3D bioprinting of in vitro porous hepatoma models:establishment,evaluation,and anticancer drug testing

Traditional tumor models do not tend to accurately simulate tumor growth in vitro or enable personalized treatment and are particularly unable to discover more beneficial targeted drugs.To address this,this study describes the use of threedimensional(3D)bioprinting technology to construct a 3D model with human hepatocarcinoma SMMC-7721 cells(3DP-7721)by combining gelatin methacrylate(GelMA)and poly(ethylene oxide)(PEO)as two immiscible aqueous phases to form a bioink and innovatively applying fluorescent carbon quantum dots for long-term tracking of cells.The GelMA(10%,mass fraction)and PEO(1.6%,mass fraction)hydrogel with 3:1 volume ratio offered distinct pore-forming characteristics,satisfactorymechanical properties,and biocompatibility for the creation of the 3DP-7721 model.Immunofluorescence analysis and quantitative real-time fluorescence polymerase chain reaction(PCR)were used to evaluate the biological properties of the model.Compared with the two-dimensional culture cell model(2D-7721)and the 3D mixed culture cell model(3DM-7721),3DP-7721 significantly improved the proliferation of cells and expression of tumor-related proteins and genes.Moreover,we evaluated the differences between the three culture models and the effectiveness of antitumor drugs in the three models and discovered that the efficacy of antitumor drugs varied because of significant differences in resistance proteins and genes between the three models.In addition,the comparison of tumor formation in the three models found that the cells cultured by the 3DP-7721 model had strong tumorigenicity in nude mice.Immunohistochemical evaluation of the levels of biochemical indicators related to the formation of solid tumors showed that the 3DP-7721 model group exhibited pathological characteristics of malignant tumors,the generated solid tumors were similar to actual tumors,and the deterioration was higher.This research therefore acts as a foundation for the application of 3DP-7721 models in drug development research.

Prognostic effect of excessive chemotherapy cycles for stage Ⅱ and Ⅲ gastric cancer patients after D2 + gastrectomy

BACKGROUND According to relevant investigation and analysis,there are few research studies on the effect of excessive chemotherapy cycles after D2 gastrectomy on the survival of patients with gastric cancer.AIM To determine whether excessive chemotherapy cycles provide extra survival benefits,reduce recurrence rate,and improve survival rate in patients with stage Ⅱ or Ⅲ gastric cancer.METHODS We analyzed and summarized 412 patients with stage Ⅱ gastric cancer and 902 patients with stage Ⅲ gastric cancer who received D2 gastrectomy plus adjuvant chemotherapy or neoadjuvant chemotherapy.Analysis and comparison at a ratio of 1:1 is aimed at reducing realistic baseline differences(n=97 in each group of stage Ⅱ,n=242 in each group of stage Ⅲ).Progression-free survival,overall survival and recurrence were the main outcome indicators.RESULTS When the propensity score was matched,the baseline features of stage Ⅱ and Ⅲ gastric cancer patients were similar between the two groups.After a series of investigations,Kaplan-Meier found that the progression-free survival and overall survival of stage Ⅱ and Ⅲ gastric cancer patients were consistent between the two groups.The local metastasis rate(P=0.002),total recurrence rate(P<0.001)and distant metastasis rate(P=0.001)in the≥9 cycle group of stage Ⅲ gastric cancer were statistically lower than those in the<9 cycle group.The interaction analysis by Cox proportional hazard regression model showed that intestinal type,proximal gastrectomy,and≥6 cm maximum diameter of tumor had a higher risk of total mortality in the<9 cycles group.CONCLUSION Overall,≥9 chemotherapy cycles is not recommended for patients with stage Ⅱ and stage Ⅲ gastric cancer because it has an insignificant role in the prognosis of gastric cancer.However,for patients with stage Ⅲ gastric cancer,≥9 cycles of chemotherapy was shown to significantly decrease recurrence.

