Pediatric living donor liver transplantation decade progress in Shanghai:Characteristics and risks factors of mortality

BACKGROUND Pediatric living donor liver transplantation(LDLT) has become the gold standard for patients with end-stage liver disease. With improvements in organ preservation, immunosuppression, and surgical and anesthesia techniques, the survival rates and long-term outcomes of patients after LDLT have significantly improved worldwide. However, data on anesthetic management and postoperative survival rate of pediatric LDLT in China are rare.AIM To review the status of pediatric LDLT in Shanghai and investigate the factors related to anesthetic management and survival rate in pediatric LDLT.METHODS We conducted a retrospective observational study to investigate the status of pediatric LDLT in Shanghai by reviewing 544 records of patients who underwent pediatric LDLT since the first operation on October 21, 2006 until August 10, 2016 at Renji Hospital and Huashan Hospital.RESULTS The 30-d, 90-d, 1-year, and 2-year survival rates were 95.22%, 93.38%, 91.36%,and 89.34%, respectively. The 2-year patient survival rate after January 1, 2011 significantly improved compared with the previous period(74.47% vs 90.74%;hazard ratio: 2.92;95% confidence interval(CI): 2.16–14.14;P = 0.0004). Median duration of mechanical ventilation in the intensive care unit(ICU) was 18 h [interquartile range(IQR), 15.25–20.25], median ICU length of stay was 6 d(IQR:4.80–9.00), and median postoperative length of stay was 24 d(IQR: 18.00–34.00).Forty-seven(8.60%) of 544 patients did not receive red blood cell transfusion during the operation.CONCLUSION Pediatric end-stage liver disease score, anesthesia duration, operation duration,intraoperative blood loss, and ICU length of stay were independent predictive factors of in-hospital patient survival. Pediatric end-stage liver disease score,operation duration, and ICU length of stay were independent predictive factors of 1-year and 3-year patient survival.

Next-generation antibody-drug conjugates revolutionize the precise classification and treatment of HER2-expressing breast cancer

The concept of antibody±drug conjugations(ADCs)can be tracked back to the early 20^(th) century when the renowned immunologist,Paul Ehrlich,proposed the idea of a"magic bullet",which utilizes ADCs for targeted destruction of microorganisms and tumor cells^(1).After nearly one century of development,ADCs have emerged as a rather promising approach in the treatment of cancer,especially breast cancer,which is the most common malignant tumor in women^(2).

Danggui Niantong decoction ameliorates joint inflammation and cardiopulmonary injury in TNF-Tg mice

Objective:Rheumatoid arthritis(RA)is a common autoimmune disease characterized by multiple joint lesions and systemic complications.Danggui Niantong decoction(DGNTT)has been clinically used for RA treatment;however,its beneficial effect on cardiopulmonary complications has not been reported.Methods:Female tumor necrosis factor-transgenic(TNF-Tg)mice were used to evaluate the therapeutic effects of DGNTT on arthritis and cardiopulmonary complications.Methotrexate(MTX)served as a positive control.Histopathological assessment of the joint sections was performed using hematoxylin and eosin(HE),Alcian Blue/Orange G,and tartrate-resistant acid phosphatase staining.Bone mass was assessed by micro-computed tomography,inflammatory infiltrates in the heart and lungs were evaluated by HE staining,cardiopulmonary fibrotic injury was identified by Masson’s trichrome staining,and hypertrophy of mouse cardiomyocytes was measured by wheat germ agglutinin(WGA)staining.Results:DGNTT mitigated the inflammation of the ankle joint synovium,decreased the number of osteoclasts,and increased the area of cartilage and bone mass in TNF-Tg mice.In addition,DGNTT decreased the infiltration of inflammatory cells into the lung and heart tissues,accompanied by a reduction in cardiopulmonary fibrosis and myocardial cell hypertrophy in TNF-Tg mice.As a positive control drug,MTX attenuated the pathological changes in joints,but had no beneficial effect on cardiopulmonary inflammation and fibrosis in TNF-Tg mice.Conclusions:DGNTT improved joint lesions and alleviated cardiopulmonary complications in TNF-Tg mice.

