ObjectiveTo investigate the effects of Congrong Zonggan capsules （CRZG） on cognitive impairment in the Alzheimer's disease （AD） model of mice and its related mechanisms. MethodsSPF grade 4-week-old 5×FAD mice were divided into a model group， low-dose CRZG （0.819 g·kg^-1） and high-dose CRZG （1.638 g·kg^-1） groups， and Donepezilepezil hydrochloride group （2 mg·kg^-1）， with eight mice in each group. Eight C57 mice with the same background were set as the normal group. After one week of adaptive feeding， mice were orally administered continuously for six months. On the 5th month of drug administration， Y maze， new object recognition， and Morris water maze tests were conducted separately. After administration， mouse brain tissue was taken， and the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in brain tissue were detected by enzyme-linked immunosorbent assay （ELISA）. Immunofluorescence （IF） was used to detect the expression of small glial cell markers Iba1， astrocyte markers GFAP， and amyloid protein 1-42 （Aβ_1-42） in the hippocampus of the brain tissue. The hematoxylin-eosin （HE） staining was used to detect pathological changes in the hippocampus of brain tissue. Western blot was used to detect the expression of nuclear factor-κB （NF-κB） p65， NOD-like receptor protein 3 （NLRP3）， cleaved Caspase-1， apoptosis-associated speck-like protein containing a CARD （ASC）， and other proteins in the brain tissue. ResultsCompared with those in the normal group， the mice in the model group had obvious cognitive impairment. The spontaneous alternation rate of the Y maze was decreased， and the discrimination index of novel object recognition was decreased significantly （P<0.01）. The escape latency in the water maze was shortened significantly （P<0.01）. The contents of IL-6 and TNF-α in brain tissue were increased. The fluorescence levels of Iba1 and Aβ_1-42 in the hippocampus were significantly increased （P<0.01）. There was a significant increase in neuronal lesions， neuronal atrophy， loose arrangement of tissue structure， and abnormal erythrocyte aggregation in the hippocampus. The protein expressions of p-NF-κB p65/NF-κB p65， cleaved Caspase-1， ASC， IL-6， and IL-1β were significantly increased （P<0.05， P<0.01）. Compared with the model group， the spontaneous alternation rate and discrimination index of the high-dose CRZG group were increased significantly （P<0.01）， and the escape latency was shortened significantly （P<0.05， P<0.01）. The content of IL-6 decreased in the brain， and that of TNF-α dropped significantly （P<0.01）. The expression of Iba1 protein and Aβ_1-42 in the hippocampus decreased significantly （P<0.05， P<0.01）. The hippocampal neurons were densely arranged， and the pyramidal nuclei were clear and centered. The abnormal aggregation of red blood cells was alleviated. The value of p-NF-κB/NF-κB proteins and the expression of ASC， cleaved Caspase-1， IL-6， and IL-1β were significantly decreased （P<0.05， P<0.01）. ConclusionCRZG can effectively improve cognitive impairment in 5×FAD mice with Alzheimer's disease， and its mechanism may be related to the regulation of the NF-κB/NLRP3 pathway to reduce the abnormal activation of microglia and inhibit neuroinflammation.

Objective:To explore the efficacy and safety of ibrutinib for the treatment of newly treated and relapsed refractory (R/R) lymphoplasmacytic lymphoma (LPL) /Waldenstr?m macroglobulinemia (WM) .Methods:Retrospectively collected clinical data of 98 cases of newly treated and R/R LPL/WM patients who received ibrutinib treatment at the Hematology & Blood Diseases Hospital of the Chinese Academy of Medical Sciences from March 2016 to June 2023, and analyzed their efficacy and safety.Results:A total of 98 LPL/WM patients were included, which consisted of 45 newly treated patients and 53 R/R patients. Of these, 74 were males (75.5%) and the cohort had a median age of 64 (42-87) years. Eighty-eight patients were eligible for efficacy evaluation with a median treatment time of 20.8 (2.1-55.0) months, a major remission rate (MRR) of 78.4%, and an overall response rate (ORR) of 85.2%. The MRR and ORR of the newly treated patients were 78.4% and 86.5%, respectively, whereas the MRR and ORR of the R/R patients were 78.4% and 84.3%, respectively. There were no statistically significant differences in MRR and ORR between the initial treatment and R/R patients (all P values >0.05) . The median follow-up period was 29.1 (2.9-50.3) months and the median overall survival time for newly treated and R/R patients was not reached. The median progression-free survival time was 23.5 (95% CI 10.5-36.5) months and 45.0 (95% CI 34.0-56.0) months, respectively, with no statistically significant differences (all P values >0.05) . There were 25 deceased patients and no deaths were related to ibrutinib treatment. The main adverse reactions of ibrutinib were thrombocytopenia (5.1%) , pneumonia (8.1%) , and hyperuricemia (21.4%) . The incidence of atrial fibrillation was 2.0%. Conclusion:Ibrutinib exhibits good efficacy and safety for newly treated and R/R LPL/WM patients.

