Primary central nervous system lymphoma (PCNSL) is a rare invasive non-Hodgkin lymphoma. Although high dose methotrexate-based induced chemotherapy regimen has significantly improved prognosis of patients, 30 percent -40 percent of patients still relapse with poor prognosis. With the development of molecular biology, new targeted drugs like cell signaling pathway kinase inhibitors have become new treatment options for PCNSL.

Central sensitization is essential in maintaining chronic pain induced by chronic pancreatitis (CP), but cortical modulation of painful CP remains elusive. Here, we examined the role of the anterior cingulate cortex (ACC) in the pathogenesis of abdominal hyperalgesia in a rat model of CP induced by intraductal administration of trinitrobenzene sulfonic acid (TNBS). TNBS treatment resulted in long-term abdominal hyperalgesia and anxiety in rats. Morphological data indicated that painful CP induced a significant increase in FOS-expressing neurons in the nucleus tractus solitarii (NTS) and ACC, and some FOS-expressing neurons in the NTS projected to the ACC. In addition, a larger portion of ascending fibers from the NTS innervated pyramidal neurons, the neural subpopulation primarily expressing FOS under the condition of painful CP, rather than GABAergic neurons within the ACC. CP rats showed increased expression of vesicular glutamate transporter 1, and increased membrane trafficking and phosphorylation of the N-methyl-D-aspartate receptor (NMDAR) subunit NR2B and the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) subunit GluR1 within the ACC. Microinjection of NMDAR and AMPAR antagonists into the ACC to block excitatory synaptic transmission significantly attenuated abdominal hyperalgesia in CP rats, which was similar to the analgesic effect of endomorphins injected into the ACC. Specifically inhibiting the excitability of ACC pyramidal cells via chemogenetics reduced both hyperalgesia and comorbid anxiety, whereas activating these neurons via optogenetics failed to aggravate hyperalgesia and anxiety in CP rats. Taken together, these findings provide neurocircuit, biochemical, and behavioral evidence for involvement of the ACC in hyperalgesia and anxiety in CP rats, as well as novel insights into the cortical modulation of painful CP, and highlights the ACC as a potential target for neuromodulatory interventions in the treatment of painful CP.
Animals ; Anxiety/etiology* ; Chronic Pain/etiology* ; GABAergic Neurons ; Gyrus Cinguli/metabolism* ; Hyperalgesia/metabolism* ; Pancreatitis, Chronic/pathology* ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate/metabolism* ; Trinitrobenzenesulfonic Acid/toxicity*

Objective:To characterize the histopathological subtypes and their clinicopathological parameters of gender and onset age by common, rare and sparse primary esophageal malignant tumors (PEMT).Methods:A total of 272 437 patients with PEMT were enrolled in this study, and all of the patients were received radical surgery. The clinicopathological information of the patients was obtained from the database established by the State Key Laboratory of Esophageal Cancer Prevention & Treatment from September 1973 to December 2020, which included the clinical treatment, pathological diagnosis and follow-up information of esophagus and gastric cardia cancers. All patients were diagnosed and classified by the criteria of esophageal tumor histopathological diagnosis and classification (2019) of the World Health Organization (WHO). The esophageal tumors, which were not included in the WHO classification, were analyzed separately according to the postoperative pathological diagnosis. The χ 2 test was performed by the SPSS 25.0 software on count data, and the test standard α=0.05. Results:A total of 32 histopathological types were identified in the enrolled PEMT patients, of which 10 subtypes were not included in the WHO classification. According to the frequency, PEMT were divided into common (esophageal squamous cell carcinoma, ESCC, accounting for 97.1%), rare (esophageal adenocarcinoma, EAC, accounting for 2.3%) and sparse (mainly esophageal small cell carcinoma, malignant melanoma, etc., accounting for 0.6%). All the common, rare, and sparse types occurred predominantly in male patients, and the gender difference of rare type was most significant (EAC, male∶ female, 2.67∶1), followed with common type (ESCC, male∶ female, 1.78∶1) and sparse type (male∶ female, 1.71∶1). The common type (ESCC) mainly occurred in the middle thoracic segment (65.2%), while the rare type (EAC) mainly occurred in the lower thoracic segment (56.8%). Among the sparse type, malignant melanoma and malignant fibrous histiocytoma were both predominantly located in the lower thoracic segment (51.7%, 66.7%), and the others were mainly in the middle thoracic segment.Conclusion:ESCC is the most common type among the 32 histopathological types of PEMT, followed by EAC as the rare type, and esophageal small cell carcinoma and malignant melanoma as the major sparse type, and all of which are mainly occur in male patients. The common type of ESCC mainly occur in the middle thoracic segment, while the rare type of EAC mainly in the lower thoracic segment. The mainly sparse type of malignant melanoma and malignant fibrous histiocytoma predominately occur in the lower thoracic segment, and the remaining sparse types mainly occur in the middle thoracic segment.