Structural shift of gut microbiota during chemopreventive effects of epigallocatechin gallate on colorectal carcinogenesis in mice

AIM To investigate the effect of epigallocatechin gallate(EGCG) on structural changes of gut microbiota in colorectal carcinogenesis.METHODS An azoxymethane(AOM)/dextran sodium sulfate(DSS)-induced colitis mouse model was established. Fortytwo female FVB/N mice were randomly divided into the following three groups: group 1(10 mice, negative control) was treated with vehicle, group 2(16 mice, positive control) was treated with AOM plus vehicle, and group 3(16 mice, EG) was treated with AOM plus EGCG. For aberrant crypt foci(ACF) evaluation, the colons were rapidly took out after sacrifice, rinsed with saline, opened longitudinally, laid flat on a polystyrene board, and fixed with 10% buffered formaldehyde solution before being stained with 0.2% methylene blue in saline. For tumor evaluation, the colon was macroscopically inspected and photographed, then the total number of tumors was enumerated and tumor size measured. For histological examination, the fixed tissues were paraffin-embedded and sectioned at 5 mm thickness. Microbial genomic DNA was extracted from fecal and intestinal content samples using a commercial kit. The V4 hypervariable regions of 16 S r RNA were PCR-amplified with the barcoded fusion primers. Using the best hit classification option, the sequences from each sample were aligned to the RDP 16 S r RNA training set to classify the taxonomic abundance in QIIME. Statistical analyses were then performed.RESULTS Treatment of mice with 1% EGCG caused a significant decrease in the mean number of ACF per mouse, when compared with the model mice treated with AOM/DSS(5.38 ± 4.24 vs 13.13 ± 3.02, P < 0.01). Compared with the positive control group, 1% EGCG treatment dependently decreased tumor load per mouse by 85%(33.96 ± 6.10 vs 2.96 ± 2.86, respectively, P < 0.01). All revealed that EGCG could inhibit colon carcinogenesis by decreasing the number of precancerous lesions as well as solid tumors, with reduced tumor load and delayed histological progression of CRC. During the cancerization, the diversity of gut microbiota increased, potential carcinogenic bacteria such as Bacteroides were enriched, and the abundance of butyrate-producing bacteria(Clostridiaceae, Ruminococcus, etc.) decreased continuously. In contrast, the structure of gut microbiota was relatively stable during the intervention of EGCG on colon carcinogenesis. Enrichment of probiotics(Bifidobacterium, Lactobacillu, etc.) might be a potential mechanism for EGCG's effects on tumor suppression. Via bioinformatics analysis, principal coordinate analysis and cluster analysis of the tumor formation process, we found that the diversity of gut microbiota increased in the tumor model group while that in the EGCG interfered group(EG) remained relatively stable.CONCLUSION Gut microbiota imbalance might be a potential mechanism for the prevention of malignant transformation by EGCG, which is significant for diagnosis, treatment, prognosis evaluation, and prevention of colorectal cancer.

Precore/basal core promoter mutants quantification throughout phases of hepatitis B virus infection by Simpleprobe

