Robot-assisted, laparoscopic and open radical cystectomy for bladder cancer: A systematic review and network meta-analysis

ABSTRACT Objectives: To evaluate the safety and effectiveness of robot-assisted radical cystectomy (RARC), laparoscopic radical cystectomy (LRC), and open radical cystectomy (ORC) in bladder cancer. Methods: A literature search for network meta-analysis was conducted using international databases up to February 29, 2024. Outcomes of interest included baseline characteristics, perioperative outcomes and oncological outcomes. Results: Forty articles were finally selected for inclusion in the network meta-analysis. Both LRC and RARC were associated with longer operative time, smaller amount of estimated blood loss, lower transfusion rate, shorter time to regular diet, fewer incidences of complications, and fewer positive surgical margin compared to ORC. LRC had a shorter time to flatus than ORC, while no difference between RARC and ORC was observed. Considering lymph node yield, there were no differences among LRC, RARC and ORC. In addition, there were statistically significant lower transfusion rates (OR=-0.15, 95% CI=-0.47 to 0.17), fewer overall complication rates (OR=-0.39, 95% CI=-0.79 to 0.00), fewer minor complication rates (OR=-0.23, 95% CI=-0.48 to 0.02), fewer major complication rates (OR=-0.23, 95% CI=-0.68 to 0.21), fewer positive surgical margin rates (OR=0.22, 95% CI=-0.27 to 0.68) in RARC group compared with LRC group. Conclusion: LRC and RARC could be considered as a feasible and safe alternative to ORC for bladder cancer. Notably, compared with LRC, RARC may benefit from significantly lower transfusion rates, fewer complications and lower positive surgical margin rates. These data thus showed that RARC might improve the management of patients with muscle invasive or high-risk non-muscle invasive bladder cancer.

Robot-assisted, laparoscopic and open radical cystectomy for bladder cancer: A systematic review and network meta-analysis.

OBJECTIVES: To evaluate the safety and effectiveness of robot-assisted radical cystectomy (RARC), laparoscopic radical cystectomy (LRC), and open radical cystectomy (ORC) in bladder cancer. METHODS: A literature search for network meta-analysis was conducted using international databases up to February 29, 2024. Outcomes of interest included baseline characteristics, perioperative outcomes and oncological outcomes. RESULTS: Forty articles were finally selected for inclusion in the network meta-analysis. Both LRC and RARC were associated with longer operative time, smaller amount of estimated blood loss, lower transfusion rate, shorter time to regular diet, fewer incidences of complications, and fewer positive surgical margin compared to ORC. LRC had a shorter time to flatus than ORC, while no difference between RARC and ORC was observed. Considering lymph node yield, there were no differences among LRC, RARC and ORC. In addition, there were statistically significant lower transfusion rates (OR=-0.15, 95% CI=-0.47 to 0.17), fewer overall complication rates (OR=-0.39, 95% CI=-0.79 to 0.00), fewer minor complication rates (OR=-0.23, 95% CI=-0.48 to 0.02), fewer major complication rates (OR=-0.23, 95% CI=-0.68 to 0.21), fewer positive surgical margin rates (OR=0.22, 95% CI=-0.27 to 0.68) in RARC group compared with LRC group. CONCLUSION: LRC and RARC could be considered as a feasible and safe alternative to ORC for bladder cancer. Notably, compared with LRC, RARC may benefit from significantly lower transfusion rates, fewer complications and lower positive surgical margin rates. These data thus showed that RARC might improve the management of patients with muscle invasive or high-risk non-muscle invasive bladder cancer.

Almonertinib and alflutinib show novel inhibition on rare EGFR S768I mutant cells.

