Rheumatoid arthritis (RA) is a chronic autoimmune disorder primarily occurred in small joints.Our previous studies suggested that sufficient lymphatic drainage was favorable for the recovery of RA.This study aimed at exploring the effect of Er Chen combined with Tao Hong Si Wu Tang (ECSWT) on RA in TNF transgenic (TNF-Tg) mice.Ten-week old TNF-Tg mice and WT littermates were detected with indocyanine green-nearinfrared (ICG-NIR) lymphatic imaging system before and after accepting the 12-week intragastric administration of ECSWT.All ankle joints were assessed by micro-CT scanning.According to three dimensional images of Micro-CT,it was found that the ankle joints in the TNF-Tg group were much eroded compared with the control group.The bone mass and structure were protected after the treatment of ECSWT.ICG-NIR results showed that lymphatic clearance rate of the TNF-Tg group decreased compared with those of the control group.In comparison with the TNF-Tg group,ECSWT promoted the repair of lymphatic function.Compared with the control group,the pulse value of the TNF-Tg group declined;while this condition could be rescued by ERSWT.In conclusion,ECSWT mitigated bone erosion of astragalus bone area in TNF-Tg mice in contrast to the saline mice,while promoted the pulse value and clearance of lymphatic vessels afferent from footpad to popliteal lymph node,implying that ECSWT was a promising agent for treating RA through its promoting lymphatic drainage function effects.

Objective To investigate the protective effect of retigabine (a M-type potassium channel opener) on brains and its mechanism in male mice after acute cerebral ischemia reperfusion(I/R)injury.Methods Seventy male C57BL/6J mice were randomly divided sham-operated group (n=10),middle cerebral artery occlusion (MCAO) group (n=10) and prevention group (n=50) according to the random number table method;mice in the prevention group were then divided into XE991 (a M-type potassium channel blocker) group,RTG-treatment 0 h group,RTG-treatment 1 h group,RTG-treatment 3 h group,and RTG-treatment 6 h group (n=10).The MCAO models were established by suture method,and reperfusion was performed 90 min after cerebral ischemia.In RTG-treatment groups,a single dose of 10.5 mg/kg RTG was injected at the designated varying time points (0,1,3 and 6 h after the reperfusion);in XE991 group,a single dose of 3.0 mg/kg XE991 was injected after the reperfusion;mice in the sham-operated group and MCAO group received the same volume of saline.Twenty-four h after model making,infarct size was measured by TTC staining.HE staining was used to observe the morphological changes of neurons in hippocampal CA1 regions.The apoptotic neurons level and membrane protein CD40L expression in the ischemic penumbra were detected by TUNEL staining and Western blotting.Results In the sham-operated group,brain tissues had no obvious change,no infarction was observed,there was no CD40L expression,and TUNEL staining positive neurons were hardly found.(1) Cerebral artery territory infarction was visible in the MCAO group and intervention group;however,the infarction volume of the RTG-treatment groups was significantly lower than that in the MCAO group (P＜0.05);the infarction volume of the RTG-treatment 6 h group was increased as compared with that of the RTG-treatment 0 h group,RTG-treatment 1 h group,and RTG-treatment 3 h group,without significant difference (P＞0.05).(2) HE staining showed that hippocampal neurons were obviously swollen and necrotic in the MCAO group and XE991 group,while the pathological damages such as brain edema and neuron necrosis were ameliorated significantly in the RTG-treatment groups.(3) As compared with those in the MCAO group,the number of TUNEL staining positive neurons in the RTG-treatment 0 h group,RTG-treatrnent 1 h group,and RTG-treatment 3 h group and CD40L number in the RTG-treatment 0 h group and RTG-treatment 3 h group were decreased significantly (P＜0.05);as compared with that in the MCAO group,the number of TUNEL staining positive neurons increased significantly in the XE991 group (P＜0.05).Conclusion RTG has protective effect on cerebral I/R,and its mechanism might relate to reducing cell excitability and inflammation,thereby inhibiting cell apoptosis;these protection would be less effective when RTG is used outside a defined critical period of time.

