Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint damage, accompanied by the accumulation of plasma cells, which contributes to its pathogenesis. Understanding the genetic alterations occurring during plasma cell differentiation in RA can deepen our comprehension of its pathogenesis and guide the development of targeted therapeutic interventions. Here, our study elucidates the intricate molecular mechanisms underlying plasma cell differentiation by demonstrating that PRDX1 interacts with DOK3 and modulates its degradation by the autophagy-lysosome pathway. This interaction results in the inhibition of plasma cell differentiation, thereby alleviating the progression of collagen-induced arthritis. Additionally, our investigation identifies Salvianolic acid B (SAB) as a potent small molecular glue-like compound that enhances the interaction between PRDX1 and DOK3, consequently impeding the progression of collagen-induced arthritis by inhibiting plasma cell differentiation. Collectively, these findings underscore the therapeutic potential of developing chemical stabilizers for the PRDX1-DOK3 complex in suppressing plasma cell differentiation for RA treatment and establish a theoretical basis for targeting PRDX1-protein interactions as specific therapeutic targets in various diseases.

A series of 2-(((5-akly/aryl-1-pyrazol-3-yl)methyl)thio)-5-alkyl-6-(cyclohexylmethyl)-pyrimidin-4(3)-ones were synthesized and their anti-HIV-1 activities were evaluated. Most of these compounds were highly active against wild-type (WT) HIV-1 strain (IIIB) with EC values in the range of 0.0038-0.4759 μmol/L. Among those compounds, had an EC value of 3.8 nmol/L and SI (selectivity index) of up to 25,468 indicating excellent activity against WT HIV-1. anti-HIV-1 activity and resistance profile studies suggested that compounds and displayed potential anti-HIV-1 activity against laboratory adapted strains and primary isolated strains including different subtypes and tropism strains (ECs range from 4.3 to 63.6 nmol/L and 18.9-219.3 nmol/L, respectively). On the other hand, it was observed that those two compounds were less effective with EC values of 2.77 and 4.87 μmol/L for HIV-1A (K103N + Y181C). The activity against reverse transcriptase (RT) was also evaluated for those compounds. Both and obtained sub-micromolar IC values showing their potential in RT inhibition. The pharmacokinetics examination in rats indicated that compound has acceptable pharmacokinetic properties and bioavailability. Preliminary structure-activity relationships and molecular modeling studies were also discussed.

Objective The clinical effect and prognosis of greenlight photoselective laser vaporization combined with intraoperative submucosa multi-point injection of gemcitabin for the treatment of non muscle-invasive bladder tumors(NMIBC).Methods Selected 105 cases of NMIBC Confirmed by pathology from Mar.2012 to Nov.2013 in Guangzhou General Hosptial of Guangzhou Military Command of PLA urology.Put the patients into three groups randomly.Greenlight photoselective laser vaporization for bladder tumors (PVBT) combined with intraoperative submucosal injection of gemcitabine (PVBT group) 38 cases,Transurethral resection of bladder tumor(TURBT) combined with intraoperative submucosal injection of gemcitabine 25 cases (TURBT group),TURBT combined with immediate postoperative bladder perfusion chemotherapy (Control group)42 cases.Maintain the bladder perfusion chemotherapy after surgery,follow-up of 2 years.To compare and analysis the effect and the prognosis of three ways of operation method,And evaluate the quality of life of three groups of patients after treatment.Results The operation of 105 cases were successful,a total of 31 cases of recurrence,included PVBT group 7 cases (18.4％),TURBT group 6 cases (24％),contrlol group 18 cases (42.9％).Tumor progression of time were 12、10、6 month for the first time.The body function,psychological function,social function and material life of four dimensions scores have no obvious difference Three groups (P ＞ 0.05).Conclusions PVBT combined with intraoperative submucosal multi-point injection of gemcitabine is a kind of simple operation,and reduce the complications and the recurrence of the operation,especially suitable for the lateral wall of superficial tumor and intolerance to TURBT surgery for high-risk patients.It is a new better method of expansion clinical application.

