Immune checkpoint blockade can promote the tumor?specific cytotoxic T?lymphocyte ( CTL) response. However, only a small proportion of patients have good response to immune checkpoint blockade. It has been reported that radiotherapy combined with immune checkpoint blockade can promote antigen presentation, which further enhances the tumor?specific CTL response;moreover, the combined therapy achieves better treatment outcomes than radiotherapy alone or immune checkpoint blockade alone. The latest study has shown that radiotherapy combined with dual immune checkpoint blockade has better efficacy than radiotherapy combined with CTLA?4 blockade in patients with melanoma. Therefore, radiotherapy combined with immune checkpoint blockade will become a new approach for treating tumor. This paper reviews the research advances in the combined therapy.

OBJECTIVE To investigate incidence and drug susceptibility of Helicobacter pylori(Hp) in local area.METHODS Strains of Hp were isolated and cultivated from gastric antrum mucosa of 141 peptic ulcer disease(PUD) patients diagnosed by gastroscope.The drug sensitive test of Hp strains was examined by K-B method.RESULTS The isolation rate of Hp in 141 PUD patients was 75.2%.Hp isolates showed a relative hypersensitivity to clinical commonly used drugs(ie furazolidone,amoxicillin,levofloxacin,cefuroxime and moxifloxacin).On the other hand,Hp isolates exhibited resistance to metronidazole and clarithromycin.CONCLUSIONS Hp is an important etiologic factor of PUD,and showing an increasing resistance to common clinical antibiotics.

Objective To discuss the treatment action and mechanism of Wenjing Tongluo Formula on oxaliplatin-induced perpheral neurotoxicity in rats. Methods Intraperitoneal injection was used to inject oxaliplatin 4 mg/kg to establish oxaliplatin-induced peripheral neurotoxicity rat models. Female Wistar rats were randomly divided into normal group, model group, and TCM group. TCM group was given Wenjing Tongluo Formula to soak rats’ limbs and tails. Rats in the model group were soaked with deionized water for comparison. Rats in the normal group received intraperitoneal injection with 5%glucose. Algesia hypersensitivity and anaphylaxis were detected under the mechanical stimulation and temperature. Immunohistochemical method was used to detect the expression of GFAP in L4-L6 spinal dorsal horn of rats. Explore the level of GLT-1 in L4-L6 dorsal root ganglia by RT-PCR. Results Rats in model group showed obvious behavioral changes compared with normal group (P<0.05);Rats in the TCM group improved in behavioristics compared with model group (P<0.01);number of positive cells in GFAP of rats in the model group increased compared with normal group (P<0.05);the increase in the TCM group was not obvious. Compared with normal group, astrocytes in spinal dorsal horn of model group were enlarged, protuberances increased, became coarse, and GLT-1 mRNA is decreased (P<0.05, P<0.01). Compared with model group, active cells and protuberances in the TCM group decreased (P<0.01), GLT-1 mRNA is increased (P<0.01). Conclusion Wenjing Tongluo Formula can improve behavioral changes of model rats under temperature and mechanical stimulation, probably related to harmful signal transmission induced by inhibition of astrocyte in spinal dorsal horn.

Clinical features and related information on diagnosis and treatment of 45 cases of Castleman's disease (CD) were retrospectively analyzed.Based on the clinical classification, localized CD (LCD) was found in 26 cases, multicentric CD (MCD) was found in 19 cases.Most cases of LCD presented the symptoms of compression, while MCD had complicated and non-specific clinical manifestations, making the early diagnosis more difficult.All 26 cases with LCD underwent surgery, among which only 2 cases relapsed.Sixteen out of 19 patients with MCD were treated with glucocorticoids or combined chemotherapy, and 14 cases achieved complete or partial remission.The results show that patients with CD have variant manifestation and the diagnosis depend on CT scan or histopathology examination.Most LCD can be cured by complete surgical resection, and MCD can achieve remission by the treatment with glucocorticoids or combined chemotherapy.

Objective: To investigate the effects of Tim-3 on osteoclast-like cell (OLC) formation and bone resorption induced by peripheral blood mononuclear cells (PBMCs). Methods: The expression levels of Tim-3 in of rheumatoid arthritis (RA) patients and healthy controls were detected by flow cytometry. The OLCs were induced by human PBMCs in vitro. The expression levels of tartrate-resistant acid phosphatase (TRAP), cathepsin K (CTSK) and matrix metalloproteinase 9 (MMP9) mRNAs in the formation of OLCs were detected by real-time quantitative PCR. The morphology of OLCs was observed by Wright′s staining and G-actin staining, and the number of OLCs was counted by TRAP staining. The number and area of bone resorption pits in OLCs were detected by the Corning Osteo Assay Surface. Results: The expression levels of Tim-3 in PBMCs of RA patients ([77.31±10.66]%) were significantly higher than that of healthy controls ([51.72±16.69]%, t=7.593, P＜0.01). When PBMCs with different Tim-3 levels were induced into OLCs, the area of bone resorption pits in the high Tim-3 level group ([1.054±0.085] S/mm 2 ) were significantly lower than those in the intermediate Tim-3 level group ([1.889±0.053] S/mm 2 ) and the low Tim-3 level group ([2.763±0.066] S/mm 2 , F=9.318, P＜0.05). Conclusion Tim-3 may negatively regulate the bone resorption of OLCs.

