The emerging roles of microbiome and short-chain fatty acids in the pathogenesis of bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease that affects premature infants and leads to long-term pulmonary complications. The pathogenesis of BPD has not been fully elucidated yet. In recent years, the microbiome and its metabolites, especially short-chain fatty acids (SCFAs), in the gut and lungs have been demonstrated to be involved in the development and progression of the disease. This review aims to summarize the current knowledge on the potential involvement of the microbiome and SCFAs, especially the latter, in the development and progression of BPD. First, we introduce the gut-lung axis, the production and functions of SCFAs, and the role of SCFAs in lung health and diseases. We then discuss the evidence supporting the involvement of the microbiome and SCFAs in BPD. Finally, we elaborate on the potential mechanisms of the microbiome and SCFAs in BPD, including immune modulation, epigenetic regulation, enhancement of barrier function, and modulation of surfactant production and the gut microbiome. This review could advance our understanding of the microbiome and SCFAs in the pathogenesis of BPD, which also helps identify new therapeutic targets and facilitate new drug development.

HIF-1α knockdown attenuates inflammation and oxidative stress in ischemic stroke male rats via CXCR4/NF-κB pathway.

BACKGROUND: Hypoxia inducible factor-1α (HIF-1α) is a sensitive indicator of oxygen homeostasis, of which the expression elevates following hypoxia/ischemia. This study reveals the specific mechanisms underlying the effects of HIF-1α on ischemic stroke (IS). METHODS: IS model was established using middle cerebral artery occlusion (MCAO)-modeled male rats and oxygen glucose deprivation/reoxygenation (OGD/R)-treated mice hippocampal cells HT22, followed by the silencing of HIF-1α and the overexpression of C-X-C motif chemokine receptor 4 (CXCR4) and nuclear factor-kappa B (NF-κB). Following the surgery, Garcia's grading scale was applied for neurological evaluation. Cerebral infarcts and injuries were visualized using 2,3,5-triphenyltetrazolium chloride and hematoxylin-eosin staining. The levels of tumor necrosis factor-α, Interleukin (IL)-6, IL-1ß, malondialdehyde, and 8-hydroxy-2'-deoxyguanosine, were calculated via ELISA. MTT assay and lactate dehydrogenase (LDH) assay kit were adopted to determine the viability and cytotoxicity of OGD/R-modeled cells. Reactive oxygen species (ROS) generation was evaluated using a 2'-7'dichlorofluorescin diacetate (DCFH-DA) probe. The levels of HIF-1α, CXCR4, and NF-κB p65 were quantified via Western blot and immunofluorescence, respectively. RESULTS: HIF-1α knockdown improved Garcia's score, attenuated the cerebral infarct, inflammation, and ROS generation, and alleviated the levels of inflammatory cytokines and CXCR4/NF-κB p65 in MCAO-modeled rats. Such effects were reversed following the overexpression of CXCR4 and NF-κB. Also, in OGD/R-treated HT22 cells, HIF-1α silencing diminished the cytotoxicity and ROS production and reduced the expressions of CXCR4/NF-κB p65, while promoting viability. However, CXCR4/NF-κB p65 overexpression did the opposite. CONCLUSION: HIF-1α knockdown alleviates inflammation and oxidative stress in IS through the CXCR4/NF-κB pathway.

Therapeutic effects of Lianhua Qingke on COPD and influenza virus-induced exacerbation of COPD are associated with the inhibition of NF-κB signaling and NLRP3 inflammasome responses.

Lianhua Qingke (LHQK), a traditional Chinese medicine (TCM) used clinically for the treatment of respiratory diseases with acute tracheobronchitis, and cough, has demonstrated promising efficacy in suppressing inflammation, inhibitingmucin secretion, reducing goblet cell hyperplasia andmaintainingairway epithelial integrity. However, its efficacy in managing chronic obstructive pulmonary disease (COPD) progression, particularly virus-induced acute exacerbations of COPD (AECOPD),remains unclear. Here, cigarette smoke (CS)-induced COPD and CS+virus (influenza H1N1)-triggered AECOPD mouse models were employed to evaluated the therapeutic potential of LHQK. The findings demonstrated that LHQK treatment led to significant improved pulmonary function, suppressed pulmonary inflammation, alleviated lung histopathological changes, and preserved airway epithelial integrity in COPD mice. Additionally, LHQK treatment effectively inhibited viral replication in the lungs of AECOPD mice and decreased recruitment of immune cells (M1 macrophages, progenitor-exhausted T cells and CD8 + T cells) to the lungs. Western blot analysis indicated that the therapeutic effects of LHQK are associated with the inhibition ofNF-κB signaling and NLRP3 inflammasome activation. Collectively, these findings elucidate the underlying mechanisms by which LHQK mitigates COPD and AECOPD, thereby supporting its potential as a therapeutic option for individuals afflicted with these conditions.

