Dual Nickel/Photoredox-Catalyzed Arylsulfonylation of Allenes.

The nickel/photoredox dual catalysis system is an efficient conversion platform for the difunctionalization of unsaturated hydrocarbons. Herein, we disclose the first dual nickel/photoredox-catalyzed intramolecular 1,2-arylsulfonylation of allenes, which can accurately construct a C(sp2)-C(sp2) bond and a C(sp3)-S bond. The reaction exhibits excellent chemoselectivity and regioselectivity, allowing modular conformations of a diverse series of 3-sulfonylmethylbenzofuran derivatives. Control experiments showed that the bipyridine ligand is crucial for the formation of a stable σ-alkyl nickel intermediate, providing the possibility for sulfonyl radical insertion. Meanwhile, the electrophilic sulfonyl radical facilitates further oxidative addition of the σ-alkyl nickel intermediate and inhibits addition with allenes. In addition, control experiments, cyclic voltammetry tests, Stern-Volmer experiments, and density functional theory calculations afford evidence for the Ni(0)/Ni(I)/Ni(II)/Ni(III) pathway in this 1,2-arylsulfonylation.

TU-LESS procedure for acute abdomen in late pregnancy: a retrospective study.

BACKGROUND: Acute abdominal conditions during pregnancy are significant risks to maternal and fetal health, necessitating timely diagnosis and intervention. The choice of surgical approach is a major concern for obstetricians. OBJECTIVE: To evaluate the safety and efficacy of the TU-LESS procedure for acute abdomen in late pregnancy. METHODS: We retrospectively analyzed 12 patients who underwent TU-LESS for acute abdominal conditions in the third trimester from 2020 to 2023. We reviewed medical records for clinical characteristics, surgical interventions, postoperative complications, and pregnancy outcomes. RESULTS: The study included patients with a median age of 27 (range 20-35) and a BMI of 24.33 kg/m2 (range 21.34-31.96). The median gestational age at surgery was 30 weeks (range, 28 + 3-32 + 4 weeks), with surgeries lasting an average of 60 min (range, 30-163 min). Blood loss was 2-20 mL, and the median hospital stay post-surgery was 6 days (range, 2-16 days). There were no significant complications. The median time to delivery after TU-LESS was 56 days (range, 26-66 days), resulting in 8 full-term deliveries, 2 preterm cesareans, and 2 preterm vaginal deliveries. All newborns were healthy, with no fetal losses or neonatal deaths. CONCLUSION: TU-LESS, performed by experienced obstetricians and gynecologists with proper preoperative preparation, is safe and effective for managing acute abdomen in late pregnancy, without the need to delay surgery due to gestational age.

Identifying new cancer genes based on the integration of annotated gene sets via hypergraph neural networks.

MOTIVATION: Identifying cancer genes remains a significant challenge in cancer genomics research. Annotated gene sets encode functional associations among multiple genes, and cancer genes have been shown to cluster in hallmark signaling pathways and biological processes. The knowledge of annotated gene sets is critical for discovering cancer genes but remains to be fully exploited. RESULTS: Here, we present the DIsease-Specific Hypergraph neural network (DISHyper), a hypergraph-based computational method that integrates the knowledge from multiple types of annotated gene sets to predict cancer genes. First, our benchmark results demonstrate that DISHyper outperforms the existing state-of-the-art methods and highlight the advantages of employing hypergraphs for representing annotated gene sets. Second, we validate the accuracy of DISHyper-predicted cancer genes using functional validation results and multiple independent functional genomics data. Third, our model predicts 44 novel cancer genes, and subsequent analysis shows their significant associations with multiple types of cancers. Overall, our study provides a new perspective for discovering cancer genes and reveals previously undiscovered cancer genes. AVAILABILITY AND IMPLEMENTATION: DISHyper is freely available for download at https://github.com/genemine/DISHyper.

CXCR4-Mediated Codelivery of FLT3 and BCL-2 Inhibitors for Enhanced Targeted Combination Therapy of FLT3-ITD Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is often associated with poor prognosis and survival. Small molecule inhibitors, though widening the treatment landscape, have limited monotherapy efficacy. The combination therapy, however, shows suboptimal clinical outcomes due to low bioavailability, overlapping systemic toxicity and drug resistance. Here, we report that CXCR4-mediated codelivery of the BCL-2 inhibitor venetoclax (VEN) and the FLT3 inhibitor sorafenib (SOR) via T22 peptide-tagged disulfide cross-linked polymeric micelles (TM) achieves synergistic treatment of FLT3-ITD AML. TM-VS with a VEN/SOR weight ratio of 1/4 and T22 peptide density of 20% exhibited an extraordinary inhibitory effect on CXCR4-overexpressing MV4-11 AML cells. TM-VS at a VEN/SOR dosage of 2.5/10 mg/kg remarkably reduced leukemia burden, prolonged mouse survival, and impeded bone loss in orthotopic MV4-11-bearing mice, outperforming the nontargeted M-VS and oral administration of free VEN/SOR. CXCR4-mediated codelivery of BCL-2 and FLT3 inhibitors has emerged as a prospective clinical treatment for FLT3-ITD AML.

