Association between maximal urethral length preservation and postoperative continence after robot-assisted radical prostatectomy: a meta-analysis and systematic review.

ABSTRACT: Urinary incontinence is a common complication following robot-assisted radical prostatectomy (RARP). Urethral length has been identified as a factor affecting postoperative continence recovery. In this meta-analysis, we examined the association between use of the maximal urethral length preservation (MULP) technique and postoperative urinary continence in patients undergoing RARP. We conducted a comprehensive search of PubMed, Web of Science, Embase, and the Cochrane Library up to December 31, 2023. The quality of the literature was assessed using the Newcastle-Ottawa Scale. A random-effects meta-analysis was performed to synthesize data and calculate the odds ratio (OR) from eligible studies on continence and MULP. Six studies involving 1869 patients met the eligibility criteria. MULP was positively associated with both early continence (1 month after RARP; Z = 3.62, P = 0.003, OR = 3.10, 95% confidence interval [CI]: 1.68-5.73) and late continence (12 months after RARP; Z = 2.34, P = 0.019, OR = 2.10, 95% CI: 1.13-3.90). Oncological outcomes indicated that MULP did not increase the overall positive surgical margin rate or the positive surgical margin status at the prostate apex (both P > 0.05). In conclusion, the use of the MULP technique in RARP significantly improved both early and late postoperative continence outcomes without compromising oncological outcomes.

Morphologic characteristics of temporomandibular joint on the patients with anterior disc displacement without osteoarthritis: a case-based research.

We investigated the effect of anterior disc displacement without osteoarthritis (ADDwoOA) on the morphology of the temporomandibular joint (TMJ) utilizing three-dimensional (3D) models of 23 asymptomatic individuals and 30 ADDwoOA patients. Statistical analyses between the groups were performed by measuring 10 morphological parameters. ADDwoOA patients showed significantly decreased levels of the sagittal ramus angle (SRA) and joint spaces compared with asymptomatic subjects. Moreover, the patients who had recovered exhibited normal joint spaces levels. Consequently, ADDwoOA caused the condyles to move backward and upward, approaching the articular fossa. Joint spaces can serve as an important observation during the treatment of ADD.

Biomechanical effects of mandibular deviation on the temporomandibular joint in patients with mandibular prognathism under incisal occlusion.

PURPOSE: The aim of this study was to investigate the biomechanical effects of mandibular deviation on the TMJ in patients with mandibular prognathism before and after orthognathic surgery using three-dimensional finite element analysis. METHODS: Eight patients with mandibular prognathism without deviation, eight patients with mandibular prognathism with deviation and sixteen normal subjects were recruited. Three-dimensional models of the maxillofacial were reconstructed using MIMICS. Nine muscle forces were used to simulate incisal occlusion and contact was used to simulate fossa-disc-condyle interactions. RESULTS: Before surgery, the stress in the TMJ was generally greater in the Pre-MD&MP group than in the Pre-MD group; it was much greater in both groups than in the control group, ranging from about 2 to 12 times as great in the Pre-MD group and from about 5 to 64 times as great in the Pre-MD&MP group. After orthognathic surgeries, the stresses in the Post-MP&MD were significantly reduced by approximately 21.7 % to 93.4 %. And in the Post-MP group, the stresses were reduced by approximately 1.4 % to 51.1 %. CONCLUSION: Mandibular deviation exacerbated the abnormal stress distribution in the TMJ of patients with mandibular prognathism. Orthognathic surgeries could improve the stress distribution in patients with mandibular prognathism (with and without deviation). TMD was closely related to the stress levels of the TMJ.

Evaluation of mandibular motions in patients with anterior disc displacement during mouth opening and closing using finite helical axis.

