Amino acids are essential nutrients for the survival of all cells in the body,and their metabolic processes are closely associ-ated with tumor development and progression.The metabolic changes of the essential amino acid tryptophan have a significance impact on tumor microenvironment.Tryptophan is mainly metabolized to kynurenine(KYN)by indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase,and the accumulation of KYN and the deficiency of tryptophan cause alterations in the immune status in tumor micro-environment,which in turn affects tumor development and progression.Based on the current studies on tryptophan,this article system-atically discusses the influence of abnormal tryptophan metabolism on tumors and the interventions targeting this pathway,in order to provide a reference for subsequent tumor therapy.

Tumor microenvironment(TME)is the cellular environment for tumor development,growth,and metastasis.Adenosine(ADO)is an immunosuppressive metabolic product that is continuously upregulated in TME,with various types and wide distribution of receptors.The complex and dynamic interactions between ADO and tumor cells constantly influence tumor progression.ADO can di-rectly or indirectly promote tumor development and progression by promoting tumor generation and metastasis,mediating the immune escape of tumor,and modulating tumor-infiltrating immune cells.Based on the characteristics of ADOs in TME,this article reviews the latest advances in the dynamic alterations of ADO in TME,in order to provide insights into tumor treatment targeting the ADO pathway.

Cholesterol,as an important component of cell membranes,plays a multifaceted role in mediating tumor immunomodulation and drug intervention.In case of cholesterol metabolic imbalance,the accumulation of cholesterol metabolic intermediates,the changes in concentrations,and the regulation of related signaling pathways can affect tumor immunity by promoting inflammation and inhibiting immune cell function.Preclinical and clinical studies have shown that controlling cholesterol metabolism can inhibit tumor growth,re-shape body immune regulation,and enhance antitumor immunity.A deep understanding of the association between immune cells and cholesterol metabolic pathways in the tumor microenvironment can help to develop novel drugs targeting cholesterol metabolism.This article reviews the multifaceted role of cholesterol and its derived metabolites in the tumor microenvironment by regulating various types of immune cells such as myeloid-derived suppressor cells,tumor-associated macrophages,dendritic cells,and T-lymphocytes,as well as the characteristics of tumor immunomodulation mediated by cholesterol metabolism and the advances in pharmaceutical re-search on improving the immune function of the body by intervening against cholesterol,in order to further provide new ideas and a thera-peutic basis for cholesterol modulation and intervention in tumor im-munotherapy.

Objective:Quantified MRCP imaging data was used as a reference for design and preparation of a modified percutaneous transhepatic cholangio drainage (PTCD) tube.Methods:3.0 T upper abdominal MR and MRCP imaging data of 2 300 patients treated from July 2015 to July 2020 at the Department of Radiology of the Affiliated Cancer Hospital of Zhengzhou University were screened and a total of 381 patients diagnosed with biliary duct structures were identified. Causative etiologies among these patients included pancreatic adenocarcinoma (pancreatic head), cholangiocarcinoma, ampullary carcinoma, as well as intrahepatic and/or extrahepatic bile duct dilation. An improved PTCD tube was designed based on MRCP quantification of left and right hepatic and common hepatic duct length.Results:In the setting of biliary obstruction caused by malignancy, the distance of the left hepatic duct from its origin to the point of left and right hepatic duct confluence was 15.9±3.8 mm, while the distance of the right hepatic duct from its origin to the point of left and right hepatic duct confluence was 12.4±3.2 mm; the length of the bile duct from its origin to the point of left and right hepatic duct confluence was 34.0±8.1 mm. The improved PTCD tube design incorporated an altered length of the drainage orifice.Conclusion:MRCP imaging of the biliary tract is effective for measuring biliary tract length in the setting of pathological dilation. Based on our biliary tract measurements, a modified PTCD tube was designed to more effectively meet drainage requirements and manage biliary obstruction caused by Bismuth-Corlette type Ⅱ and Ⅲ malignancies.

Background: Gout is the most prevalent form of inflammatory arthritis in the world. Total hip arthroplasty (THA) has emerged as a widely sought-after and highly effective surgical procedure for advanced hip diseases. However, there is a lack of research on the impact of gout on primary THA outcomes in large cohorts. This study aimed to address this gap by primarily investigating complications following THA in patients with or without gout. Methods: Patients with records of gout in the 2 years leading up to their primary THA and who also have at least 2 years of follow-up were identified using a national insurance database and compared to a 5:1 matched control. A total of 32,466 patients with gout and 161,514 patients without gout undergoing THA were identified. Multivariable logistic regression analyses were done for medical complications up to 90 days and surgical complications up to 2 years. In addition, 90-day emergency department (ED) visits and inpatient readmission were also documented. Results: Patients with gout demonstrated higher rates of medical complications including deep vein thrombosis, transfusion, acute kidney injury, and urinary tract infection than non-gout patients (p < 0.001). Gout patients also showed higher rates of pulmonary embolism (p = 0.017). Increased incidences of surgical complications were identified in gout patients, specifically wound complications and periprosthetic joint infection (p < 0.001). There was an increased risk of revision for gout patients up to 90 days (p = 0.003), 1 year (p = 0.027), and 2 years (p = 0.039). There was also an increased risk of dislocation for gout patients up to 90 days (p = 0.022) and 1 year (p = 0.047), but not at 2 years. No significant difference was observed in aseptic loosening or periprosthetic fracture. Additionally, gout patients also demonstrated a higher likelihood of 90-day ED visits and readmission (p < 0.001). Conclusions Primary THA in gout patients is associated with increased risks of multiple medical and surgical complications. Our findings provide insights into the planning and expectation of THA for patients with gout. These insights have the potential to benefit the decision-making process for gout patients considering THA.

