The role of adjuvant chemotherapy after radical surgery in patients with lymph node-positive bladder cancer or locally advanced (pT3, pT4a) bladder cancer: A meta-analysis and systematic review.

PURPOSE: This study aims to evaluate the impact of adjuvant chemotherapy (AC) on survival outcomes in patients with lymph node-positive bladder cancer or locally advanced (pT3, pT4a) bladder cancer after surgery. We also seek to identify which patients with pN+ bladder cancer are most likely to benefit from AC after radical cystectomy (RC). METHODS: We searched databases including Embase, PubMed, Cochrane, and ClinicalTrials.gov to identify relevant literature published in English up to February 2024. We used Stata to compare various parameters. The study has been registered in PROSPERO. RESULTS: A total of 21 studies were analyzed, including 1 randomized controlled trial, 6 prospective studies, and 14 retrospective studies, encompassing 12,888 patients. The meta-analysis showed that for patients with lymph node-positive bladder cancer, the adjuvant chemotherapy (AC) group had higher overall survival (OS) (I2=58.2%, HR 0.69; 95% CI: 0.57-0.83; P=0.019) and recurrence-free survival (RFS) (I2=66.6%, HR 0.71; 95% CI: 0.57-0.89; P=0.006) compared to the radical cystectomy (RC) group. For patients with pT3 and pT4a bladder cancer, the AC group had higher overall survival (OS) (I2=57.3%, HR 0.77; 95% CI: 0.67-0.89; P=0.022) and cancer-specific survival (CSS) (I2=47.2%, HR 0.75; 95% CI: 0.64-0.88; P=0.0048) compared to the RC group. At the same time, according to the different chemotherapy regimens, we divided the cisplatin-based chemotherapy regimen and carboplatin based chemotherapy or other regimens into two subgroups for analysis, and found that the OS (I2=41.4%, HR 0.64; 95%CI: 0.51~0.80; P=0.000) was better than carboplatin and other chemotherapy regimens (I2=64.1%, HR 0.77; 95%CI: 069~0.86; P=0.000); Lymph node density (LND) was found to be an independent predictor of overall survival (HR=1.6; 95% CI: 1.31-1.95; P=0.0000). CONCLUSION: This study found that postoperative adjuvant chemotherapy (AC) improves overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) in patients with pT3, pT4a, It was also confirmed that cisplatin-based chemotherapy regimen was more beneficial for patients with bladder cancer; and lymph node-positive bladder cancer. Additionally, our analysis revealed that patients with lymph node-positive bladder cancer benefit more from postoperative AC. It was further demonstrated that cisplatin-based chemotherapy regimens are more beneficial than other regimens for patients with locally advanced bladder cancer.

Network pharmacology, molecular docking and experimental validation to elucidate the anti-T2DM mechanism of Lanxangia tsaoko.

Lanxangia tsaoko (L. tsaoko) is a natural medicine which could be used to treat type 2 diabetes mellitus (T2DM). However, there is no systematic and comprehensive research on the its active compounds and mechanism. This study aimed to investigate the active ingredients and potential mechanism of L. tsaoko for the treatment of T2DM. The chemical constituents of L. tsaoko were identified by UPLC-Q-Exactive Orbitrap/MS. The active compounds and mechanism of L. tsaoko were predicted by network pharmacology. Then the docking modes of key components and core targets were analyzed by molecular docking. Finally, animal experiments were conducted to verify the efficacy and targets of L. tsaoko in T2DM treatment. 70 compounds from L. tsaoko were identified. We obtained 37 active components, including quercetin, genistein and kaempferol, 5 core targets were AKT1, INS, TP53, TNF and IL-6. Mainly involved in PI3K/Akt, MAPK, RAGE/AGE, HIF-1, FoxO signaling pathways. Molecular docking results showed that the L. tsaoko had good binding potential to TNF. Therefore, we took the inflammatory mechanism as the prediction target for experimental verification. Animal experiments showed that L. tsaoko could alleviated colon injury of T2DM mice, improve glucose metabolism and decrease inflammatory levels. L. tsaoko exerted therapeutic effects on T2DM through multi-component, multi-target and multi-pathway regulation. Its action mechanisms were related to PI3K/Akt, MAPK, RAGE/AGE, HIF-1 and FoxO signaling pathways. This study provided new insights for the clinical treatment of T2DM.

Efficacy and safety of platelet-rich plasma (PRP) in erectile dysfunction (ED): a systematic review and meta-analysis.