Effect of Noise Management in Interventional Radiology Suites on Patients Undergoing Transarterial Chemoembolization: A Retrospective Study.

OBJECTIVE: This study aims to evaluate the effect of noise management in interventional radiology suites on patients undergoing transarterial chemoembolization (TACE). METHODS: A retrospective cohort study design was employed. The study included a total of 141 patients with hepatocellular carcinoma who underwent TACE surgery in interventional radiology suite of the First People's Hospital of Nantong from January 2022 to December 2022. The patients were divided into an observation group (received noise management, n = 70) and a control group (did not receive noise management, n = 71) on the basis of whether they received noise management. Patient demographics and surgical data were collected, and heart rate, blood pressure, and anxiety levels were assessed before, during and after surgery. Satisfaction and the incidence of adverse reactions were also documented. RESULTS: No significant differences were found in general characteristics. The comparison between the observation and control groups revealed statistically significant differences in noise levels (P < 0.001). Additionally, anxiety levels significantly differed between the two groups (P = 0.040) as well as across different time points (P < 0.001). However, no significant difference was found in the occurrence of adverse events between groups (P = 0.772). Furthermore, patient satisfaction was significantly higher in the observation group than that in the control group (P < 0.001). Although no significant differences were found in heart rate and systolic blood pressure between groups (P > 0.05), and a significant main effect of time was observed for both variables (P < 0.001). CONCLUSION: Noise management in the interventional radiology suite effectively alleviates intraoperative anxiety among patients with TACE and improves treatment satisfaction but has no significant effect on physiological changes and the incidence of adverse events.

Machine Learning Algorithm for Predicting Distant Metastasis of T1 and T2 Gallbladder Cancer Based on SEER Database.

(1) Background: This study seeks to employ a machine learning (ML) algorithm to forecast the risk of distant metastasis (DM) in patients with T1 and T2 gallbladder cancer (GBC); (2) Methods: Data of patients diagnosed with T1 and T2 GBC was obtained from SEER, encompassing the period from 2004 to 2015, were utilized to apply seven ML algorithms. These algorithms were appraised by the area under the receiver operating characteristic curve (AUC) and other metrics; (3) Results: This study involved 4371 patients in total. Out of these patients, 764 (17.4%) cases progressed to develop DM. Utilizing a logistic regression (LR) model to identify independent risk factors for DM of gallbladder cancer (GBC). A nomogram has been developed to forecast DM in early T-stage gallbladder cancer patients. Through the evaluation of different models using relevant indicators, it was discovered that Random Forest (RF) exhibited the most outstanding predictive performance; (4) Conclusions: RF has demonstrated high accuracy in predicting DM in gallbladder cancer patients, assisting clinical physicians in enhancing the accuracy of diagnosis. This can be particularly valuable for improving patient outcomes and optimizing treatment strategies. We employ the RF algorithm to construct the corresponding web calculator.

Prime Editing of Vascular Endothelial Growth Factor Receptor 2 Attenuates Angiogenesis In Vitro.

Vascular endothelial growth factor receptor (VEGFR)-2 is a key switch for angiogenesis, which is observed in various human diseases. In this study, a novel system for advanced prime editing (PE), termed PE6h, is developed, consisting of dual lentiviral vectors: (1) a clustered regularly interspaced palindromic repeat-associated protein 9 (H840A) nickase fused with reverse transcriptase and an enhanced PE guide RNA and (2) a dominant negative (DN) MutL homolog 1 gene with nicking guide RNA. PE6h was used to edit VEGFR2 (c.18315T>A, 50.8%) to generate a premature stop codon (TAG from AAG), resulting in the production of DN-VEGFR2 (787 aa) in human retinal microvascular endothelial cells (HRECs). DN-VEGFR2 impeded VEGF-induced phosphorylation of VEGFR2, Akt, and extracellular signal-regulated kinase-1/2 and tube formation in PE6h-edited HRECs in vitro. Overall, our results highlight the potential of PE6h to inhibit angiogenesis in vivo.

