Antigens ; chemistry ; Fixatives ; chemistry ; Humans ; Hydrogen-Ion Concentration ; Immunohistochemistry ; methods ; Microwaves ; Staining and Labeling ; methods

Aged ; Antigens, CD20 ; analysis ; Gene Rearrangement ; Humans ; Immunoblastic Lymphadenopathy ; genetics ; metabolism ; pathology ; Immunoglobulin Heavy Chains ; genetics ; Immunohistochemistry ; Lymph Nodes ; metabolism ; pathology ; Lymphoma, T-Cell ; genetics ; metabolism ; pathology ; Male ; Polymerase Chain Reaction ; RNA, Viral ; analysis ; Receptors, Antigen, T-Cell, gamma-delta ; genetics ; Reed-Sternberg Cells ; metabolism ; pathology

Antigens, CD34 ; metabolism ; Cytokines ; metabolism ; Diagnosis, Differential ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Mucin-1 ; metabolism ; Perineum ; pathology ; Phosphopyruvate Hydratase ; metabolism ; Sarcoma ; metabolism ; pathology ; surgery ; Vimentin ; metabolism

Abstract: Objective To analyze the changes of coagulation indicators in patients with hepatitis B complicated with Clonorchis sinensis (C. Sinensis), and provide reference value for diagnosis, drug using and prognosis monitoring. Methods　The patient samples were collected from the Third Affiliated Hospital of Sun Yat-sen University from June 2018 to February 2022 and divided into six groups. They were 40 healthy patients, 47 patients with simple chronic hepatitis B, 47 patients with post-hepatitis B liver cirrhosis, 40 patients with C. Sinensis mono-infection, 30 patients with chronic hepatitis B patients co-infected with C. Sinensis and 27 patients with post-hepatitis B liver cirrhosis patients coinfected with C. Sinensis. Four coagulation indexes, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and fibrinogen (FIB), were detected and compared among the groups. Results Compared with the healthy group, C. Sinensis mono-infection group had higher level of FIB and delayed PT, APTT; chronic hepatitis B group and chronic hepatitis B patients co-infected with C. Sinensis group had delayed PT, APTT, TT and significant lower FIB, these differences were statistically significant (all P<0.05). Compared with simple chronic hepatitis B group, post-hepatitis B liver cirrhosis and chronic hepatitis B patients co-infected with C. Sinensis had significant delayed PT, APTT, TT and lower FIB (all P<0.05). Compared with the post-hepatitis B liver cirrhosis and chronic hepatitis B patients co-infected with C. Sinensis, post-hepatitis B liver cirrhosis patients coinfected with C. Sinensis group had significant delayed PT, APTT, TT and lower FIB (all P<0.05). Conclusions The coinfection of C. Sinensis will further aggravate the coagulation dysfunction of HBV patients, leading to poor treatment and prognosis. HBV patients will have worse coagulation function in the process to post-hepatitis B liver cirrhosis; Therefore, it is important to pay attention to C. Sinensis co-infection when treating HBV patients, so that further guidance on clinical use and monitoring of prognosis can be provided.

italic>α-Conotoxin ArIB[V11L,V16D] is currently the most optimal selective inhibitor of α7 nicotinic acetylcholine receptor (nAChR) known. In order to explore chemical modification methods and enrich its application in targeting nAChR, this study utilized the linker to covalently connect camptothecin and 7-amino-4-methylcoumarin to the [2,4] disulfide bond of ArIB[V11L,V16D]. Therefore, two peptide-drug conjugates (PDCs), ArIB[V11L,V16D]-5 and ArIB[V11L,V16D]-6, and one fluorescent-labeled peptide, ArIB[V11L,V16D]-7 were constructed. Cytotoxicity evaluation showed that the IC₅₀ values against non-small cell lung cancer cell line A549 of the two PDCs were respectively 1.3 and 4.1 times of camptothecin, indicating slight reduction in activity at the cellular level which was related to the linker structure. Fluorescence spectrum scanning revealed that the excitation and emission wavelength of the fluorescent-labeled peptide were 340 nm and 403 nm respectively, and the fluorescence features of 7-amino-4-methylcoumarin as a marker were retained without fluorescence quenching. This modification strategy laid a solid foundation for the further application of α-conotoxin ArIB[V11L,V16D] in PDCs and fluorescent probes.

Objective To evaluate the efficacy and safety of ESHAP regimen,as a salvage regimen, in treating patients with relapsed or refractory aggressive NHL.Methods 38 patients with relapsed or refrac- tory aggressive NHL were selected to be treated by ESHAP regimen.Results The 38 patients received ES- HAP regimen with a range of 2～6 cycles. The total RR was 55.3 % with complete response(CR)rate of 26.3 %.The major toxicity was myelosuppression with infection,which was tolerable.Conclusion ESHAP regimen is one of safe and effective salvage regimens for the patients with relapsed or refractory aggressive NHL.

