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Abstract Background and objective Cancer ratio (CR), which is defined as serum lactate dehydrogenase (LDH) to pleural fluid adenosine deaminase (ADA) ratio, has been reported to be a useful diagnostic marker for malignant pleural effusion (MPE). Whether its diagnostic accuracy is affected by age remains unknown. This study aimed to investigate the effects of age on the diagnostic accuracy of CR. Methods The participants in this study were from a prospective cohort (SIMPLE cohort, n = 199) and a retrospective cohort (BUFF cohort, n = 158). All participants were patients with undiagnosed pleural effusion (PE). We used receiver operating characteristic (ROC) curves to evaluate the diagnostic accuracy of CR. The effect of age on the diagnostic accuracy of CR was investigated by adjusting the upper limit of age for participant enrolment. Results Eighty-eight MPE patients were verified in the SIMPLE cohort, and thirty-five MPE patients were verified in the BUFF cohort. The AUCs of CR in the SIMPLE and BUFF cohorts were 0.60 (95% CI: 0.52–0.68) and 0.63 (95% CI: 0.54–0.71), respectively. In both cohorts, the AUCs of CR decreased with the advancement of age. Conclusion Age can affect the diagnostic accuracy of CR for MPE. CR has limited diagnostic value in older patients. Key message Cancer ratio is a promising diagnostic marker for malignant pleural effusion. This study revealed that its diagnostic accuracy decreased in older patients. Its diagnostic accuracy is overestimated by previous studies using tuberculosis and pneumonia patients as controls.

Abstract Background The response of advanced clear cell renal cell carcinoma (ccRCC) to immunotherapy is still not durable, suggesting that the immune landscape of ccRCC still needs to be refined, especially as some molecules that have synergistic effects with immune checkpoint genes need to be explored. Methods The expression levels of CENPM and its relationship with clinicopathological features were explored using the ccRCC dataset from TCGA and GEO databases. Quantitative polymerase chain reaction (qPCR) analysis was performed to validate the expression of CENPM in renal cancer cell lines. Kaplan-Meier analysis, COX regression analysis and Nomogram construction were used to systematically evaluate the prognostic potential of CENPM in ccRCC. Besides, single gene correlation analysis, protein–protein interaction (PPI) network, genetic ontology (GO), kyoto encyclopedia of genes and genomes (KEGG) and gene set enrichment analysis (GSEA) were used to predict the biological behaviour of CENPM and the possible signalling pathways involved. Finally, a comprehensive analysis of the crosstalk between CENPM and immune features in the tumor microenvironment was performed based on the ssGSEA algorithm, the tumor immune dysfunction and exclusion (TIDE) algorithm, the TIMER2.0 database and the TISIDB database. Results CENPM was significantly upregulated in ccRCC tissues and renal cancer cell lines and was closely associated with poor clinicopathological features and prognosis. Pathway enrichment analysis revealed that CENPM may be involved in the regulation of the cell cycle in ccRCC and may have some crosstalk with the immune microenvironment in tumors. The ssGSEA algorithm, CIBERSOPT algorithm suggests that CENPM is associated with suppressor immune cells in ccRCC such as regulatory T cells. The ssGSEA algorithm, CIBERSOPT algorithm suggests that CENPM is associated with suppressor immune cells in ccRCC such as regulatory T cells. Furthermore, the TISIDB database provides evidence that not only CENPM is positively associated with immune checkpoint genes such as CTLA4, PDCD1, LAG3, TIGIT, but also chemokines and receptors (such as CCL5, CXCL13, CXCR3, CXCR5) may be responsible for the malignant phenotype of CENPM in ccRCC. Meanwhile, predictions based on the TIDE algorithm support that patients with high CENPM expression have a worse response to immunotherapy. Conclusions The upregulation of CENPM in ccRCC predicts a poor clinical outcome, and this malignant phenotype may be associated with its exacerbation of the immunosuppressive state in the tumor microenvironment.