Microneedle percutaneous immunization is achieved by puncturing the stratum corneum of the skin with microneedles so that the vaccine is efficiently recognized by antigen-presenting cells to induce a specific immune response. Due to the advantages of efficient induction of immune response, low pain and easy storage, transdermal immunization by microneedles has been widely used for immunization of various vaccines in recent years. This review summarizes the materials of microneedles, application for transcutaneous immunization, as well as the challenges that need to be addressed.
Administration, Cutaneous ; Drug Delivery Systems ; Needles ; Vaccination ; Vaccines

OBJECTIVE: To investigate the effects of different acupuncture manipulations on Deqi sensations and surface myoelectricity, and explore the correlation between Deqi sensations and needling manipulations. METHODS: Forty-five healthy participants accepted twirling, lifting-thrusting, and twirling plus lifting-thrusting manipulanions at right Zusanli (ST 36), respectively. The acupuncturist's and participants' Deqi sensations were collected by MGH Acupuncture Sensation Scale (MASS). The intensity and occurrence rate of soreness, dull pain, pressure, heaviness, fullness, numbness, sharp pain, warmth, coolness, and throbbing feelings of participants, and tightness, smooth, and tangle feelings of acupuncturist were measured. The correlation between the acupuncturist's and participant's Deqi sensations was analyzed. Surface electromyogram (EMG) were recorded before, during and after needling in 30 participants. The integrated EMG (iEMG), mean power frequency (MPF) and media frequency (MF) were analyzed. RESULT: Both fullness and soreness of participants and tightness of acupuncturist were the most frequently occurred ones. A positive correlation between participants' fullness and acupuncturist's tightness was observed during the three aforementioned needling manipulations (P<0.05, OR>1). Almost all the needling sensations measured in the present study could be induced by the three needling manipulations. However, strength of Deqi sensations was exhibited as lifting-thrusting > twirling plus lifting-thrusting > twirling according to MASS index. The iEMG values were increased and MPF, MF values were decreased during needling compaired to those before needling, especially during lifting-thrusting (P<0.01). CONCLUSIONS The intensity and occurrence rate of the different Deqi sensations induced by different needling manipulations were basically similar. The fullness and soreness were both the most frequently induced Deqi sensations. The strongest Deqi sensation could be induced by lifting-thrusting manipulation. There is a positive correlation between participants' fullness and acupuncturist's tightness during the three needling manipulations. The myoelectricity around the acupoint is related to Deqi responses. (Registration No. AMCTR-IOR-20000314).