Understanding temporomandibular joint (TMJ) kinematics is essential for the clinical diagnosis and treatment of TMJ disorders. Yet, a comprehensive description of mandibular motion information in patients with anterior disc displacement (ADD) is lacking. The finite helical axis (FHA) is a mathematical model describing the motion of a rigid body in space. This model quantifies mandibular motion patterns by differentiating between rotation around the FHA and translation along it. This study aimed to compare the mandibular motion patterns between patients with ADD and asymptomatic subjects during mouth opening and closing utilizing the FHA. Ten asymptomatic subjects (2 females and 8 males, aged 19-22) and ten patients with ADD (8 females and 2 males, aged 19-57) were tracked using an optical motion tracking system for mouth opening and closing. The FHA during mouth opening and closing was determined from motion trajectory. The distance from the condylar center to the FHA (dCP), the angles between the FHA and the head coordinate system (θx, θy, θz), and the global fluctuation of the FHA spatial orientation (θf) were further calculated. In addition, the helical axis of each frame relative to the initial frame was computed to determine the maximum rotation angle (Θmax) and maximum offset (Tmax) of mandibular motion during mouth opening and closing. It was found that Θmax, Tmax, dLCPmean, dLCPmin, θx, and θf for patients with ADD differed significantly from those of asymptomatic subjects. These findings imply that the FHA effectively describes the disparities between patients with ADD and asymptomatic subjects.

Evaluation method of ore grade estimation effectiveness.

This study proposes a new method to evaluate the effectiveness of orebody grade estimations, drawing upon the analysis of existing evaluation methods for grade estimation. This new approach addresses factors such as uneven sampling and asymmetric estimation range, which are challenging to overcome with existing evaluation techniques. The core principle of this method involves documenting how frequently individual samples are used during grade estimation and calculating the total distance weights for each sample. Subsequently, the usage frequency and total weight of the samples are standardized, and these standardized values are weighted based on the sample grades. A comparison is made between the weighted sample grades and the estimated grades, with the closeness between the two serving as a metric for assessing the effectiveness of the estimation. This study compares the new evaluation method to the direct comparison and cross-validation methods, examining the effectiveness of grade estimation using the inverse distance weighting (IDW) method. The findings revealed that: (1) The new evaluation method theoretically accounts for the systematic deviation between the statistical measures of estimated and sample grades resulting from uneven sample distribution, offering a fresh approach for enhancing the effectiveness of orebody grade estimation. (2) In the grade estimation of experimental Fe samples, the frequency of usage and the sum of distance weights were unequal. This inequality significantly contributes to the systematic deviation between the estimated and sample grades. (3) Comparing the new evaluation method to others confirms the stability and reliability of the new approach for evaluating the effectiveness of orebody grade estimation. This novel method demonstrates theoretical advantages and practical utility. (4) The deviation between the estimated grades and the statistical results of sample grades is influenced by the distribution pattern of sample grades, the spatial relationship between samples and estimation blocks, and the inherent systematic error associated with the IDW method. This systematic error cannot be overlooked.

Catalytic selectivity and evolution of cytochrome P450 enzymes involved in monoterpene indole alkaloids biosynthesis.

Cytochrome P450 enzyme (CYP)-catalyzed functional group transformations are pivotal in the biosynthesis of metabolic intermediates and products, as exemplified by the CYP-catalyzed C7-hydroxylation and the subsequent C7-C8 bond cleavage reaction responsible for the biosynthesis of the well-known antitumor monoterpene indole alkaloid (MIA) camptothecin. To determine the key amino acid residues responsible for the catalytic selectivity of the CYPs involved in MIA biosynthesis, we characterized the enzymes CYP72A728 and CYP72A729 as stereoselective 7-deoxyloganic acid 7-hydroxylases (7DLHs). We then conducted a comparative analysis of the amino acid sequences and the predicted structures of the CYP72A homologs involved in camptothecin biosynthesis, as well as those of the CYP72A homologs implicated in the pharmaceutically significant MIAs biosynthesis in Catharanthus roseus. The crucial amino acid residues for the catalytic selectivity of the CYP72A-catalyzed reactions were identified through fragmental and individual residue replacement, catalytic activity assays, molecular docking, and molecular dynamic simulations analysis. The fragments 1 and 3 of CYP72A565 were crucial for its C7-hydroxylation and C7-C8 bond cleavage activities. Mutating fragments 1 and 2 of CYP72A565 transformed the bifunctional CYP72A565 into a monofunctional 7DLH. Evolutionary analysis of the CYP72A homologs suggested that the bifunctional CYP72A in MIA-producing plants may have evolved into a monofunctional CYP72A. The gene pairs CYP72A728-CYP72A610 and CYP72A729-CYP72A565 may have originated from a whole genome duplication event. This study provides a molecular basis for the CYP72A-catalyzed hydroxylation and C-C bond cleavage activities of CYP72A565, as well as evolutionary insights of CYP72A homologs involved in MIAs biosynthesis.