Prognostic significance of regional lymphadenectomy in T1b gallbladder cancer:Results from 24 hospitals in China

BACKGROUND Whether regional lymphadenectomy(RL)should be routinely performed in patients with T1b gallbladder cancer(GBC)remains a subject of debate.AIM To investigate whether RL can improve the prognosis of patients with T1b GBC.METHODS We studied a multicenter cohort of patients with T1b GBC who underwent surgery between 2008 and 2016 at 24 hospitals in 13 provinces in China.The logrank test and Cox proportional hazards model were used to compare the overall survival(OS)of patients who underwent cholecystectomy(Ch)+RL and those who underwent Ch only.To investigate whether combined hepatectomy(Hep)improved OS in T1b patients,we studied patients who underwent Ch+RL to compare the OS of patients who underwent combined Hep and patients who did not.RESULTS Of the 121 patients(aged 61.9±10.1 years),77(63.6%)underwent Ch+RL,and 44(36.4%)underwent Ch only.Seven(9.1%)patients in the Ch+RL group had lymph node metastasis.The 5-year OS rate was significantly higher in the Ch+RL group than in the Ch group(76.3%vs 56.8%,P=0.036).Multivariate analysis showed that Ch+RL was significantly associated with improved OS(hazard ratio:0.51;95%confidence interval:0.26-0.99).Among the 77 patients who underwent Ch+RL,no survival improvement was found in patients who underwent combined Hep(5-year OS rate:79.5%for combined Hep and 76.1%for no Hep;P=0.50).CONCLUSION T1b GBC patients who underwent Ch+RL had a better prognosis than those who underwent Ch.Hep+Ch showed no improvement in prognosis in T1b GBC patients.Although recommended by both the National Comprehensive Cancer Network and Chinese Medical Association guidelines,RL was only performed in 63.6%of T1b GBC patients.Routine Ch+RL should be advised in T1b GBC.

PD-1 antibody in combination with chemotherapy for the treatment of SMARCA4-deficient advanced undifferentiated carcinoma of the duodenum:Two case reports

BACKGROUND SMARCA4 is a component of chromatin remodeling of SWItch/sucrose-nonfermenting(SWI/SNF)complexes and plays an essential role in oncogenesis.SMARCA4-deficient malignancies arising from the gastrointestinal tract are rare and have a poor prognosis.There is no standard treatment for advanced and undifferentiated SMARCA4-deficient duodenal malignancies.Programmed death 1(PD-1)antibodies,known as immune checkpoint inhibitor antibodies,potentially play a role in treating gastrointestinal tract malignancies.CASE SUMMARY We present two patients with SMARCA4 deficiency and TP53 gene mutation in advanced undifferentiated carcinomas of the duodenum.For both patients,SMARCA4 deficiency was confirmed by immunohistochemical staining for the BRG1 protein,while TP53 gene mutations were observed via next-generation sequencing.Both patients were administered chemotherapy in combination with an anti-PD-1 antibody.The two patients exhibited completely different responses to treatment and had different prognoses.Case 1 experienced rapid progression after PD-1 infusion and chemotherapy,case 2 experienced a remarkable response after treatment,and the progression-free survival was more than 6 months.CONCLUSION This study described our clinical and pathological observations of SMARCA4-deficient advanced undifferentiated carcinoma of the duodenum.PD-1 combined with chemotherapy showed a certain efficacy in select patients,providing options for treating these highly malignant tumors.Patients with liver metastases had a worse prognosis than did those with only lymph node metastasis.

