as follows: 8 cases of fibrosis in the portal area, 7 cases of small bile duct hyperplasia, 4 cases of positive copper staining, and 5 cases of cirrhosis. A total of 17 ABCB4 gene variants were detected, including 9 new variants: c.589C>T(p.Q197X), c.1230+1G>A(Splicing), c.2914G>A(P.D972N), c.1058G>A(p.C353Y), c.956G>T(p.G319V), c.473T>A(p.L158Q), c.164T>C(p.L55S), c.2493G>C(p.R831S), and c.1150G>C(p.G384R). All 11 patients were treated with ursodeoxycholic acid and followed up for 5.1(0.6, 7.4) years. Among them, 4 cases of cirrhosis progressed continuously, 3 cases had liver transplantations, and the remaining 4 cases were stable after medical treatment.Conclusions:Children with PFIC3 have early onset, diverse clinical manifestations, rapid progression of fibrotic and cholestasis, as well as poor prognosis. Genetic testing helps to confirm the diagnosis.

China prospective multicenter birth cohort (Prospective Omics Health Atlas birth cohort, POHA birth cohort) study was officially launched in 2022. This study, in collaboration with 12 participating units, aims to establish a high-quality, multidimensional cohort comprising 20 000 naturally conceived families and assisted reproductive families. The study involves long-term follow-up of parents and offspring, with corresponding biological samples collected at key time points. Through multi-omics testing and analysis, the study aims to conduct multi-omics big data research across the entire maternal and infant life cycle. The goal is to identify new biomarkers for maternal and infant diseases and provide scientific evidence for risk prediction related to maternal diseases and neonatal health.

Common iliac artery ureteral fistula is a rare but potentially life-threatening disease which is difficult to diagnose clinically. This paper reports a case of common iliac artery ureteral fistula. The patient was admitted to our hospital due to ureterostomy bleeding for one day. He underwent radical cystectomy and bilateral ureterostomy for bladder cancer 4 years ago, and also underwent radiotherapy and bilateral ureteral stents indwelling after the operation. Angiography revealed a left common iliac artery pseudoaneurysm, and a left common iliac artery ureteral fistula was considered. The left common iliac artery stent-graft was implanted. The patient recovered well after the operation, and there was no obvious hematuria during follow-up period of 6 months.

Objective     To systematically evaluate the safety and efficacy of percutaneous closure of atrial septal defect (ASD) guided by echocardiography alone versus fluoroscopy. Methods     The databases of PubMed, The Cochrane Library, EMbase, VIP, Wanfang Data and CNKI from January 2000 to October 2021 were searched by computer for relevant research literature. Two reviewers independently screened the literature, extracted the data and evaluated the quality according to the inclusion and exclusion criteria. Meta-analysis was performed using RevMan 5.4 software. Results     A total of 19 cohort studies and 1 randomized controlled study were collected, including 2 825 patients. The Newcastle-Ottawa Scale score for cohort studies was≥7 points. Meta-analysis showed that there was no statistical difference in the operative success rate (RR=1.01, 95%CI 1.00 to 1.02, P=0.17), incidence of occluder displacement/shedding (RR=0.77, 95%CI 0.26 to 2.27, P=0.63), incidence of arrhythmia (RR=0.50, 95%CI 0.21 to 1.14, P=0.10), incidence of pericardial effusion (RR=0.98, 95%CI 0.32 to 2.98, P=0.97), operative time (MD=–0.23, 95%CI –7.56 to 7.10, P=0.95) or cost (SMD=–0.39, 95%CI –1.09 to 0.30, P=0.27) between the two groups. The echocardiography group reduced the incidence of total postoperative complications (RR=0.42, 95%CI 0.30 to 0.60, P<0.001) and residual shunt (RR=0.70, 95%CI 0.50 to 0.98, P=0.04), and shortened length of hospital stay (MD=–0.43, 95%CI –0.77 to 0.09, P=0.01). Conclusion     Compared with traditional fluoroscopy-guided percutaneous closure of ASD, echocardiography guidance alone is equivalent in terms of operative success rate, major postoperative complications, operative time and total cost, but it reduces the incidence of total postoperative complications and residual shunt, and has a shorter length of hospital stay.

The glucose metabolism is crucial for sustained brain activity as it provides energy and is a carbon source for multiple biomacromolecules; glucose metabolism decreases dramatically in Alzheimer’s disease (AD) and may be a fundamental cause for its development. Recent studies reveal that the alternative splicing events of certain genes effectively regulate several processes in glucose metabolism including insulin receptor, insulin-degrading enzyme, pyruvate kinase M, receptor for advanced glycation endproducts, and others, thereby, influencing glucose uptake, glycolysis, and advanced glycation end-products-mediated signaling pathways. Indeed, the discovery of aberrant alternative splicing that changes the proteomic diversity and protein activity in glucose metabolism has been pivotal in our understanding of AD development. In this review, we summarize the alternative splicing events of the glucose metabolism-related genes in AD pathology and highlight the crucial regulatory roles of splicing factors in the alternative splicing process. We also discuss the emerging therapeutic approaches for targeting splicing factors for AD treatment.

Chest trauma is one of the most common injuries. Venous thromboembolism (VTE) as a common complication of chest trauma seriously affects the quality of patients′ life and even leads to death. Although there are some consensus and guidelines on the prevention and treatment of VTE at home and abroad, the current literatures lack specificity considering the diagnosis, treatment and prevention of VTE in patients with chest trauma have their own characteristics, especially for those with blunt trauma. Accordingly, China Chest Injury Research Society and editorial board of Chinese Journal of Traumatology organized relevant domestic experts to jointly formulate the Chinese expert consensus on the diagnosis, treatment and prevention of chest trauma venous thromboembolism associated with chest trauma (2022 version). This consensus provides expert recommendations of different levels as academic guidance in terms of the characteristics, clinical manifestations, risk assessment, diagnosis, treatment, and prevention of chest trauma-related VTE, so as to offer a reference for clinical application.