Primary plasma cell leukemia (pPCL) is a rare and aggressive plasma cell disorder with distinct clinical and biological features.Thanks to the application of novel agents such as proteasome inhibitors (e.g.bortezomib) and immunomodulatory drugs (e.g.thalidomide and lenalidomide),along with stem cell transplantation,the outcome of pPCL has been improved a lot.Despite therapeutic advances,the current understanding of pPCL biology is still limited due to the lack of availability of clinical samples.This review provides the recent progress of the diagnostic and therapeutic options in pPCL.

Huntington's disease (HD) is an autosomal dominant inherited disease with insidious onset and slow progression, mainly characterized by chorea-like symptom, intelligence decline, and psychiatric abnormalities. Cause of the disease is abnormal expansion of CAG trinucleotide repeat sequences in the first exon of the Huntington gene (HTT) on chromosome 4. Despite the clear etiology, currently, no effective therapeutic measures to control the disease progress is noted, and symptomatic treatment is still the main treatment in clinical practice. This article provides a brief overview of the current clinical trials, clinical challenges, and future development of HD gene therapy to provide references for subsequent related research.

Objective To investigate the clinical characteristics of plasma cell malignancies with t(11;14) and the effect of t(11;14) on prognosis. Methods A cohort of 380 newly diagnosed patients with plasma cell malignancies were analyzed,including 146 females and 234 males.There were 370 cases of newly diagnosed multiple myeloma (NDMM), as well as 10 cases of primary plasma cell leukemia (PCL). The relationship between the categorical variables was evaluated by using the bilateral Fisher exact probability test, with 95 % confidence interval. Results Of 370 NDMM cases, t(11;14) was detected in 101 cases (27.3 %). Of 10 PCL cases, 8 cases displayed t(11;14). The detection rate of t(11;14) was significantly higher in IgD, IgM and non-secreting MM [50.9 % (27/53)] than that in IgA MM [21.6 % (16/78)] and IgG [28.4 % (52/183)] (both P= 0.002). The rate of CD56+in t(11;14) positive group was lower than that in t(11;14) negative group [51.6 % (48/93) vs. 72.0 % (167/232), P= 0.001], and the rate of CD117+was also significantly decreased [23.7 % (22/93) vs. 37.7 % (87/231), P= 0.019]. There were 86 cases of non-t(11;14) IgH rearrangement in 269 cases of NDMM without t(11;14), which mainly were t(4;14) or t(14;16). The detection rate of high risk MM was only 11.9 %(12/101)in t(11;14)positive group,while that rate was 27.5 % (74/269) in t(11;14) negative group, the difference was statistically significant (P = 0.001). Conclusion MM with t(11;14)displays distinct biological,clinical and laboratory features,it is a heterogeneous disease.

Objective: To elucidate the expression levels of key immune biomarkers, phosphate and tension homology deleted on chromosome ten (PTEN) and programmed cell death protein1(PD-1),of different immune tolerance pathway in classic Hodgkin’s lymphoma (CHL) to further determine their clinical role and prognostic significance. Methods: The clinical features and prognostic factors of 56 CHL patients, who were admitted to the TianJin Medical University Cancer Institute from February 2003 to August 2013, were retrospectively analyzed. PTEN and PD-1 protein expression levels were analyzed by immunohistochemistry, Epstein-Barr virus encoded RNA (EBER) was performed by in situ hybridization assay. Correlations between the expression of biomarkers and clinicopathologic parameters were examined and survival analyses were performed. Results: This cohort of 56 CHL patients included 34 males and 22 females with a median age of 25 years (ranged from 7 to 71 years). In a univariate analysis, age≥45, IPS score >2, EBER positive, high expression of PTEN protein conferred inferior 5-year OS and 5-year PFS; In a multivariate model, age≥45, IPS score >2, EBER positive, high expression of PTEN protein were identified as the independent adverse prognostic factors for CHL. Conclusions This study suggested for the first time that PTEN was independent prognostic immune biomarkers in CHL, which provided the novel therapeutic strategy of immune therapy for CHL.