Risk Factors of Depression Screened by Two-Sample Mendelian Randomization Analysis:A Systematic Review

Objective This study explored the potentially modifiable factors for depression and major depressive disorder(MDD)from the MR-Base database and further evaluated the associations between drug targets with MDD.Methods We analyzed two-sample of Mendelian randomization(2SMR)using genetic variant depression(n=113,154)and MDD(n=208,811)from Genome-Wide Association Studies(GWAS).Separate calculations were performed with modifiable risk factors from MR-Base for 1,001 genomes.The MR analysis was performed by screening drug targets with MDD in the DrugBank database to explore the therapeutic targets for MDD.Inverse variance weighted(IVW),fixed-effect inverse variance weighted(FE-IVW),MR-Egger,weighted median,and weighted mode were used for complementary calculation.Results The potential causal relationship between modifiable risk factors and depression contained 459 results for depression and 424 for MDD.Also,the associations between drug targets and MDD showed that SLC6A4,GRIN2A,GRIN2C,SCN10A,and IL1B expression are associated with an increased risk of depression.In contrast,ADRB1,CHRNA3,HTR3A,GSTP1,and GABRG2 genes are candidate protective factors against depression.Conclusion This study identified the risk factors causally associated with depression and MDD,and estimated 10 drug targets with significant impact on MDD,providing essential information for formulating strategies to prevent and treat depression.

Possible roles of insulin, IGF-1 and IGFBPs in initiation and progression of colorectal cancer

AIM: To investigate the roles of serum insulin, insulinlike growth factor-1(IGF-1), and insulin-like growth factor binding proteins(IGFBPs) in the initiation and progression of colorectal cancer. METHODS: We determined serum insulin, IGF-1 and IGFBPs levels in 615 colorectal cancer patients and 650 control healthy donors by enzyme-linked immunosorbent assay(ELISA). In the meantime, their body mass index(BMI) and waist-to-hip ratio(WHR) were measured. RESULTS: Serum levels of insulin and IGF-1 as well as IGF-1/IGFBP-3 ratio in pre-operation patients were significantly elevated, but the level of IGFBP-3 was significantly decreased compared with normal controls and post-operation patients(P < 0.05 and P < 0.001,respectively). There is no significant difference(P > 0.05) in the levels of insulin, IGF-1, IGFBP-1, IGFBP-3 and IGF-1/IGFBP-3 between the patients with and without hepatic as well as distal abdominal metastases. WHR and BMI of colon cancer patients were positively and significantly correlated with the levels of insulin and IGF-1/IGFBP-3. In contrast, WHR and BMI were negatively correlated with IGFBP-3 level. CONCLUSION: The elevation of insulin, IGF-1 as well as IGF-1/IGFBP-3 ratio and the reduction of IGFBP-3 may be related to the initiation of colorectal cancer, but they are not related to the progression and outcome of the disease.

Non-anthracycline-containing docetaxel and cyclophosphamide regimen is associated with sustained worse outcome compared with docetaxel, anthracycline and cyclophosphamide in neoadjuvant treatment of triple negative and HER2-positive breast cancer patients:

Objective： A previous study demonstrated that non-anthracycline-containing docetaxel plus cyclophosphamide（TC） regimen was inferior to docetaxel, anthracycline and cyclophosphamide（TAC） in neoadjuvant treatment of triple-negative breast cancer（TNBC） and human epidermal growth factor receptor-2-（HER2）-positive breast cancer in a short-term follow-up. Herein, long-term follow-up survival outcomes have been investigated.Methods： TNBC or HER2-positive patients were randomized to receive 6 cycles of TC or TAC neoadjuvant treatment. The primary endpoint was pathological complete remission（p CR）. Secondary endpoints included clinical response rate, event-free survival（EFS）, and overall survival（OS）.Results： A cohort of 96 patients consisted of 45 in TC and 51 in TAC arm. With a median follow-up period of53（range, 8-76） months, the patients achieving p CR post neoadjuvant chemotherapy exhibited superior EFS and OS than patients without p CR（P〈0.05）. TAC treatment resulted in consistently better EFS than TC treatment：the estimated 5-year EFS was 66.1% vs. 29.8%（P=0.002）. Moreover, the estimated 5-year OS was also in favor of TAC： 88.4% vs. 51.6%（P〈0.001）. Multivariable analysis demonstrated that the treatment regimen was an independent prognostic factor, and patients treated with TAC had a superior EFS [hazard ratio（HR）, 0.48; 95%confidence interval（95% CI）, 0.26-0.90; P=0.021] and OS（HR, 0.20; 95% CI, 0.08-0.60; P=0.003）.Conclusions： The updated long-term follow-up data demonstrated a sustained benefit in EFS and OS from anthracycline-containing TAC treatment, indicating that anthracycline is an essential and effective drug in this clinical trial.