Background: Erectile dysfunction (ED) is a prevalent condition in aging men. Meanwhile, platelet-rich plasma (PRP), an emerging treatment alternative, has demonstrated potential in mitigating symptoms associated with ED. Our research aimed to explore the safety and effectiveness of employing PRP as a treatment strategy for ED. Methods: Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocols, our research involved a thorough search across multiple databases: PubMed, Web of Science, Embase, and the Cochrane Controlled Trials Register. To assess the methodological rigor of the studies selected, we applied the modified Jadad scale and the Methodological Index for Non-Randomized Studies (MINORS) scale as evaluation tools. Subsequent to these evaluations, data analysis was conducted. Results: Our analysis included seven non-randomized studies and three randomized controlled trials (RCTs). These studies showed that the International Index of Erectile Function-Erectile Function (IIEF-EF) scores improved significantly after 1, 3, and 6 months of PRP treatment, with increases of 4.05 [95% confidence interval (CI): 2.42, 5.68; P<0.001], 3.73 (95% CI: 2.93, 4.53; P<0.001), and 3.92 (95% CI: 3.00, 4.85; P<0.001) respectively, compared to the baseline scores. Additionally, compared to the placebo group, the PRP group showed significantly higher IIEF-EF scores. PRP treatment also had a beneficial impact on minimal clinically important difference (MCID) and peak systolic velocity (PSV). However, no significant differences were found between the PRP and placebo groups in terms of erectile hardness score (EHS) [mean difference (MD) =0.63; 95% CI: 0.26, 0.99; P<0.001] or visual analog scale (VAS) pain scores (MD =0.24; 95% CI: -0.05, 0.54; P=0.11). Conclusions: Our study results demonstrated significant efficacy and safety of PRP in treating ED. Due to the fact that most of the literature we included was single-arm studies, it was imperative for future research to provide higher-quality evidence for validation.

Nomogram-based risk assessment for emergency cervical cerclage failure in patients with cervical insufficiency.

Background: Cervical insufficiency can lead to preterm birth and neonatal mortality. Emergency cervical cerclage is a surgical intervention aimed at preventing preterm birth in patients with cervical insufficiency. However, some patients may experience cerclage failure. This study aimed to identify the risk factors associated with cerclage failure and develop a predictive nomogram model for patients with cervical insufficiency undergoing emergency cervical cerclage. Methods: Data of 200 patients who underwent emergency cervical cerclage for cervical insufficiency were retrospectively analyzed. Patients were categorized into successful and failed groups based on their ability to take the infant home. Univariate and multivariate logistic regression analyses were performed to identify risk factors for cerclage failure. A nomogram model was developed based on multivariate logistic regression results, and its performance was assessed using receiver operating characteristic curves, calibration plots, and decision curve analysis (DCA). Results: Univariate logistic regression analysis identified 11 potential risk factors for cerclage failure, including the presence of polycystic ovary syndrome (PCOS), vaginitis, cervical dilation, preoperative C-reactive protein, routine vaginal lavage after cervical cerclage, delivery, gestational age, extended days, chorioamnionitis, intrauterine infection, cervical laceration, and premature rupture of membranes. Multivariate logistic regression analysis revealed that PCOS, cervical dilation after cervical cerclage were independent risk factors for cerclage failure while routine vaginal lavage was a protective factor against failure. The nomogram predictive model demonstrated an area under the curve value of 0.975, indicating excellent discriminatory ability. The calibration plot showed good consistency between the nomogram predictions and actual observations. DCA demonstrated the strong clinical applicability of the nomogram. Conclusions: This study successfully identified risk factors associated with emergency cervical cerclage failure in patients with cervical insufficiency and developed a predictive nomogram model. This model can assist clinicians in making informed decisions and accurately predicting the risk of cerclage failure in these patients.

Chrysomycins, Anti-Tuberculosis C-Glycoside Polyketides from Streptomyces sp. MS751.

A new dimeric C-glycoside polyketide chrysomycin F (1), along with four new monomeric compounds, chrysomycins G (2), H (3), I (4), J (5), as well as three known analogues, chrysomycins A (6), B (7), and C (8), were isolated and characterised from a strain of Streptomyces sp. obtained from a sediment sample collected from the South China Sea. Their structures were determined by detailed spectroscopic analysis. Chrysomycin F contains two diastereomers, whose structures were further elucidated by a biomimetic [2 + 2] photodimerisation of chrysomycin A. Chrysomycins B and C showed potent anti-tuberculosis activity against both wild-type Mycobacterium tuberculosis and a number of clinically isolated MDR M. tuberculosis strains.