Objective: The purpose of this study is to investigate the anti-diabetic effects of linarin, a flavonoid extracted from Chrysanthemi Indici Flos (CIF), and its potential mechanisms. Methods: The effects of linarin on cell viability and glucose consumption in HepG2 cells were measured. Meanwhile, monosodium glutamate (MSG) mouse model was constructed to monitor the changes of insulin tolerance, glucose tolerance, triglyceride and cholesterol. The protein expression levels of p-AMPK, p-ACC, PEPCK and p-GS were detected by Western blot. Results: Linarin could increase the relative glucose consumption of HepG2 cells, improve insulin tolerance and glucose tolerance, and decrease the levels of triglyceride and cholesterol of MSG mice. Simultaneously, the expression levels of p-AMPK and p-ACC in HepG2 cells and the liver tissue of MSG mice were increased, while the expression levels of PEPCK and p-GS were decreased after treatment with linarin. Conclusion: Insulin resistance could be ameliorated by linarin in type 2 diabetes, and its mechanism may be related to AMPK signaling pathway.

ObjectiveTo observe the intervention effect of Ruyi Zhenbao pills （RYZBP） on central pain after thalamic stroke in mice and explore the underlying mechanism. MethodThe central post-stroke pain syndrome （CPSP） model was induced by stereotactic injection of type Ⅳ collagenase into the hypothalamus in mice. The mice were divided into a sham group， a model group， low-， medium-， and high-dose RYZBP groups （0.65， 1.3， 2.6 g·kg^-1）， and a pregabalin group （0.075 g·kg^-1）. Seven days after modeling， the mice in the groups with drug intervention were administered with corresponding drugs by gavage according to the body mass， once per day for 25 days， while those in the sham group and the model group received an equal volume of normal saline. During this period， mechanical pain and cold pain were detected at different time points， and the apoptotic state of brain tissue cells was detected by in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling （TUNEL）. The 36 classical broad-spectrum inflammatory factors were quantitatively analyzed by liquid-phase chip technology， and differential molecules were screened out and verified by Western blot and enzyme-linked immunosorbent assay （ELISA）. ResultCompared with sham operation group, mechanical pain threshold and cold sensitive pain threshold in model group were significantly changed （P<0.01）. TUNEL results showed that apoptosis of brain cells was obvious. Western blot and ELISA results showed that the expressions of interleukin-1α (IL-1α) and chemokine ligand 5 (CCL5) increased in hypothalamus tissue and serum， while the expressions of Ang-2, granulocyte-colony-stimulating factor (G-CSF) and IL-4 decreased significantly （P<0.01）. Compared with model group， RYZBW dose groups significantly increased mechanical pain threshold， decreased cold sensitivity pain threshold， decreased hypothalamus cell apoptosis ratio （P<0.01）， decreased the expression of IL-1α and CCL5 in hypothalamus tissue and serum， while the expression of ANG-2， G-CSF and IL-4 were significantly increased （P<0.05）. ConclusionRYZBP can relieve hyperalgesia in CPSP mice， and its mechanism is related to the regulation of the expression of pro-/anti-inflammatory factors IL-1α， CCL5， IL-4， G-CSF， and Ang-2.

ObjectiveTo evaluate the effect of Tripterygium wilfordii polyglycoside tablets （TWPT） combined with conventional synthetic disease-modifying antirheumatic drugs （csDMARDs） including methotrexate （MTX） and/or leflunomide （LEF） on autoantibodies in rheumatoid arthritis （RA） patients. MethodPubMed， EMBASE， Web of Science， Cochrane Library， China National Knowledge Infrastructure （CNKI）， VIP， Wanfang Data， and China Biomedical Literature Service System （SinoMed） were searched for randomized controlled trials （RCTs） of TWPT combined with MTX and/or LEF in the treatment of RA patients from database inception to December 1， 2021. Primary outcome indicators included rheumatoid factor （RF） and anti-citrullinated protein antibody （ACPA）， and secondary outcome indicators included immunoglobulin （IgA， IgG， and IgM） and adverse drug events （ADE）. ResultThirty-one RCTs， involving 2 643 adult patients， were included， including 20 RCTs of TWPT combined with MTX， 10 of TWPT combined with LEF， and one of TWPT combined with MTX and TWPT. The follow-up time ranged from two weeks to 13 months. Compared with csDMARDs alone， TWPT combined with other drugs significantly improved serum RF of RA patients ［SMD=-2.45， 95% CI ［-2.97， -1.93］， P<0.000 01］， anti-CCP ［SMD=-1.41， 95% CI （-2.35， -0.48）， P=0.003］， IgM ［SMD=-1.90， 95% CI （-3.03， -0.76）， P=0.001］， and IgA ［SMD=-1.18， 95% CI （-2.23， -0.12）， P=0.03］. There were no significant effects on IgG ［SMD=-1.02， 95% CI （-2.04， 0.01）， P=0.05］ and ADE ［RR=0.87， 95% CI （0.66， 1.15）， P=0.32］. ConclusionThe results of this study show that compared with csDMARDs alone， TWPT combined with csDMARDs can effectively improve the levels of autoantibodies in RA patients without increasing the incidence of ADE. However， due to the limited quality and quantity of the included RCTs， the relevant conclusions are only used as a reference for the clinical diagnosis and treatment of RA， and more high-quality studies are still needed to further confirm their efficacy.