AIM:To investigate precore/basal core promoter(PC/BCP) mutants throughout hepatitis B virus(HBV) infection and to determine their relationship to hepatitis B early antigen(HBeA g) titers.METHODS:We enrolled 191 patients in various stages of HBV infection at the Huashan Hospital and the Taizhou Municipal Hospital from 2010 to 2012.None of the patients received antiviral therapy.HBV DNA from serum,was quantified by real-time PCR.The HBV genotype was determined by direct sequencing of the S gene.We used the Simpleprobe ultrasensitivequantitative method to detect PC/BCP mutants in each patient.We compared the strain number,percentage,and the changes in PC/BCP mutants in different phases,and analyzed the relationship between PC/BCP mutants and HBe Ag by multiple linear regression and logistic regression.RESULTS:Patients with HBV infection(n = 191) were assigned to groups by phase:Immune tolerance(IT) = 55,Immune clearance(IC) = 67,Low-replicative(LR) = 49,and HBeA g-negative hepatitis(ENH) = 20.Of the patients(male,112; female,79) enrolled,122 were HBe Ag-positive and 69 were HBe Ag-negative.The median age was 33 years(range:18-78 years).PC and BCP mutation detection rates were 84.82%(162/191) and 96.86%(185/191),respectively.In five HBe Ag-negative cases,we detected double mutation G1896A/G1899 A.The logarithm value of PC mutant quantities(log10 PC) significantly differed in IT,IC,and LR phases,as well as in the ENH phase(F = 49.350,P < 0.001).The logarithm value of BCP mutant quantities(log10 BCP) also differed during the four phases(F = 25.530,P < 0.001).Log10 PC and log10 BCP values were high in the IT and IC phases,decreased in the LR phase,and increased in the ENH phase,although the absolute value at this point remained lower than that in the IT and IC phases.PC mutant quantity per total viral load(PC%) and BCP mutant quantity per total viral load(BCP%) differed between phases(F = 20.040,P < 0.001; F = 10.830,P < 0.001),with PC% and BCP% gradually increasing in successive phases.HBeA g titers negatively correlated with PC%(Spearman's rho =-0.354,P < 0.001) and BCP%(Spearman's rho =-0.395,P < 0.001).The negative correlation between PC% and HBeA g status was significant(B =-5.281,P = 0.001),but there was no such correlation between BCP% and HBeA g status(B =-0.523,P = 0.552).CONCLUSION:PC/BCP mutants become predominant in a dynamic and continuous process.Log10 PC,log10 BCP,PC% and BCP% might be combined to evaluate disease progression.PC% determines HBeA g status.

The efficacy of the seamless transfer of care model to apply for the patients with cerebral apoplexy in China

Purpose:To evaluate the efficacy of the Seamless Transfer of Care Model(STCM)to improve readmission occurrence of patients withstroke.Methods:The sample was comprised of fifty-nine subjects with stroke who were hospitalized in the geriatric and neurology departments of a large university hospital in China.Subjects were allocated to an STCM group(n=30)or a routine care(control)group(n=29).Results:Compared with the control group,the STCM group had a higher quality of life(p<0.05),higher compliance(p<0.05)and a lower readmission rate(p<0.05).Conclusion:Based on our results,the application of the STCM in Chinese stroke patients can improve quality of life and compliance,and reduce readmission rate.

The role of autophagic and lysosomal pathways in ischemic brain injury

Autophagy is involved in neural cell death after cerebral ischemia. Our previous studies showed that rapamycin-induced autophagy decreased the rate of apoptosis, but the rate of apoptosis was in- creased after the autophagy inhibitor, 3-methyladenine, was used. In this study, a suture-occluded method was performed to generate a rat model of brain ischemia. Under a transmission electron microscope, autophagic bodies and autophagy lysosomes were markedly accumulated in neurons at 4 hours post brain ischemic injury, with their numbers gradually reducing over time. Western blotting demonstrated that protein levels of light chain 3-11 and cathepsin B were significantly in- creased within 4 hours of ischemic injury, but these levels were not persistently upregulated over time. Confocal microscopy showed that autophagy was mainly found in neurons with positive light chain 3 signal. Injection of rapamycin via tail vein promoted the occurrence of autophagy in rat brain tissue after cerebral ischemia and elevated light chain 3 and cathepsin B expression. However, in- jection of 3-methyladenine significantly diminished light chain 3-11 and cathepsin B expression. Results verified that autophagic and lysosomal activity is increased in ischemic neurons. Abnormal components in cells can be eliminated through upregulating cell autophagy or inhibiting autophagy after ischemic brain injury, resulting in a dynamic balance of substances in cells. Moreover, drugs that interfere with autophagy may be potential therapies for the treatment of brain injury.