Abstract Background Mindfulness-based cognitive therapy (MBCT) is a promising alternative treatment for generalized anxiety disorder (GAD). The objective of this study was to examine whether the efficacy of group MBCT adapted for treating GAD (MBCT-A) was noninferior to group cognitive behavioural therapy (CBT) designed to treat GAD (CBT-A), which was considered one of first-line treatments for GAD patients. We also explored the efficacy of MBCT-A in symptomatic GAD patients compared with CBT-A for a variety of outcomes of anxiety symptoms, as well as depressive symptoms, overall illness severity, quality of life and mindfulness. Methods This was a randomized, controlled, noninferiority trial with two arms involving symptomatic GAD patients. Adult patients with GAD (n = 138) were randomized to MBCT-A or CBT-A in addition to treatment as usual (TAU). The primary outcome was the anxiety response rate assessed at 8 weeks after treatment as measured using the Hamilton Anxiety Scale (HAMA). Secondary outcomes included anxiety remission rates, scores on the HAMA, the state-trait anxiety inventory (STAI), the Hamilton Depression Scale (HAMD), the Severity Subscale of the Clinical Global Impression Scale (CGI-S), and the 12-item Short-Form Health Survey (SF-12), as well as mindfulness, which was measured by the Five Facet Mindfulness Questionnaire (FFMQ). Assessments were performed at baseline, 8 weeks after treatment, and 3 months after treatment. Both intention-to-treat (ITT) and per-protocol (PP) analyses were performed for primary analyses. The χ2 test and separate two-way mixed ANOVAs were used for the secondary analyses. Results ITT and PP analyses showed noninferiority of MBCT-A compared with CBT-A for response rate [ITT rate difference = 7.25% (95% CI: -8.16, 22.65); PP rate difference = 5.85% (95% CI: − 7.83, 19.53)]. The anxiety remission rate, overall illness severity and mindfulness were significantly different between the two groups at 8 weeks. There were no significant differences between the two groups at the 3-month follow-up. No severe adverse events were identified. Conclusions Our data indicate that MBCT-A was noninferior to CBT-A in reducing anxiety symptoms in GAD patients. Both interventions appeared to be effective for long-term benefits. Trial registration Registered at chictr.org.cn (registration number: ChiCTR1800019150 , registration date: 27/10/2018).

Abstract Background Patients who do not respond to conservative treatment of the isthmus are often treated with surgery. We used direct repair plus intersegment pedicle screw fixation for the treatment of lumbar spondylolysis. The aim of this observational study was to assess the effects of this technique and evaluate various risk factors potentially predicting the probability of disc and facet joint degeneration after instrumentation. Methods The study included 54 male L5 spondylolysis patients who underwent pars repair and intersegment fixation using pedicle screws. Bony union was evaluated using reconstruction images of computed tomography. Radiographic changes, including disc height, vertebral slip, facet joint and disc degeneration in the grade of adjacent and fixed segments, were determined from before to final follow-up. Logistic regression analysis was performed to identify factors associated with the incidence of disc and facet joint degeneration. Results Bony union was achieved in all cases. Logistic regression analysis revealed that instrumentation durations of greater than 15.5 months and 21.0 months were significant risk factors for the incidence of L4/5 and L5S1 facet degeneration, respectively. Conclusions Intersegmental pedicle screw fixation provides good surgical outcomes and good isthmic bony union rates in patients with lumbar spondylolysis. The duration of fixation was confirmed as a risk factor for facet joint degeneration. Once bony union is achieved, instrument removal should be recommended.

Abstract Background Despite the continuous development and evolution of surgical methods and techniques, proximal hypospadias remains one of the most challenging issues for pediatric urologists. This study aims to evaluate the indications and postoperative complications of our new modified Duckett urethroplasty. Methods A total of 133 patients with proximal hypospadias who underwent repair of the modified Duckett urethroplasty from February 2016 to February 2021 were reviewed. The median age of patients was 3 years (range 1–16). All patients had severe chordee. One senior experienced pediatric urologist performed all the surgeries. Catheter was removed 14 days after the surgery. Results The location of the urethral meatus was proximal penile in 26 patients (19.5%), penoscrotal in 60 (45.1%), scrotal in 31 (23.3%), and perineal in 16 (12.0%). The mean length of the urethral defect was 4.5 cm (range 2.5–10). The median duration of follow-up was 46 months (range 8–67). Complications occurred in 31 patients (23.3%), including urethra-cutaneous fistula in 22 (16.5%), urethral stenosis in 7 (5.3%), and urethral diverticulum in 2 (1.5%). No recurrent chordee were found in all cases. All patients who developed complications were treated successfully at our hospital. Conclusions Our modified Duckett urethroplasty showed functionally and cosmetically favorable outcomes, with a lower incidence of postoperative complications. To the best of our knowledge, the novel Duckett technique is a feasible and suitable option for patients who suffer from proximal hypospadias with severe chordee and dysplasia of the urethral plate.

