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.

Two new nor-ent-halimane diterpenes and three previously unreported nor-clerodane diterpenes,designated callicain-tides A-E(1-5),were isolated from Callicarpa integerrima.Compounds 1 and 2 feature a distinctive 5/6-membered ring system,while compounds 3-5 are characterized by progressively truncated carbon skeletons,containing 18,17,and 16 carbons,respectively.In addition,four known compounds 6-9 were also identified.Their structures were elucidated using advanced spectroscopic tech-niques,including nuclear magnetic resonance(NMR),high-resolution electrospray ionization mass spectrometry(HR-ESI-MS),ultra-violet(UV),infrared radiation(IR),optical rotatory dispersion(ORD),DP4+analysis and electronic circular dichroism(ECD),sup-ported by quantum chemical calculations.Compounds 1-9 were evaluated for their anti-MRSA activity.Among them,compound 6 demonstrated significant anti-MRSA activity,with a minimum inhibitory concentration(MIC)of 16 μg·mL-1.

Objective: To study the chemical constituents from the leaves and twigs of Callicarpa cathayana. Methods: The chemical constituents were isolated and purified by column chromatography on silica gel, MCI gel CHP 20P/P120, Sephadex LH-20, and HPLC. The structures of the compounds were determined by HR-ESI-MS, 1D and 2D NMR data. Results: A total of 24 compounds were isolated from the 85% methanol extract of leaves and twigs of C. cathayana. They were identified as cathayanalactone G (1), a new diterpene, and 23 known compounds as patagonic acid (2), (-)-16-hydroxycledroda-3,13-dien-16,15-olide-18-oic acid (3), 15-methoxypatagonic acid (4), oleanolic acid (5), ursolic acid (6), siaresinolic acid (7), pomolic acid (8), α-amyrin (9), tormentic acid (10), lupeol (11), 5,7-dihydroxy-3,4′-dimethoxyflavone (12), 5,4′-dihydroxy-3,7,3′-dimethoxyfla-vone (13), 5-hydroxy-3,6,7,4′- tetramethoxyflavone (14), salvigenin (15), kaemferol (16), astragalin (17), pinoresinol 4-O-β-D-glucopyranoside (18), paulownin (19), β-sitosterol (20), β-sitosterol β-D-glucopyranoside (21), 5-hydroxy-coumarin (22), isocopoletin (23), and 4-hydroxycinnamic acid (24). Conclusion: Compound 1 is a new labdane diterpene. Compounds 10, 13, 16 and 17 are isolated from the genus Callicarpa for the first time. Compounds 7, 8, 9, 12, 14, 23 and 24 are reported from C. cathayana for the first time.

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 To compare the perioperative safety and curative effects oflaparoscopic adrenal sparing surgery (ASS) with laparoscopic total adrenalectomy (TA) for aldosterone producing adenoma (APA).Methods An online systematical retrieval was performed with Pubmed,ScienceDirect,Springerlink,the Cochrane library,CNKI and China Biology Medicine disc for clinical comparative studies published before May 2016,these studies reported the treatment of ASS/partial adrenalectomy (PA) versus TA for APA.The selected studies were applied to Revman 5.3 software for meta-analysis.The main contents were perioperative outcomes (operative time,intra-operative blood loss,and length of hospital stay) and postoperative efficacy (cure rate,partial response rate,inefficiency rate).Results A total of 9 clinical studies (3 English documents and 6 Chinese documents) with 1036 patients were included into the final analysis,among which 544 patients were assigned to ASS group and 492 in TA group.The analyzed results demonstrated no statistical significance between ASS group and TA group on operative time (WMD:-2.09min,95％CI:-9.86-5.67,P=0.60),length of hospital stay (WMD:-0.10d,95％CI:-0.32-0.12,P=0.36),intra-operative blood loss (WMD:1.13ml,95％CI:-8.86-11.12,P=0.82),cure rate (OR=l.07,95％CI:0.73-1.58,P=0.72),partial response rate (OR=0.85,95％CI:0.57-1.27,P=0.43) and inefficiency rate (OR=2.15,95％CI:0.32-14.34,P=0.43).Conclusion For surgical treatment of APA,ASS is technically safe,can achieve reliable postoperative efficacy and a similar therapeutic effect compared with TA,so deserves further application in clinical practice.