Comprehensive analysis of the functions, prognostic and diagnostic values of RNA binding proteins in head and neck squamous cell carcinoma.

BACKGROUND: Accumulating evidence has suggested that RNA binding protein (RBP) dysregulation plays an essential role during tumorigenesis. Here, we sought to explore the potential biological functions and clinical significance of RBP and develop diagnostic and prognostic signatures based on RBP in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: The differently expressed RBPs between HNSCC samples and their normal counterparts were identified using the Limma package. The immunohistochemistry (IHC) images of several RBPs were collected from the Human Protein Atlas database. The diagnostic signature based on RBP was built by LASSO-logistic regression and random forest. The prognostic signature based on RBP was constructed by LASSO and stepwise Cox regression analysis in the training cohort and validated in the validation cohort. RESULTS: Eighty-four aberrantly expressed RBPs were obtained, comprising 41 up-regulated and 43 down-regulated RBPs. Seven RBP genes (CPEB3, PDCD4, ENDOU, PARP12, DNMT3B, IGF2BP1, EXO1) were identified as diagnostic-related hub genes. They were used to establish a diagnostic RBP signature risk score (DRBPS) model by the coefficients in least absolute shrinkage and selection operator (LASSO)-logistic regression analysis and showed high specificity and sensitivity in the training (area under the receiver operating characteristic curve (AUC) = 0.998), and in all validation cohorts (AUC > 0.95 for all). Similarly, seven RBP genes (MKRN3, ZC3H12D, EIF5A2, AFF3, SIDT1, RBM24, and NR0B1) were identified as prognosis-associated hub genes by LASSO and stepwise multiple Cox regression analyses and were used to construct the prognostic model named as PRBPS. The AUC of the time-dependent receiver operator characteristic curve of the prognostic model was 0.664 at 3 years and 0.635 at 5 years in the training cohort and 0.720, 0.777 in the validation cohort, showing a favorable predictive efficacy for prognosis in HNSCC. CONCLUSIONS: Our results demonstrate the value of consideration of RBP in the diagnosis and prognosis for HNSCC and provide a novel insight into understanding the potential role of dysregulated RBP in HNSCC.

Crohn disease but not ulcerative colitis increases the risk of acute pancreatitis: A 2-sample Mendelian randomization study.

Accumulating evidence has indicated an increased risk of acute pancreatitis in individuals with inflammatory bowel disease (IBD); however, the establishment of a clear and direct causal connection between IBD and acute pancreatitis remains uncertain. Utilizing genetic data from publicly accessible genome-wide association studies (GWAS), we conducted a 2-sample MR analysis to identify the associations between IBD, ulcerative colitis (UC), Crohn disease (CD), and acute pancreatitis risk. Rigorous quality control steps ensured the selection of eligible single nucleotide polymorphisms (SNPs) with strong associations to IBD. The primary estimation used the inverse-variance weighted method. We also assessed heterogeneity, potential pleiotropy, and conducted sensitivity analyses. The direction of causality was confirmed using the Steiger test. The MR analysis showed that IBD increased the risk of acute pancreatitis (IVW: OR = 1.032, 95% CI: 1.006-1.06, P = .015). Among the subgroup of IBD, CD (IVW: OR = 1.034, 95% CI: 1.008-1.06, P = .007) indicates a significant increase in the risk of acute pancreatitis compared to UC (IVW: OR = 1.02, 95% CI: 0.99-1.051, P = .189). The MR analysis assessing the association between CD and acute pancreatitis showed no evidence of heterogeneity or horizontal pleiotropy. Likewise, the leave-one-out (LOO) method indicated no significant influence of any individual SNP on the overall findings. In addition, the Steiger direction test revealed that CD was the cause for increased risk of acute pancreatitis, but not vice versa. In summary, this research pioneers in proposing a causal relationship between CD and acute pancreatitis among the European population.

Pan-cancer analysis of CDKN2A alterations identifies a subset of gastric cancer with a cold tumor immune microenvironment.