A systematic review and meta-analysis of the role of perineal hydrodissection in perioperative, oncologic, and functional outcomes for patients undergoing robot-assisted radical prostatectomy.

This study aims to compare the perioperative, oncological, and functional outcomes of perineal hydrodissection (HD) with standard treatment (ST) in patients undergoing robot-assisted radical prostatectomy. We performed an exhaustive search in databases such as PubMed, Embase, Web of Science, and the Cochrane Library, seeking English-language studies relevant to our research question, with a cutoff date of April 2024. The pooled results were assessed using the weighted mean differences (WMDs), standardized mean differences (SMDs), and odds ratios (ORs) metrics. We also performed a sensitivity analysis. The meta-analysis was conducted utilizing Stata/MP version 18 software. The study was registered with PROSPERO (ID: CRD 42024536400). We included a total of five studies (three RCTs and two retrospective studies). According to the data from the Meta-analysis, the HD group showed positive effects in promoting urinary continence (OR 2.64, 95% CI 1.36, 5.12; p = 0.004 < 0.05) and erectile function (SMD 0.92, 95%CI 0.56, 1.27; p < 0.05) within 3 months after surgery. However, no notable disparities were observed in terms of operative time, estimated blood loss, bilateral nerve-sparing rate, or the rate of positive surgical margin. Perineal hydrodissection can be safely applied in robot-assisted radical prostatectomy (RARP), offering a distinct advantage in functional outcomes compared to those who undergo standard robot-assisted prostatectomy alone.

Comparative analysis of perioperative outcomes in obese patients undergoing robot-assisted radical prostatectomy (RARP) versus open radical prostatectomy (ORP): a systematic review and meta-analysis.

The purpose of this study was to conduct a comparative analysis of the perioperative outcomes associated with robot-assisted laparoscopic prostatectomy (RARP) versus open radical prostatectomy (ORP) in the obese population diagnosed with prostate cancer. We performed a comprehensive search in key databases such as PubMed, Embase, Web of Science, and the Cochrane Library, encompassing studies of all languages, with a final search date of April 2024. We also omitted articles that consisted of conference abstracts and content that was not pertinent to our study. The aggregated outcomes were evaluated utilizing the metrics of weighted mean differences (WMDs) and odds ratios (ORs). A sensitivity analysis was also integrated into our assessment. The meta-analysis was facilitated by employing Stata/MP version 18 software. Additionally, the study was duly registered with PROSPERO under the identifier: CRD 42024540216. This meta-analysis, which included five trials, shows that compared to ORP, RARP is associated with a reduced estimated blood loss (EBL) (WMD -445.77, 95%CI -866.08, -25.45; p = 0.038), a decreased transfusion rate (OR 0.17, 95%CI 0.13, 0.21; p < 0.001), and a diminished overall complication rate (OR 0.71, 95%CI 0.58, 0.86; p = 0.001). No statistically significant differences were found in operative time (OT) (WMD 1.88, 95%CI -46.53, 50.28; p = 0.939) or length of stay (LOS) (WMD -0.41, 95%CI -1.07, 0.25; p = 0.221). Among patients with obesity and prostate cancer, RARP demonstrates advantages over ORP by reducing estimated blood loss, transfusion requirements, and the incidence of complications. Notably, there were no significant differences in operative duration and hospital stay between the two surgical approaches. These findings suggest that RARP could be a preferable surgical option for obese individuals with prostate cancer.

Exploring the dynamic adaptive responses of Epimedium pubescens to phosphorus deficiency by Integrated transcriptome and miRNA analysis.

