Clinical treatment considerationsin the intensity-modulated radiotherapy era for patients with NO-category nasopharyngeal carcinoma and enlarged neck lymph nodes

Background:Nasopharyngeal carcinoma(NPC) shows a high proportion of lymph node metastasis,and treatment guidelines have been developed for positive nodes.However,no irradiation guidelines have been proposed for patients with enlarged neck lymph nodes(ENLNs) that do not meet the radiological criteria of 10 mm in diameter for positive lymph nodes.This study aimed to determine the prognostic value and radiation dose for ENLNs in NO-category NPC patients treated with intensity-modulated radiotherapy(IMRT).Methods:We reviewed the medical data of 251 patients with non-metastatic,NO-category NPC treated with IMRT.Receiver operating characteristic curves were used to calculate the cut-off value of the ENLN diameter for the prediction of disease failure.The biological equivalent dose(BED) for ENLNs was calculated.Patient survival was compared between the small and large ENLN groups.Independent prognostic factors were identified using the Cox proportional hazards model.Results:The estimated 4-year regional relapse-free survival rate was higher in patients with ENLNs ≥5.5 mm than in those with ENLNs <5.5 mm(100%vs.98.8%,P=0.049),whereas disease-free,overall,and distant metastasis-free survival rates were similar between the two groups.After adjusting for various factors,ENLN diameter was not identified as an independent prognostic factor(P > 0.05 for all survival rates).In the subgroup analysis,patients receiving BED ≥72 Gy had a similar prognosis as patients receiving BED <72 Gy in both the small and large ENLN groups.The multivariate analysis also confirmed that BED≥72 Gy was not associated with significantly improved prognosis in patients with NO-category NPC.Conclusions:A BED of 72 Gy to ENLNs is considerably sufficient to provide a clinical benefit to patients with NO-category NPC.Prospective studies are warranted to validate the findings in the present study.

Elevated Kallistatin promotes the occurrence and progression of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease worldwide,and the development of nonalcoholic steatohepatitis(NASH)might cause irreversible hepatic damage.Hyperlipidemia(HLP)is the leading risk factor for NAFLD.This study aims to illuminate the causative contributor and potential mechanism of Kallistatin(KAL)mediating HLP to NAFLD.221 healthy control and 253 HLP subjects,62 healthy control and 44 NAFLD subjects were enrolled.The plasma KAL was significantly elevated in HLP subjects,especially in hypertriglyceridemia(HTG)subjects,and positively correlated with liver injury.Further,KAL levels of NAFLD patients were significantly up-regulated.KAL transgenic mice induced hepatic steatosis,inflammation,and fibrosis with time and accelerated inflammation development in high-fat diet(HFD)mice.In contrast,KAL knockout ameliorated steatosis and inflammation in high-fructose diet(HFruD)and methionine and choline-deficient(MCD)diet-induced NAFLD rats.Mechanistically,KAL induced hepatic steatosis and NASH by down-regulating adipose triglyceride lipase(ATGL)and comparative gene identification 58(CGl-58)by LRP6/Gas/PKA/GSK3βpathway through down-regulating peroxisome proliferator-activated receptor(PPARy)and up-regulating kruppel-like factor four(KLF4),respectively.CGl-58 is bound to NF-kB p65 in the cytoplasm,and diminishing CGl-58 facilitated p65 nuclear translocation and TNFa induction.Meanwhile,hepatic CGl-58-overexpress reverses NASH in KAL transgenic mice.Further,free fatty acids up-regulated KAL against thyroid hormone in hepatocytes.Moreover,Fenofibrate,one triglyceride-lowering drug,could reverse hepatic steatosis by down-regulating KAL.These results demonstrate that elevated KAL plays a crucial role in the development of HLP to NAFLD and may be served as a potential preventive and therapeutic target.

STAT5 promotes PD-L1 expression by facilitating histone lactylation to drive immunosuppression in acute myeloid leukemia

Immunotherapy is a revolutionized therapeutic strategy for tumor treatment attributing to the rapid development of genomics and immunology,and immune checkpoint inhibitors have successfully achieved responses in numbers of tumor types,including hematopoietic malignancy.However,acute myeloid leukemia(AML)is a heterogeneous disease and there is stll a lack of systematic demonstration to apply immunotherapy in AML based on PD-1/PD-L1 blockage.