BACKGROUND: Although CDKN2A alteration has been explored as a favorable factor for tumorigenesis in pan-cancers, the association between CDKN2A point mutation (MUT) and intragenic deletion (DEL) and response to immune checkpoint inhibitors (ICIs) is still disputed. This study aims to determine the associations of CDKN2A MUT and DEL with overall survival (OS) and response to immune checkpoint inhibitors treatment (ICIs) among pan-cancers and the clinical features of CDKN2A-altered gastric cancer. METHODS: This study included 45,000 tumor patients that underwent tumor sequencing across 33 cancer types from four cohorts, the MSK-MetTropism, MSK-IMPACT, OrigiMed2020 and TCGA cohorts. Clinical outcomes and genomic factors associated with response to ICIs, including tumor mutational burden, copy number alteration, neoantigen load, microsatellite instability, tumor immune microenvironment and immune-related gene signatures, were collected in pan-cancer. Clinicopathologic features and outcomes were assessed in gastric cancer. Patients were grouped based on the presence of CDKN2A wild type (WT), CDKN2A MUT, CDKN2A DEL and CDKN2A other alteration (ALT). RESULTS: Our research showed that CDKN2A-MUT patients had shorter survival times than CDKN2A-WT patients in the MSK MetTropism and TCGA cohorts, but longer OS in the MSK-IMPACT cohort with ICIs treatment, particularly in patients having metastatic disease. Similar results were observed among pan-cancer patients with CDKN2A DEL and other ALT. Notably, CDKN2A ALT frequency was positively related to tumor-specific objective response rates to ICIs in MSK MetTropism and OrigiMed 2020. Additionally, individuals with esophageal carcinoma or stomach adenocarcinoma who had CDKN2A MUT had poorer OS than patients from the MSK-IMPACT group, but not those with adenocarcinoma. We also found reduced levels of activated NK cells, T cells CD8 and M2 macrophages in tumor tissue from CDKN2A-MUT or DEL pan-cancer patients compared to CDKN2A-WT patients in TCGA cohort. Gastric cancer scRNA-seq data also showed that CDKN2A-ALT cancer contained less CD8 T cells but more exhausted T cells than CDKN2A-WT cancer. A crucial finding of the pathway analysis was the inhibition of three immune-related pathways in the CDKN2A ALT gastric cancer patients, including the interferon alpha response, inflammatory response, and interferon gamma response. CONCLUSIONS: This study illustrates the CDKN2A MUT and DEL were associated with a poor outcome across cancers. CDKN2A ALT, on the other hand, have the potential to be used as a biomarker for choosing patients for ICI treatment, notably in esophageal carcinoma and stomach adenocarcinoma.

Association between pretreatment emotional distress and immune checkpoint inhibitor response in non-small-cell lung cancer.

Emotional distress (ED), commonly characterized by symptoms of depression and/or anxiety, is prevalent in patients with cancer. Preclinical studies suggest that ED can impair antitumor immune responses, but few clinical studies have explored its relationship with response to immune checkpoint inhibitors (ICIs). Here we report results from cohort 1 of the prospective observational STRESS-LUNG study, which investigated the association between ED and clinical efficacy of first-line treatment of ICIs in patients with advanced non-small-cell lung cancer. ED was assessed by Patient Health Questionnaire-9 and Generalized Anxiety Disorder 7-item scale. The study included 227 patients with 111 (48.9%) exhibiting ED who presented depression (Patient Health Questionnaire-9 score ≥5) and/or anxiety (Generalized Anxiety Disorder 7-item score ≥5) symptoms at baseline. On the primary endpoint analysis, patients with baseline ED exhibited a significantly shorter median progression-free survival compared with those without ED (7.9 months versus 15.5 months, hazard ratio 1.73, 95% confidence interval 1.23 to 2.43, P = 0.002). On the secondary endpoint analysis, ED was associated with lower objective response rate (46.8% versus 62.1%, odds ratio 0.54, P = 0.022), reduced 2-year overall survival rate of 46.5% versus 64.9% (hazard ratio for death 1.82, 95% confidence interval 1.12 to 2.97, P = 0.016) and detriments in quality of life. The exploratory analysis indicated that the ED group showed elevated blood cortisol levels, which was associated with adverse survival outcomes. This study suggests that there is an association between ED and worse clinical outcomes in patients with advanced non-small-cell lung cancer treated with ICIs, highlighting the potential significance of addressing ED in cancer management. ClinicalTrials.gov registration: NCT05477979 .