Phosphorus, a crucial macronutrient essential for plant growth and development. Due to widespread phosphorus deficiency in soils, phosphorus deficiency stress has become one of the major abiotic stresses that plants encounter. Despite the evolution of adaptive mechanisms in plants to address phosphorus deficiency, the specific strategies employed by species such as Epimedium pubescens remain elusive. Therefore, this study observed the changes in the growth, physiological reponses, and active components accumulation in E. pubescensunder phosphorus deficiency treatment, and integrated transcriptome and miRNA analysis, so as to offer comprehensive insights into the adaptive mechanisms employed by E. pubescens in response to phosphorus deficiency across various stages of phosphorus treatment. Remarkably, our findings indicate that phosphorus deficiency induces root growth stimulation in E. pubescens, while concurrently inhibiting the growth of leaves, which are of medicinal value. Surprisingly, this stressful condition results in an augmented accumulation of active components in the leaves. During the early stages (30 days), leaves respond by upregulating genes associated with carbon metabolism, flavonoid biosynthesis, and hormone signaling. This adaptive response facilitates energy production, ROS scavenging, and morphological adjustments to cope with short-term phosphorus deficiency and sustain its growth. As time progresses (90 days), the expression of genes related to phosphorus cycling and recycling in leaves is upregulated, and transcriptional and post-transcriptional regulation (miRNA regulation and protein modification) is enhanced. Simultaneously, plant growth is further suppressed, and it gradually begins to discard and decompose leaves to resist the challenges of long-term phosphorus deficiency stress and sustain survival. In conclusion, our study deeply and comprehensively reveals adaptive strategies utilized by E. pubescens in response to phosphorus deficiency, demonstrating its resilience and thriving potential under stressful conditions. Furthermore, it provides valuable information on potential target genes for the cultivation of E. pubescens genotypes tolerant to low phosphorus.

Comparison of laser versus cold knife visual internal urethrotomy in the treatment of urethral stricture (stricture length <2 cm): A systematic review and meta-analysis.

PURPOSE: There is still controversy regarding the safety and efficacy of cold knife visual internal urethrotomy and laser incisions for the treatment of urethral stricture. This study aims to compare the results of postoperative long-term and short-term maximum urinary flow rates (Qmax), surgical time, postoperative complications, and 1-year recurrence rates between the cold knife and laser surgery. METHODS: We searched databases including Embase, PubMed, Cochrane, and Clinical Trials.gov to identify relevant literature published in English up to September 2023. We used Stata to compare various parameters. This study is registered in PROSPERO (CRD42023471634). Nine comparative experiments were conducted, involving a total of 659 participants. RESULTS: The laser group showed significantly better results compared to the cold knife group in terms of postoperative 12-month maximum urinary flow rate (mean differences [MD] 2.131; 95% [1.015, 3.249], P < .0001), postoperative bleeding (RR 0.277, 95% [0.079, 0.977], P = .046), and 1-year recurrence rate (RR 0.667, 95% [0.456, 0.976], P = .037). However, there were no significant differences in postoperative 6-month and 3-month Qmax, surgical time, urethral leakage complications, overall complications, and Visual Analog Scale (VAS) scores. CONCLUSION: The current study results suggest that laser urethral incision has greater advantages in the long-term (12 months), 1-year recurrence rate, and bleeding complications compared to cold knife urethral incision in the treatment of urethral stricture (<2 cm). Therefore, laser urethral incision may be a better choice for patients with urethral stricture.

Effects of natural extract interventions in prostate cancer: A systematic review and network meta-analysis.

BACKGROUND: Over years, there has been a widespread quest for effective dietary patterns and natural extracts to mitigate prostate cancer risk. However, despite numerous experimental studies conducted on various natural extracts, the evidence substantiating their efficacy remains largely insufficient. This dearth of compelling evidence presents a significant challenge in advocating for their widespread use as preventive measures against prostate cancer. OBJECTIVE: Our study endeavors to undertake a network meta-analysis to evaluate the influence of natural extracts on prostate cancer. METHODS: Researchers systematically searched through Embase, PubMed, Cochrane Library, and Web of Science databases until December 2023. The main focus was on assessing primary outcomes comprising prostate-specific antigen (PSA), insulin-like growth factor-binding protein-3 (IGFBP-3), insulin-like growth factor-1 (IGF-1). We conducted data analysis utilizing StataMP 15.0 software. Therapeutic effects were ranked based on the probability values derived from Surface Under the Cumulative Ranking curve (SUCRA). Additionally, cluster analysis was employed to assess the impacts of natural extracts on three distinct outcomes. RESULTS: Following screening procedures, the 28 eligible studies were incorporated, the selected studies encompassed 1,566 prostate cancer patients and evaluated 16 different natural extract treatments. Specifically, 24 trials included PSA indicators, 10 included IGF-1 indicators, and 8 included IGFBP-3 indicators. The findings revealed that, based on the SUCRA values, the combined therapy of silybin with selenium (74%) appears to be the most effective approach for reducing serum PSA levels. Simultaneously, silybin alone (84.6%) stands out as the most promising option for decreasing serum IGF-1 levels. Lastly, concerning IGFBP-3, silybin alone (67.7%) emerges as the optimal choice. Twelve studies provided comprehensive information on adverse drug reactions/events (ADR/ADE), whereas five articles did not report any significant ADR/ADE. CONCLUSION: The NMA suggests that, compared to placebo, utilizing silybin either alone or in combination with selenium has been shown to enhance therapeutic effects, offering potential benefits to patients with prostate cancer. This study can offer valuable insights for prostate patients considering natural extract treatments. Further evidence is required to confirm the safety profile of these treatments.