PURPOSE: EGFR classical mutations respond well to EGFR tyrosine kinase inhibitors. However, it is uncertain whether currently available EGFR-TKIs are effective against rare EGFR mutations and compound mutations. Herein, the effectiveness of almonertinib and alflutinib, the third-generation tyrosine kinase inhibitors developed in China, on rare EGFR S768I mutations and compound mutations is identified. METHODS: In this study, using CRISPR method, four EGFR S768I mutation cell lines were constructed, and the sensitivity of EGFR to almonertinib and alflutinib was tested, with positive controls being the 1st (gefitinib), 2nd (afatinib), and 3rd (osimertinib) generation drugs. RESULTS: The present results indicate that almonertinib and alflutinib can effectively inhibit cell viability and proliferation in rare EGFR S768I mutations through the ERK or AKT pathways in a time-dependent manner, by blocking the cell cycle and inhibiting apoptosis. CONCLUSIONS: These findings suggest that almonertinib and alflutinib may be potential therapeutic options for non-small cell lung cancer patients with the EGFR S768I mutation.

Clinical efficacy and safety of flumatinib versus dasatinib combined with multi-drug chemotherapy in adults with Philadelphia-positive acute lymphoblastic leukemia.

INTRODUCTION: Flumatinib, a highly selective ABL kinase inhibitor, exhibits stronger inhibition of intracellular BCR-ABL tyrosine kinase activity, compared to Imatinib. However, there is limited research comparing the real-world efficacy and safety of flumatinib and dasatinib in patients with Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). OBJECTIVE: Investigating the differences in therapeutic efficacy and safety between flumatinib and dasatinib in combination with multi-drug chemotherapy for the treatment of newly diagnosed Ph+ ALL. METHOD: In this study, we assessed 43 patients with newly diagnosed Ph+ ALL (20 in the flumatinib group, 23 in the dasatinib group). RESULTS: There were no significant differences in gender, age, fusion gene type, initial blood routine, bone marrow blast cell ratio or chromosome karyotype between the two groups. Within 1 month, there were no significant differences in the complete response (CR), major molecular response (MMR) or minimal residual disease (MRD) negativity rate between the flumatinib and dasatinib groups. Similarly, within 3 months, there were no significant differences in CR or MMR rates between the two groups. However, the rates of complete molecular response (CMR) and MRD negativity within 3 months were significantly higher in the flumatinib group, compared to the dasatinib group (P < 0.05). Additionally, the flumatinib group exhibited fewer adverse reactions compared to the dasatinib group. CONCLUSION: These findings suggest that flumatinib is a safe and effective tyrosine kinase inhibitor (TKI) for achieving CMR and MRD negativity in patients with Ph+ ALL, as supported by this small series of patients.

Overexpression SPRY2 Suppresses Esophageal Squamous Cell Carcinoma Progression Via Inactivation of ERK/AKT Signaling / La Sobreexpresión SPRY2 Suprime la Evolución del Carcinoma de Células Escamosas de Esófago Mediante la Inactivación de la Señalización ERK/AKT

SUMMARY: Esophageal cancer is one of the most aggressive gastrointestinal cancers. Invasion and metastasis are the main causes of poor prognosis of esophageal cancer. SPRY2 has been reported to exert promoting effects in human cancers, which controls signal pathways including PI3K/AKT and MAPKs. However, the expression of SPRY2 in esophageal squamous cell carcinoma (ESCC) and its underlying mechanism remain unclear. In the present study, we aimed to investigate the detailed role of SPRY2 in the regulation of cell proliferation, invasion and ERK/AKT signaling pathway in ESCC. It was identified that the expression level of SPRY2 in ESCC was remarkably decreased compared with normal tissues, and it was related to clinicopathologic features and prognosis ESCC patients. The upregulation of SPRY2 expression notably inhibited the proliferation, migration and invasion of Eca-109 cells. In addition, the activity of ERK /AKT signaling was also suppressed by the SPRY2 upregulation in Eca-109 cells. Our study suggests that overexpression of SPRY2 suppress cancer cell proliferation and invasion of by through suppression of the ERK/AKT signaling pathways in ESCC. Therefore, SPRY2 may be a promising prognostic marker and therapeutic target for ESCC.