Constructing condylar cartilage organoid to explore primary cilia functions.

An organoid culture system better recapitulates the cellular structure, function, and interaction between cells and the extracellular matrix (ECM) than a two-dimensional (2D) culture system. We here constructed a condylar cartilage organoid to explore the regulatory role of primary cilia. Similar to the natural condylar cartilage, the condylar cartilage organoid exhibited abundant ECM and comprised superficial, proliferative, and hypertrophic zones. Primary cilia in the condylar cartilage organoid were shorter on average than those in the 2D culture chondrocytes, but their average length was equivalent to those in the natural condylar cartilage. Notably, primary cilia in each zone of the condylar cartilage organoid had an average length similar to that of primary cilia in the natural condylar cartilage. According to transcriptomic and biochemical analyses, the expression of cilia-related genes and cilia-related Hedgehog (HH) signaling differed between the condylar cartilage organoid and 2D culture systems. IFT88 knockdown promoted the protein levels of COL-Ⅹ, TRPV4, and HH signaling molecules in the condylar cartilage organoid, but decreased them in the 2D culture system. Notably, the protein levels of COL-Ⅹ, TRPV4, and HH signaling molecules increased in the superficial zone of the si IFT88 condylar cartilage organoid compared with the condylar cartilage organoid. However, the protein levels of aforementioned molecules were not significantly different in proliferative and hypertrophic zones. Collectively, we successfully constructed the condylar cartilage organoid with a better tissue structure and abundant ECM. Moreover, the condylar cartilage organoid is more suitable for exploring primary cilia functions.

[Efficacy and Safety of Reduced Dose Azacitidine in the Treatment of Elderly Patients with Myelodysplastic Syndromes].

OBJECTIVE: To analyze the efficacy and safety of low-dose azacitidine in the treatment of senile myelodysplastic syndromes (MDS). METHODS: A total of 92 elderly MDS patients who were initially diagnosed in the Huaibei Miners General Hospital and the Affiliated Hospital of Xuzhou Medical University from January 2018 to June 2022 were randomly divided into the observation group and the control group with 46 patients in each group. The observation group received a low dose of azacitidine 100 mg/d, d1-7, 28 days as a course of treatment, 6 courses in total, and the control group received a standard dose of azacitidine 75 mg(m2·d), d1-7, 28 days as a course of treatment, a total of 6 courses of treatment. The clinical efficacy, overall survival (OS) and adverse reactions of the two groups of patients were observed. RESULTS: There was no statistically significant difference in the clinical data between the two groups (P >0.05). After treatment, the hemoglobin and platelet levels of the two groups of patients were significantly higher than before treatment in each group (P < 0.05). There was no statistically significant difference in leukocyte, hemoglobin and platelet levels between patients in the observation group and control group (P >0.05). The number of cases with complete remission, partial remission, hematological remission, disease stabilization and disease progression in the observation group were 4, 10, 22, 6 and 4, respectively, with a total effective rate of 78.26%. The numbers of cases with complete remission, partial remission, hematological remission, disease stabilization and disease progression in control group were 8, 12, 18, 4 and 4, respectively, with a total effective rate of 82.61%. The total effective rate of patients in the observation group was slightly lower than that of the control group(χ2=0.457, P =0.254). There was no significant difference between the two treatment schemes in the treatment of patients with blood transfusion dependence and patients with low risk, medium risk and high risk (P >0.05). It takes 4 and 6 courses of treatment to achieve the best treatment response in the control group and observation group respectively. There was no significant difference in OS between the two groups (P >0.05). In the observation group, there were 4, 6 and 2 cases of infection, III-IV degree myelosuppression and gastrointestinal reaction, respectively, with the incidence rate of adverse events being 26.09%. In the control group, there were 6, 16 and 6 cases of infection, III-IV degree myelosuppression and gastrointestinal reaction, respectively, with the adverse event rate was 60.87%. The incidence of adverse events in the control group was significantly higher than that in the observation group (χ2=7.095, P =0.036). CONCLUSION: Elderly patients with MDS have poor tolerance to chemotherapy. Reducing azacitidine in the treatment of elderly MDS patients shows good efficacy and safety.

Constructing in-situ and real-time monitoring methods during soy sauce production by miniature fiber NIR spectrometers.