Suppression of colorectal tumorigenesis by recombinant Bacteroides fragilis enterotoxin-2 in vivo

AIM To evaluate the impact of recombinant Bacteroides fragilis enterotoxin-2(BFT-2, or Fragilysin) on colorectal tumorigenesis in mice induced by azoxymethane/dextran sulfate sodium(AOM/DSS).METHODS Recombinant pro BFT-2 was expressed in Escherichia coli strain Rosetta(DE3) and BFT-2 was obtained and tested for its biological activity via colorectal adenocarcinoma cell strains SW-480. Seventy C57BL/6J mice were randomly divided into a blank(BC; n = 10), model(AD; n = 20), model + low-dose toxin(ADLT; n = 20, 10 μg), and a model + high-dose toxin(ADHT; n = 20, 20 μg) group. Mice weight, tumor formation and pathology were analyzed. Immunohistochemistrydetermined Ki-67 and Caspase-3 expression in normal and tumor tissues of colorectal mucosa.RESULTS Recombinant BFT-2 was successfully obtained, along with its biological activity. The most obvious weight loss occurred in the AD group compared with the ADLT group(21.82 ± 0.68 vs 23.23 ± 0.91, P < 0.05) and the ADHT group(21.82 ± 0.68 vs 23.57 ± 1.06, P < 0.05). More tumors were found in the AD group than in the ADLT and ADHT groups(19.75 ± 3.30 vs 6.50 ± 1.73, P < 0.05; 19.75 ± 3.30 vs 6.00 ± 2.16, P < 0.05). Pathology showed that 12 mice had adenocarcinoma and 6 cases had adenoma in the AD group. Five mice had adenocarcinoma and 15 had adenoma in the ADLT group. Four mice had adenocarcinoma and 16 had adenoma in the ADHT group. The incidence of colorectal adenocarcinoma in both the ADHT group and the ADHT group was reduced compared to that in the AD group(P < 0.05, P < 0.05). The positive rate of Ki-67 in the ADLT group and the ADHT group was 50% and 40%, respectively, both of which were lower than that found in the AD group(94.44%, P < 0.05, P < 0.05). Caspase-3 expression in the ADLT group and the ADHT group was 45% and 55%, both of which were higher than that found in the BC group(16.67%, P < 0.05, P < 0.05).CONCLUSION Oral administration with lower-dose biologically active recombinant BFT-2 inhibited colorectal tumorigenesis in mice.

Evaluation of specific fecal protein biochips for the diagnosis of colorectal cancer

AIM: To develop and initially test a potential fecal protein biochip for the screening of colorectal cancer(CRC). METHODS: Fecal protein from 20 colorectal cancer patients and 20 healthy controls were extracted from all of the fecal samples and screened for proteomic differences using a Biotin label-based protein array. Candidate proteins were then verified by ELISA. Finally, we will select out the significant protein and a seven-target multiplex fecal protein biochip was generated and tested for 20 fecal samples to determine the effectiveness of the biochip on identifying CRC. And the value of the protein biochip would be discussed. RESULTS: After tested by protein biochip of the fecal protein from 20 colorectal cancer patients and 20 healthy controls and levels of calprotectin, M2-pyruvatekinase, angiopoietin-2, fibroblast growth factor-23(FGF-23), proteins of the matrix metalloproteinase, thrombopoietin(TPO) and interleukin-13(IL-13) were significantly different between CRC and healthy controls. The sensitivity of all the seven proteins combined was 0.7, specificity was 0.4, and area under the receiver operating characteristics was 0.729. The most promising combinations of test proteins were FGF-23, TPO, and IL-13, reaching a sensitivity of 0.7 and a specificity of 0.7. The combination of FGF-23 and TPO scored highest with sensitivity of 0.7 and specificity of 0.8. Its mean that the combination of FGF-23 and TPO has the highest value for the diagnosis of CRC in our study. CONCLUSION: A protein biochip composed of proteins found to be elevated in the feces of colorectal cancer patients has great potential as a noninvasive diagnostic for colorectal cancer. The addition of new protein biomarkers and technologies, as they are discovered, is an excellent avenue of future research.