ObjectiveTo investigate the therapeutic effect of Lycopi Herba extract on chronic prostatitis （CNP） and explore the underlying action mechanism via the inflammasome NOD-like receptor protein 3 （NLRP3） pathway. MethodNormal human prostatic stromal cells， namely WPMY-1 were induced by lipopolysaccharide （LPS） of 5 mg·L^-1， and the effects of Lycopi Herba extract of 3.125， 6.25， 12.5， 25， 50， and 100 mg·L^-1 on interleukin-6 （IL-6） level released by LPS-induced WPMY-1 cells were detected by enzyme-linked immunosorbent assay （ELISA）. The half-maximal inhibitory concentration （IC₅₀） was calculated. The expression of key proteins in the NLRP3 pathway was detected by western blot after Lycopi Herba extract of 50， 75， and 100 mg·L^-1 was administered to WPMY-1 cells. The rat model of CNP was established by injecting carrageenan salt solution into the abdominal lobe of the prostate gland. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes in the prostate gland in rats. The prostate organ index of rats was measured. The level of 5α-dihydrotestosterone （5α-DHT） in serum， as well as the levels of IL-6， tumor necrosis factor-α （TNF-α）， transforming growth factor-β₁ （TGF-β₁）， cyclooxygenase-2 （COX-2）， prostaglandin E₂ （PGE₂）， and inducible nitric oxide synthase （iNOS） in prostate tissue were detected by ELISA. The key protein expressions of COX-2， TGF-β₁， and NLRP3 pathway in prostate tissue were detected by Western blot. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the expressions of COX-2， IL-1β， TGF-β₁， and TNF-α mRNA in prostate tissue. ResultCompared with the normal group， the level of IL-6 and the protein expression levels of NLRP3， ASC， Caspase-1， and IL-1β of WPMY-1 cells in the model group were increased （P<0.05， P<0.01）. Compared with the model group， Lycopi Herba extract could inhibit the levels of IL-6 （P<0.01） released by LPS-induced WPMY-1 cells， with IC₅₀ of 38.26 mg·L^-1. The protein expression levels of NLRP3， ASC， and IL-1β in the low-， medium-， and high-dose groups of Lycopi Herba extract were significantly down-regulated （P<0.05， P<0.01）. The expression levels of Caspase-1 protein in medium- and high-dose groups of Lycopi Herba extract were significantly down-regulated （P<0.05， P<0.01）. Compared with the sham operation group， the prostate organ index of rats in the model group was significantly increased （P<0.01）， a large number of inflammatory cells were infiltrated in the prostate tissue， and the histopathological score was significantly increased （P<0.05）； the levels of 5α-DHT in serum， the levels of TNF-α， PGE₂， IL-6， TGF-β₁， NOS₂/iNOS， and COX-2 in prostate tissue， and expression levels of COX-2， IL-1β， and TGF-β₁ were significantly increased （P<0.05， P<0.01）. The mRNA expression levels of COX-2， TGF-β₁， NLRP3， Caspase-1， ASC， and IL-1β in prostate tissue were significantly up-regulated （P<0.05， P<0.01）. Compared with model group， the low and high doses of Lycopi Herba extract could alleviate the pathological changes in prostate tissue induced by carrageenan， significantly reduce the level of 5α-DHT in serum， levels of TNF-α， PGE₂， TGF-β₁， and iNOS in prostate tissue （P<0.05， P<0.01）， and mRNA expression levels of COX-2， IL-1β， and TGF-β₁ （P<0.05， P<0.01）. The protein expression levels of COX-2， Caspase-1， ASC， and NLRP3 in prostate tissue were significantly down-regulated （P<0.05， P<0.01）. The prostate organ index of the low-dose group of Lycopi Herba extract was significantly decreased （P<0.01）. The level of COX-2 in prostate tissue of the high-dose group of Lycopi Herba extract was significantly decreased， and the protein expression levels of TGF-β₁ and IL-1β were significantly down-regulated （P<0.05）. ConclusionLycopi Herba extract has an obvious therapeutic effect on CNP and may reduce inflammation by inhibiting the activation of the inflammasome NLRP3 signaling pathway.