Impact of slit compared with nonslit mesh in laparoscopic groin hernia repairs-A comprehensive propensity score analysis of a cohort of 611 hernias.

BACKGROUND: The slit-mesh technique for laparoscopic groin hernia repair remains controversial. We present the largest cohort of patients to date that have undergone laparoscopic hernia repair with this technique and aim to evaluate the impact of both techniques on postoperative recurrence and other secondary outcomes. METHODS: A retrospective, single-institution cohort study of patients who underwent a laparoscopic groin hernia repair over a 5.5-year period was performed. Univariate and multivariate analyses were performed to identify factors associated with recurrence, chronic pain, complications, length of stay, and operative time. A propensity score analysis also was performed. Time to recurrence was then subsequently plotted on a Kaplan-Meier survival analysis. RESULTS: In total, 611 laparoscopic groin hernia repairs (nonslit: n = 353; slit: n = 258) were reviewed. Mean follow-up duration was 6.6 months. On the multivariate analysis, body mass index was inversely correlated with recurrence (odds ratio, 0.792; 95% confidence interval, 0.656-0.956), whereas a slit mesh had lower recurrence (odds ratio, 0.228; 95% confidence interval, 0.064-0.809). In the propensity score-adjusted analysis, slit mesh remained significantly associated with reduced recurrence (adjusted odds ratio, 0.251; 95% confidence interval, 0.070-0.900), with no differences in chronic pain (adjusted odds ratio, 1.297; 95% confidence interval, 0.275-6.128) or postoperative complications (adjusted odds ratio, 1.808; 95% confidence interval, 0.429-7.620). Operative time also was reduced in the slit-mesh group (P = .009). CONCLUSIONS: The slit-mesh technique was associated with a reduced likelihood of postoperative recurrence and shorter operative time, with no impact on postoperative chronic pain or complications. A lower body mass index was also correlated with increased likelihood of postoperative recurrence.

Speed of lung inflation at birth influences the initiation of lung injury in preterm lambs.

Gas flow is fundamental for driving tidal ventilation and, thus, the speed of lung motion, but current bias flow settings to support the preterm lung after birth do not have an evidence base. We aimed to determine the role of gas bias flow rates to generate positive pressure ventilation in initiating early lung injury pathways in the preterm lamb. Using slower speeds to inflate the lung during tidal ventilation (gas flow rates 4-6 L/min) did not affect lung mechanics, mechanical power, or gas exchange compared with those currently used in clinical practice (8-10 L/min). Speed of pressure and volume change during inflation were faster with higher flow rates. Lower flow rates resulted in less bronchoalveolar fluid protein, better lung morphology, and fewer detached epithelial cells. Overall, relative to unventilated fetal controls, there was greater protein change using 8-10 L/min, which was associated with enrichment of acute inflammatory and innate responses. Slowing the speed of lung motion by supporting the preterm lung from birth with lower flow rates than in current clinical use resulted in less lung injury without compromising tidal ventilation or gas exchange.

Cyclo(L-Pro-L-Trp) from Chilobrachys jingzhao alleviates formalin-induced inflammatory pain by suppressing the inflammatory response and inhibiting TRAF6-mediated MAPK and NF-κB signaling pathways.