The digestion rate of steamed soybean (DRSS), protease activity of koji (PAK) and formaldehyde nitrogen content of moromi (FNCM) are key indicators to monitor soy sauce production. Currently, monitoring these indicators relies on workers' experience, which can sometimes lead to low material utilization rates and even fermentation failures. Near-infrared spectra were collected during soybean steaming, as well as koji and moromi fermentation, using miniature fiber spectrometers. These spectra were optimized using four pretreatment methods, and regression models were constructed using PLS, iPLS, and Si-PLS. The evaluation of models in prediction sets was based on the correlation coefficient (Rp) and root mean square error (RMSEP). Results indicated that Rp = 0.9327, RMSEP = 4.37% for DRSS, Rp = 0.9364, RMSEP = 228 U/g for PAK, and Rp = 0.9237, RMSEP =0.148 g/100 mL for FNCM were obtained. The above results coupling with validation experiments demonstrated that the developed in-situ and real-time spectroscopy system could ensure high-quality soy sauce production.

Mechanoimmune-Driven Backpack Sustains Dendritic Cell Maturation for Synergistic Tumor Radiotherapy.

Cell backpacks present significant potential in both therapeutic and diagnostic applications, making it essential to further explore their interactions with host cells. Current evidence indicates that backpacks can induce sustained immune responses. Our original objective was to incorporate a model antigen into the backpacks to promote dendritic cell maturation and facilitate antigen presentation, thereby inducing immune responses. However, we unexpectedly discovered that both antigen-loaded backpacks and empty backpacks demonstrated comparable abilities to induce dendritic cell maturation, resulting in nearly identical potency in T-cell proliferation. Our mechanistic studies suggest that the attachment of backpacks induces mechanical forces on dendritic cells via opening the PIEZO1 mechanical ion channel. This interaction leads to the remodeling of the intracellular cytoskeleton and facilitates the production of type I interferons by dendritic cells. Consequently, the mechano-immune-driven dendritic cell backpacks, when combined with radiotherapy, induce a robust antitumor effect. This research presents an avenue for leveraging mechanotransduction to enhance combination immunotherapeutic strategies, potentially leading to groundbreaking advancements in the field.

Study of the Pharmacodynamic Material Basis And Mechanisms of the Action of Fubai Chrysanthemum in Relieving Visual Fatigue.

Fubai chrysanthemum is a kind of traditional Chinese medicine, which can be used as a common food, and is commonly used to improve and relieve visual fatigue. However, its pharmacodynamic material basis and action mechanisms in relieving visual fatigue have not been systematically studied. In this article, 11 absorbed ingredients from Fubai chrysanthemum were detected in rat plasma. Then, the target network pharmacology and KEGG pathway analysis were performed. It was found that Fubai chrysanthemum could inhibit various apoptotic cells and reduce oxidative damage of eyes by regulating the apoptosis pathway, thus alleviating visual fatigue. Further in vitro experiments showed that Fubai chrysanthemum could effectively protect against oxidation damage of adult retinal pigment epithelial cells (ARPE-19), retinal ganglion cells (RGC-5), and lens. The results of cell experiments showed that Fubai chrysanthemum could increase the cell activity, GSH content, and SOD content of ARPE-19 and RGC-5 after oxidative injury, while decreasing the IL-18 content. Similarly, in the study of lens transparency, we found that Fubai chrysanthemum could effectively alleviate the oxidative damage degree of the lens, and significantly increase the content of CAT, GSH, and SOD. The above results suggested that Fubai chrysanthemum could play an important role in alleviating visual fatigue through regulating cell apoptosis and antioxidative damage.

Altered dynamic joint space in the lateral condyle compartment following medial unicompartmental knee arthroplasty.