El cáncer de esófago es uno de los cánceres gastrointestinales más agresivos. La invasión y la metástasis son las principales causas de mal pronóstico del cáncer de esófago. Se ha informado que SPRY2 ejerce efectos promotores en los cánceres humanos, que controla las vías de señales, incluidas PI3K/AKT y MAPK. Sin embargo, la expresión de SPRY2 en el carcinoma de células escamosas de esófago (ESCC) y su mecanismo subyacente aún no están claros. En el presente estudio, nuestro objetivo fue investigar el papel detallado de SPRY2 en la regulación de la proliferación celular, la invasión y la vía de señalización ERK/AKT en ESCC. Se identificó que el nivel de expresión de SPRY2 en ESCC estaba notablemente disminuido en comparación con los tejidos normales, y estaba relacionado con las características clínico-patológicas y el pronóstico de los pacientes con ESCC. La regulación positiva de la expresión de SPRY2 inhibió notablemente la proliferación, migración e invasión de células Eca-109. Además, la actividad de la señalización de ERK/AKT también fue suprimida por la regulación positiva de SPRY2 en las células Eca-109. Nuestro estudio sugiere que la sobreexpresión de SPRY2 suprime la proliferación y la invasión de células cancerosas mediante la supresión de las vías de señalización ERK/AKT en ESCC. Por lo tanto, SPRY2 puede ser un marcador de pronóstico prometedor y un objetivo terapéutico para la ESCC.

Sensitivity analysis of EGFR L861Q mutation to six tyrosine kinase inhibitors.

PURPOSE: Lung cancer is one of the most common carcinomas with the highest mortality in the world. Non-small cell lung carcinoma has a large proportion of epidermal growth factor receptor (EGFR) mutations, of which rare EGFR mutations account for about 10%-20%. Currently, tyrosine kinase inhibitors (TKIs) therapy is a standard treatment for patients with non-small cell lung carcinoma with EGFR mutations. To date, the toxicological effects of the EGFR L861Q variant (less than 2%) have been rarely reported, so further investigation of its sensitivity to six first-in-class TKIs is of great clinical interest. METHODS: In this study, two EGFR L861Q variants cell lines (EGFR L861Q variant and EGFR L861Q + exon 19 deletion variant) were established by CRISPR-Cas9 gene-editing technology. The steady-state plasma concentrations of six TKIs (gefitinib/erlotinib/icotinib, the first generation; dacomitinib/afatinib, the second generation; and osimertinib, the third generation) were tested, respectively. The change of cell viability, proliferation, cloning ability, mitochondrial membrane potential and apoptosis were detected by MTT assay, EdU staining assay, colony formation assay, mitochondrial membrane potential and apoptosis test. TUNEL and Annexin V / PI staining were used to detect cell apoptosis, and flow cytometry was employed to explore the sensitivity of two variants to six TKIs. RESULTS: Our study indicated that the six TKIs inhibited the viability of the two cell lines in a time-dependent manner, and the inhibitory time of six TKIs on proliferation was different between the two cell lines. The proliferation and cloning ability of two cell lines were inhibited by six TKIs. The cytoskeleton morphology, microfilament structure and distribution of the two cell lines were changed by six TKIs. Compared with the control, the mitochondrial membrane potential decreased while the apoptosis increased of the two of variants after treatment with the six TKIs, and the associated mechanisms were elucidated. CONCLUSIONS: Based on the above results, EGFR L861Q + 19del variant and EGFR L861Q variant showed significant sensitivity to six first-in-class TKIs. Among the six TKIs, the first generation TKIs (gefitinib/erlotinib/icotinib), showed stronger inhibition ability to the EGFR L861Q + 19del variant and EGFR L861Q variant, among which gefitinib showed the strongest inhibition.

Optimization of cationic polymer-mediated transfection for RNA interference.