Adult ; Fabry Disease ; pathology ; Female ; Follow-Up Studies ; Humans ; Kidney Glomerulus ; pathology ; ultrastructure ; Proteinuria

Nicotinic acetylcholine receptors (nAChRs) belong to ligand-gated ion channel receptors, of which α7 nAChR subtype is widely distributed in the cerebral cortex, thalamus, hippocampus, and also identified in microglia, macrophages, bone marrow cells, etc. Previous studies revealed that α7 nAChR is closely related to the function of the cholinergic anti-inflammatory pathway, and is a vital target for drug development of Alzheimer's disease and schizophrenia. The establishment of a stable α7 nAChR in vitro drug screening system is crucial for the efficient screening of novel drugs targeting this target. Recombinant expression of different subtypes of nAChRs on Xenopus laevis oocyte membranes and current detected by two-electrode voltage clamp (TEVC) is an advanced and complex model for novel drug screening. Molecular chaperones can assist the assembly of some nAChR subunits to form functional receptors, providing a stable expression model for the screening of compounds targeting this receptor. In this study, a molecular chaperone gene of α7 nAChR, transmembrane protein 35A (Tmem35a), was isolated and cloned from rats. We constructed the recombinant expression vector and obtained the cRNA of Tmem35a by in vitro transcription technique. Two cRNAs (Tmem35a and α7) were mixed and injected into X. laevis oocytes for expression. Then, the effects of this molecular chaperone on the current expression and pharmacological properties of α7 nAChR were evaluated by the TEVC. The results revealed that TMEM35A, also known as novel acetylcholine receptor chaperone (NACHO) could effectively increase the expression of α7 nAChR protein on oocyte membranes, and the amount of α7 nAChR protein was increased about 1-fold. The peak current induced by agonist acetylcholine (ACh) was increased about 10-fold. After injection of Tmem35a cRNA, the median effect concentration (EC₅₀) value of α7 nAChR to agonist ACh is 228.5 μmol·L^-1, which shows almost no difference from native α7 nAChR (EC₅₀: 223.3 μmol·L^-1), indicating the preservation of the normal properties of α7 nAChR. The results of this investigation indicate that the molecular chaperone NACHO effectively assists the heterologous expression of α7 nAChR in X. laevis oocytes, which provides a model for screening the potency of lead compounds targeting α7 nAChR. All animal experiments in this study were reviewed and approved by the Ethics Committee of Guangxi University (approval number: GXU-2023-0249).

N-type voltage-gated calcium (Ca²⁺) channels (N-type VGCC, Ca_V2.2) mediate Ca²⁺ influx in response to action potential at the presynaptic terminal, and play an important role in synaptogenesis, neurotransmitter release and nociceptive signal transduction. It is a new target for the development of drugs for the treatment of neuralgia (chronic pain) and other major diseases. Due to the difficulty of calcium channel expression in vitro and the detection of channel current, there is a great lack of new drug screening models. In this study, we established and optimized the electrophysiological drug screening model using Xenopus laevis oocytes for the recombinant expression of Ca_V2.2 in vitro (this study were reviewed and approved by the Ethics Committee of Guangxi University, approval number: GXU-2023-0249). Firstly, the linear plasmids encoding cDNA of major subunit α1B and auxiliary subunits α2δ1 and β3 of rat Ca_V2.2 were used as templates for in vitro transcription to generate their related mRNA (cRNA), after which three kinds of cRNA were injected into Xenopus laevis oocytes at the mass ratio of 2∶1∶1 for expression. The two-electrode voltage clamp (TEVC) technique was used to detect the inward current produced by Ca_V2.2. At the same time, the expression conditions of Ca_V2.2 were optimized, and its gating function was characterized from the aspects of channel activation and inactivation. The results showed that 3-5 days after cRNA microinjection, stable Ca_V2.2-mediated barium ion (Ba²⁺) currents were successfully detected. The interference of endogenous potassium channels and Ca²⁺-activated chloride channels can be eliminated by tetraethylammonium hydroxide (TEAOH) and 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis (BAPTA-AM) treatment. The maximum potential for Ca_V2.2 activation is 0 mV, and the current reverses to be outward when the membrane potential is greater than +50 mV. By fitting the steady-state activation and inactivation curves, the half-maximal activation potential and half-maximal inactivation potential of Ca_V2.2 are identified as -15.9 and -60.2 mV. In this study, a stable Ca_V2.2 expression system was established based on Xenopus laevis oocytes. The in vitro expression system can provide a new way for the screening of Ca_V2.2 active compounds or lead drugs.

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cyclophosphamide ; therapeutic use ; Doxorubicin ; therapeutic use ; Female ; Follow-Up Studies ; Genes, Immunoglobulin Heavy Chain ; Genes, bcl-2 ; Genes, myc ; Humans ; Lymphoma, B-Cell ; drug therapy ; genetics ; pathology ; Male ; Methotrexate ; therapeutic use ; Prednisone ; therapeutic use ; Translocation, Genetic ; Vincristine ; therapeutic use