ObjectiveTo explore the efficacy and mechanism of the alcohol extract DH50 of Angelicae Pubescentis Radix in treating gouty arthritis induced by monosodium urate （MSU） crystals in vivo and in vitro. MethodFifty male SD rats were randomly assigned into five groups （n=10）： a normal group， a model group， a dexamethasone （DXMS， 0.07 mg·kg^-1） group， and low- （DH50-D， 9 mg·kg^-1） and high-dose （DH50-G， 18 mg·kg^-1） DH50 groups. The rats in the normal group and model group were administrated with the same amount of pure water. On day 5， the gouty arthritis model was established by injecting MSU into the right ankle joint of rats. The toe volume and joint inflammation index were measured 4， 8， 24， and 48 h after modeling. The pathological changes of the synovial tissue were detected by hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of tumor necrosis factor-alpha （TNF-α）， interleukin （IL）-1β， and IL-6 in the synovial tissue. Western blot was employed to measure the protein levels of NOD-like receptor protein 3 （NLRP3）， cysteine-aspartic protease-1 （Caspase-1）， apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain （ASC）， IL-1β， and cyclooxygenase-2 （COX-2） in the synovial tissue. Furthermore， the cell inflammation model was established with RAW264.7 cells stimulated with MSU （75 mg·L^-1）. The cell experiments were carried out with 6 groups： a normal group， a model group， a positive drug （DXMS， 100 μmol·L^-1） group， and low- （DH50-D， 25 mg·L^-1）， medium- （DH50-Z， 50 mg·L^-1）， and high-dose （DH50-G， 100 mg·L^-1） DH50 groups. Methyl thiazolyl tetrazolium （MTT） assay was employed to determine the cell viability， ELISA to determine the content of TNF-α in the supernatant of cell culture， and Western blot to determine the protein levels of NLRP3， cleaved Caspase-1， IL-1β， TNF-α， and COX-2. ResultCompared with the normal group， the rat model group showed increased toe swelling degree and joint inflammatory index （P<0.01）， serious infiltration of the synovium， elevated levels of inflammatory cytokines in the tissue homogenate （P<0.01）， and up-regulated protein levels of NLRP3， Caspase-1， ASC， IL-1β， and COX-2 （P<0.05， P<0.01）. Compared with the rat model group， low- and high-dose DH50 mitigated the toe swelling degree， decreased the joint inflammatory index， alleviated the inflammatory infiltration， lowered the levels of inflammatory cytokines in the tissue homogenate （P<0.01）， and down-regulated the expression of related proteins （P<0.05， P<0.01）. Compared with the normal group， the cell model group showed elevated level of TNF-α in the supernatant （P<0.01） and up-regulated protein levels of NLRP3， cleaved Caspase-1， IL-1β， TNF-α， and COX-2 （P<0.05）. Compared with the model group， low， medium， and high doses of DH50 lowered the level of TNF-α in the supernatant of cell culture in a dose-dependent manner and down-regulated the expression of related proteins （P<0.05， P<0.01）. ConclusionDH50 can mitigate gouty arthritis both in vitro and in vivo by inhibiting the activation of NLRP3 inflammasomes and the production of inflammatory cytokines.

