Patterns of Oncogene Coexpression at Single-Cell Resolution Influence Survival in Lymphoma.

Cancers often overexpress multiple clinically relevant oncogenes, but it is not known if combinations of oncogenes in cellular subpopulations within a cancer influence clinical outcomes. Using quantitative multispectral imaging of the prognostically relevant oncogenes MYC, BCL2, and BCL6 in diffuse large B-cell lymphoma (DLBCL), we show that the percentage of cells with a unique combination MYC+BCL2+BCL6- (M+2+6-) consistently predicts survival across four independent cohorts (n = 449), an effect not observed with other combinations including M+2+6+. We show that the M+2+6- percentage can be mathematically derived from quantitative measurements of the individual oncogenes and correlates with survival in IHC (n = 316) and gene expression (n = 2,521) datasets. Comparative bulk/single-cell transcriptomic analyses of DLBCL samples and MYC/BCL2/BCL6-transformed primary B cells identify molecular features, including cyclin D2 and PI3K/AKT as candidate regulators of M+2+6- unfavorable biology. Similar analyses evaluating oncogenic combinations at single-cell resolution in other cancers may facilitate an understanding of cancer evolution and therapy resistance. SIGNIFICANCE: Using single-cell-resolved multiplexed imaging, we show that selected subpopulations of cells expressing specific combinations of oncogenes influence clinical outcomes in lymphoma. We describe a probabilistic metric for the estimation of cellular oncogenic coexpression from IHC or bulk transcriptomes, with possible implications for prognostication and therapeutic target discovery in cancer. This article is highlighted in the In This Issue feature, p. 1027.

Clinical features, electrophysiological characteristics and treatment of thallium poisoning in twelve patients / 中国神经精神疾病杂志

Objective To investigate the clinical and electrophysiological features and treatments for thallium poisoning. Methods Twelve cases of thallium poisoning patients were from hospital 307 of PLA between June 2012 and October 2017 and their data were retrospectively analyzed. Twelve sex-and age-matched healthy subjects were selected as control group. Result The clinical manifestations of thallium poisoning were mainly symptoms of nervous and gastrointestinal systems as well as hair loss. Thallium poisoning compromised function of motor nerves including the prolonged distal latency of ulnar and common peroneal nerve, the decreased amplitude and slowed nerve conduction velocity of common peroneal nerve and tibial nerve, which were statistically different from control group (P<0.05). Thallium poisoning also impaired function of sensory nerve including the prolonged distal latency and decreased amplitude of median , ulnar and sural nerve, the slowed nerve conduction velocity of median , ulnar, radial and sural nerve which were statistically different from control group (P<0.05 or P<0.01 ). Electroencephalogram (EEG) of 7 cases revealed mild abnormality EEG in 6 cases and moderate abnormality EEG in one case. Patients received potassium supplementation, diuresis, oral Prussian blue, intramuscular injection of sodium dimercaptopropanesulfonate and other treatment. Severe cases had good outcome after hemoperfusion and plasma exchange. Conclusions Thallium poisoning is rare in clinic and typical clinical features and electrophysiological examination are helpful to the diagnosis and differential diagnosis of diseases. Timely increasing thallium excretion and symptomatic support treatment can effectively improve the prognosis of the patients.

Clopidogrel resistance: genetic polymorphism and drug interactions / 国际脑血管病杂志

Some patients with cardiocerebral vascular diseases still have recurrent ischemic events after clopidogrel administration,suggesting clopidogrel may not play an expected antiplatelet effect.Studies demonstrated that clopidogrel resistance was seen in some patients.The mechanism of clopidogrel resistance is still unclear.This article reviews the relationship between clopidogrel resistance and gene polymorphism and drug interactions.

L-calcium channel involving the generation and maintenance of bursting firing in rat substantia nigra pars compacta dopaminergic neurons / 中华神经科杂志

Objective To evaluate the role of calcium channel in the mechanism of the generation and maintenance of bursting firing of substantia nigra pars compacta (SNc) dopaminergic neurons in rats.Methods Using the patch clamp technique,we observed the firing pattern switching features after adding 10 μmol/L N-methyl-D-aspartic acid (NMDA),compared the changes of whole-calcium current and L-type calcium current with or without NMDA,and analyzed the correlation between the generation of burst firing and L-type calcium channel activation.Results After NMDA treatment,the firing pattern of SNc dopaminergic neurons changed to burst firing,which was compromised by a charastistic high plateau potential and series of action potential on it.The current density of L-type calcium current increased significantly after adding NMDA,which,from (2.86 ±0.26) pA/pF (n =28),significantly increased to (3.75 ± 0.18) pA/pF (n =34 ; t =7.52,P =0.002 8).The high plateau potential was almost abolished with the application of verapamil,a specific antagonist of L-type calcium channel.Consiusion NMDA could induce the firing pattern changed to burst firing in SNc dopaminergic neurons,while L-type calcium channel contributes to the process of generation and maintenance of burst firing.

Clinicopathologic features of post-transplant lymphoproliferative disorders / 中华器官移植杂志

ObjectiveTo study the clinicopathologic features of post-transplant lymphoproliferative disorders (PTLD).Methods Three cases of PTLD in renal transplant recipients were studied.The clinical data,diagnosis and differential diagnosis,and relevant literatures were also reviewed.Results All the 3 cases studied had received cyclosporine A or Tac after transplantation.The duration between organ transplantation and diagnosis of PTLD was 10 years,4 years and 2 months respectively.Two cases were suffered from monomorphic PTLD and 1 from plasmacytic hyperplasialike PTLD in morphology.Two cases of monomorphic PTLD died within one year after diagnosis.Conclusion PTLD is a lymphoproliferative disease with distinctive morphologic and clinical characteristics.The main treatments included the dosage reduction of immunosuppressive agents,radiotherapy and chemotherapy.The prognosis of monomorphic PTLD was poor.

Continuous renal replacement therapy for rhabdomyolysis-induced acute renal failure following trauma / 中华创伤杂志

Objective To improve diagnose and therapy of post-traumatic acute renal failure induced by rhabdomyolysis. Methods A total of 20 patients with post-traumatic acute renal failure induced by rhabdomyolysis were analyzed retrospectively in aspects of clinical manifestation, laboratory examination and treatment. Of all, there were 9 patients treated with continuous renal replacement therapy (CRRT), while the other 11 were set as control, receiving no CRRT. Results After treatment with CRRT, 7 patients obtained clinical curing, with 2 deaths. As for control patients, there were 5 patients with secondary chronic renal insufficiency, 1 with clinical curing and 5 deaths. Conclusions Early diagnosis, CRRT, sufficient hydration, hematedialysis and supportive treatment are key points to improve the cure rate. It is important to apply CRRT for patients with renal inadequacy.