Impact of obesity on kidney function and blood pressure in children

In recent years, obesity has become an increasingly important epidemic health problem in children and adolescents. The prevalence of the overweight status in children grew from 5% to 11% from 1960 s to 1990 s. The epidemic of obesity has been paralleled by an increase in the incidence of chronic kidney disease(CKD) and hypertension. Results of several studies have demonstrated that obesity and metabolic syndrome were independent predictors of renal injury. The pathophysiology of obesity related hypertension is complex, including activation of sympathetic nervous system, renin angiotensin aldosterone system, hyperinsulinemia and inflammation. These same mechanisms likely contribute to the development of increased blood pressure in children. This review summarizes the recent epidemiologic data linking obesity with CKD and hypertension in children, as well as the potential mechanisms.

Feasibility of sentinel lymph node biopsy omission after integration of ^(18)F-FDG dedicated lymph node PET in early breast cancer: a prospective phase II trial

Objective:Sentinel lymph node biopsy(SLNB)is currently the standard of care in clinically node negative(cN0)breast cancer.The present study aimed to evaluate the negative predictive value(NPV)of 18F-FDG dedicated lymph node positron emission tomography(LymphPET)in cN0 patients.Methods:This was a prospective phase II trial divided into 2 stages(NCT04072653).In the first stage,cN0 patients underwent axillary LymphPET followed by SLNB.In the second stage,SLNB was omitted in patients with a negative preoperative axillary assessment after integration of LymphPET.Here,we report the results of the first stage.The primary outcome was the NPV of LymphPET to detect macrometastasis of lymph nodes(LN-macro).Results:A total of 189 patients with invasive breast cancer underwent LymphPET followed by surgery with definitive pathological reports.Forty patients had LN-macro,and 16 patients had only lymph node micrometastasis.Of the 131 patients with a negative LymphPET result,16 patients had LN-macro,and the NPV was 87.8%.After combined axillary imaging evaluation with ultrasound and LymphPET,100 patients were found to be both LymphPET and ultrasound negative,9 patients had LN-macro,and the NPV was 91%.Conclusions:LymphPET can be used to screen patients to potentially avoid SLNB,with an NPV>90%.The second stage of the SOAPET trial is ongoing to confirm the safety of omission of SLNB according to preoperational axillary evaluation integrating LymphPET.

Application of traditional Chinese medicine nursing technique in hyperten hypertension with insomnia: A literature review

目前,高血压合并失眠仍缺乏统一有效的治疗手段,而中医护理技术能够有效高血压合并失眠患者的失眠症状,降低血压,缓解疲劳,改善焦虑、抑郁情绪,提高生活质量等。中医护理技术在高血压合并失眠患者中的应用不仅包括穴位按摩、穴位贴敷、耳穴压豆等单一中医护理技术的应用,还包括两种或多种中医护理技术的应用等。本文通过综述有关高血压合并失眠的中医护理技术应用现状,旨在为高血压合并失眠患者的治疗提供参考。

EXPERIMENTAL STUDY ON THE CYTOCIDAL EFFECT OF AT-1840 AND PARVOVIRUS H-1 AGAINST STOMACH CANCER CELLS

We had given evidences of cytocidal effect in vitro of either parvovirus H-I(PV H-1) or AT-1840 (lycobetaine) on gastric cancer cells. They act on different phase of the cell cycle of the gastric cancer cells, with PV H-1 on the late stage of S phase and AT-1840 on M phase. Combined use of these drugs gives better killing effect than the individual drug alone. In gastric cancer-bearing nude mice (ascites and solid tumor forms), both AT-1840 and PV H-1 increased the survival peroids and decreased the size of solid tumors. Depsite these are the experimental study which may not to be the same in human being. However, the study has layed down a solid foundation for our further exploration of these two substances as anti-gastric cancer drugs in the future.