Treatment of advanced rectal cancer after renal transplantation

Renal transplantation is a standard procedure for endstage renal disease today. Due to immunosuppressive drugs and increasing survival time after renal transplantation, patients with transplanted kidneys carry an increased risk of developing malignant tumors. In this case report, 3 patients with advanced rectal cancer after renal transplantation for renal failure were treated with anterior resection or abdominoperineal resection plus total mesorectal excision, followed by adjuvant chemotherapy. One patient eventually died of metastasized cancer 31 mo after therapy, although his organ grafts functioned well until his death. The other 2 patients were well during the 8 and 21 mo followup periods after rectal resection. We therefore strongly argue that patients with advanced rectal cancer should receive standard oncology treatment, including operation and adjuvant treatment after renal transplantation. Colorectal cancer screening in such patients appears justified.

Immune signature profiling identified prognostic factors for gastric cancer

Objective: Tumor microenvironment, especially the host immune system, plays a pivotal role in tumor initiation and progression. Profiling of immune signature within tumor might uncover biomarkers for targeted therapies and clinical outcomes. However, systematic analysis of immune-related genes in gastric cancer(GC) has not been reported.Methods: Expressions of a total of 718 immune-related genes were generated in 372 stomach adenocarcinoma(STAD) patients from The Cancer Genome Atlas(TCGA) database using RNA-sequencing data. Integrated bioinformatics analyses were performed to identify prognostic factors as well.Results: Survival analyses revealed 73 genes, which were significantly associated with patient’s overall survival(OS). Taken together with clinicopathological parameters, we established a predictive model, containing 10 immune-related genes, which were NRP1, C6, CXCR4, LBP, PNMA1, TLR5, ITGA6, MICB, PBK and TNFRSF18,with powerful efficiency in distinguishing satisfactory or poor survival of STAD patients. Moreover, the top 3 ranked prognostic genes, NRP1, TGFβ2 and MFGE8, were also significantly associated with patient’s OS by an independent validation achieved from Kaplan-Meier plotter database.Conclusions: We profiled prognostic immune signature and established prognostic predictive model for GC,which could reflect immune disorders within tumor microenvironment, and also may provide novel predictive and therapeutic targets for GC patients in the near future.

Acute pulmonary embolism originating from upper limb venous thrombosis following breast cancer surgery:Two case reports

BACKGROUND Upper limb venous thrombosis(ULVT)is rarer than lower-extremity deep venous thrombosis,and is related to Paget-Schroetter syndrome,central venous catheterization,and malignancy.There are few reports of pulmonary embolism(PE)from upper-extremity vein thrombosis due to surgery.Herein,we report two cases of PE that originated from upper limb venous thrombosis on the surgical side in two patients undergoing modified radical mastectomy for breast cancer.These cases challenge the traditional theory that PE originate only from the lower extremities.CASE SUMMARY We describe two female patients,aged 68 and 65 years,respectively,who had undergone modified radical mastectomy for breast cancer.They did not have a central venous catheter and did not undergo preoperative neoadjuvant chemotherapy.They were transferred to the intensive care unit due to symptomatic PE on the first day after surgery.Colour Doppler ultrasound identified fresh thrombosis in their upper limb veins,which was the presumed source of the PE.They all received anticoagulation therapy,and one of them experienced bleeding that required discontinuation of the drug.Ultimately,they were discharged in stable condition.CONCLUSION ULVT as a source of PE after breast cancer surgery cannot be ignored.