Chronic pain has emerged as a significant public health issue, seriously affecting patients' quality of life and psychological well-being, with a lack of effective pharmacological treatments. Numerous studies have indicated that macrophages play a crucial role in inflammatory pain, and targeting neuro-immune interactions for drug development may represent a promising direction for pain management. Chilobrachys jingzhao (C. jingzhao) is used as a folk medicine of the Li nationality with the efficacy of eliminating swelling, detoxicating, and relieving pain, and the related products are widely used in the market. However, the chemical constituents of C. jingzhao have not been reported, and the pharmacodynamic substance and the precise functional mechanism are unrevealed. Here we isolated a cyclic dipeptide, cyclo(L-Pro-L-Trp) (CPT) from C. jingzhao for the first time. CPT remarkably alleviated formalin-induced inflammatory pain and significantly inhibited inflammatory responses. In vivo, CPT attenuated neutrophil infiltration and plantar tissue edema and suppressed the mRNA expression of pro-inflammatory molecules. In vitro, CPT suppressed inflammation triggered by lipopolysaccharide (LPS) in both RAW 264.7 and iBMDM cells, reducing expressions of inducible nitric oxide synthase (iNOS), superoxide, and pro-inflammatory molecules. A mechanistic study revealed that CPT exerted an anti-inflammatory activity by blocking the mitogen-activated protein kinases (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways, as well as alleviating the ubiquitination of tumor necrosis factor receptor-associated factor 6 (TRAF6). Our results elucidated the pharmacodynamic material basis of C. jingzhao, and CPT can be a promising lead for alleviating inflammation and inflammatory pain.

Sarcopenia adversely impacts clinical outcomes in patients undergoing pancreaticoduodenectomy: A systematic review and meta-analysis.

BACKGROUND: Sarcopenia is a syndrome marked by a gradual and widespread reduction in skeletal muscle mass and strength, as well as a decline in functional ability, which is associated with malnutrition, hormonal changes, chronic inflammation, disturbance of intestinal flora, and exercise quality. Pancreatoduodenectomy is a commonly employed clinical intervention for conditions such as pancreatic head cancer, ampulla of Vater cancer, and cholangiocarcinoma, among others, with a notably high rate of postoperative complications. Sarcopenia is frequent in patients undergoing pancreatoduodenectomy. However, data regarding the effects of sarcopenia in patients undergoing pancreaticoduodenectomy (PD) are both limited and inconsistent. AIM: To assess the influence of sarcopenia on outcomes in patients undergoing PD. METHODS: The PubMed, Cochrane Library, Web of Science, and Embase databases were screened for studies published from the time of database inception to June 2023 that described the effects of sarcopenia on the outcomes and complications of PD. Two researchers independently assessed the quality of the data extracted from the studies that met the inclusion criteria. Meta-analysis using RevMan 5.3.5 and Stata 14.0 software was conducted. Forest and funnel plots were used, respectively, to demonstrate the outcomes of the sarcopenia group vs the non-sarcopenia group after PD and to evaluate potential publication bias. RESULTS: Sixteen studies encompassing 2381 patients were included in the meta-analysis. The patients in the sarcopenia group (n = 833) had higher overall postoperative complication rates [odds ratio (OR) = 3.42, 95% confidence interval (CI): 1.95-5.99, P < 0.0001], higher Clavien-Dindo class ≥ III major complication rates (OR = 1.41, 95%CI: 1.04-1.90, P = 0.03), higher bacteremia rates (OR = 4.46, 95%CI: 1.42-13.98, P = 0.01), higher pneumonia rates (OR = 2.10, 95%CI: 1.34-3.27, P = 0.001), higher pancreatic fistula rates (OR = 1.42, 95%CI: 1.12-1.79, P = 0.003), longer hospital stays (OR = 2.86, 95%CI: 0.44-5.28, P = 0.02), higher mortality rates (OR = 3.17, 95%CI: 1.55-6.50, P = 0.002), and worse overall survival (hazard ratio = 2.81, 95%CI: 1.45-5.45, P = 0.002) than those in the non-sarcopenia group (n = 1548). However, no significant inter-group differences were observed regarding wound infections, urinary tract infections, biliary fistulas, or postoperative digestive bleeding. CONCLUSION: Sarcopenia is a common comorbidity in patients undergoing PD. Patients with preoperative sarcopenia have increased rates of complications and mortality, in addition to a poorer overall survival rate and longer hospital stays after PD.

Preoperative prediction of lymphovascular invasion and T-staging of rectal cancer via a dual-energy computed tomography iodine map: a feasibility study.