Transfection efficiency was estimated to optimize the conditions for RNA interference (RNAi), including transfection time, validity, and nucleic acid concentration and type, using the EZ Trans Cell Reagent, a cationic polymer. An shRNA against GFP was designed and transfected into cells using the EZ transfection reagent. The shRNA significantly decreased the expression of GFP. In addition, pre-diluted transfection reagent at room temperature and small nucleic acids increased the transfection efficiency, which peaked at 24 h. Compared with circular nucleic acids, linear nucleic acids showed higher transfection efficiency and a higher genome integration rate. We optimized cationic polymer-mediated RNAi conditions, and our data will be useful for future RNAi studies.

Organic Electrochemical Transistors for In Vivo Bioelectronics.

Organic electrochemical transistors (OECTs) are presently a focus of intense research and hold great potential in expanding the horizons of the bioelectronics industry. The notable characteristics of OECTs, including their electrolyte-gating, which offers intimate interfacing with biological environments, and aqueous stability, make them particularly suitable to be operated within a living organism (in vivo). Unlike the existing in vivo bioelectronic devices, mostly based on rigid metal electrodes, OECTs form a soft mechanical contact with the biological milieu and ensure a high signal-to-noise ratio because of their powerful amplification capability. Such features make OECTs particularly desirable for a wide range of in vivo applications, including electrophysiological recordings, neuron stimulation, and neurotransmitter detection, and regulation of plant processes in vivo. In this review, a systematic compilation of the in vivo applications is presented that are addressed by the OECT technology. First, the operating mechanisms, and the device design and materials design principles of OECTs are examined, and then multiple examples are provided from the literature while identifying the unique device properties that enable the application progress. Finally, one critically looks at the future of the OECT technology for in vivo bioelectronic applications.

Efficacy of autologous platelet-rich plasma gel in the treatment of refractory pressure injuries and its effect on wound healing time and patient quality of life.

OBJECTIVES: To evaluate the efficacy of autologous platelet-rich plasma (PRP) gel in the treatment of refractory pressure injuries and its effect on wound healing time and quality of life of patients. METHODS: A random number table method was used to group 102 patients with refractory pressure injuries into either a control group (CG) (51 cases) receiving negative pressure wound therapy (NPWT) or a study group (SG) (51 cases) receiving NPWT+PRP gel. RESULTS: The total efficacy rate in the SG (92.16%) was higher than that in the CG (76.47%) (p<0.05). The SG exhibited lower visual analog scale (VAS) scores and pressure ulcer scale for healing (PUSH) scores, smaller wound sizes and depths, and shorter wound healing times than the CG after 21 days of treatment (p<0.05). After 6 months of treatment, the SG scored higher than the CG on the psychological, physiological, social functions, and daily activity domains on the World Health Organization Quality of Life (WHOQOL-BREF) scale (p<0.05). The incidence of postoperative complications in the SG (13.73%) was not significantly different from that of the CG (7.84%) (p>0.05). CONCLUSION: In the treatment of refractory pressure injuries, PRP gel can accelerate wound healing, reduce wound pain, shorten the treatment cycle, regulate tissue inhibitor matrix metalloproteinase-1 (TIMP-1) and matrix metalloproteinase-9 (MMP-9) levels and the expression of specific proteins in granulation tissue, reduce the levels of the inflammatory factors interleukin-1ß (IL-1ß), IL-8, and tumor necrosis factor-α (TNF-α), and improve the quality of life of patients without increasing complications.

Efficacy of autologous platelet-rich plasma gel in the treatment of refractory pressure injuries and its effect on wound healing time and patient quality of life