Urea Cycle of Bacillus thuringiensis Affects Its Survival under UV Stress.

Bacillus thuringiensis (Bt) is widely used to produce biological pesticides. However, its persistence is limited because of ultraviolet (UV) rays. In our previous study, we found that exogenous intermediates of the urea cycle were beneficial to Bt for survival under UV stress. To further explore the effect of the urea cycle on the resistance mechanism of Bt, the rocF/argG gene, encoding arginase and argininosuccinate synthase, respectively, were knocked out and recovered in this study. After the target genes were removed, respectively, the urea cycle in the tested Bt was inhibited to varying degrees. The UV stress test showed that the urea cycle disorder could reduce the resistance of Bt under UV stress. Meanwhile, the antioxidant enzyme activities of Bt were also decreased to varying degrees due to the knockout of the target genes. All of these results revealed that the urea cycle can metabolically regulate the stress resistance of Bt.

Gut microbiota in patients with prostate cancer: a systematic review and meta-analysis.

BACKGROUND: Increasing evidence indicates that gut microbiota are closely related to prostate cancer. This study aims to assess the gut microbiota composition in patients with prostate cancer compared to healthy participants, thereby advancing understanding of gut microbiota's role in prostate cancer. METHODS: A systematic search was conducted across PubMed, Web of Science, and Embase databases, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The methodological quality of included studies was evaluated using the Newcastle-Ottawa Scale (NOS), and pertinent data were analyzed. The kappa score assessed interrater agreement. RESULTS: This study encompassed seven research papers, involving 250 prostate cancer patients and 192 controls. The kappa was 0.93. Meta-analysis results showed that alpha-diversity of gut microbiota in prostate cancer patients was significantly lower than in the control group. In terms of gut microbiota abundance, the ratio of Proteobacteria, Bacteroidia, Clostridia, Bacteroidales, Clostridiales, Prevotellaceae, Lachnospiraceae, Prevotella, Escherichia-Shigella, Faecalibacterium, and Bacteroides was higher in prostate cancer patients. Conversely, the abundance ratio of Actinobacteria, Bacteroidetes, Firmicutes, Selenomonadales, Veillonella, and Megasphaera was higher in the control group. CONCLUSION: Our study reveals differences in alpha-diversity and abundance of gut microbiota between patients with prostate cancer and controls, indicating gut microbiota dysbiosis in those with prostate cancer. However, given the limited quality and quantity of selected studies, further research is necessary to validate these findings.

Ester-related volatile compounds reveal the diversity and commonalities of different types of late-ripening peaches.

To recognize the key ester-related volatile compounds, 5 types of peaches including 54 late-ripening peach materials were examined by headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry and E-nose. Here, a large number of esters were identified to be released by ripe peach fruits and were mainly characterized by fruity, green, and fatty notes. The variety and content of esters had greatly changed within or between cultivars, indicating that the fruit volatiles were highly differentiated depending on the specific genotypes and cultivation conditions. The ester types showed that fatty acid-derived C6 alcohols and methyl-/ethyl- short-chain alcohol were the main ester precursors, which were more likely to be utilized and well selected by alcohol acyltransferases, whereas the preference of acyl donors was not observed. The common peach type, which exhibited a unique volatile profile, displayed broader diversity and more abundant characteristics in ester-related volatiles than the other four types. A total of 19 key esters were identified as the main components and the content of most esters showed no significant difference among different peach types. Some key esters had even been enriched in nectarines. Moreover, the multiple discriminant analysis revealed a possible relationship between peach types and the domestication of the peach evolution. This study investigated ester-related volatiles released by different types of peach fruits and can be further used to evaluate the peach qualities, providing an important reference for peach breeding and processing.

Genotype and environment factors driven licorice growth and rhizospheric soil fungal community changes.