PURPOSE: To investigate the value of dual-energy computed tomography (DECT) in predicting lymphovascular invasion (LVI) and the accuracy of preoperative T-staging of rectal cancer (RC). METHODS: Forty-nine patients with RC who had not received radiotherapy were enrolled to undergo a DECT scan. All patients underwent surgical tumor resection within 3-5 days after the DECT scan. Preoperative T-staging of RC based on images was performed by experienced radiologists. The normalized iodine concentrations (NIC) of the tumor and the perirectal adipose tissue (PAT) from the arterial phase (AP) and venous phase (VP) were measured using DECT. The tumor LVI and T-staging confirmed by pathology were used as the gold standard for grouping (group A, LVI-; group B, LVI+; group C, T1-2; and group D, T3-4a). The NIC values between two groups were compared using the Mann-Whitney U test, with P < 0.05 indicating a statistically significant difference. The accuracy of NIC in predicting LVI and distinguishing T1-2 RC from T3-4a RC were determined via receiver operating characteristic curve analysis, and the optimal cut-off of NIC was determined using the area under the curve. RESULTS: The tumor NIC values were significantly higher in the LV+ group than in the LVI- group in the VP (0.728 ± 0.031 vs. 0.669 ± 0.034, P < 0.001). The NIC values of PAT were significantly higher in the T3-4a group than in the T1-2 group in both the AP (4.034 ± 0.991 vs. 3.115 ± 0.581, P < 0.05) and the VP (5.481 ± 1.054 vs. 3.450 ± 0.980, P < 0.001). The accuracy of using NIC values to distinguish between the LVI+ group and the LVI- group and to diagnose the T3-4a group were 85.7% and 89.8%, respectively. However, there was no statistically significant difference between the NIC value in the LVI+ group and in the LVI- group in the AP. There was also no statistical difference in the tumor NIC value between the T1-2 group and the T3-4a group. CONCLUSION: The tumor and PAT NIC are valuable indicators in RC that can preoperatively predict LVI and improve the accuracy of preoperative RC T-staging. CLINICAL SIGNIFICANCE: The use of DECT improves the T-staging and LVI prediction of RC, which is helpful in guiding the clinical selection of appropriate treatment modalities and improving prognostic outcomes.

PD-1/CD80+ small extracellular vesicles from immunocytes induce cold tumours featured with enhanced adaptive immunosuppression.

Only a minority of cancer patients benefit from immune checkpoint blockade therapy. Sophisticated cross-talk among different immune checkpoint pathways as well as interaction pattern of immune checkpoint molecules carried on circulating small extracellular vesicles (sEV) might contribute to the low response rate. Here we demonstrate that PD-1 and CD80 carried on immunocyte-derived sEVs (I-sEV) induce an adaptive redistribution of PD-L1 in tumour cells. The resulting decreased cell membrane PD-L1 expression and increased sEV PD-L1 secretion into the circulation contribute to systemic immunosuppression. PD-1/CD80+ I-sEVs also induce downregulation of adhesion- and antigen presentation-related molecules on tumour cells and impaired immune cell infiltration, thereby converting tumours to an immunologically cold phenotype. Moreover, synchronous analysis of multiple checkpoint molecules, including PD-1, CD80 and PD-L1, on circulating sEVs distinguishes clinical responders from those patients who poorly respond to anti-PD-1 treatment. Altogether, our study shows that sEVs carry multiple inhibitory immune checkpoints proteins, which form a potentially targetable adaptive loop to suppress antitumour immunity.

Mechanically robust and personalized silk fibroin-magnesium composite scaffolds with water-responsive shape-memory for irregular bone regeneration.

The regeneration of critical-size bone defects, especially those with irregular shapes, remains a clinical challenge. Various biomaterials have been developed to enhance bone regeneration, but the limitations on the shape-adaptive capacity, the complexity of clinical operation, and the unsatisfied osteogenic bioactivity have greatly restricted their clinical application. In this work, we construct a mechanically robust, tailorable and water-responsive shape-memory silk fibroin/magnesium (SF/MgO) composite scaffold, which is able to quickly match irregular defects by simple trimming, thus leading to good interface integration. We demonstrate that the SF/MgO scaffold exhibits excellent mechanical stability and structure retention during the degradative process with the potential for supporting ability in defective areas. This scaffold further promotes the proliferation, adhesion and migration of osteoblasts and the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro. With suitable MgO content, the scaffold exhibits good histocompatibility, low foreign-body reactions (FBRs), significant ectopic mineralisation and angiogenesis. Skull defect experiments on male rats demonstrate that the cell-free SF/MgO scaffold markedly enhances bone regeneration of cranial defects. Taken together, the mechanically robust, personalised and bioactive scaffold with water-responsive shape-memory may be a promising biomaterial for clinical-size and irregular bone defect regeneration.