Severity evaluation value of serum myeloperoxidase content detection in patients with acute coronary syndrome

Objective:To analyze the value of serum myeloperoxidase content detection for severity evaluation in patients with acute coronary syndrome.Methods: Acute coronary syndrome (ACS) group included 32 cases, stable angina pectoris (SAP) group included 46 cases, levels of myeloperoxidase (MPO), inflammatory factors and lipid metabolism indexes in serum were compared, coronary echocardiography blood flow parameters were detected, and the correlation between MPO and ACS severity-associated indexes was further analyzed.Results:MPO content in serum of ACS group was significantly higher than those of SAP group and control group;inflammatory factors hs-CRP, IL-6, MCP-1 and LP-PLA2 content in serum were higher than those of SAP group and control group while IL-13 and TGFβ content were lower than those of SAP group and control group;lipid metabolism indexes TC, TG, LDL-C, ApoAI and ApoB content in serum were higher than those of SAP group and control group while HDL-C content was lower than that of SAP group and control group;ultrasonic coronary blood flow parameters SPV, DPV, A, CFVR and CTVⅠ levels were lower than those of SAP group and control group. The serum MPO content in patients with ACS was directly correlated with the content of inflammatory factors and lipid metabolism indexes as well as thelevels of coronary blood flow parameters.Conclusions:Serum MPO content in patients with ACS is directly correlated with the disease severity, and can be used as a reliable index for long-term guide of treatment and prediction of treatment outcome.

Improvement of Parkinsonian behavior with co-grafts of Schwann cells and neural stem cells in the rat

BACKGROUND： Due to the lack of autograft transplant rejection, Schwann cells （SCs） can promote the proliferation of embryonic stem cells and the induction of dopaminergic neurons. Mesencephalic stem cells can be induced to produce dopaminergic neurons. The therapeutic effects of co-grafts of SCs and neural stem cells （NSCs） deserves further study and verification in Parkinsonian animal models. OBJECTIVE： To investigate the effects of Schwann cells and mesencephalic NSC co-grafts in Parkinsonian animal models on animal behavior and histology. DESIGN： Randomized controlled experiment. SETTING： Fudan University; Institute of Neuroscience, Chinese Academy of Sciences. MATERIALS： The following animals were obtained from the Experimental Animal Center, Shanghai Institute for Biological Science, Chinese Academy of Sciences： 5 Sprague-Dawley rats, embryonic day （E） 13-16; 16 neonatal Sprague-Dawley rats, postnatal day 1-3; and 18 adult SD rats of both genders. Animal experimentation met animal ethical approval. METHODS： The experiment was performed at the Department of Anatomy, Histology and Embryology, Shanghai Medical Center, Fudan University from September 2005 to January 2007. The mesencephalic NSCs were obtained from the brains of SD rats at E 13-16, and SCs were harvested from the sciatic nerves of neonatal rats at day 1-3. Hemiparkinsonian rats （n =18） were selected for transplantation after estimating rotational behavior in response to apomorphine and were randomly assigned to three groups： control group, NSC group, and co-graft group. There were 6 rats in each group. Either phosphate buffered saline （PBS）, NSCs, or SCs plus NSCs were transplanted into the right neostriatum of Parkinsonian rats, respectively. MAIN OUTCOME MEASURES： （1） Rotational behavior was induced by apomorphine （0.05 mg/kg, i.p.） 2, 4, 6, 8, and 10 weeks after transplantation, and the number of rotations were counted. （2） Differentiation and survival of dopaminergic neurons in the right neostriatum were quantified by tyrosine hydroxylase immunohistochemistry 10 weeks after grafting. RESULTS： All 18 Parkinsonian rats were included in the final analysis,without any loss. （1）Rotation behavior and turning： Compared with the control group, the percent of apomorphine-induced rotations were significantly decreased （P 〈 0.01 ） in both the NSC group and co-graft group. （2）Differentiation and survival of dopaminergic neurons in each group： TH-immunoreactive neurons were detected in the striatum of both the NSC group and co-graft group 10 weeks after transplantation. The neuronal volume, size of the nucleus, and neuronal numbers were larger in the co-graft group compared to the NSC group （P 〈 0.05）. CONCLUSION： SC and NSC co-grafts not only improve Parkinsonian behavior in rats, but also improve the survival of NSCs.