Introduction: Licorice (Glycyrrhiza uralensis Fisch.) is a widely recognized significant form of medicine in China, with a long-standing history and extensive usage. It is considered the oldest and most prevalent herbal medicine in China. Currently, the licorice market is confronted with the primary challenges of mixed genotypes, inconsistent quality, and inadequate glycyrrhizic acid content. Methods: We conducted field experiments to investigate the impact of various cultivation locations on the growth characteristics, active ingredients, rhizospheric soil physicochemical properties and fungal communities of licorice that ten different genotypes. Results: The findings indicated significant variations in these parameters across ten different genotypes of licorice originating from two distinct production regions. The growth characteristics of licorice were primarily influenced by genotype, whereas the active ingredients of licorice were mainly influenced by environmental factors and soil physicochemical properties. Furthermore, the rhizospheric soil physicochemical properties of licorice plants were more influenced by environmental factors than genotypes. Additionally, the distribution of rhizospheric soil fungi in licorice plants of the same genotype exhibited significant variations across different cultivation areas. The utilization of structural equation model synthesis reveals variations in the quantity and strength of pathways that influence the growth characteristics, active ingredients, and rhizospheric soil microbial community of licorice across different cultivation regions. Discussion: Based on the main results, according to its growth characteristics and active ingredients, Z009 proved to be the most suitable genotype for cultivation in Jingtai. From a perspective centered on the active ingredient, Z010 proved to be the most optimal genotype for licorice cultivation in both production areas. Our study aims to enhance the understanding of the ecological adaptability of various genotypes of licorice resources and to identify appropriate licorice genotypes for specific cultivation regions. This research holds significant practical implications for enhancing the yield and quality of licorice, thereby improving its overall development.

Comparing efficacy of first-line treatment of metastatic castration resistant prostate cancer: a network meta-analysis of randomized controlled trials.

Background: Metastatic castration-resistant prostate cancer (mCRPC) presents significant treatment selection challenges due to limited therapeutic options. This study aimed to comprehensively assess the efficacy of multiple treatment regimens for mCRPC through a network meta-analysis (NMA) of randomized controlled trials (RCTs). Methods: A systematically comprehensive search for randomized controlled trials (RCTs) was performed in Pubmed, Cochrane Library, Embase, and Web of Science databases. The network meta-analysis was employed to compare the overall survival (OS), progression-free survival (PFS), and radiographic progression-free survival (rPFS) among different interventions at specific time points. This study was prospectively registered with PROSPERO (CRD42023422823). Results: A total of 29 RCTs, involving 12,706 patients and investigating 16 interventions, were included in the analysis. Chempretarget ((capivasertib or cabozantinib) + docetaxel + prednisone)) and PARP (Olaparib or rucaparib) inhibitors emerged as interventions that significantly improved survival outcomes compared to first-line treatment in mCRPC patients. Chempretarget demonstrated superior overall survival starting from the 12th month, while PARP inhibitors showed a clear advantage in progression-free survival within the 3-18 months range. Notably, chempre ((Docetaxel or Cabazitaxel) + prednisone) exhibited favorable performance in radiographic progression-free survival during the 3-18 month period. Conclusion: Our findings underscore the efficacy of chempretarget, PARP inhibitors, and chempre in enhancing survival outcomes for mCRPC patients. Further head-to-head comparisons are warranted to validate these results. These findings carry important implications for treatment decision-making in mCRPC and may guide the development of more effective therapeutic strategies.

Case report: Differential diagnosis of highly amplified anti-CD5 CAR T cells and relapsed lymphoma cells in a patient with refractory ALK positive anaplastic large cell lymphoma.

Background: Anaplastic Large Cell Lymphoma (ALCL) is one of the most common subtypes of T-cell lymphoma. Among these, refractory and relapsed (r/r) ALK positive ALCL lacks effective therapies. The chimeric antigen receptor-modified T (CAR-T) cell therapy holds great promise as a therapeutic strategy for this disease. However, it is not known yet whether anti-CD5 CAR-T cells are sufficient for the definitive treatment of relapsed ALK+ ALCL, nor the role of accurate laboratory-based diagnoses during CAR-T treatment. Case presentation: The adolescent patient received autologous T cells containing sequences encoding VH domains specific to CD5. Following the infusion, there was an increase in both the copy number and proportion of CAR-T cells in peripheral blood. IL-6 and ferritin levels in the patient exhibited significant fluctuations, with increases of 13 and 70 folds respectively, compared to baseline after the treatment. Additionally, adverse effects were observed, including grade 4 rash, grade 1 headache, nausea, and neck-pain. Surprisingly, a relapsed disease phenotype was identified based on the results of PET/CT and histopathological analysis of the inguinal lymph node biopsy. After conducting a thorough diagnostic assessment, which included flow cytometry, next-generation sequencing (NGS), examination of immune-related gene rearrangements, and analysis of the immune repertoire of T-cell receptors (TCR), we conclusively determined that the hyperplastic T cells identified in the lymph node were the result of an expansion of CAR-T cells. Ultimately, the patient has attained complete remission (CR) and has sustained a disease-free survival state for 815 days as of the cutoff date on August 30, 2023. Conclusion: Taken together, the results demonstrate that anti-CD5 CAR-T cells can induce a clinical response in r/r ALK+ ALCL patient. Furthermore, this case underscores the importance of utilizing advanced technologies with high sensitivity and accuracy for biological detection in clinical laboratory diagnosis and prognosis in CAR-T cell treatment. Trial registration number: NCT04767308.