The Effect of a Psycho-Educational Intervention on Quality of Life of Patients with Advanced Lung Cancer Undergoing Chemotherapy

Objective: Cancer patients undergoing chemotherapy commonly experience depression and anxiety, which, along with adverse effects of chemotherapy, inevitably compromise quality of life (QOL) of the patients. The aim of this study was to investigate the effect of a psycho-educational intervention on the quality of life (QOL) of patients with advanced lung cancer undergoing chemotherapy. Methods: Two hundred in-patients with unresectable advanced lung cancer undergoing chemotherapy in Shanxi Cancer Hospital from January to October 2013 were randomized into the intervention group (n = 100) and the control group (n = 100). Patients in the intervention group received a purposely designed and nurse-delivered psycho-educational intervention in addition to routine caring and chemotherapy, whereas those in the control group underwent chemotherapy and routine caring only. QOL of patients was assessed according to QOL instrument for lung cancer (QLICP-LU). The impact of the psycho-educational intervention on QOL was analyzed using independent-sample t test and χ2 test. Results: The psychological, physical, and social function, and the overall QOL scores were significantly improved in patients who received the psycho-educational intervention compared with those in the control group. Conclusions: A nurse-delivered psycho-educational intervention is a useful strategy to improve QOL of patients with advanced lung cancer undergoing chemotherapy.

Lynch syndrome pre-screening and comprehensive characterization in a multi-center large cohort of Chinese patients with colorectal cancer

Objective:Lynch syndrome(LS)pre-screening methods remain under-investigated in colorectal cancers(CRCs)in Asia.Here,we aimed to systematically investigate LS pre-screening and comprehensively characterize LS CRCs.Methods:Microsatellite instability(MSI)and germline variants of DNA mismatch repair(MMR)genes were examined in 406 deficient MMR(dMMR)and 250 proficient MMR CRCs.The genetic differences between LS and sporadic CRCs were studied with whole exome sequencing analysis.Results:The incidence of dMMR in Chinese patients with CRCs was 13.8%.Consistency analysis between MMR immunohistochemistry(IHC)and MSI testing showed the kappa value was 0.758.With next-generation sequencing(NGS),germline variants were detected in 154 CRCs.Finally,88 patients with CRC were identified as having LS by Sanger sequencing.Among them,we discovered 21 previously unreported pathogenic germline variants of MMR genes.Chinese patients with LS,compared with sporadic CRCs,tended to be early-onset,right-sided,early-stage and mucinous.Overall,the performance of MMR IHC and MSI testing for LS pre-screening was comparable:the area under the ROC curve for dMMR,MSI-H,and MSI-H/L was 0.725,0.750,and 0.745,respectively.dMMR_MSI-H LS and sporadic CRCs showed substantial differences in somatic genetic characteristics,including different variant frequencies of APC,CREBBP,and KRAS,as well as different enriched pathways of VEGF,Notch,TGFβR,mTOR,ErbB,and Rac protein signal transduction.Conclusions:MMR IHC and MSI testing were effective methods for LS pre-screening.The revealed clinical and somatic genetic characteristics in LS CRCs may have the potential to improve the performance of LS pre-screening in combination with dMMR/MSI.

Molecular mechanism of Turmeric in the treatment of liver cancer based on network pharmacology

Objective:The aim of this study was to use network pharmacology to predict the targets and related signaling pathways of turmeric in the treatment of liver cancer.Methods:The active ingredients of turmeric turmeric and their corresponding targets were screened and collected through the traditional Chinese medicine components and systematic Chinese medicine pharmacology database and analysis platform(TCMSP)database.Through the online human Mendelian network(OMIM),the human genome annotation database(Genecards)and the GAD database,the targets related to liver cancer were collected and compared with the targets corresponding to the drug components,the common parts were screened out to obtain the potential target genes that overlap between turmeric and liver cancer.Cytoscape was used to construct the"compound-target"action network,and the protein interaction(PPI)network was constructed through STRING software to screen the key components and key targets of turmeric for the treatment of liver cancer,and the GO enrichment and KEGG enrichment analysis were conducted on the key targets to analyze their potential mechanism of action.Results:There were 15 active components and 45 target genes in the treatment of liver cancer with turmeric turmeric,and the drug-component-target-disease network showed that the key genes mainly included:MAPK1,MAPK3,AKT1,JUN,RELA,BCL2,CASP8,ESR1,ADRB2,etc.GO functional enrichment showed that biological processes and functions were concentrated in cofactor binding,phosphatase binding,amide binding,g-protein-coupled amide receptor activity,antioxidant activity,steroid activity,nuclear receptor activity,transcription factor activity,direct ligand regulation of sequence-specific DNA binding,and steroid hormone receptor activity.KEGG functional enrichment showed that the enriched pathways mainly included hepatitis b,human immunodeficiency virus 1 infection,apoptosis,hepatitis c and some cancer signaling pathways.Conclusion:The role of turmeric in the treatment of liver cancer may be realized through the above molecular mechanism,providing theoretical evidence for subsequent studies and clinical applications.