PURPOSE: The progression of osteoarthritis in lateral compartment has been identified as a primary complication in medial unicompartmental knee arthroplasty (UKA) revisions, irrespective of whether employing fixed bearing (FB) or mobile bearing (MB) designs. Compared to the previous contact point analyses, the tibiofemoral contacts during knee movements are comprehended by a more comprehensive understanding of joint spaces. This study aims to dynamically map the joint spaces in the lateral compartment during the single-leg lunge following FB and MB UKA procedures, and compare them with the respective contralateral native knees. It is hypothesized that the significant change in joint space for post-UKA compared to their native knees. METHODS: Twelve patients with unilateral medial FB UKA and eleven patients with unilateral medial MB UKA were included and underwent computed tomography scans. The exclusion criteria included anterior cruciate ligament deficiency, postoperative knee pain, any postoperative complications, and musculoskeletal illnesses. A dual fluoroscopic imaging system was utilized to capture the single-leg lunge, and 2D-to-3D registration facilitated the visualization of knee motion. According to the knee motions, joint spaces on tibial and femoral surfaces in the lateral compartments of native, FB, and MB UKA knees were calculated and mapped. RESULTS: In comparison to the native knees, FB UKA knees exhibited significant increases in medial, lateral, central, and posterior joint spaces in the lateral compartment (p < 0.05), while MB UKA knees showed significant increases only in central and posterior joint spaces (p < 0.05). Moreover, FB UKA demonstrated greater increases in medial, central, and posterior joint spaces compared to MB UKA. Tibial varus and valgus during lunges, as well as the Oxford Knee Score (OKS) and Hip-Knee-Ankle angle (HKA), correlated with joint spaces. CONCLUSIONS: Dynamic joint space analysis provided a more comprehensive insight into contact dynamics. FB UKA led to an enlargement of joint spaces, whereas MB UKA resulted in joint spaces closer to native knees. These findings contribute to understanding potential postoperative complication in UKAs.

Motion reconstruction and finite element analysis of the temporomandibular joint during swallowing in healthy adults.

There is a close physiological connection between swallowing and the temporomandibular joint (TMJ). However, a shortage of quantitative research on the biomechanical behavior of the TMJ during swallowing exists. The purpose of this study was to reconstruct the movement of the temporomandibular joint (TMJ) based on in vivo experiment and analyze the biomechanical responses during swallowing in healthy adults to investigate the role of the TMJ in swallowing. Motion capture of swallowing, computed tomography (CT), and magnet resonance images (MRI) were performed on six healthy subjects. The movements of the TMJ during swallowing were reconstructed from the motion capture data. The three-dimensional finite element model was constructed. The dynamic finite element analysis of the swallowing process was performed based on the motion data. The range of condylar displacement was within 1 mm in all subjects. The left and right condyle movements were asymmetrical in two-thirds of the subjects. The peak stresses of the discs were relatively low, with a maximum of 0.11 MPa. During swallowing, the condylar displacement showed two trends: slow retraction and slow extension. The tendency to extend could lead to a gradual increase in stress on the disc.

Effect of condylar rotation on the stress environment of the temporomandibular joint in patients with mandibular protrusion.

PURPOSE: The study aims to analyse the effects of condylar rotation on the biomechanical environment of the TMJ after bilateral sagittal split ramus osteotomy (BSSRO) through the finite element method (FEM). METHODS: Thirteen patients with mandibular prognathism and twenty-three normal subjects were recruited. The three-dimensional (3D) models were reconstructed. 13 representative morphological parameters were measured for comparison. A patient was selected to perform virtual BSSRO surgery by rotating the condyles in MIMICS. The preoperative and postoperative 3D models of the patient were subsequently imported into ABAQUS for finite element analysis. The preoperative and postoperative stresses and joint spaces in the TMJs were investigated. RESULTS: The maxillofacial morphologies of the patients with mandibular protrusion was significantly different from those of the asymptomatic subjects (P<.05). Stresses in the postoperative group were lower than those in the preoperative group. The rotation of the condyle could cause the variations in stress levels and joint spaces within the TMJs. Inward and upward rotation of the condyle was associated with higher stress in the TMJ, whereas the lowest stress was observed when the condyle remained stationary following surgical intervention. SIGNIFICANCE: Lateral, medial and superior joint spaces were more related to the stresses in the TMJs. The condyle should be kept in place as much as possible to avoid disrupting the balance of the TMJ in patients with mandibular protrusion.

Analysis of the improved mechanism of Rhodobacter sphaeroides VK-2-3 coenzyme Q10 by reverse metabolic engineering.