Background: While it is known that patients with end-stage renal disease (ESRD) are at an increased risk of complications following total hip arthroplasty (THA), there is a gap in the literature in comparing patients with ESRD to patients who undergo renal transplant (RT) before or after THA. This study is to address this gap by analyzing outcomes of THA in ESRD patients, RT patients, and RT candidates. Methods: Using the PearlDiver Mariner database, ESRD patients, RT patients, and RT candidates undergoing primary THA were identified and compared. Multivariable logistic regression analyses were done for medical complications up to 90 days and surgical complications up to 2 years. Ninety-day emergency department (ED) visits and inpatient readmission were also documented. Results: A total of 7,868 patients were included: 5,092 had ESRD, 2,520 had RT before THA, and 256 were candidates for RT. Compared to patients with ESRD, RT patients demonstrated lower rates of medical complications such as pneumonia (3.61% vs. 5.99%, p = 0.039) and transfusion (4.60% vs. 7.66%, p < 0.001). Additionally, RT patients displayed decreased rates of surgical complications, including wound complications (2.70% vs. 4.22%, p = 0.001), periprosthetic joint infection (PJI) at 1 year (2.30% vs. 4.81%, p < 0.001) and 2 years (2.58% vs. 5.42%, p < 0.001), and aseptic loosening at 2 years (0.79% vs. 1.43%, p = 0.006). Similarly, when compared to RT candidates, RT patients demonstrated a lower incidence of postoperative complications, including 1-year PJI (2.30% vs. 5.08%, p = 0.013), 2-year PJI (2.58% vs. 5.08%, p = 0.028), 1-year aseptic loosening (0.56% vs. 2.73%, p < 0.001), and 2-year aseptic loosening (0.79% vs. 2.73%, p = 0.005). RT patients also had lower rates of ED visits and hospital readmissions. Conclusions Compared to ESRD patients and RT candidates, patients with RT have a significantly lower likelihood of medical complications, PJI, aseptic hardware loosening, ED visits, and hospital readmission. Patients with ESRD on the RT waiting list should delay THA until after RT surgery. For those not eligible for RT, it is vital to take extra precautions to reduce the risk of complications.

Objective : To study the neuropathological changes and process brain astrocyte microglia and neuron injury in rats at different time after mild blast-related traumatic brain injury(bTBI), and to investigate the neuroprotective potential of dietary supplementation with fish oil on mild bTBI rats. Methods : 54 newly weaned SD rats were randomly divided into control group(n=18), model group(n=18) and treatment group(n=18). The model group and treatment group were fed with ordinary diet and oil-rich diet for 33 days to establish the mild bTBI model by shock wave, respectively. The control group rats were fed with ordinary diet without shock wave injury. Results : Compared with control group, the weight of rats in the model group and treatment group decreased to a certain extent within 2 days after injury, and then recovered to the level before injury. After bTBI injury for 6 h, 24 h and 3 d, the number of GFAP positive staining astrocytes and vertebral cells in hippocampal area decreased in both model group and treatment group, whereas the number of activated microglia and apoptotic neurons in the hippocampus increased in a time-dependent manner in model group and treatment group. In addition, compared with the model group, the treatment group with oil-rich diet increased the number of astrocytes and pyramidal cells in the hippocampus after injury, and decreased the number of activated microglia and apoptotic neurons in the lesions area. Conclusion Pre-injury dietary supplementation with fish oil shows neuroprotective benefits in alleviating neurons injury and inhibiting neuroinflammatory response in a rat model of mild bTBI.

OBJECT IVE To analyze the situation of comprehensive drug evaluation research in China. METHODS Using the method of bibliometrics ，CiteSpace 5.8.R3 analysis tool was used to summarize the research situation and hotspots from 6 dimensions，such as safety ，effectiveness，economy，innovation，suitability and accessibility. RESULTS & CONCLUSIONS At present，there were many types of researches on safety and effectiveness. The economic evaluation was increasing. There were still not much researches on the comprehensive evaluation of drugs from 6 dimensions. Researchers were concentrated ，and there was less collaboration between researchers or research institutions. In terms of methods ，systematic review ，meta-analysis，clinical observational research and retrospective research were more common. The topic selection of antibacterial drugs ，anti-tumor drugs ， and cardiovascular drugs were more popular. It is recommended to establish a unified method and standard for clinical comprehensive evaluation of drugs ，clarify the coordination medianism of the comprehensive drug evaluation ，make full use of real-world data to enrich the contents of 6 dimensions，implement quality control for all segments of the evaluation ，and form a comprehensive evaluation report with sufficient evidence and definite results ，so as to promote the clinical application of the results.