Efficacy and safety of chemotherapy combined with bevacizumab in Chinese patients with metastatic colorectal cancer:A prospective,multicenter,observational,non-interventional phaseⅣtrial

Objective:Bevacizumab has an important and evolving role in improving outcomes in patients with metastatic colorectal cancer(mCRC)worldwide and was approved in China in 2010.However,there are limited real-world data on the efficacy and safety of chemotherapy regimens combined with bevacizumab in Chinese patients with mCRC.This observational,phase IV trial study aimed to obtain more experience on the efficacy and safety of bevacizumab combined with chemotherapy in Chinese mCRC patients.Methods:Between September 2013 and November 2016,patients with histologically confirmed mCRC were enrolled in a prospective,multicenter,observational,non-interventional phase IV trial at 26 centers across China.Eligible patients received different chemotherapeutic regimens combined with bevacizumab.The efficacy and safety data in the intention-to-treat study population were analyzed.Results:A total of 611 patients were included in the efficacy analysis.The median overall survival and median progression-free survival was 18.00 and 10.05 months,respectively.The objective response rate was 21.00%and disease control rate was 89.40%.In subgroup analyses,the survival differences were observed according to metastatic status,duration of treatment and elevation in blood pressure.A total of 613 patients were evaluable for safety assessments.And 569(92.82%)patients reported at least one adverse event(AE),and 151(24.63%)experienced grade 3 or higher AEs.The incidence of bevacizumab-associated AEs of special interest was reported in 31(5.06%)patients with hypertension(n=12),abscesses and fistulae(n=7),bleeding(n=6),proteinuria(n=3),gastrointestinal perforation(n=2)and venous thrombotic events(n=1).Conclusions:This observational phase IV trial broadens our experience and knowledge of bevacizumab in the Chinese population and provides a good indication of its overall efficacy and safety.Bevacizumab in combination with chemotherapy offers clinical benefits to Chinese patients with mCRC and has an acceptable and manageable safety profile.

Characteristics of cancer susceptibility genes mutations in 282 patients with gastric adenocarcinoma

Objective:To reveal the distribution signature of cancer susceptibility genes in patients with gastric adenocarcinoma,offering a diagnostic and prognostic surrogate for disease risk management and therapeutic decisions.Methods:A total of 282 patients with gastric adenocarcinoma(182 males and 100 females)were enrolled in this study,with peripheral blood genomic DNA extracted.Mutations of 69 canonical cancer susceptibility genes or presumably tumor-related genes were analyzed by targeted capture-based high-throughput sequencing.Candidate mutations were particularly selected for discussion on tumor pathogenesis according to the American College of Medical Genetics and Genomics(ACMG)guidelines.Results:In this study,7.1%(20/282)of patients with gastric adenocarcinoma were found to harbor mutations of canonical or presumable cancer susceptibility genes.The detection rate in male patients(3.8%,7/182)was significantly lower than that in female patients(13%,13/100)(P=0.004).The most recurrent mutations were in AT mutated(ATM)(1.1%,3/282),followed by BRCA1,BRIP1 and RAD51D,all showed a detection rate of 0.7%(2/282).Mutations in three genes associated with hereditary gastric cancer syndromes were detected,namely,PMS2 and EP CAM associated with Lynch syndrome and CDH1 associated with hereditary di ffuse gastric cancer.The detection frequencies were all 0.4%(1/282).Notwithstanding no significant difference observed,the age of patients with pathogenic mutations or likely pathogenic mutations is slightly younger than that of non-carriers(median age:58.5 vs.60.5 years old),while the age of patients with ATM mutations was the youngest overall(median age:49.3 years old).Conclusions:Our study shed more light on the distribution signature and pathogenesis of mutations in gastric cancer susceptibility genes,and found the detection rate of pathogenic and likely pathogenic mutations in male patients was significandy lower than that in female patients.Some known and unidentified mutations were found in gastric cancer,which allowed us to gain more insight into the hereditary gastric cancer syndromes from the molecular perspective.