Machine learning for predicting liver and/or lung metastasis in colorectal cancer: A retrospective study based on the SEER database.

OBJECTIVE: This study aims to establish a machine learning (ML) model for predicting the risk of liver and/or lung metastasis in colorectal cancer (CRC). METHODS: Using the National Institutes of Health (NIH)'s Surveillance, Epidemiology, and End Results (SEER) database, a total of 51265 patients with pathological diagnosis of colorectal cancer from 2010 to 2015 were extracted for model development. On this basis, We have established 7 machine learning algorithm models. Evaluate the model based on accuracy, and AUC of receiver operating characteristics (ROC) and explain the relationship between clinical pathological features and target variables based on the best model. We validated the model among 196 colorectal cancer patients in Beijing Electric Power Hospital of Capital Medical University of China to evaluate its performance and universality. Finally, we have developed a network-based calculator using the best model to predict the risk of liver and/or lung metastasis in colorectal cancer patients. RESULTS: 51265 patients were enrolled in the study, of which 7864 (15.3 %) had distant liver and/or lung metastasis. RF had the best predictive ability, In the internal test set, with an accuracy of 0.895, AUC of 0.956, and AUPR of 0.896. In addition, the RF model was evaluated in the external validation set with an accuracy of 0.913, AUC of 0.912, and AUPR of 0.611. CONCLUSION: In this study, we constructed an RF algorithm mode to predict the risk of colorectal liver and/or lung metastasis, to assist doctors in making clinical decisions.

[A Real-World Single-Center Study of Adult Hodgkin's Lymphoma].

OBJECTIVE: To summarize the clinical characteristics, therapeutic effect and prognostic factors of patients with Hodgkin's lymphoma (HL). METHODS: A total of 129 patients with HL diagnosed in Peking University Third Hospital from January 2010 to March 2021 who were given at least one efficacy assessment after treatment were enrolled, and their clinical data, including sex, age, pathological type, Ann Arbor stage, ECOG score, blood test, ß2-microglobulin, lactate dehydrogenase level, albumin level were collected. The clinical characteristics, therapeutic effect and long-term prognosis of the patients were summarized and analyzed. RESULTS: In classical HL, nodular sclerosis HL accounted for the highest proportion of 51.6%, followed by mixed cellularity HL (36.5%), lymphocyte-rich classical HL (3.2%), and lymphocyte depletion HL (0.7%), while nodular lymphocyte predominant HL accounted for 4.8%. The 3-year overall survival (OS) rate of HL patients was 89.8%, and 5-year OS was 85.0%. The 3-year progression-free survival (PFS) rate was 73.4%, and 5-year PFS was 63.1%. Multivariate regression analysis indicated that IPI score was an independent negative factor, while hemoglobin (Hb) level was an independent positive factor for OS in HL patients. When the mediastinal mass size was 9.2 cm, it was most significant to judge the survival status of HL patients. 5-year OS and 5-year PFS were 97.4% and 76.0% in early-stage HL patients without large mass, respectively, while in patients with advanced-stage HL was 83.4% and 55.9% (both P < 0.05). After 2-4 courses of treatment, the overall response rate (ORR) of patients who received chemotherapy combined with radiotherapy was 95.0%, while that was 89.6% in those with chemotherapy alone. CONCLUSIONS: The overall prognosis of patients with HL is satisfactory, especially those in early-stage without large mass. IPI score and Hb level are independent risk factors for the prognosis of HL patients. A 9.2 cm mediastinal mass can be used as the cut-off value for the prognosis of Chinese HL patients.

BMSC-Derived Exosomes Attenuate Rat Osteoarthritis by Regulating Macrophage Polarization through PINK1/Parkin Signaling Pathway.