Assessment and predictive ability of the absolute neutrophil count in peripheral blood for in vivo CAR T cells expansion and CRS.

BACKGROUND: Chimeric antigen receptor (CAR) T cell therapy is an advanced and effective immunotherapy for relapsed or refractory B-cell malignancies. High expansion of CAR T cells in vivo and durable antitumor activity indicate a persistent therapeutic response. However, this treatment is linked to a high frequency of adverse events, such as cytokine release syndrome (CRS), which affects its efficacy and can even be life-threatening. At present, a variety of markers associated with clinical response and treatment toxicity after CAR T cells infusion have been reported. Although these biomarkers can act as effective indicators reflecting CAR T cells expansion as well as CRS, they fail to predict the expansion rate of CAR T cells. Hence, further investigation is urgent to find a new biomarker to fill this void. METHODS: We analyzed the association between the absolute neutrophil count (ANC) and CAR expansion and CRS in 45 patients with B-cell malignancies from two clinical trials. We proposed that ANC could be a practical biomarker for CAR T cells expansion and CRS, and conducted a feasibility analysis on its predictive ability. RESULTS: In this study, 17 B-cell hematological malignancy patients with anti-B-cell maturation antigen CAR-treated and 28 with CAR19/22 T-cell-treated were enrolled and divided into an ANC-absence group and an ANC-presence group. The results showed that ANC absence correlated positively with CAR expansion and the expansion rate. The ANC can be used as a predictive marker for CAR T cells expansion. Moreover, the patients with ANC absence experienced a more severe CRS, and ANC performed a predictive ability for CRS. In addition, the peak serum concentration of several cytokines involved in CRS was higher in patients with ANC absence. CONCLUSION: Thus, we suggest ANC as an evaluative and predictive biomarker for CAR expansion and CRS during CAR T cell therapy, which can help to maximize clinical efficacy, reduce treatment-related toxicity and prolong survival.

Efficacy and safety of minimally invasive percutaneous nephrolithotomy versus retrograde intrarenal surgery in the treatment of upper urinary tract stones (> 1 cm): a systematic review and meta-analysis of 18 randomized controlled trials.

BACKGROUND: The advantages and disadvantages of retrograde intrarenal surgery (RIRS) and minimally invasive percutaneous nephrolithotomy (mPCNL) for treatment of upper urinary tract calculi have not been conclusively determined. METHODS: In this meta-analysis, We comprehensively evaluated the performance of the two surgical approaches in treatment of upper urinary calculi. We searched the Pubmed, Embase, Cochrane and Web of science databases for randomized controlled trial (RCT) articles on RIRS and mPCNL upto December 2022. Data were extracted by two independent reviewers and subjected to the meta-analysis using the Stata 15.1 software (StataSE, USA). RESULTS: A total of 18 eligible RCTs involving 1733 patients were included in this study. The meta-analysis revealed that mPCNL of 1-2 cm or 2-3 cm stones had a higher stone clearance rate (RR:1.08, 95%CI (1.03, 1.14), p = 0.002) and shorter operation time (WMD : -10.85 min, 95%CI (-16.76, -4.94), p<0.001). However, it was associated with more hospital stay time (WMD :1.01 day, 95%CI(0.53, 1.5), p<0.001), hemoglobin drops (WMD :0.27 g/dl, 95%CI (0.14, 0.41), p<0.001), blood transfusion rate (RR:5.04, 95%CI(1.62, 15.65), p = 0.005), pain visual analogue score (WMD:0.75, 95%CI (0.04, 1.46), p = 0.037), hospital costs (SMD :-0.97, 95%CI (-1.19, -0.76), p<0.001) and major complications (RR:1.89, 95%CI(1.01, 3.53), p = 0.045). CONCLUSION: Therefore, in terms of surgical effects and operation time, mPCNL is superior to RIRS, but is inferior with regards to other perioperative parameters. These factors should be fully considered in clinical decision making.