Effect of microbiome group on immune checkpoint inhibitors in treatment of gastrointestinal tumors

In recent years,immune checkpoint blockade(ICB)therapy has become an important treatment strategy for gastrointestinal tumors,however,it only benefits about 1/3 of patients.Since the microbiome has been shown to play an important role in the human body for a long time,a growing number of studies are focusing on its relationship to ICB therapy in cancer,specifically how intestinal microbes affect the efficacy of immune checkpoint inhibitors(ICIs)therapy in patients.On this basis,probiotic interventions,fecal microbiota transplantation(FMT),dietary interventions,and other methods which improve or maintain the structure of the intestinal flora have attracted widespread attention.This article discusses the four aspects of the microbiome,ICB,combined treatment of gastrointestinal tumors,and regulation of gut microbiome.Particularly,the discussion focuses on the contribution of probiotic intervention in improving the therapeutic effect of ICIs to prolong the survival time of patients and reduce the severity of immune-related adverse effects(irAEs).

Pneumocystis jirovecii diagnosed by next-generation sequencing of bronchoscopic alveolar lavage fluid: A case report and review of literature

BACKGROUND The advent of molecular targeted agents and immune checkpoint inhibitors has greatly improved the treatment of advanced renal cell carcinoma(RCC), thus significantly improving patient survival. The incidence of rare drug-related adverse events has gained increased attention.CASE SUMMARY We report a patient with advanced RCC treated with multiple lines of molecular targeted agents and immune checkpoint inhibitors, who developed a pulmonary infection after treatment with everolimus in combination with lenvatinib. Determining the pathogenic organism was difficult, but it was eventually identified as Pneumocystis jirovecii by next-generation sequencing(NGS) of bronchoscopic alveolar lavage fluid(BALF) and successfully treated with trimethoprim-sulfamethoxazole.CONCLUSION Rare pulmonary infections caused by molecular targeted agents are not uncommon in clinical practice, but their diagnosis is difficult. Evaluating BALF with NGS is a good method for rapid diagnosis of such infections.

2022 Chinese expert consensus and guidelines on clinical management of toxicity in anti-CD19 chimeric antigen receptor T-cell therapy for B-cell non-Hodgkin lymphoma

Adoptive cellular immunotherapy with chimeric antigen receptor(CAR)T cells has emerged as a novel modality for treating relapsed and/or refractory B-cell non-Hodgkin lymphoma(B-NHL).With increasing approval of CAR T-cell products and advances in CAR T cell therapy,CAR T cells are expected to be used in a growing number of cases.However,CAR T-cell-associated toxicities can be severe or even fatal,thus compromising the survival benefit from this therapy.Standardizing and studying the clinical management of these toxicities are imperative.In contrast to other hematological malignancies,such as acute lymphoblastic leukemia and multiple myeloma,anti-CD19 CAR T-cell-associated toxicities in B-NHL have several distinctive features,most notably local cytokine-release syndrome(CRS).However,previously published guidelines have provided few specific recommendations for the grading and management of toxicities associated with CAR T-cell treatment for B-NHL.Consequently,we developed this consensus for the prevention,recognition,and management of these toxicities,on the basis of published literature regarding the management of anti-CD19 CAR T-cell-associated toxicities and the clinical experience of multiple Chinese institutions.This consensus refines a grading system and classification of CRS in B-NHL and corresponding measures for CRS management,and delineates comprehensive principles and exploratory recommendations for managing anti-CD19 CAR T-cell-associated toxicities in addition to CRS.