ObjectiveTo investigate the effect of alcohol extract of Oroxylum indicum （MHD-80） on reducing uric acid （UA） and protecting the kidney in the hyperuricemia （HUA） model in vivo. MethodPotassium oxazine （350 mg·kg^-1） and adenine （80 mg·kg^-1） were used to construct an HUA model of mice in vivo to evaluate the mechanism related to UA reduction and the protective effect of renal function of MHD-80. Seventy male ICR mice were randomly divided into seven groups， including the normal group， model group， allopurinol group （5 mg·kg^-1）， febusotan group （5 mg·kg^-1）， and MHD-80 low-， medium-， and high-dose groups （3， 6， 12 mg·kg^-1）， with 10 in each group. Except for the normal group， the other groups were given intragastric administration of potassium oxazine and adenine for 14 consecutive days to establish the HUA model. On the 8^th to 14^th day after modeling， each group was given corresponding drugs by intragastric administration， once a day. 1 h after the last administration， blood was collected from the eyeballs， and kidney and liver tissues of mice were collected. Serum levels of UA， urea nitrogen （BUN）， and creatinine （Cr） and liver activity of xanthine oxidase （XOD） were determined by enzyme colorimetry. Serum contents of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） were determined by enzyme-linked immunosorbent assay （ELISA）. Hematoxilin-eosin （HE） staining was used to observe the pathological changes in kidney tissues. The protein expression levels of ATP-binding box transporter G2 （ABCG2） and glucose-facilitating transporter 9 （GLUT9） in kidney tissues were detected by Western blot. ResultIn vivo experiment shows that compared with the normal group， the serum levels of UA， Cr， BUN， inflammatory factors TNF-α， IL-1β， and liver XOD activity in the serum of mice in the model group were significantly increased （P<0.05， P<0.01）， and the expression of GLUT9 in kidney tissues was significantly up-regulated （P<0.05）. ABCG2 protein expression was significantly down-regulated （P<0.05）， and renal injury was obvious. Compared with the model group， the levels of UA， BUN， Cr， TNF-α， IL-1β， and liver XOD activity in the serum of mice in the high-dose group of MHD-80 were decreased to different degrees （P<0.05， P<0.01）， GLUT9 protein expression was significantly down-regulated （P<0.01）， ABCG2 protein expression was significantly up-regulated （P<0.05） in the high-dose group of MHD-80， and the degree of renal injury was reduced. ConclusionMHD-80 has certain uric acid reduction， anti-inflammatory， and anti-renal injury effects， which are related to inhibiting XOD activity and regulating the expression of ABCG2 and GLUT9 uric acid transporter.

Objective:This retrospective, single-center study aimed to evaluate the efficacy and safety of programmed death-1 (PD-1) inhibitors, either as monotherapy or in combination with chemotherapy, in the management of relapse/refractory classical Hodgkin's lymphoma (R/R cHL) .Methods:A total of 35 patients with R/R cHL who received treatment at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College from September 2016 to December 2020 were enrolled in this study. Among them, 17 patients received PD-1 inhibitor monotherapy (PD-1 inhibitor group), while 18 patients received a combination of PD-1 inhibitor and chemotherapy (PD-1 inhibitor + chemotherapy group). Clinical data and follow-up information were retrospectively analyzed, and survival analysis was conducted using the Kaplan-Meier method and Cox proportional hazards model.Results:The median age of the 35 patients with R/R cHL was 29 years (range: 11-61 years), with 54.3% being male. According to the Ann Arbor staging system, 62.9% of patients presented with advanced (stage Ⅲ/Ⅳ) disease, and 48.6% had extranodal involvement. Before PD-1 inhibitor therapy, the median number of prior lines of therapy was 2 (range: 1-3). Objective responses were observed in 28 patients, including 22 complete response (CR) cases, resulting in an overall response rate (ORR) of 80.0% and a CR rate of 62.9%. Specifically, the ORR and CR rates were 64.7% and 58.8%, respectively, in the PD-1 inhibitor group and 94.4% and 66.7%, respectively, in the PD-1 inhibitor + chemotherapy group. Among the 18 patients who underwent sequential autologous hematopoietic stem cell transplantation (auto-HSCT) [13 CR and five partial response (PR) cases], eight patients received PD-1 inhibitor therapy after auto-HSCT as consolidation therapy. All patients maintained a CR status after transplantation, and they exhibited significantly improved progression-free survival (PFS) rates compared with those who did not undergo sequential auto-HSCT (4-year PFS rates: 100% vs 53.5% ; P=0.041). The incidence of immune-related adverse events was 29%, with only one patient experiencing grade≥3 adverse reactions, which indicated a favorable safety profile for the treatment approach. Conclusions:PD-1 inhibitor monotherapy demonstrates notable efficacy and sustained response in patients with R/R cHL. PD-1 inhibitors combined with chemotherapy significantly improve response rates. Additionally, for salvage therapy-sensitive patients, consolidation treatment with PD-1 inhibitors after auto-HSCT exhibits the potential for prolonging PFS.

