The NOD-like receptor protein 3(NLRP3)inflammasome is essential in innate immune-mediated inflammation,with its overactivation implicated in various autoinflammatory,metabolic,and neurode-generative diseases.Pharmacological inhibition of NLRP3 offers a promising treatment strategy for in-flammatory conditions,although no medications targeting the NLRP3 inflammasome are currently available.This study demonstrates that clioquinol(CQ),a clinical drug with chelating properties,effec-tively inhibits NLRP3 activation,resulting in reduced cytokine secretion and cell pyroptosis in both human and mouse macrophages,with a half maximal inhibitory concentration(IC50)of 0.478 μM.Additionally,CQ mitigates experimental acute peritonitis,gouty arthritis,sepsis,and colitis by lowering serum levels of interleukin-1β(IL-1β),IL-6,and tumor necrosis factor-α(TNF-α).Mechanistically,CQ covalently binds to Arginine 335(R335)in the NACHT domain,inhibiting NLRP3 inflammasome assembly and blocking the interaction between NLRP3 and its component protein.Collectively,this study identifies CQ as an effective natural NLRP3 inhibitor and a potential therapeutic agent for NLRP3-driven diseases.

The current clinical treatment of bladder cancer (BCa) is mainly surgical treatment，supplemented by postoperative chemotherapy and immunotherapy.However，due to the lack of specificity，targeting and other reasons，the therapeutic effect is not satisfactory.In recent years，it has been found that metal nanoparticles (MNPs) prepared by gold，silver，and so on，as bladder infusion drugs or drug carriers，can not only accurately target BCa cells，but also have high stability and drug release rate，thereby reducing the side-effects of chemotherapy drugs.Based on domestic and foreign studies，this paper reviews the progress of MNPs in the treatment of BCa，including gold，silver，copper and other MNPs，and prospects the trend of bladder perfusion combined with nanomedical drugs.

The NOD-like receptor protein 3 (NLRP3) inflammasome is essential in innate immune-mediated inflammation, with its overactivation implicated in various autoinflammatory, metabolic, and neurodegenerative diseases. Pharmacological inhibition of NLRP3 offers a promising treatment strategy for inflammatory conditions, although no medications targeting the NLRP3 inflammasome are currently available. This study demonstrates that clioquinol (CQ), a clinical drug with chelating properties, effectively inhibits NLRP3 activation, resulting in reduced cytokine secretion and cell pyroptosis in both human and mouse macrophages, with a half maximal inhibitory concentration (IC₅₀) of 0.478 μM. Additionally, CQ mitigates experimental acute peritonitis, gouty arthritis, sepsis, and colitis by lowering serum levels of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α). Mechanistically, CQ covalently binds to Arginine 335 (R335) in the NACHT domain, inhibiting NLRP3 inflammasome assembly and blocking the interaction between NLRP3 and its component protein. Collectively, this study identifies CQ as an effective natural NLRP3 inhibitor and a potential therapeutic agent for NLRP3-driven diseases.

Objective:To investigate the efficacy and safety of darolutamide in the treatment of patients with metastatic hormone-sensitive prostate cancer.Methods:A retrospective analysis was conducted on 17 cases of prostate cancer patients who received treatment with darolutamide in combination with ADT at our hospital from January to December 2022. The median age was 70 (range: 56 to 92) years old. The median pre-treatment prostate-specific antigen (PSA) level was 63.50 (range: 29.16 to 700.74) ng/ml. Sixteen cases had a Gleason score of 8 or above, and 11 cases were classified as high tumor burden (with four or more bone metastases and/or visceral metastases). The patients were treated with darolutamide in combination with goserelin (10.8 mg, subcutaneous injection, every 12 weeks). The decrease in PSA levels was observed at 2 weeks and at 1, 2, 3, and 6 months post-treatment. The time to achieve a 50% decrease in PSA level (PSA50), a 90% decrease (PSA90), and a PSA level of ≤0.2 ng/ml was recorded.Adverse drug reactions were also documented.Results:All the 17 patients were followed up and continued to receive darolutamide at our center without any loss to follow-up. The median follow-up time was 11.4(8.9, 15.3)months. It showed a median PSA decrease from baseline of 83.33% at 2 weeks, 95.37% at 1 month, 96.71% at 2 months, 97.22% at 3 months, and 99.10% at 6 months. The median time to achieve PSA50, PSA90, and PSA ≤ 0.2 ng/ml were 1.3 (0.9, 1.7)months, 1.7 (1.2, 2.4)months, and 3.6 (2.9, 4.5)months respectively. Six patients with bone metastases experienced relief of metastatic lesions after treatment. Only one patient developed papules on the left upper limb, which were assessed as grade 1 rash, and the rash disappeared after three days treatment of topical application of hydrocortisone cream.Conclusions:Darolutamide could rapidly control and significantly reduce PSA levels in prostate cancer patients, with a favorable safety profile.