Comparison of the conventional tube and erythrocyte-magnetized technology in titration of red blood cell alloantibodies

BACKGROUND Erythrocyte alloantibodies are mainly produced after immune stimulation,such as blood transfusion,pregnancy,and transplantation,and are the leading causes of severe hemolytic transfusion reactions and difficulty in blood grouping and matching.Therefore,antibody screening is critical to prevent and improve red cell alloantibodies.Routine tube assay is the primary detection method of antibody screening.Recently,erythrocyte-magnetized technology(EMT)has been increasingly used in clinical practice.This study intends to probe the application and efficacy of the conventional tube and EMT in red blood cell alloantibody titration to provide a reference for clinical blood transfusion.AIM To investigate the application value of conventional tube and EMT in red blood cell alloantibody titration and enhance the safety of blood transfusion practice.METHODS A total of 1298 blood samples were harvested from blood donors at the Department of Blood Transfusion of our hospital from March 2021 to December 2022.A 5 mL blood sample was collected in tubing,which was then cut,and the whole blood was put into a test tube for centrifugation to separate the serum.Different red blood cell blood group antibody titers were simultaneously detected using the tube polybrene test,tube antiglobulin test(AGT),and EMT screening irregular antibody methods to determine the best test method.RESULTS Simultaneous detection was performed through the tube polybrene test,tube AGT and EMT screening irregular antibodies.It was discovered that the EMT screening irregular antibody method could detect all immunoglobulin G(IgG)and immunoglobulin M(IgM)irregular antibodies,and the results of manual tube AGT were satisfactory,but the operation time was lengthy,and the equipment had a large footprint.The EMT screening irregular antibody assay was also conducted to determine its activity against type O Rh(D)red blood cells,and the outcomes were satisfactory.Furthermore,compared to the conventional tube method,the EMT screening irregular antibody method was more cost-effective and had significantly higher detection efficiency.CONCLUSION With a higher detection rate,the EMT screening irregular antibody method can detect both IgG and IgM irregular antibodies faster and more effectively than the conventional tube method.

An Artificial Neural Network Model Combined with Dietary Retinol Intake from Different Sources to Predict the Risk of Nonalcoholic Fatty Liver Disease

Objective This study aimed to develop an artificial neural network(ANN) model combined with dietary retinol intake from different sources to predict the risk of non-alcoholic fatty liver disease(NAFLD) in American adults.Methods Data from the 2007 to 2014 National Health and Nutrition Examination Survey(NHANES)2007–2014 were analyzed. Eligible subjects(n = 6,613) were randomly divided into a training set(n1 =4,609) and a validation set(n2 = 2,004) at a ratio of 7:3. The training set was used to identify predictors of NAFLD risk using logistic regression analysis. An ANN was established to predict the NAFLD risk using a training set. Receiver operating characteristic(ROC) curve analysis was performed to evaluate the accuracy of the model using the training and validation sets.Results Our study found that the odds ratios(ORs) and 95% confidence intervals(CIs) of NAFLD for the highest quartile of plant-derived dietary retinol intake(i.e., provitamin A carotenoids, such as β-carotene)(OR = 0.75, 95% CI: 0.57 to 0.99) were inversely associated with NAFLD risk, compared to the lowest quartile of intake, after adjusting for potential confounders. The areas under the ROC curves were 0.874 and 0.883 for the training and validation sets, respectively. NAFLD occurs when its incidence probability is greater than 0.388.Conclusion The ANN model combined with plant-derived dietary retinol intake showed a significant effect on NAFLD. This could be applied to predict NAFLD risk in the American adult population when government departments formulate future health plans.