OBJECTIVE: Exosomes derived from bone marrow mesenchymal stem cells (BMSC-Exos) may modulate the M1/M2 polarization of macrophages during osteoarthritis (OA). However, the underlying mechanisms of BMSC-Exos in this process still need to be elucidated. In this study, we explored the role of BMSC-Exos in the polarization of macrophages in vitro and the OA rats in vivo. METHODS: The effects of BMSC-Exos on RAW264.7 cells were determined, including the production of reactive oxygen species (ROS) and the protein expression of Akt, PINK1, and Parkin. We prepared an OA model by resecting the anterior cruciate ligament and medial meniscus of Sprague-Dawley (SD) rats. Hematoxylin-eosin (H&E) and safranin O-fast green staining, immunohistochemistry and immunofluorescence analyses, and the examination of interleukin 6 (IL-6), interleukin 1ß (IL-1ß), tumor necrosis factor alpha (TNF-α), and interleukin 10 (IL-10) were performed to assess changes in cartilage and synovium. RESULTS: BMSC-Exos inhibited mitochondrial membrane damage, ROS production, and the protein expression of PINK1 and Parkin. Akt phosphorylation was downregulated under lipopolysaccharide (LPS) induction but significantly recovered after treatment with BMSC-Exos. BMSC-Exos alleviated cartilage damage, inhibited M1 polarization, and promoted M2 polarization in the synovium in OA rats. The expression of PINK1 and Parkin in the synovium and the levels of IL-6, IL-1ß, and TNF-α in the serum decreased, but the level of IL-10 increased when BMSC-Exos were used in OA rats. CONCLUSION: BMSC-Exos ameliorate OA development by regulating synovial macrophage polarization, and one of the underlying mechanisms may be through inhibiting PINK1/Parkin signaling.

Learning curves for itinerant nurses to master the operation skill of Ti-robot-assisted spinal surgery equipment by CUSUM analysis: A pilot study.

This study aimed to investigate the minimum number of operations required for itinerant nurses in the operating room to master the skills needed to operate the Ti-robot-assisted spinal surgery equipment. Additionally, we aimed to provide a corresponding basis for the development of qualification admission criteria and skill training for nurses who cooperate with this type of surgery. Nine operating room itinerant nurses independently performed Ti-robot equipment simulations using a spine model as a tool, with 16 operations per trainee. Four evaluation indices were recorded: time spent on equipment preparation and line connections, time spent on image acquisition and transmission, time spent on surgical spine screw placement planning, and time spent on robot arm operation. Individual and general learning curves were plotted using cumulative sum analysis. The number of cases in which the slope of the individual learning curves began to decrease was 3-11 cases, and the number of cases in which the slope of the general learning curve began to decrease was 8 cases. The numbers of cases in which the learning curves began to decrease in the four phases were the 5th, 8th, 11th, and 3rd cases. Itinerant nurses required at least eight cases to master the equipment operation skills of Ti-robot-assisted spinal surgery. Among the four phases, the image acquisition and transmission phases and the surgical spine screw placement planning phase were the most difficult and must be emphasized in future training.

Identification of Treg-related prognostic molecular subtypes and individualized characteristics in clear cell renal cell carcinoma through single-cell transcriptomes and bulk RNA sequencing.

BACKGROUND: In clear cell renal cell carcinoma (ccRCC), the role of Regulatory T cells (Treg cells) as prognostic and immunotherapy response predictors is not fully explored. METHODS: Analyzing renal clear cell carcinoma datasets from TISCH, TCGA, and GEO, we focused on 8 prognostic Treg genes to study patient subtypes in ccRCC. We assessed Treg subtypes in relation to patient prognosis, tumor microenvironment, metabolism. Using Cox regression and principal component analysis, we devised Treg scores for individual patient characterization and explored the molecular role of C1QL1, a critical gene in the Treg model, through in vivo and in vitro studies. RESULTS: Eight Treg-associated prognostic genes were identified, classifying ccRCC patients into cluster A and B. Cluster A patients showed poorer prognosis with distinct clinical and molecular profiles, potentially benefiting more from immunotherapy. Low Treg scores correlated with worse outcomes and clinical progression. Low scores also suggested that patients might respond better to immunotherapy and targeted therapies. In ccRCC, C1QL1 knockdown reduced tumor proliferation and invasion via NF-kb-EMT pathways and decreased Treg cell infiltration, enhancing immune efficacy. CONCLUSIONS: The molecular subtype and Treg score in ccRCC, based on Treg cell marker genes, are crucial in personalizing ccRCC treatment and underscore C1QL1's potential as a tumor biomarker and target for immunotherapy.