Objective:To investigate the efficacy and safety of darolutamide in the treatment of patients with metastatic hormone-sensitive prostate cancer.Methods:A retrospective analysis was conducted on 17 cases of prostate cancer patients who received treatment with darolutamide in combination with ADT at our hospital from January to December 2022. The median age was 70 (range: 56 to 92) years old. The median pre-treatment prostate-specific antigen (PSA) level was 63.50 (range: 29.16 to 700.74) ng/ml. Sixteen cases had a Gleason score of 8 or above, and 11 cases were classified as high tumor burden (with four or more bone metastases and/or visceral metastases). The patients were treated with darolutamide in combination with goserelin (10.8 mg, subcutaneous injection, every 12 weeks). The decrease in PSA levels was observed at 2 weeks and at 1, 2, 3, and 6 months post-treatment. The time to achieve a 50% decrease in PSA level (PSA50), a 90% decrease (PSA90), and a PSA level of ≤0.2 ng/ml was recorded.Adverse drug reactions were also documented.Results:All the 17 patients were followed up and continued to receive darolutamide at our center without any loss to follow-up. The median follow-up time was 11.4(8.9, 15.3)months. It showed a median PSA decrease from baseline of 83.33% at 2 weeks, 95.37% at 1 month, 96.71% at 2 months, 97.22% at 3 months, and 99.10% at 6 months. The median time to achieve PSA50, PSA90, and PSA ≤ 0.2 ng/ml were 1.3 (0.9, 1.7)months, 1.7 (1.2, 2.4)months, and 3.6 (2.9, 4.5)months respectively. Six patients with bone metastases experienced relief of metastatic lesions after treatment. Only one patient developed papules on the left upper limb, which were assessed as grade 1 rash, and the rash disappeared after three days treatment of topical application of hydrocortisone cream.Conclusions:Darolutamide could rapidly control and significantly reduce PSA levels in prostate cancer patients, with a favorable safety profile.

Objective To investigate the effect of ACOT4 expression on the formation of calcium oxalate stones.Methods The HK2 cell of human tubular epithelial cells was used as subject,HK2 cell was treated with calcium oxalate,and the expression of ACOT4 was interfered with by siRNA.The gene expression levels in HK2 cell were detected by qPCR and Western blot.The cell viability was de-tected by CCK-8 assay.The cell apoptosis was detected by flow cytometry.The cell damage was detected by LDH assay.The adhesion ability of HK2 cell to calcium oxalate crystals was detected by crystal adhesion experiment.Results Calcium oxalate could regulate the expression of ACOT4 in HK2 cell.Interfering with ACOT4 can significantly inhibit the proliferation ability of HK2 cell,and promote the effect of cell activity reduction,damage and apoptosis of calcium oxalate to HK2 cell.At the same time,interfering with ACOT4 can sig-nificantly promote the adhesion ability of HK2 cells to calcium oxalate crystals.Conclusion Knocking down of ACOT4 can promote the damage of calcium oxalate to HK2 cell and promote the adhesion ability of HK2 cell to calcium oxalate crystals.