OBJECTIVETo detect memory B lymphocyte (Bm) in peripheral blood (PB) of immune-related pancytopenia (IRP).

METHODS86 patients with IRP and 11 health volunteers were enrolled in this study. Bm (CD5⁺ CD19⁺ CD27⁺) and bone marrow mononucleated cell antibodies (BMMNC-Ab) were determined via fluorescence-activated cell sorting, and clinical outcomes of these patients were analyzed.

RESULTS(1)43 initial patients achieved obvious remission in all 52 initial cases after conventional immunosuppression therapy. 16 relapsed patients with IRP received Rituximab (RTX) and 14 cases achieved obvious remission, among which 7 cases were refractory to conventional immunosuppression therapy, 5 cases exhibited obvious remission, and 2 cases did not respond. Other 18 relapsed cases received conventional immunosuppression therapy and 13 cases achieved obvious remission. (1)The level of Bm in PB in 52 initial patients with IRP was(1.81 ± 0.97)%, and no significant difference was observed between the initial patients and health volunteers (1.75 ± 0.55)% (P>0.05). The level of Bm in PB in 34 relapsed patients with IRP was obviously higher than that in the initial IRP patients and health volunteers (P<0.05). Significant difference was observed in the level of Bm in PB in 16 relapsed IRP patients between pre-therapy and post-therapy with RTX (P<0.05). No statistical difference was found between the remission and no-response groups in relapsed patients treated with RTX. RTX regimen produced more effective outcome than conventional immunosuppression therapy, which better eliminated Bm than the latter (P<0.05). Initial patients with IRP who relapsed within a two-year follow-up period had a lower level of Bm in PB compared with un-relapsed patients (P<0.05). Majority of BMMNC- Ab antibodies in relapsed patients were IgG (82.4%) and IgM (69.2%) autoantibodies in patients with initial IRP.

CONCLUSIONThe level of Bm in PB was associated with relapsed patients with IRP. Bm did not respond to conventional immunosuppression therapy,but responded to RTX.

Adolescent ; Adult ; Antibodies, Monoclonal, Murine-Derived ; therapeutic use ; B-Lymphocyte Subsets ; immunology ; Female ; Humans ; Immunologic Memory ; Immunosuppression ; Male ; Middle Aged ; Pancytopenia ; immunology ; therapy ; Recurrence ; Rituximab ; Treatment Outcome ; Young Adult

Background Exposure to perfluoroalkyl and polyfluoroalkyl substances (PFAS) during pregnancy might affect thyroid-related hormone levels in pregnant women. However, most previous studies focused on the effects of PFAS containing 8-10 carbon atoms, and few studies have estimated the associations between PFAS with longer carbon chain and thyroid-related hormone levels. Objective To examine the associations between PFAS exposure and thyroid-related hormones in pregnant women. Methods The present study was based on the Jiashan Birth Cohort from September 2016 to April 2018. We analyzed 13 PFAS in maternal blood samples (n=781) by high-performance liquid chromatography-tandem mass spectrometry, as well as total triiodothyronine (T3), total thyroxine (T4), free T3 (FT3), free T4 (FT4), thyroid stimulating hormone (TSH), thyroglobulin antibody (TG-Ab), and thyroid peroxidase antibody (TPOAb) by electrochemiluminescence immunoassay. PFAS were divided into three groups:low concentration, medium concentration and high concentration according to the tertile of their concentrations. We estimated the associations between PFAS concentrations and thyroid-related hormones in pregnant women by multiple linear regression. Results In the multiple linear regression models, a change in perfluorododecanoic acid (PFDoA) concentrations from the low concentration group to the high concentration group was associated with a −0.10 (95%CI: −0.20, 0) nmol·L⁻¹ change in T3, −0.15 (95%CI: −0.28, −0.02) pmol·L⁻¹ change in FT3, and −3.02 (95%CI: −5.66, −0.39) pmol·L⁻¹ change in FT4, respectively. A change in perfluorotridecanoic acid (PFTrDA) concentrations from the low concentration group to the high concentration group was associated with a −0.10 (95%CI: −0.20, 0) nmol·L⁻¹ change in T3. Compared with the low concentration group, the concentration of T4 in the medium concentration group of perfluorohexane sulfonate (PFHxS) increased by 6.10 (95%CI: 0.44, 11.75) nmol·L⁻¹. No statistically significant associations were found between PFAS and TSH concentration. The negative associations of PFAS with thyroid-related hormones were more pronounced in pregnant women with positive TG-Ab and/or TPOAb. Conclusion Exposure to PFAS during pregnancy may affect thyroid-related hormone homeostasis in pregnant women, and the effect is stronger in TG-Ab and/or TPOAb-positive pregnant women.