Objective:To investigate the efficacy of fludarabine and cyclophosphamide combined with rituximab (FCR) in previously untreated patients with chronic lymphocytic leukemia (CLL) .Methods:The clinical data of 43 enrolled patients from May 2004 to December 2017 were analyzed the efficacy and survival results.Results:A total of 43 patients with 31 males and 12 females, and the median age was 58 years old (range 36 to72) before treatment. There were 8 patients with symptom B. The median number of peripheral blood lymphocyte was 26 (3-550) ×10 9/L. IGHV unmutated was detected in 62.1% (18/29) patients, P53 deletion in 14% (6/43) patients, RB1 deletion in 18.6% (8/43) patients, Trisomy 12 in 25.6% (11/33) patients, ATM deletion in 16.7% (7/42) patients, respectively. The median number of treatment courses administered was 4 (range 2-6) . Twenty patients obtained CR (46.5%) , 18 patients obtained PR, 4 patients were SD, 1 patient was PD. The overall response rate (ORR) was 88.37%. Seven patients obtained MRD negative. After the median follow-up time of 51 (6-167) months, median PFS was 67 (29-105) months, median OS was not reach, 5-year PFS was (62.1±8.6) %, 10-year PFS was (31±14.3) %, 5-year OS was (70.5±8.3) %, and 10-year OS was (51.3±13.8) %. Less than 4 courses predicted adverse OS ( P<0.05) . P53 deletion and less than 4 courses were associated with poor PFS ( P<0.001) , and the prognostic value still remained after multivariate analysis[ HR=7.65 (95% CI 1.74-33.60) , P=0.007; HR=3.75 (95% CI 1.19-11.80) , P=0.025]. Eighteen patients (41.9%) appeared grade 2-3 infection after chemotherapy, and 19 patients (44.2%) appeared grade 3-4 hematological adverse reactions. One patient (2.3%) was developed tumor lysis syndrome. All adverse reactions were controlled or recovered spontaneously. Conclusion:Previously untreated CLL patients treated with FCR had a high response rate and good survival rate, which is an important treatment choice for fit patients.