Ultrasound image segmentation of renal tumors based on UNet++ with fusion of multiscale residuals and dual attention.

Objective. Laparoscopic renal unit-preserving resection is a routine and effective means of treating renal tumors. Image segmentation is an essential part before tumor resection. The current segmentation method mainly relies on doctors manual delineation, which is time-consuming, labor-intensive, and influenced by their personal experience and ability. And the image quality of segmentation is low, with problems such as blurred edges, unclear size and shape, which are not conducive to clinical diagnosis.Approach. To address these problems, we propose an automated segmentation method, i.e. the UNet++ algorithm fusing multiscale residuals and dual attention (MRDA_UNet++). It replaces two consecutive 3 × 3 convolutions in UNet++ with the 'MultiRes block' module, which incorporates coordinate attention to fuse features from different scales and suppress the impact of background noise. Furthermore, an attention gate is also added at the short connections to enhance the ability of the network to extract features from the target area.Main results. The experimental results show that MRDA_UNet++ achieves 93.18%, 92.87%, 93.66%, and 92.09% on the real-world dataset for MIoU, Dice, Precision, and Recall, respectively. Compared to the baseline model UNet++ on three public datasets, the MIoU, Dice, and Recall metrics improved by 6.00%, 7.90% and 18.09% respectively for BUSI, 0.39%, 0.27% and 1.03% for Dataset C, and 1.37%, 1.75% and 1.30% for DDTI.Significance. The proposed MRDA_UNet++ exhibits obvious advantages in feature extraction, which can not only significantly reduce the workload of doctors, but also further decrease the risk of misdiagnosis. It is of great value to assist doctors diagnosis in the clinic.

Lianhua Qingke Preserves Mucociliary Clearance in Rat with Acute Exacerbation of Chronic Obstructive Pulmonary Disease by Maintaining Ciliated Cells Proportion and Protecting Structural Integrity and Beat Function of Cilia.

Purpose: Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD) is a sudden worsening of symptoms in patients with Chronic Obstructive Pulmonary Disease (COPD), such as cough, increased sputum volume, and sputum purulence. COPD and AECOPD are characterized by damage to cilia and increased mucus secretion. Mucociliary clearance (MCC) functions as part of the primary innate system of the lung to remove harmful particles and pathogens together with airway mucus and is therefore crucial for patients with COPD. Methods: AECOPD was induced by cigarette smoke exposure (80 cigarettes/day, 5 days/week for 12 weeks) and lipopolysaccharide (LPS) instillation (200 µg, on days 1, 14, and 84). Rats administered Lianhua Qingke (LHQK) (0.367, 0.732, and 1.465 g/kg/d) or Eucalyptol, Limonene, and Pinene Enteric Soft Capsules (ELP, 0.3 g/kg/d) intragastrically. Pulmonary pathology, Muc5ac+ goblet cell and ß-tubulin IV+ ciliated cells, and mRNA levels of forkhead box J1 (Foxj1) and multiciliate differentiation and DNA synthesis associated cell cycle protein (MCIDAS) were assessed by hematoxylin and eosin staining, immunofluorescence staining, and RT-qPCR, respectively. Ciliary morphology and ultrastructure were examined through scanning electron microscopy and transmission electron microscopy. Ciliary beat frequency (CBF) was recorded using a high-speed camera. Results: Compared to the model group, LHQK treatment groups showed a reduction in inflammatory cell infiltration, significantly reduced goblet cell and increased ciliated cell proportion. LHQK significantly upregulated mRNA levels of MCIDAS and Foxj1, indicating promoted ciliated cell differentiation. LHQK protected ciliary structure and maintained ciliary function via increasing the ciliary length and density, reducing ciliary ultrastructure damage, and ameliorating random ciliary oscillations, consequently enhancing CBF. Conclusion: LHQK enhances the MCC capability of ciliated cells in rat with AECOPD by preserving the structural integrity and beating function of cilia, indicating its therapeutic potential on promoting sputum expulsion in patients with AECOPD.