Objective: To compare the effects between crude and processed Epimedii Folium on the rats of kidney-Yang deficiency and edema, in order to discuss the mechanism. Method: The rat model of kidney-Yang edema was duplicated with hydrocortisone and doxorubicin hydrochloride. At day 1 and day 8 of modeling, the rats were injected with doxorubicin hydrochloride (3.5 mg·kg^-1) via tail vein, while being intraperitoneally injected with hydrocortisone (3.75 mg·kg^-1·d^-1) for 15 days.After modeling,the rats were divided into model group,crude Epimedii Folium group(204.86 mg·kg^-1)and processed Epimedii Folium group(204.86 mg·kg^-1), and a normal control group was set up additionally.Rats in each treatment group were given the corresponding drugs,and those in normal and model groups were given the same volume of normal saline by gavage for continuous 14 days.At the end of the administration,24 h urine was measured by rat metabolic cage method; 24 h urinary protein was detected by ultraviolet spectrophotometry; the content of plasma albumin (ALB) and total serum protein (TP) were measured by an automatic biochemical analyzer; and the content of adenosine monophosphate was measured by enzyme-linked immunosorbent assay(ELISA). Cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), triiodothyronine (T₃), thyroxine (T₄), serum creatinine (SCr), serum urea(BUN), estradiol (E₂), testosterone (T) indicator content were determined by enzyme-linked immunosorbent assay(ELISA). Kidney tissues were collected to make pathological section by htoxylin eosin(HE) staining. Result: Compared with the normal group, all the indicators of appearance, biochemistry and pathological section in the model group indicated kidney Yang deficiency edema in the rats (P<0.05, P<0.01). Compared with the model group, both crude Epimedii Folium group and processed Epimedii Folium group showed a regulatory effect on indicators of appearance and pathological section kidney Yang deficiency edema; and in biochemical indicators, both crude Epimedii Folium group and processed Epimedii Folium group can regulate urine, urine protein, SCr, BUN, cAMP/cGMP, E₂, T indicators to varying degrees(P<0.05, P<0.01). Crude Epimedii Folium group showed a significantly regulatory effect on urine, urine protein, SCr, BUN (P<0.01); whereas processed Epimedii Folium group showed a significantly regulatory effect on cAMP/cGMP, E₂, T (P<0.01). In addition, crude Epimedii Folium group can also regulate ALB, TP (P<0.05, P<0.01), while processed Epimedii Folium group had no regulatory effect on these two indicators; however, processed Epimedii Folium group could regulate T₃, T₄ and anal temperature (P<0.05, P<0.01), while crude Epimedii Folium group had no regulatory effect on these two indicators. Conclusion: Both crude Epimedii Folium group and processed Epimedii Folium group have certain effect in treating kidney Yang deficiency edema, and the possible mechanism is to alleviate glomerular podocyte injury induced by doxorubicin. Their emphasis in the treatment of kidney Yang deficiency edema is different. Crude Epimedii Folium has a cold property, and can treat kidney Yang deficiency edema by strengthening renal excretion function of rats with kidney Yang deficiency edema. Processed Epimedii Folium is processed with sheep oil to produce icariin and other substances, and its property changed from cold to warm, with a focus on alleviating the kidney Yang deficiency status of rats with kidney Yang deficiency edema.

Objective:Flavonoids,as the major constituents in Oroxyli Semen,had a variety of pharmacological effects against inflammation,infections,and oxidation. In this study,an ultra-high performance liquid chromatography (UPLC-Q-TOF-MS) method was established to analyze and identify the various flavonoids in Oroxyli Semen. Method:The separation was performed on an Kinetex-XB C₁₈ column(2.1 mm×50 mm,1.7 μm)with gradient elution,which was carried out with 0.1%formic acid acetonitrile as mobile phase. The flow rate was 0.25 mL·min^-1,and the injection volume was 3 μL. Electrospray ionization source was in the negative ion mode. Target and non-target screenings were carried out by Peakview 2.2 and Masterview 1.0 software. Then the identification of target compounds were completed based on accurate mass,isotopic abundance ratio and MS/MS fragment,and the non-target compounds were determined according to literature reports and MS cleavage mechanism. Result:According to the high resolution MS spectra data,fragmentation ion information and retention time,36 peaks of Oroxyli Semen were identified, including 10 flavonoids and 26 flavonoid glycosides according to literature reports and MS cleavage mechanism. Conclusion:The study comprehensively analyzes the chemical composition of Oroxyli Semen,which is significant to study of the chemical constituents, quality control and material basis of Oroxyli Semen.