Coenzyme Q10 (CoQ10) is an essential medicinal ingredient. In this study, we obtained a high-yielding mutant strain of CoQ10, VK-2-3, by subjecting R. sphaeroides V-0 (V-0) to a 12C6+ heavy ion beam and high-voltage prick electric field treatment. To investigate the mutation mechanism, the complete genomes of VK-2-3 and V-0 were sequenced. Collinearity analysis revealed that the nicotinamide adenine dinucleotide-dependent dehydrogenase (NAD) gene underwent rearrangement in the VK-2-3 genome. The NAD gene was overexpressed and silenced in V-0, and this construct was named RS.NAD and RS.ΔNAD. The results showed that the titers of CoQ10 in the RS.NAD and RS.ΔNAD increased and decreased by 16.00 and 33.92%, respectively, compared to those in V-0, and these differences were significant. Our results revealed the mechanism by which the VK-2-3 CoQ10 yield increases through reverse metabolic engineering, providing insights for genetic breeding and mechanistic analysis.

A comparative study of acupuncture combined with rehabilitation gymnastics on postoperative anal function of lower rectal cancer.

BACKGROUND: From the anal function, inflammatory response and other indicators, acupuncture combined with rehabilitation gymnastics was applied to patients with cancer undergoing low resection, aiming to improve the prognosis of patients. AIM: To explore the effects of acupuncture combined with rehabilitation gymnastics on anal function after lower rectal cancer surgery. METHODS: From January 2020 to December 2022, 128 patients who underwent rectal cancer surgery in the Department of Oncology of Hebei Provincial Hospital of Traditional Chinese Medicine Hospital were selected and divided into two groups using the random number table method, with 64 patients in each group. Patients in the control group were not treated with acupuncture or rehabilitation gymnastics and served as blank controls. Patients in the study group were treated with acupuncture and rehabilitation gymnastics from the 7th postoperative day. The anal incontinence scores, changes in serum interleukin-4, interleukin-6, and interleukin-10 Levels, and serum motilin, 5-hydroxytryptamine, and vasoactive intestinal peptide levels were compared. RESULTS: There were no significant differences in serum interleukin-4, interleukin-6, and interleukin-10 Levels between the groups before treatment (P > 0.05). After treatment, these levels were better than those of the control group (P < 0.05). There was no significant difference in the anal incontinence scores between the groups before and 7 d after surgery (P > 0.05). Anal incontinence scores in the study group were lower than those in the control group at 14 d, 21 d, and 28 d postoperatively (P < 0.05). There were no significant differences in serum motilin, 5-hydroxytryptamine, or vasoactive intestinal peptide levels between the groups before treatment (P > 0.05). After treatment, these levels were higher in the study group than in the control group, and vasoactive intestinal peptide level was lower in the study group than in the control group (P < 0.05). CONCLUSION: Acupuncture combined with rehabilitation gymnastics can promote the recovery of anal function and reduce the inflammatory response in patients with lower rectal cancer after surgery.

Evaluating the clinical application and effect of acupuncture therapy in anal function rehabilitation after low-tension rectal cancer surgery.

BACKGROUND: According to the indexes of serum and anal function, acupuncture therapy was applied to patients with low rectal cancer in order to avoid the occurrence of anal incontinence and reduce complications. AIM: To explore the clinical application and evaluate the effect of acupuncture therapy for anal function rehabilitation after low-tension rectal cancer surgery. METHODS: From the anorectal surgery cases, we selected 120 patients who underwent colorectal cancer surgery between January 2020 and December 2022 and randomly divided them into a control group (n = 60), observation group (n = 60), and control group after surgery for lifestyle intervention (including smoking cessation and exercise), dietary factor adjustment, anal movement, and oral loperamide treatment. The serum levels of motilin, 5-hydroxytryptamine, and vasoactive intestinal peptide (VIP), Wexner score for anal incontinence, and incidence of complications were compared between groups. RESULTS: After treatment, the VIP and 5-hydroxytryptamine levels in the observation group were lower than those in the control group (P < 0.05). The motilin level was higher than that in the control group (P < 0.05). Postoperative anal incontinence was better in the observation group than in the control group (P < 0.05). The incidence of complications in the observation group was 6.67%, which was significantly lower than that in the control group (21.67%; P < 0.05). CONCLUSION: Acupuncture therapy has a positive effect on the rehabilitation of anal function after low-tension rectal cancer surgery; it can effectively help to improve the serum indices of patients, avoid the occurrence of anal incontinence, and reduce the incidence of complications. Popularizing and applying it will be valuable.

Neoadjuvant targeted therapy versus targeted combined with chemotherapy for resectable EGFR-mutant non-small cell lung cancer: a retrospective controlled real-world study.