Simultaneous radical cystectomy and nephroureterectomy in the treatment of panurothelial carcinoma: a systematic review and single-arm meta-analysis.

Background: Panurothelial carcinoma is a rare and aggressive malignancy that requires effective treatment strategies to enhance patient outcomes. Methods: We conducted a systematic search of English publications in databases including PubMed, Embase, Cochrane Library, and Web of Science up to May 2023. The quality of the literature was assessed using the Newcastle-Ottawa Scale (NOS) and the Methodological Quality and Synthesis of Case Series and Case Reports tool. Data statistics and analysis were performed using Stata 15.1 software (StataSE, USA). Results: Six studies involving 339 patients were included in the analysis. Meta-analysis revealed that Simultaneous Radical Cystectomy and Nephroureterectomy had 2-year and 5-year overall survival rates of 68% (95% CI 60%-76%, I2 = 12.4%, P < 0.001) and 44% (95% CI 36%-53%, I2 = 0, P < 0.001), respectively. The 2-year and 5-year progression-free survival rates were 91% (95% CI 86%-95%, I2 = 95%, P < 0.001) and 65% (95% CI 58%-73%, I2 = 91.5%, P < 0.001), respectively. The 2-year and 5-year cancer-specific survival rates were 73% (95% CI 66%-81%, I2 = 16.7%, P < 0.001) and 57% (95% CI 49%-66%, I2 = 0, P < 0.001), respectively. Additionally, the incidence of minor complications was 19% (95% CI 15%-23%, P < 0.01), major complications was 49% (95% CI 34%-63%, P < 0.01), and the intraoperative blood transfusion rate was 53% (95% CI 44%-61%, P < 0.01). Conclusions: Simultaneous radical cystectomy and nephroureterectomy represent feasible approaches for the treatment of Panurothelial carcinoma. Nonetheless, a comprehensive assessment of the surgical risks and benefits is imperative, and larger-scale prospective cohort studies are required to validate therapeutic efficacy. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023426401.

Efficacy and safety of transurethral thulium laser enucleation versus robot-assisted prostatectomy for large-volume benign prostatic hyperplasia: a systematic review and meta-analysis.

To compare perioperative outcomes between Holmium laser enucleation of the prostate (HoLEP) and robotic-assisted simple pasta-ectomy (RASP)for large-volume benign prostatic hyperplasia(> 80 ml). In August 2023, we undertook a comprehensive search of major global databases including PubMed, Embase, and Google Scholar, focusing solely on articles written in English. Studies that were merely reviews or protocols without any specific published data were omitted. Furthermore, articles that comprised conference abstracts or content not pertinent to our subject of study were also disregarded. To calculate the inverse variances and 95% confidence intervals (CIs) for categorical variables' mean differences, we employed the Cochran-Mantel-Haenszel approach along with random-effects models. The findings were denoted in the form of odds ratios (ORs) and 95% CIs. A p-value less than 0.05 was deemed to indicate statistical significance. Our finalized meta-analysis incorporated six articles, including one randomized controlled trial (RCT) and five cohort studies. These studies accounted for a total of 1218 patients, 944 of whom underwent Holmium Laser Enucleation of the Prostate (HoLEP) and 274 who underwent Robotic-Assisted Simple Prostatectomy (RASP). The pooled analysis from these six papers demonstrated that compared to RASP, HoLEP had a shorter hospital stay, shorter catheterization duration, and a lower blood transfusion rate. Moreover, HoLEP patients exhibited a smaller reduction in postoperative hemoglobin levels. Statistically, there were no significant differences between the two procedures regarding operative time, postoperative PSA, the weight of prostate specimens, IPSS, Qmax, PVR, QoL, and postoperative complications. (HoLEP) and (RASP) are both effective and safe procedures for treating large-volume benign prostatic hyperplasia. HoLEP, with its benefits of shorter catheterization and hospitalization duration, lesser decline in postoperative hemoglobin, and reduced blood transfusion needs, stands as a preferred choice for treating extensive prostate enlargement. However, further validation through more high-quality clinical randomized trials is required.