Objective To investigate the clinical significance of bone marrow immunopathogenesis in the diagnosis and staging of lymphoma. Methods Clinical data of 266 patients with newly diagnosed lymphoma admitted to Department of Hematology in the First Hospital of Jilin University from August 2015 to December 2017 were retrospectively analyzed. The results of lymphoma diagnosis and staging in different bone marrow detection methods were compared, SPSS 22.0 software was used to make statistical analysis and χ2 test was used to compare the positive rates of lymphoma bone marrow infiltration in different methods. Results In the 266 patients, 64 cases (24.1 %) were diagnosed with lymphoma by using bone marrow detection on the condition that no lymph node pathology was available and all the immunophenotypes of 64 cases were identified by bone marrow immunopathology. Bone marrow infiltration was identified in 121 patients (45.5 %), among which the rate of bone marrow infiltration was 0 (0/12) in Hodgkin lymphoma (HL) and 47.6 % (121/254) in non-Hodgkin lymphoma (NHL). The rate of bone marrow infiltration was 50.0 % (105/210) and 36.4 % (16/44) in B type and T type NHL respectively. The positive rate of bone marrow infiltration detected by bone marrow smear, bone marrow biopsy, bone marrow flow cytometry and bone marrow immunopathology were 78.5 % (95/121), 87.6 % (106/121), 89.3 % (108/121), 96.7 % (117/121) respectively. Bone marrow immunopathology was more advantageous than any other methods, and there was a statistical difference (χ2＝18.38, 9.09, 3.76; all P < 0.05). Among 121 patients who were identified with bone marrow infiltration by bone marrow detection, the staging of 42 patients (34.7 %) were amended, including the staging of 39 amended patients (32.2 %) through bone marrow immunopathologic detection. Conclusion Bone marrow immunopathology can be used for the diagnosis and classification of lymphoma, which has an obvious advantage in detecting bone marrow infiltration of lymphoma compared with bone marrow smear, bone marrow biopsy, bone marrow flow cytometry, and it can be used to amend the clinical staging.

Aim To investigate the effects of Periplane-ta americana extract Ento-A on the immune function in immunosuppressed mice . Methods Immunosup-pressed mouse model was induced by intraperitoneal injection of cyclophosphamide in KM mice .To evalu-ate the effects of Ento-A on the immune function in im-munosuppressed mice , neutral red method and MTT assay were used respectively to detect the effects of En-to-A on the phagocytosis of peritoneal macrophages and T cell proliferation rate in mice; with sheep red blood cell as immunogen , the effects of Ento-A on the pro-duction of serum hemolysin were evaluated;peripheral blood was tested and immune organ index calculated . Results Compared with model control group , the high, medium and low doses of Ento-A could improve the expression of serum hemolysin in immunosup-pressed mice ( P<0.01 ) , and increase the spleen in-dex(P<0.01) and thymus index (P>0.05), signifi-cantly increased the content of WBC ( P<0.01 ) , PLT ( P<0.01 ) , HGB ( P<0.01 ) , while the contents of RBC was on the rise , with no significant difference ( P>0.05 ) in peripheral blood , significantly enhanced phagocytic function and T lymphocyte proliferative abil-ity in a dose-dependent manner ( P<0.01 ) .Conclu-sion Ento-A can enhance the immune function of im-munosuppressed mice .

Objective To investigate the molecular mechanisms of upregulated expression of cellular Fas-associated death domain-like interleukin-1 beta converting enzyme inhibitory protein(c-FLIP)by calreticulin(CRT)in patients with rheumatoid arthritis (RA). Methods The semi-quantitative analysis and localization of c-FLIP in RA and osteoarthritis (OA)synovium were detected by immunohistochemistry.The fibroblast-like synoviocytes(FLS)were isolated by enzymatic digestion of synovial tissue specimens obtained from RA and OA patients,and cultured as an in vitro experiment model.The expressions of c-FLIP in RA and OA synovial fibroblasts were detected by immunofluorescence and Western blot assay. Whether CRT influenced c-FLIP expression and its molecular mechanism were explored by Western blot assay. Results The high expression of c-FLIP was found in RA synovium, mainly in the lining and sublining areas of FLS and vascular endothelial cells detected by immunohistochemistry.Meanwhile,weak staining of c-FLIP was observed in OA synovium.The expression of c-FLIP was significantly higher in RA synovium than that of OA synovium(t=11.717,P<0.001).Results of immunofluorescence and Western blot assay showed that c-FLIP was mainly located in cytoplasm, and which was higher expressed in FLS of RA than that of OA. The increased c-FLIP expression and phosphorylation of NF-κB were detected after being co-incubated with exogenous CRT (0, 10, 50, 100 μg/L), in dose-dependent manner. The effect of CRT upregulating c-FLIP expression was blocked by NF-κB inhibitor BAY 11-7082.Conclusion CRT can increase c-FLIP expression at least partly through NF-κB pathway in RA,which may provide therapeutic target for the treatment of RA.