Monosodium urate (MSU)-induced the gouty arthritis (GA) model was used to investigate the effect of Nod-like receptor protein 3 (NLRP3) inhibitor N14 in alleviating GA. Firstly, the effect of NLRP3 inhibitor N14 on the viability of mouse monocyte macrophage J774A.1 was examined by the cell counting kit-8 (CCK-8) assay. The expression of mature interleukin 1β (IL-1β) and cysteinyl aspartate specific proteinase-1 (caspase-1) p20 in the cell supernatant and the expression of NLRP3, caspase-1 and pro-IL-1β proteins in the cell lysates was detected by Western blot for the inhibitory effect of N14 on the MSU-induced NLRP3 inflammasome activation in J774A.1 cells. Animal behavioral tests were used to detect redness, swelling, heat and pain in mice with gouty arthritis. Hematoxylin-eosin (H&E) staining revealed pathologic changes and inflammatory infiltration in foot sections. Protein expression of NLRP3, caspase-1, and pro-IL-1β in mouse hind paw tissues were assessed by Western blot. The effect of N14 on the plasma levels of alanine transaminase (ALT), aspartate transaminase (AST), creatinine (CRE), urea, and uric acid (UA) was investigated by the MSU-induced gouty arthritis model in mice. All animal experiments in this paper were approved by the Scientific Ethics Review Board of Qingdao Marine Biomedical Research Institute (grant No. E-MBWNL-2024-20). The experimental results showed that N14 did not exhibit cytotoxicity in mouse monocyte macrophage J774A.1 cells at concentrations up to 100 μmol·L^-1, and N14 effectively prevented MSU-induced activation of NLRP3 inflammasome. In the mouse gouty arthritis model, N14 significantly ameliorated the redness, swelling, heat and pain caused by GA, and down-regulated the levels of NLRP3 inflammasome-associated proteins in mouse hind paw tissues. Meanwhile, N14 appeared to be well tolerated, as it did not significantly affect various biochemical indices in mouse plasma. In conclusion, N14 effectively alleviated GA in mice by inhibiting the NLRP3 inflammasome pathway, which is important for both prevention and treatment of related diseases.

OBJECTIVE: To analyze the characteristics of gene mutation and overexpression in newly diagnosed multiple myeloma (NDMM) patients. METHODS: Bone marrow cells from 208 NDMM patients were collected and analyzed. The gene mutation of 28 genes and overexpression of 6 genes was detected by DNA sequencing. Chromosome structure abnormalities were detected by fluorescence in situ hybridization (FISH). RESULTS: Gene mutations were detected in 61 (29.33%) NDMM patients. Some mutations occurred in 5 or more cases, such as NRAS, PRDM1, FAM46C, MYC, CCND1, LTB, DIS3, KRAS, and CRBN. Overexpression of six genes (CCND1, CCND3, BCL-2, CCND2, FGFR3, and MYC) were detected in 83 (39.9%) patients, and cell cycle regulation gene was the most common. Single nucleotide polymorphisms (SNP) changes were detected in 169 (81.25%) patients, the TP53 P72R gene SNP (70.17%) was the most common. Abnormality in chromosome structure was correlated to gene overexpression. Compared to the patients with normal chromosome structure, patients with 14q32 deletion showed higher proportion of CCND1 overexpression. Similarly, patients with 13q14 deletion showed higher proportion of FGFR3 overexpression, whereas patients with 1q21 amplification showed higher proportion of CCND2, BCL-2 and FGFR3 overexpression. CONCLUSION There are multiple gene mutations and overexpression in NDMM. However, there is no dominated single mutation or overexpression of genes. The most common gene mutations are those in the RAS/MAPK pathway and the genes of cyclin family CCND are overexpression.
Chromosome Aberrations ; Humans ; In Situ Hybridization, Fluorescence ; Multiple Myeloma/genetics* ; Mutation

Tibetan medicine is an essential part of Chinese medicine and has unique theoretical experience and therapeutic advantages. According to the development principle of inheriting the essence, sticking to the truth, and keeping innovative, the supervision department should give clear and reasonable guidance considering the characteristics of Tibetan medicine, establish a standard system for quality control, clinical verification and evaluation, and accelerate the research and commercialization of new drugs. In view of the needs of drug supply-side reform and the current situation of Tibetan medicine and new pharmaceutical research, we ponder and provide suggestions on the confusion faced by the current supervision of Tibetan drug registration, hoping to contribute to the supervision strategy of Tibetan drug registration and the high-quality development of Tibetan medicine industry.
Tibet ; Medicine, Tibetan Traditional ; Quality Control ; Pharmaceutical Research ; Drug Industry

Objective To analyze the infection of human parvovirus B19 among women of childbearing age in Xiangyang City, and to provide a reference for pregnant women's health care. Methods A total of 303 women of childbearing age in Xiangyang City from 2018 to 2019 were selected as the research subjects. B19 virus DNA in serum of the subjects was detected by nested PCR technology. The differences in the detection rate of B19 viral DNA among normal pregnancy, abnormal pregnancy, and infertility serum were statistically analyzed. The differences in the detection rate of B19 virus DNA among women of childbearing age at different ages were compared. Results The detection rate of B19 viral DNA in all 303 women of child-bearing age was 27.72%. The detection rate of B19 virus DNA in 26-35 year old women was higher than that in other age groups. The detection rate of B19 virus DNA in abnormal pregnancy group was significantly higher than that in normal pregnancy group (P <0.05). Conclusion The detection rate of B19 virus DNA in abnormal pregnancy and infertility group was significantly higher than that in normal pregnancy group, with the detection rate of B19 virus in 26-35 year old women of childbearing age being the highest among all age groups. It is necessary to strengthen the screening of B19 virus in pregnant women of childbearing age in this region to reduce its impact on fetal abortion.