Factors affecting male fertility include lifestyle,psychology,environment.and so on.Pathogenic microorganisms in the genitourinary system can also lead to decline of male fertility.However,doctors tend to ignore the effects of immune responses and oxidative stress caused by pathogenic microorganisms on fertility,thus delaying the optimal time of treatment.This paper reviews the relationship between bacteria(such as Escherichia coli,Helicobacter pylori),viruses((severe acute respiratory syndrome coronavirus 2,human papilloma virus),and other pathogenic microorganisms(mycoplasma and chlamydia)and male infertility,and summarizes the latest research progress,aiming to provide guidance for the multidimensional treatment and to provide new ideas for the prevention of male infertility.

This article retrospectively analyzed the clinical data of 8 patients with vesicovaginal fistula after radiotherapy for cervical cancer admitted in our hospital from January 2015 to October 2021. All of them underwent cystostomy under local anesthesia. A single J tube of bilateral ureters was retained under cystoscope, and the single J tube was introduced into the fistula bag through the cystostomy opening. All patients wore diapers for a long time before operation, and used urine pads 0-2 pieces/day after operation. QOL score was 5.3±0.5 points before operation, and 2.5±0.5 points after operation. The patient's body odor basically disappeared. The vesicovaginal fistula can be repaired by surgery, but for patients who cannot be operated or failed repeatedly due to various reasons, a single J tube of bilateral ureters can be drawn out through the cystostomy opening, which can improve the quality of life of patients through minor trauma.

Objective:To systematically evaluate the efficacy of different kinds of smoking cessation drugs by network Meta-analysis.Methods:Literature was retrieved from PubMed, Web of Science, Embase, Cochrane Library, CBM, CNKI, VIP, Wan fang database, from the establishment of the database to November 2022, and randomized controlled trials (RCT) about bupropion, varenicline, nicotine replacement therapy (NRT) versus placebo in the treatment of smoking patients were collected. After data extraction from included literature which met inclusion criteria, and quality evaluation with Cochrane 5.1 risk bias evaluation tool, network Meta-analysis was performed by Stata15.1 software.Results:A total of 19 RCTs, involving 6106 patients and three interventions measures (bupropion, varenicline, NRT) and one control measure (placebo) were included. The results of network Meta-analysis showed that in terms of short-term abstinence rate, varenicline [ OR=4.21, 95% CI (2.32, 7.63)], bupropion [ OR=2.81, 95% CI(1.05, 7.54)] were better than placebo ( P<0.05). The surface under the cumulative ranking area (SUCRA): varenicline (90.2%)>bupropion (64.8%)>NRT (41.7%)>placebo (3.2%). In terms of the long-term abstinence rate, varenicline [ OR=3.06, 95% CI (1.59, 5.90)], NRT [ OR=3.39, 95% CI (2.20, 5.21)] were better than placebo ( P<0.05). SUCRA: varenicline (83.8%)>NRT (73.9%)>bupropion (37.2%)>placebo (5.2%). Conclusion:The existing evidence shows that compared with bupropion, NRT, varenicline has the best effect on quitting smoking, but more high-quality randomized trial evidence is needed for verification.

Lung cancer is one of the most harmful global diseases with high morbidity and mortality rate. As a unique kind of driver gene, the pathogenic fusion gene is a common mechanism of lung cancer. Most fusion genes are produced by chromosome rearrangement and encoding receptor tyrosine kinases, which could be potential lung cancer therapeutic targets. Since ALK was first identified in 2007, methods like FISH, IHC, RT-PCR and NGS have been intensively applied, leading to identification of multiple other lung cancer fusion genes including ROS1, RET, FGFR, NTRK1, NRG1, DNAH5 and LTK. These works broaden the spectrum of lung cancer related gene mutations, and support the customized treatment for clinical patients. For some fusion genes, corresponding kinase inhibitors have been developed with good efficacy, however, the treatment is still being challenged by several problems like drug resistance. Based on recent studies, the research development of lung cancer fusion genes will be discussed.