The emerging role of long noncoding RNA RMRP in cancer development and targeted therapy

The RNA component of mitochondrial RNA-processing endoribonuclease(RMRP)was first described as an entity that cleaved mitochondrial RNA at a priming site of mitochondrial DNA replication.This long noncoding RNA(lncRNA)was encoded by an evolutionarily conserved nuclear gene that has been characterized in many species,including human,mouse,cattle,zebrafish,toad,and yeast.It was soon learned that RMRP as a component of the RNase MRP complex was also located in the nucleus,and was critical for ribosomal RNA(rRNA)processing,particularly the biosynthesis of 5.8S rRNAs.In 2001,the first evidence of the role of RMRP in the pathogenesis of human disorders was reported,involving mutations in the RMRP gene,which caused cartilage-hair hypoplasia(CHH)1,a recessively inherited developmental disorder characterized by short stature,hypoplastic anemia,defective immunity,and predisposition to several cancers.

Gut Microbiota Community Shift with Severity of Coronary Artery Disease

Gut microbiota community shift with coronary artery disease(CAD)has been reported in several limited cohorts during the past several years.However,whether the enriched or decreased microbiota taxa with CAD can be reproducible deserves further investigation and validation.In this study,78 human subjects were recruited.Of these,19 were diagnosed without stenosis in coronary artery(control group,referred to herein as Ctrl),14 with stenosis less than 50%(LT50),and 45 with stenosis greater than 50%(GT50).Fecal samples were collected and DNA was extracted to perform 16S ribosomal RNA(rRNA)gene sequencing.The operational taxonomic units(OTUs)were analyzed to identify taxa specific to different groups;next,multivariate logistic regression was employed to test whether the defined taxa could independently predict CAD risk.We found that Deltaproteobacteria,Fusobacterium,Bilophila,Actinomyces,and Clostridium XIX were enriched in Ctrl;Prevotellaceae,Parabacteriodes,and Butyricicoccus were enriched in LT50;and Roseburia and Butyricimonas were enriched in GT50.Further analysis revealed that increased populations of Deltaproteobacteria,Fusobacterium,Bilophila,and Desulfovibrionaceae were associated with a 0.26-fold,0.21-fold,0.18-fold,and 0.26-fold decreased risk of CAD,respectively(p<0.05),and an increased Prevotellaceae population was associated with a 5.63-fold increased risk of CAD(p<0.01).A combination of the 20 microbial taxa achieved an area under the receiver operating characteristic(ROC)curve of higher than 0.88 for all discriminations between LT50 vs Ctrl,GT50 vs Ctrl,LT50+GT50 vs Ctrl,and GT50 vs Ctrl+LT50.However,the microbial taxa previously reported as enriched in CAD patients or healthy controls could not be observed in our cohort except for Bacteroides.In conclusion,CAD patients showed a different microbial taxa signature than the healthy controls.However,the non-reproducibility of the microbiota taxa enriched in CAD across different cohorts limits the use of this signature in early diagnosis and prevention.Only decreased Bacteroides abundance was found to be a reliable marker to indicate CAD progression.