Objective: To evaluate the efficacy and long-term outcome of a combined protocol for multiple myeloma (MM) , including induction therapy, autologous hematopoietic stem cell transplantation (ASCT) and consolidation and maintenance therapy. Methods: Clinical records of 144 patients with MM from January 1, 2005 to February 1, 2016 were retrospectively analyzed. Results: The overall response rate (ORR) after ASCT was 100.0%, in which the complete remission (CR) was 64.1% and the best treatment response rate of superior to PR was 89.4%. During a median follow-up of 47 months, patients with an overall survival (OS) and progression free survival (PFS) was 120.9 and 56.9 months respectively. 5y-OS (73.7±4.7) %, 7y-OS (60.5±6.3) %; 3y-PFS (69.2±4.2) %, 5y-PFS (47.8±5.3) %. The median OS and PFS between the first line transplantation group and salvage transplantation group were 120.9 months vs 50.1 months and 60.2 months vs 16.7 months (all P=0.000). In 127 patients with R-ISS staging, the median survival of Ⅰ, Ⅱ, Ⅲ stage was 120.9 months (n=43) , 88.4 months (n=64) , 35.6 months (n=20) , respectively (P=0.000). For subgroup analysis of survival in early and late ASCT, the median OS of patients with R-ISS stage Ⅲ (35.6 months vs 15.8 months, P=0.031) and the median PFS of two groups (phase Ⅰ: 72.1 months vs 18.9 months, P=0.000; Ⅱ: 53.4 months vs 16.7 months, P=0.012; Ⅲ: 28.5 months vs 5.9 months, P=0.001) were different. Multivariate analysis showed that only R-ISS and the degree of remission before transplantation had impact on OS (HR=8.486, 95% CI 2.549-28.255, P=0.003) and PFS (HR=2.412, 95% CI 1.364-4.266, P=0.002) , respectively. Conclusion The combined protocol containing ASCT is effective for MM patients, improving remission rate and remission depth, prolonging PFS and OS. First line transplantation could significantly prolong the OS and PFS as compared with salvage transplantation. R-ISS and pre-transplantation remission depth are prognostic factors for survival.

Aim To investigate the effects of Sanjie Zhentong capsule on cultured mouse myometrial cell contraction induced by prostaglandin F2α( PGF2α) , and to elucidate the mechanism of Sanjie Zhentong capsule in treating dysmenorrheal. Methods Primary mouse myometrial cells were cultured and identified. Intracel-lular calcium ( [ Ca2+] i ) was monitored under a Flex-Station 3 Benchtop Multi-Modo Microplate Reader u-sing Calcium 6-QF. Myometrial cells were labeled to observe the changes of contraction. The expressions of calmodulin ( CaM ) , myosin light chain kinase ( ML-CK) , myosin light chain phosphorylation( p-MLC20 ) in mouse uterine smooth muscle cells ( USMCs ) were determined by immunofluorescence. Results Sanjie Zhentong capsule suppressed the intracellular[Ca2 + ]i inflow and reduced the areas of myometrial cells induced by PGF2α. Then it significantly decreased CaM and p-MLC20 levels. Conclusion Our results indicate that Sanjie Zhentong capsule has inhibitory effect on dysmenorrheal induced by PGF2α. Furthermore,its major mechanism may be related with the regulation of intracellular[ Ca2 + ]i inflow and the levels of CaM and p- MLC20.

OBJECTIVETo observe the clinical and biological characteristics of Non-IgM-secreting lymphoplasmacytic lymphoma (LPL) and draw the differences between non-IgM LPL and Waldenström macroglobulinemia (WM).

METHODSRecords of 13 patients with non-IgM LPL were retrospectively analyzed between January 2000 and December 2013. The cytogenetic aberrations were detected by fluorescence in situ hybridisation (FISH).

RESULTSIn the cohort, 7 males and 6 females with a median age of 63 years (range 43 to 74), two patients were IgA secreting, 6 with IgG secreting and 5 patients without monoclonal globulin. The major complaint at diagnosis included anemia associated symptom (53.8%), mucocutaneous hemorrhage and superficial lymphadenopathy (15.4%). Eight patients had B symptom at diagnosis. All of the 13 patients had bone marrow involvement and anemia, and 10 patients had 2 or 3 lineage cytopenia. In 5 patients with available immunophenotypic data, all expressed CD19, CD20, CD22 and CD25, but missed the expression of CD10, CD103 and CD38. Two cases had CD5 or sIgM positive alone. Another 2 patients were CD23 or CD11c positive and 3 patients were FMC7 positive. Cytogenetic aberrations had been detected by FISH in 7 patients, but only two (28.6%) patients had aberrations with del(6q).

CONCLUSIONThe clinical and biological characteristics had no significantly difference between non-IgM LPL and WM.

Adult ; Aged ; Antigens, CD ; Chromosome Aberrations ; Female ; Humans ; Immunoglobulin M ; In Situ Hybridization, Fluorescence ; Integrin alpha Chains ; Leukemia, Lymphocytic, Chronic, B-Cell ; Male ; Middle Aged ; Retrospective Studies ; Waldenstrom Macroglobulinemia