OBJECTIVES: To evaluate the efficacy of autologous platelet-rich plasma (PRP) gel in the treatment of refractory pressure injuries and its effect on wound healing time and quality of life of patients. METHODS: A random number table method was used to group 102 patients with refractory pressure injuries into either a control group (CG) (51 cases) receiving negative pressure wound therapy (NPWT) or a study group (SG) (51 cases) receiving NPWT+PRP gel. RESULTS: The total efficacy rate in the SG (92.16%) was higher than that in the CG (76.47%) (p<0.05). The SG exhibited lower visual analog scale (VAS) scores and pressure ulcer scale for healing (PUSH) scores, smaller wound sizes and depths, and shorter wound healing times than the CG after 21 days of treatment (p<0.05). After 6 months of treatment, the SG scored higher than the CG on the psychological, physiological, social functions, and daily activity domains on the World Health Organization Quality of Life (WHOQOL-BREF) scale (p<0.05). The incidence of postoperative complications in the SG (13.73%) was not significantly different from that of the CG (7.84%) (p>0.05). CONCLUSION: In the treatment of refractory pressure injuries, PRP gel can accelerate wound healing, reduce wound pain, shorten the treatment cycle, regulate tissue inhibitor matrix metalloproteinase-1 (TIMP-1) and matrix metalloproteinase-9 (MMP-9) levels and the expression of specific proteins in granulation tissue, reduce the levels of the inflammatory factors interleukin-1β (IL-1β), IL-8, and tumor necrosis factor-α (TNF-α), and improve the quality of life of patients without increasing complications.

Genome of Bacillus sp. strain QHF158 provides insights into its parasporal inclusions encoded by the S-layer gene.

Bacillus sp. strain QHF158, a Gram-positive, spore-forming and parasporal crystal-secreting bacterium, was isolated from soil of Limushan National Forest Park in China. Here we present the significant feature of parasporal inclusions of this organism, together with the draft genome sequence and annotation. Phylogenetic analysis suggested that strain QHF158 is possibly a novel species, most closely related to Bacillus mycoides. Genome annotation results revealed that strain QHF158 did not contain any typical Cry or Cyt toxin coding gene. Furthermore, the mass spectrometry analyses demonstrated that the parasporal crystalline inclusions were encoded by the orf_05273 gene, with 95% similarity to the S-layer protein (SLP) EA1 of B. mycoides, which indicated that the parasporal crystal from Bacillus sp. strain QHF158 was mainly formed by SLP, instead of the typical Cry or Cyt toxin proteins.

Combinative effects of Azospirillum brasilense inoculation and chemical priming on germination behavior and seedling growth in aged grass seeds.

Germination of seeds during the transportation or after prolonged storage naturally and inevitably decreases because of ageing, but germination potential can be partially restored with seed priming treatments. A novel attempt was made to investigate the effects of combined treatments and to optimize the conditions for naturally aged seeds of tall fescue (Festuca arundinacea Schreb.), orchardgrass (Dactylis glomerata L.) and Russian wild rye (Psathyrostachys juncea (Fisch.) Nevski) using an orthogonal activity level experimental design [factor A: Azospirillum brasilense concentration, factor B: three seed priming treatments (H2O, MgSO4 and H2O2) and factor C: different priming times]. Multivariate regression model analysis was applied to determine the interactive effects of pairwise factors (A and C) and to optimize experimental conditions. The results showed that the mixed treatments positively affected seed germination and seedling growth. The three seed priming treatments were the dominant factors for germination promotion, whereas the bacterial concentration had the largest effect on seedling growth and the activity of superoxide dismutase (SOD), especially root elongation. The malondialdehyde content was reduced, the activities of SOD, peroxidase and catalase were triggered, and ascorbate peroxidase activity was also affected by the co-treatment. The combined results of all determined attributes showed that A. brasilense bio-priming with H2O2 priming constituted the optimal combination. The optimal bacterial concentration of A. brasilense and the time of seed priming were 52.3 × 106 colony forming units (CFU) mL-1 and 17.0 h, respectively.

Prevalence and Predictors of Patient-Reported Long-term Mental and Physical Health After Donation in the Adult-to-Adult Living-Donor Liver Transplantation Cohort Study.