Abstract Background When symptomatic spondylolysis fail to respond to nonoperative treatment, surgical management may be required. A number of techniques have been described for repair by intrasegmental fixation with good results; however, there are still some problems. We reported a repair technique with temporary intersegmental pedicle screw fixation and autogenous iliac crest graft. The aim of present study is to assess the clinical outcomes of L5 symptomatic spondylolysis with this technique. Methods A retrospective analysis of 128 patients with L5 spondylolysis treated with this method was performed. According to CT scan, the spondylolysis were classified into 3 categories: line, intermediate, and sclerosis type. The diagnostic block test of L5 bilateral pars defect was done in all patients preoperatively. The sagittal and axial CT images were used to determine the bone union. The healing time, complications, number of spina bifida occulta, Japanese Orthopedic Association (JOA) score, and VAS for back pain were recorded. After fixation removal, the rate of ROM preservation at L5S1 was calculated. Results There were 97 patients (194 pars) followed with mean follow-up of 23 months (range, 12–36 months). The union rate of pars was 82.0% at 12 months and 94.3% at 24 months postoperatively. Low back pain VAS significantly (P < 0.05) improved from preoperative mean value of 7.2 to 1.3 at the final follow-up postoperatively (P < 0.05). JOA score increased significantly postoperatively (P < 0.05) with average improvement rate of 79.3%. The rates of L5S1 ROM preservation were 79.8% and 64.0% after fixation removal at 1 and 2 years postoperatively. There were 3 patients of delayed incision healing without other complications. Conclusions Although sacrificing L5S1 segment motion temporarily, more stability was obtained with intersegmental fixation. This technique is reliable for spondylolysis repair which has satisfactory symptom relief, high healing rate, low incidence of complications, and preserve a large part of ROM for fixed segment.

Abstract Background Several studies demonstrate that endoplasmic reticulum (ER) stress-mediated epithelial-mesenchymal transition (EMT) is involved in the process of bleomycin (BLM)-induced pulmonary fibrosis. Tauroursodeoxycholic acid (TUDCA), a bile acid with chaperone properties, is an inhibitor of ER stress. This study aimed to investigate the preventive effects of TUDCA on BLM-induced EMT and lung fibrosis. Methods The model of lung fibrosis was established by intratracheal injection with a single dose of BLM (3.0 mg/kg). In TUDCA + BLM group, mice were intraperitoneally injected with TUDCA (250 mg/kg) daily. Results BLM-induced alveolar septal destruction and inflammatory cell infiltration were alleviated by TUDCA. BLM-induced interstitial collagen deposition, as determined by Sirius Red staining, was attenuated by TUDCA. BLM-induced elevation of pulmonary α-smooth muscle actin (α-SMA) and reduction of pulmonary E-cadherin were attenuated by TUDCA. BLM-induced pulmonary Smad2/3 phosphorylation was suppressed by TUDCA. BLM-induced elevation of Ki67 and PCNA was inhibited by TUDCA in mice lungs. In addition, BLM-induced elevation of HO-1 (heme oxygenase-1) and 3-NT (3-nitrotyrosine) was alleviated by TUDCA. Finally, BLM-induced upregulation of pulmonary GRP78 and CHOP was attenuated by TUDCA. Conclusions These results provide evidence that TUDCA pretreatment inhibits Smad2/3-medited EMT and subsequent lung fibrosis partially through suppressing BLM-induced ER stress and oxidative stress.