This study designed a studio English classroom which was based on foreign nursing jobs related language.It included high-frequency words,foreign nurse-patient dialogue,and European and American nursing video which was foreign patients’ nursing procedures oriented.The studio classroom was characterized as interactive internet platform.It provided a complete system for input and output in English language,and motivated students to learn nursing English.Therefore,it improved students’ professional verbal competencies.

Objective To analyze the effect of antibiotic treatment on prostate specific antigen (PSA) derivations in patients with and without prostate cancer and to further determine if the changes of PSA values after antibiotic treatment could help to exclude inflammation in the differential diagnosis of an abnormal PSA.MethodsA total of 100 patients with lower urinary tract symptoms,a PSA level of 4 to 10 μg/L,free PSA/total PSA (fPSA/tPSA) ratio ＜ 0.25,and a negative digital rectal examination and transrectal ultrasonography were enrolled in this study.All patients received 500 mg of ciprofloxacin twice a day for 3 weeks.Free and total PSA values were measured before and after antibiotic treatment.All the patients were then scheduled for 12-core prostate biopsy.Results The mean tPSA value was (6.5 ± 1.2) and (5.1 ± 1.2) μg/L respectively before and after antibiotic treatment ( P ＜ 0.01 ).Ninety-one patients (91.0％) showed tPSA reduction after antibiotic therapy,of which 13 ( 14.3％ ) had prostate cancer on biopsy.In 17 cases (18.7％) post-treatment tPSA was less than 4 μg/L.Three of the 17 cases (17.6％)had prostate cancer on biopsy.In 6 of the 100 men post-treatment tPSA was between 4 and 10 μg/L and the fPSA/tPSA ratio was above 0.25.One of these cases had prostate cancer on biopsy.Seven cases had a ＞50％ reduction in PSA levels with no positive biopsy results.Although mean total PSA and PSAD decreased after treatment in both groups,the reductions within these parameters were not significantly different between patients with and without prostate cancer (P ＞ 0.05).Furthermore,no differences emerged in terms of the changes of other PSA derivations including fPSA and fPSA/tPSA ( P ＞ 0.05 ).ConclusionsThe PSA levels may change with long-term antibiotic treatment in patients with elevated PSA values.A decrease in PSA after antibiotic treatment does not rule out the presence of prostate cancer even if PSA decreases to a normal level.But a ＞ 50％ reduction in PSA levels may be associated with a decreasing risk of prostate cancer,which may allow a postponement of prostate biopsy in selected patients.

ObjectiveTo assess the diagnostic value of preoperative lymphoscintigraphy for lateral lymph node metastasis in low rectal cancer. MethodsFrom May 1999 to March 2001, pelvic and lower abdominal lymphoscintigraphy with 99mTc sulfur colloid was performed on 32 patients with proven colorectal cancer one day prior to operation. Among these patients were 27 rectal cancers, 3 sigmoid cancers and 2 colon cancers. Fifteen cases of rectal cancer with the tumor located at or below the peritoneal reflection received extended lymphadenectomy with lateral dissection (D3 lymphadenectomy). The result of lymphoscintigrams was correlated with histologic lateral node examination. Results The image ratio of pararectal nodes, obturator nodes, and internal iliac aorti lymph trains was 69%, 91%, and 100% respectively. In 15 patients receiving D3 lymphadenectomy, 10 had negative lymphoscintigrams whereas 5 had positive image, and the lateral pathology positive rate was 13%(2/15). Analysis of these results revealed the sensitivity (100%), specificity (77%) and accuracy (80%) of this diagnostic method. ConclusionPelvic and lower abdominal lymphoscintigraphy with 99mTc sulfur colloid could demonstrate the lateral lymph node drainage of low rectal cancer, and the correlation with postoperative histologic lateral node examination was high enough to enable surgeons to adopt an individualized surgical approach.