The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of gastric cancer, 2023

The 2023 update of the Chinese Society of Clinical Oncology(CSCO)Clini-cal Guidelines for Gastric Cancer focuses on standardizing cancer diagnosis and treatment in China,reflecting the latest advancements in evidence-based medicine,healthcare resource availability,and precision medicine.These updates address the differences in epidemiological characteristics,clinicopatho-logical features,tumor biology,treatment patterns,and drug selections between Eastern and Western gastric cancer patients.Key revisions include a structured template for imaging diagnosis reports,updated standards for molecular marker testing in pathological diagnosis,and an elevated recommendation for neoadju-vant chemotherapy in stage III gastric cancer.For advanced metastatic gastric cancer,the guidelines introduce new recommendations for immunotherapy,anti-angiogenic therapy and targeted drugs,along with updated management strategies for human epidermal growth factor receptor 2(HER2)-positive and deficient DNA mismatch repair(dMMR)/microsatellite instability-high(MSI-H)patients.Additionally,the guidelines offer detailed screening recommendations for hereditary gastric cancer and an appendix listing drug treatment regimens for various stages of gastric cancer.The 2023 CSCO Clinical Guidelines for Gastric Cancer updates are based on both Chinese and international clinical research and expert consensus to enhance their applicability and relevance in clinical practice,particularly in the heterogeneous healthcare landscape of China,while maintaining a commitment to scientific rigor,impartiality,and timely revisions.

Inflammatory response-based subtyping and potential therapeutic strategies for triple-negative breast cancer

objective:Inflammatory response plays a crucial role in the development and treatment of cancer.However,the role of inflammatory response in triple-negative breast cancer(TNBC)remains unclear.Based on the heterogeneity of the inflammatory response,we classified TNBC,elucidated its subtype features,and revealed potential therapeutic strategies.Methods:We established inflammatory response subtyping based on the RNA sequencing data of TNBCs derived from a cohort at the Fudan University Shanghai Cancer Center(FUSCC).Next,we explored the features and potential therapeutic strategies for each subgroup by analyzing transcriptome data.Using a machine-learning method,we validated and generalized the TNBC inflammatory response subtypes in an external dataset.Results:A total of 360 TNBC samples and 88 normal tissues were collected from a cohort at FUSCC.Patients with TNBC were divided into four inflammatory response groups(IRGs)based on the expression of inflammatory response genes:high inflammatory response gene expression with pronounced pyroptosis phenotype and high immune cellinfiltration(IRG 1),low inflammatory response gene expression and low immune cell infiltration(IRG 2),ITGB8 specific inflammatory response with a predominant proliferation phenotype(IRG 3),and low M1/M2 ratio with a marked angiogenesis phenotype(IRG 4).Relapse-free survival(RFS)was better in iRG 1 and 2 and worse in IRG 3 and 4.Owing to their poor prognosis,we mainly focused on IRG 3 and IRG 4 to investigate potential treatment strategies.ITGB8 was highly expressed in IRG 3;thus,targeting ITGB8 may be a potential therapeutic strategy for patients in IRG 3.IRG 4 had a lower M1/M2 ratio and a marked angiogenesis phenotype;therefore,therapeutic strategies,such as anti-angiogenesis or M2 to M1 repolarization of macrophages,could be recommended for these patients.Additionally,we validated and generalized the TNBC inflammatory response subtyping in an external dataset using a machine-learning method.Conclusion:TNBC patients with different inflammatory response subtypes have different characteristics and may need subtype-specific treatment strategies.

CBX4 deletion promotes tumorigenesis under Kras^(G12D) background by inducing genomic instability

Chromobox protein homolog 4(CBX4)is a component of the Polycomb group(PcG)multiprotein Polycomb repressive complexes 1(PRC1),which is participated in several processes including growth,senescence,immunity,and tissue repair.CBX4 has been shown to have diverse,even opposite functions in different types of tissue and malignancy in previous studies.