BACKGROUND: Prospective and longitudinal studies have examined liver donors' medical outcomes beyond the first 1 to 2 years postdonation. There is no analogous longitudinal evidence on long-term psychosocial outcomes, including patient-reported clinically significant mental health problems and perceptions of physical well-being. We examined prevalence, descriptive characteristics, and predictors of diagnosable mental health conditions and self-reported physical health problems, including fatigue and pain, in the long-term years after liver donation. METHODS: Donors from 9 centers who initially completed telephone interviews at 3 to 10 years postdonation (mean, 5.8 years; SD, 1.9) were reinterviewed annually for 2 years using validated measures. Outcomes were examined descriptively. Repeated-measures regression analyses evaluated potential predictors and correlates of outcomes. RESULTS: Of 517 donors initially interviewed (66% of those eligible), 424 (82%) were reassessed at least once. Prevalence rates of major depression and clinically significant pain were similar to general population norms; average fatigue levels were better than norms. All prevalence rates showed little temporal change. Anxiety and alcohol use disorder rates exceeded normative rates at 1 or more assessments. Longer postdonation hospitalization, female sex, higher body mass index, concerns about donation-related health effects, and burdensome donation-related financial costs were associated with increased risk for most outcomes (P's < 0.05). Men were at higher risk for alcohol use disorder (P < 0.001). CONCLUSIONS: Anxiety and alcohol use disorders were more common than would be expected; they may warrant increased research attention and clinical surveillance. Surveillance for long-term problems in the areas assessed may be optimized by targeting donors at higher risk based on identified predictors and correlates.

The correlation between the central carbon metabolic flux distribution and the number of shared enzyme regulators in Saccharomyces cerevisiae

The central carbon metabolic system is the upstream energy source for microbial fermentation. In addition, it is a master switch for increasing the production of metabolites and an important part of the microbial metabolic network. Investigation into the relationship between genes, environmental factors, and metabolic networks is a main focus of systems biology, which significantly impacts research in biochemistry, metabolic engineering, and synthetic biology. To this end, the central carbon metabolic flux under a variety of growth conditions or using strains with various genetic modifications was previously measured in Saccharomyces cerevisiae using 13C tracer technology. However, the measured values were not integrated and investigated further. In this study, we collected and analyzed the metabolic flux rates of the central carbon metabolic system in S. cerevisiae measured in recent studies. We carried out preliminary analyses of flux values of each pathway, performed regression analyses on relationship between different fluxes, and extracted principal component factors of the flux variables. Based on the results, the general characteristics of pathway flux distribution were clustered and explored, and the effects of environmental and genetic factors on the flux distribution were analyzed. Furthermore, this study explored the relationship between similarity in the enzyme's transcriptional regulation and the correlations in the enzyme's reaction flux. Our results provide a foundation for further studies on the control of the central carbon metabolic flux and facilitate the search for targets in metabolic engineering research.

Nippostrongylus brasiliensis can induce B7-independent antigen-specific development of IL-4-producing T cells from naive CD4 T cells in vivo.

Th2 immune responses to a number of infectious pathogens are dependent on B7-1/B7-2 costimulatory molecule interactions. We have now examined the Th2 immune response to Nippostrongylus brasiliensis (Nb) in B7-1/B7-2(-/-) mice and show that Th2 effector cells develop that can mediate worm expulsion and produce substantial Th2 cytokines comparable with wild-type infected mice; however, in marked contrast, B cell Ag-specific Ab production is abrogated after B7 blockade. To examine the mechanism of T cell activation, OVA-specific DO11.10 T cells were transferred to recipient mice, which were then immunized with a combination of Nb plus OVA or either alone. Only the combination of Nb plus OVA triggered T cell differentiation to OVA-specific Th2 cells, suggesting that Nb acts as an adjuvant to stimulate Ag-specific naive T cells to differentiate to effector Th2 cells. Furthermore, using the DO11.10 TCR-transgenic T cell adoptive transfer model, we show that blocking B7-1/B7-2 interactions does not impair nonparasite Ag-specific DO11.10 Th2 cell differentiation; however, DO11.10 T cell cycle progression and migration to the B cell zone are inhibited.