Objective:Study on the feature of thrombin-antithrombin complex (TAT) during traumatic brain injury and the predicting performance with adverse clinical outcomes.Methods:From January 2018 to December 2019, 147 patients with traumatic brain injury(TBI) were enrolled, including 112 males and 35 females, aged 36 (26-48) years old. The plasma levels of TAT were detected on the 0th, 1st, 3rd and 7th day after TBI attack. Kruskal-Wallis H test was used for comparison among multiple groups; Mann-Whitney U test was used for data comparison between the two groups; continuous comparison of patient data in the same group using Friedman rank test; the diagnostic performance of TAT with adverse event risk predicting was evaluated by ROC analysis; Kaplan-Meier curve was used to analyze the survival curve; the risk ratio (HR) was obtained by Cox proportional hazard regression model.Results:Among the patients groups with mild, moderate and severe phenotype, the TAT levels were gradually decreased on the 0th, 1st, 3rd and 7th day after TBI attack(χ 2 values were 95.612, 133.555, and 132.453, respectively, all P values<0.001). The TAT levels on the 0th, 1st, 3rd and 7th day in the adverse event group were higher than in the group of patients with stable condition ( U values were 959.0, 321.0, 36.0 and 1.0 respectively, all P values<0.001). In the stable condition group, the TAT levels on the 0th and 1st day in the severe group were higher than in the mild group ( U values were 0 and 1.0 respectively, both P values<0.001), while there was no statistically significant difference of TAT levels between the 3rd and 7th day in the severe group ( U values were 342.5 and 272.5, P values were 0.486 and 0.065 respectively). The TAT levels of the moderate group on 0th and 1st day were higher than those of the mild group ( U values were 0 and 280.0, respectively, both P<0.001), while there was no significant difference between the TAT levels on the 3rd and 7th day ( U values were 628.0 and 647.0, P values were 0.826 and 0.996, respectively). ROC curves analysis showed that when the TAT diagnostic thresholds were 68.75 ng/ml, 29.05 ng/ml, 17.25 ng/ml and 13.85 ng/ml on the 0th, 1st, 3rd and 7th day, the diagnostic sensitivities of predicting adverse events were 86.8%, 94.3%, 100% and 100%; while the diagnostic specificities were 71.3%, 78.7%, 91.5% and 96.8%, respectively. Survival analysis showed that the cumulative probability of adverse outcomes was significantly higher in patients above the critical value. Cox analysis showed that the HR on the 0th, 1st, 3rd and 7th day to predict adverse clinical outcomes by TAT levels were 1.818, 2.257, 3.526 and 4.813, respectively ( P value<0.001). Conclusion:There was strong relationship between the plasma TAT level and the severity of the patient′s condition, and persistent increasing with TAT level could reflect the risk of adverse events, which could be used as an effective index to comprehensively predicting the development tendency of the TBI patient′s condition.

Mitochondrial diseases are maternally inherited heterogeneous disorders that are primarily caused by mitochondrial DNA (mtDNA) mutations. Depending on the ratio of mutant to wild-type mtDNA, known as heteroplasmy, mitochondrial defects can result in a wide spectrum of clinical manifestations. Mitochondria-targeted endonucleases provide an alternative avenue for treating mitochondrial disorders via targeted destruction of the mutant mtDNA and induction of heteroplasmic shifting. Here, we generated mitochondrial disease patient-specific induced pluripotent stem cells (MiPSCs) that harbored a high proportion of m.3243A>G mtDNA mutations and caused mitochondrial encephalomyopathy and stroke-like episodes (MELAS). We engineered mitochondrial-targeted transcription activator-like effector nucleases (mitoTALENs) and successfully eliminated the m.3243A>G mutation in MiPSCs. Off-target mutagenesis was not detected in the targeted MiPSC clones. Utilizing a dual fluorescence iPSC reporter cell line expressing a 3243G mutant mtDNA sequence in the nuclear genome, mitoTALENs displayed a significantly limited ability to target the nuclear genome compared with nuclear-localized TALENs. Moreover, genetically rescued MiPSCs displayed normal mitochondrial respiration and energy production. Moreover, neuronal progenitor cells differentiated from the rescued MiPSCs also demonstrated normal metabolic profiles. Furthermore, we successfully achieved reduction in the human m.3243A>G mtDNA mutation in porcine oocytes via injection of mitoTALEN mRNA. Our study shows the great potential for using mitoTALENs for specific targeting of mutant mtDNA both in iPSCs and mammalian oocytes, which not only provides a new avenue for studying mitochondrial biology and disease but also suggests a potential therapeutic approach for the treatment of mitochondrial disease, as well as the prevention of germline transmission of mutant mtDNA.
Animals ; DNA, Mitochondrial ; genetics ; Humans ; Induced Pluripotent Stem Cells ; cytology ; metabolism ; MELAS Syndrome ; genetics ; Male ; Mice ; Microsatellite Repeats ; genetics ; Mitochondria ; genetics ; metabolism ; Mutation ; genetics