Objective To explore the efficacy and prognosis of haploidentical allogeneic hematopoietic stem cell transplantation (haplo-HSCT) for severe aplastic anemia (SAA).Methods The clinical data were retrospectively analyzed for 40 SAA cases undergoing haplo-HSCT from September 2013 to February 2018.The conditioning regimen contained cyclophosphamide,fludarabine and antithymocyte globulin with or without busulfan or low-dose total body irradiation.Cyclosporin A,short-term methotrexate and mycophenolate mofetil were dosed for preventing graft versus host disease (GVHD).The median counts of mononuclear cell and CD34+ stem cell were 5.3(2.0～13.5) × 108/kg and 5.6 (1.6 ～ 15.9) × 106/kg respectively.Results Among them,hematopoietic reconstitution was achieved (n =36,90.0 ％).The median times for myeloid engraftment and platelet engraftment were 15(10-25) and 17(10～58) days respectively.The incidence of acute graft-versushost disease(aGVHD)was (35.0± 6.8) ％.The incidence of chronic GVHD (cGVHD) was (23.0 ±7.4) ％.And 28 SAA cases (70.0 ％) survived during a median follow-up period of 353(30～1226)days,The cumulative overall survival (OS) was (67.8 ± 7.8) ％,the average survival time (883 ± 82)days and transplantation-related death (TRM) within 100 days (10.0 ± 3.1) ％.Conclusions Haplo-HSCT is an effective treatment for SAA patients.And a larger number of cases are required for enhancing OS.

OBJECTIVE: To investigate the effect of pre-surgical orthodontic treatment on temporomandibular joint (TMJ) in patients with skeletal class Ⅲ malocclusion treated with orthodontic-orthognathic surgical treatment. METHODS: Twenty-four patients with skeletal class Ⅲ malocclusion who underwent orthodontic-orthognathic surgical treatment were included in the study. Before and after the completion of orthodontic treatment, the symptoms of TMJ were examined and recorded, and the short- and the long-axis diameter of the condylar (d), condylar height (h), joint space (L) at different angles, bilateral condylar spacing (R), and the condylar angles were measured, with scanning performed by using cone-beam computed tomography (CBCT). Then, the changes of TMJ symptoms and bone structure at different periods were analyzed. RESULTS: No significant changes were observed in the joint symptoms before and after the pre-surgical orthodontic treatment. No significant changes were found in the measurements of the bone structure of TMJ in the dimensional direction (P>0.05). CONCLUSIONS In the orthodontic-orthognathic surgical treatment procedure, the pre-surgical orthodontic process does not have a significant effect on TMJ.
Cone-Beam Computed Tomography ; Humans ; Malocclusion, Angle Class II ; Malocclusion, Angle Class III ; Mandibular Condyle ; Temporomandibular Joint

OBJECTIVE: To investigate the clinical features, accompanying gene mutation characteristics and prognostic factors of adult patients with acute myeloid leukemia with mutated NPM1 (NPM1AML). METHODS: Seventy-three patients with newly diagnosed adult NPM1AML were selected. The mutations of 22 genes were detected by second generation sequencing and 43 fusion genes of AML were detected by real-time fluorescent quantitative PCR. The Kaplan-Meier survival curve and Cox multivariate regression analysis were used to study the prognostic factors. RESULTS: A total of 74 NPM1 site mutations were detected in 73 patients with NPM1AML. The incidence rates were 92.0% L287fs, 2.7% Q289fs and W288fs, 1.4% L258fs and Q289H, among which 1 patient had 2 NPM1 mutations; the different mutation sites had no effect on the prognosis of NPM1AML. The median value of NPM1 variant allele frequency (VAF) was 35.4% (1.8%-56.6%). Based on the uppermost quartile of 38.4%, the patients were classified as NPM1 VAF>38.4% (NPM1AML) and NPM1 VAF≤38.4% (NPM1AML). Compared with NPM1AML, the early mortality rate was statistically significantly higher (33.3% vs 7.3%, P<0.05), and median EFS (148 d，95%CI 58-238 d vs 372 d，95%CI 264-480 d) (P<0.01) and median OS (179 d 95%CI 6-352 d vs 444 d) (P<0.01) were significantly shorter in NPM1 AML. A total of 126 accompanying gene mutation sites were detected in 87.7% of patients with NPM1AML. The patients with NRAS gene mutation displayed a higher rate of complete remission (100% vs 58%) (P<0.05) and longer median OS (not reached to 320 d, 95%CI 150-490 d) (P<0.05). The 43 fusion genes were examined in 65 out of 73 cases of NPM1AML, and in all the patients the fusion gene test was negative. Multivariate analysis showed that NPM1 VAF>38.4% was an independent prognostic factor for EFS (HR=3.1, 95% CI 1.6-6.4, P<0.01) and OS (HR=3.0, 95% CI 1.4-6.2, P<0.01). CONCLUSION The NPM1 gene mutation in AML patients often is accompanied by other gene mutations, while the coexistence of fusion genes is rare; high NPM1 mutant allele burden is an independent prognostic factor for adult AML patients with mutated NPM1.
Alleles ; Humans ; Leukemia, Myeloid, Acute ; genetics ; Mutation ; Nuclear Proteins ; genetics ; Prognosis ; fms-Like Tyrosine Kinase 3