[Abstract ] Objective The purpose of this study was to construct a short hairpin RNA (shRNA) interference lentiviral vector targeting the humanβ-COP gene and to evaluate its inhibitory effect on β-COP in THP-1 cells. Methods We designed and synthesized 4 humanβ-COP-specific oligonucleotide sequences and inserted them into the pGMLV-SC1 vector to construct a recombinant vector fol-lowed by transfection of HEK 293T cells with the recombinant vector and Lenti-HG Mix to produce lentiviruses and detect the viral con-tent.After infecting the THP-1 cells with the packaged lentiviruses , we analyzed the inhibitory effect of β-COP-shRNA on the β-COP gene by quantitative PCR and Western blot . Results Sequencing confirmed that the β-COP-specific oligonucleotide sequences were in-serted into the lentiviral vector and the lentiviruses were packaged in the transfected HEK 293T cells, with the final viral content of 1 × 109 TU/mL.Quantitative PCR showed that the 4 β-COP-shRNA vectors significantly decreased the mRNA expression of β-COP (P<0.01), with interference rates of 16.9 %,32.5%, 74.0%, and 50.3%, respectively.Western blot also indicated their inhibitory effect on the protein expression of β-COP, with an inhibition rate of 76.4% onβ-COP-shRNA3. Conclusion Lentiviral shRNA interference vectors targeting human β-COP were constructed successfully , which could suppress the expression of the human β-COP gene.

Objective To evaluate the efficacy and safety of InVance bulbourethral sling for stress urinary incontinence after radical prostatectomy.Methods Six male patients with stress urinary incontinence after radical prostatectomy were treated with perineal sling (InVance) from March 2005 to March 2011,and the clinical data were analyzed.Results The operation time was 80-120 min and intra-operative blood loss was 20-50 ml.The catheter was removed at the second day after surgery.In a follow-up of 12 to 29 months,4 patients were dry,1 patient was improved,and 1 patient suffered treatment failure.There were 2 patients transient acute urinary retention and 1 patient short-term perineal pain in the main post-operative complication.In six months after the operation,urodynamic examination showed (15.9 ± 7.7) ml/s at Qmax and 0-20 ml/s at postvoid residual.Conclusion InVance bulbourethral sling for the treatment of stress urinary incontinence after radical prostatectomy appears to be safe,simple in the procedure and good effect to mild and middle incontinence.

Objective To observe the different expressions of androgen and estrogen receptor in nucleus membrane of human prostate stromal cells under anoxic or normoxic conditions.Methods Human prostate stromal cell line WPMY-1 was cultured in vitro.At 4,8,12,24,48 h after cellswere seeded,the mRNA and protein expression of androgen receptor (AR) and estrogen receptor (ER) in prostate stromal cells were tested by RT-PCR and immunohistochemistry method,respectively.Results The exprcssions of AR and ER were significantly increased in prostate stromal cells under anoxic conditions compared with under normoxic conditions.The relative expression of AR mRNA was 0.35±0.01 in anoxic prostate stromal cells at 4 h,and increased to 1.40±0.02 at 48 h,which was higher than in normoxic prostate epithelial cells [0.27 ± 0.01 and0.36± 0.01] synchronously (t=28.182,both P ＜ 0.001).Immunohistochemistry showed significantly increased AR-positive cells under anoxic conditions as compared with under-normoxiccondition from 12 h synchronously [(33.72±4.19) per 200 cells,(23.84±1.31) per 200 cells,t=3.902,P=0.018].The expression of ER mRNA was 0.39±0.01 in prostate stromal cells at 4 h,and increased to 0.59±0.01 at 48 h under anoxic conditions,which were higher than under normoxic conditions (0.31±0.01 and 0.46±0.13) synchronously (both P＜0.001).Immunohistochemistry showed the significantly increased ER-positive cells under anoxic conditions as compared with under normoxic condition from 4 h to 48 h synchronously [(13.42±0.80) per 200 cells and (55.16±0.41) per 200 cells； (9.68±0.63) per 200 cells and (22.95±0.55) per 200 cells,t=81.130,P＜0.001].Conclusions The expression of androgen and estrogen receptors is upregulated in human prostatestromal cells under anoxic conditions.

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.

Objective To evaluate the two-stage repair in hypospadias cripples.Methods 35 patients with hypospadias cripples underwent two-stage repair.At the first stage,a full-thickness graft of skin or buccal mucosa was used for urethral plate reconstruction after the release of chordee.The second stage was performed 6 months after completion of the first stage.Tubularization of the replaced urethral plate was the preferred technique.Results There was no urethra stricture or “preplaced urethral plate ” atrophy.Fistula developed in 2 of 35 cases.Conclusion The twostaged technique was a useful strategy to deal with the myriad abnormalities encountered in crippled hypospadias.This technique could not only create a neourethra successfully,but also give the penis a near-normal shape and appearance.