Background: This study aimed to assess the role and effect of neoadjuvant targeted therapy (TT) versus targeted combined with chemotherapy (TC) for resectable EGFR-mutant non-small cell lung cancer (NSCLC). Methods: Between March 2021 and June 2023, 20 patients with stage IA3-IIIB NSCLC were enrolled in the study. Eleven patients received EGFR-TKIs in the TT group, while nine patients received EGFR-TKIs and two cycles of cisplatin-based doublet chemotherapy (TC group). We compare the differences between the two groups through the following variables, including age, sex, surgical approach, postoperative complications, neoadjuvant therapy adverse events, complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), objective response rate (ORR), major pathologic response (MPR), and pathologic complete response (pCR). Results: Patients were predominantly female (75%) and never-smokers (95%). The average age was 59.2 years (range 46-79 years). Fifty-five percent harbored an exon 19 EGFR mutation and 45% an exon 21 mutation. The average targeted drug dosing time was 2.91 ± 1.7 (range 1-6) months in the TT group and 3.56 ± 3.54 (range 1-12) months in the TC group (P=0.598). The most common side effects were rash and diarrhea. No grade 5 events with neoadjuvant therapy were observed. The rate of R0 resection was 100% in all patients. Among the 11 patients in the TT group, 6 achieved a PR and 5 had SD, resulting in an ORR of 54.5%. Among the 9 patients in the TC group, 6 had PR and the remaining 3 had SD, resulting in an ORR of 66.6%. one patient (11.1%) in the TC group achieved pCR, while no patients in the TT group achieved pCR (P = 0.142). Two patients (18.2%) in the TT group reached MPR, and 2 patients (22.2%) in the TC group reached MPR (P = 0.257). The overall clinical downstage rate is 60%. Only 9 (45%) cases of yield clinical TNM (ycTNM) were consistent with yield pathologic TNM (ypTNM). Conclusion: Results from this retrospective controlled research indicate that the neoadjuvant TT group is likely to be more effective outcomes and has safer profile in patients with EGFR-positive NSCLC than the neoadjuvant TC group. However, our results need to be validated in a multicenter, large sample prospective study.

LIMA1 links the E3 ubiquitin ligase RNF40 to lipid metabolism.

LIMA1 is a LIM domain and Actin binding 1 protein that acts as a skeleton protein to promote cholesterol absorption, which makes it an ideal target for interfering with lipid metabolism. However, the detailed regulation of LIMA1 remains unclear. Here, we identified that ring finger protein 40 (RNF40), an E3 ubiquitin ligase previously known as an epigenetic modifier to increase H2B ubiquitination, mediated the ubiquitination of LIMA1 and thereby promoted its degradation in a proteasome-dependent manner. Fraction studies revealed that the 1-166aa fragment of LIMA1 was indispensable for the interaction with RNF40, and at least two domains of RNF40 might mediate the association of RNF40 with LIMA1. Notably, treatment with simvastatin dramatically decreased the levels of CHO and TG in control cells rather than cells with overexpressed LIMA1. Moreover, RNF40 significantly decreased lipid content, which could be reversed by LIMA1 overexpression. These findings suggest that E3 ubiquitin ligase RNF40 could directly target LIMA1 and promote its protein degradation in cytoplasm, leading to the suppression of lipid accumulation mediated by LIMA1. Collectively, this study unveils that RNF40 is a novel E3 ubiquitin ligase of LIMA1, which underpins its high therapeutic value to combat dysregulation of lipid metabolism.

Seasonal dynamics of the microbiota and nutritional composition in bee bread from Apis cerana and Apis mellifera colonies.

Bee bread is a product of honeybees, which collect and ferment pollen, that contains highly nutritious and easily digestible active substances. However, its nutritional composition varies significantly with fermentation strains and seasonal changes. To unveil the patterns of microbial community and nutritional component changes in bee bread across seasons, we employed high-throughput techniques to assess the diversity of bacteria and fungi in bee bread. The results indicated that the compositions of bacteria and fungi in bee bread undergo significant seasonal variation, with noticeable changes in the microbial diversity of bee bread from different bee species. Subsequently, metabolomic analysis revealed high activity of glycerophospholipid metabolism in bee bread. Furthermore, our analysis identifaied noteworthy differences in nutritional components, including pH values, sugar content, and free amino acid levels, in bee bread across different seasons.