Recognition of high-specificity hERG K+ channel inhibitor-induced arrhythmia in cardiomyocytes by automated template matching

Cardiovascular disease(CVD)is the number one cause of death in humans.Arrhythmia induced by gene mutations,heart disease,or hERG K+channel inhibitors is a serious CVD that can lead to sudden death or heart failure.Conventional cardiomyocyte-based biosensors can record extracellular potentials and mechanical beating signals.However,parameter extraction and examination by the naked eye are the traditional methods for analyzing arrhythmic beats,and it is difficult to achieve automated and efficient arrhythmic recognition with these methods.In this work,we developed a unique automated template matching(ATM)cardiomyocyte beating model to achieve arrhythmic recognition at the single beat level with an interdigitated electrode impedance detection system.The ATM model was established based on a rhythmic template with a data length that was dynamically adjusted to match the data length of the target beat by spline interpolation.The performance of the ATM model under long-term astemizole,droperidol,and sertindole treatment at different doses was determined.The results indicated that the ATM model based on a random rhythmic template of a signal segment obtained after astemizole treatment presented a higher recognition accuracy(100%for astemizole treatment and 99.14%for droperidol and sertindole treatment)than the ATM model based on arrhythmic multitemplates.We believe this highly specific ATM method based on a cardiomyocyte beating model has the potential to be used for arrhythmia screening in the fields of cardiology and pharmacology.

Outcomes in patients with Fournier’s gangrene originating from the anorectal region with a particular focus on those without perineal involvement

Background and aim:Fournier’s gangrene(FG)is a fulminant infection in the external genital region and perineum.The present study explored the clinical features of FG originating from the anorectal region,from primary conditions such as anal fistulas and abscesses.Methods:A retrospective analysis was performed in order to identify the factors associated with clinical outcomes in FG patients derived from two hospitals—the Sixth Affiliated Hospital of Sun Yat-sen University and People’s Hospital Affiliated to Fujian University of Traditional Chinese—over the period from May 2013 to April 2017.Results:Sixty FG patients were included in this study.The common causative microorganisms cultured were Escherichia coli species.Genital and perirectal regional involvement was evident in 52 and 59 cases,respectively,although the perineum was unaffected in 7 cases(12%),as confirmed by imaging examination and surgical exploration.Management with early radical debridement and broad-spectrum antibiotic therapy is effective with an acceptably sepsis mortality(1.7%).Ten patients underwent protective colostomy.No patient underwent an orchidectomy and required urinary diversion.Conclusions:FG originating from the anorectal region can be rapidly progressive and life-threatening.Infection can spread superiorly to the genital region without the involvement in perineal tissue.An aggressive surgical debridement of nonviable tissue is essential for satisfactory outcomes and a protective colostomy is not mandatory.

Machine learning accelerated carbon neutrality research using big data-from predictive models to interatomic potentials

Carbon neutrality has been proposed as a solution for the current severe energy and climate crisis caused by the overuse of fossil fuels, and machine learning(ML) has exhibited excellent performance in accelerating related research owing to its powerful capacity for big data processing. This review presents a detailed overview of ML accelerated carbon neutrality research with a focus on energy management, screening of novel energy materials, and ML interatomic potentials(MLIPs), with illustrations of two selected MLIP algorithms: moment tensor potential(MTP) and neural equivariant interatomic potential(NequIP). We conclude by outlining the important role of ML in accelerating the achievement of carbon neutrality from global-scale energy management, unprecedented screening of advanced energy materials in massive chemical space, to the revolution of atomicscale simulations of MLIPs, which has the bright prospect of applications.

Mesenchymal stem cells for treatment of steroid-resistant acute rejection after liver transplantation

A patient with steroid-resistant acute rejection 50 days after ABO-compatible orthotopic liver transplantation(LT)received regular infusion of allogeneic mesenchymal stem cells(MSCs)after three sessions of steroid pulse therapy which failed to control the pathogenetic condition as shown by biopsy.Liver function improved gradually after intravenous injection of MSCs once weekly for 10 weeks(as confirmed by biopsy)and remained stable under administration of conventional immunosuppressive agents.There was no evidence of neoplasms 5 years after treatment.MSCs infusion appears to successfully reverse resistance to immunosuppressive agents and may be a useful treatment for post-liver transplant steroid-resistant rejection.