ObjectiveTo observe the anti-swelling and analgesic effects of Jianpi Tongluo prescription （JPTL） and to explore its mechanism initially. MethodA total of 120 ICR mice were divided into normal group， model group， JPTL low-， medium- and high-dose groups （5， 10， 20 g·kg^-1） and positive drug （celecoxib， 0.03 g·kg^-1） group， with 10 in each group （po，once a day）. Complete freund's adjuvant （CFA） was used to induce the model of chronic inflammatory pain， and xylene-induced ear swelling test， hot plate test and acetic acid writhing test were performed to observe the anti-swelling and analgesic effects of different doses of JPTL in these four acute and chronic models. Further， enzyme-linked immunosorbent assay （ELISA） was used to detect the expressions of prostaglandin E₂ （PGE₂）， interleukin-1β （IL-1β）， interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） in serum and inflammatory paw of mice with chronic inflammatory pain， and the expressions of aquaporin 1 （AQP1）， aquaporin 3 （AQP3）， cyclooxygenase 1 （COX1）， cyclooxygenase 2 （COX2） and mitogen-activated protein kinases （MAPKs） in inflammatory paw were detected by Western blot， to explore the preliminary mechanism of JPTL. ResultCompared with the conditions in the normal group， there was a significant increase in the ear swelling of xylene-induced model mice， a shortened paw withdrawal latency in the hot plate test （P<0.01）. Compared with the model group， JPTL remarkably increased the inhibition rate of xylene-induced ear swelling （P<0.05， P<0.01）， prolonged the latency period of writhing caused by acetic acid and reduced the number of writhing （P<0.05， P<0.01）. Compared with normal group, the degree of feet swelling in chronic inflammatory pain mice was significantly increased， the threshold of mechanical pain was decreased and the threshold of cold pain was increased （P<0.05， P<0.01）， the protein contents of AQP1 and AQP3 in inflammatory feet were increased， and the contents of IL-1β， IL-6， TNF-α， PGE₂ and COX2 in inflammatory feet were increased in serum and/or inflammatory feet. The protein expression levels of p-p38 MAPK， p-JNK and p-ERK in inflammatory feet were increased （P<0.01）. Compared with the model group， JPTL relieved paw swelling of mice with chronic inflammatory pain， elevated mechanical withdrawal threshold while decreased cold withdrawal threshold， with analgesia lasting for 4 h and the optimal time point for analgesia being 2 h after administration （P<0.05， P<0.01）. Moreover， JPTL down-regulated AQP1， AQP3， COX2， p-p38 MAPK， p-JNK and p-ERK in inflammatory paw of mice with chronic inflammatory pain and reduced IL-1β， IL-6， TNF-α， and PGE₂ in serum and/or inflammatory paw， but it had no significant effect on COX1 （P<0.05， P<0.01）. ConclusionJPTL has anti-swelling and analgesic effects， and its mechanism is related to inhibiting the production of cytokines and inflammatory mediators via the down-regulation of MAPKs signaling pathway， which provides an experimental basis for the clinical application of JPTL.