Exosomes derived from mesenchymal stem cells containing berberine for ulcerative colitis therapy.

Berberine (Ber), an isoquinoline alkaloid, is a potential drug therapy for ulcerative colitis (UC) because of its anti-inflammatory activity, high biological safety, and few side effects. Nevertheless, its clinical application is hindered by its limited water solubility and low bioavailability. Currently, compared to synthetic nanocarriers, exosomes as carriers possess advantages such as low toxicity, high stability, and high specificity. Human placental mesenchymal stem cell-derived exosomes (HplMSC-Exos) have emerged as a promising drug delivery system, offering intrinsic anti-inflammatory and antioxidant activities. Therefore, we engineered MSC-Exos loaded with Ber (Exos-Ber) to enhance the solubility and bioavailability of Ber and for colon targeting, revealing a novel approach for treating UC with natural compounds. Structurally and functionally, Exos-Ber closely resembled unmodified Exos. Both in vitro and in vivo investigations confirmed the antioxidant and anti-inflammatory properties of Exos-Ber. Notably, Exos-Ber exhibited reparative effects on injured epithelial cells and reduced cellular apoptosis. Furthermore, Exos-Ber concurrently demonstrated anti-inflammatory and antioxidant activities, contributing to the mitigation of UC, possibly through its modulation of the MAPK signaling pathway. Overall, our findings demonstrate the potential of Exos-Ber as a promising therapeutic option for alleviating UC, highlighting its capacity to enhance the clinical applicability of Ber.

Pleiotropic role of GAS6 in cardioprotection against ischemia-reperfusion injury.

INTRODUCTION: Myocardial ischemia-reperfusion (IR) injury is a common medical issue contributing to the onset and progression of ischemic heart diseases (IHD). Growth arrest-specific gene 6 (GAS6), a vitamin K-dependent secretory protein, promotes cell proliferation and inhibits inflammation and apoptosis through binding with Tyro3, Axl, and Mertk (TAM) receptors. OBJECTIVES: Our study aimed to examine the effect of GAS6 pathways activation as a potential new treatment in myocardial IR injury. METHODS: Gain- and loss-of-function experiments were utilized to determine the roles of GAS6 in the pathological processes of myocardial IR injury. RESULTS: Our results revealed down-regulated levels of GAS6, Axl, and SIRT1 in murine hearts subjected to IR injury, and cardiomyocytes challenged with hypoxia reoxygenation (HR) injury. GAS6 overexpression significantly improved cardiac dysfunction in mice subjected to myocardial IR injury, accompanied by reconciled mitochondrial dysfunction, oxidative stress, and apoptosis. In vitro experiments also observed a protective effect of GAS6 in cardiomyocytes. SIRT1 was found to function as a downstream regulator for GAS6/Axl signaling axis. Through screening a natural product library, a polyphenol natural compound catechin was identified to exhibit a protective effect by turning on GAS6/Axl-SIRT1 cascade. CONCLUSIONS: Together, our findings indicate that GAS6 emerges as a potential novel target in the management of myocardial IR injury and other related anomalies.

Eosinophil Recovery Time Is Associated with Clinical Outcomes in Patients with Type A Acute Aortic Dissection: a Retrospective Cohort Study.

Type A acute aortic dissection (TA-AAD) patients are prone to life-threatening complications and death. This study aimed to analyze the association between eosinophil (EOS) recovery and clinical outcomes in TA-AAD. A total of 274 patients with TA-AAD were eligible for inclusion, and 54 patients died within 1 month. The patients with poor clinical outcomes showed significantly lower EOS count within 8 days after surgery. The time-dependent ROC analysis showed that EOS recovery days predicted 1-month death with an AUC of 0.886 and a cutoff of 6 days. EOS recovery within 6 days was associated with a lower incidence of postoperative infection, a poorer prognosis, and a lower risk of 1-month and 6-month mortality than those requiring more recovery days. Collectively, postoperative early recovery of EOS predicted lower mortality and better prognosis and may be applied as an effective, rapid, and simple tool for the risk stratification and prognostic prediction of patients with TA-AAD.Clinical trial registration number: NCT05409677.

PTK6: An emerging biomarker for prognosis and immunotherapeutic response in clear cell renal carcinoma (KIRC).

Kidney renal clear cell carcinoma (KIRC), one of the most prevalent form of kidney carcinoma, is highly aggressive cancer known for significant immune infiltration and high mortality rates. The absence of sensitivity to traditional therapy has spurred the search for new treatments. Protein Tyrosine Kinase 6 (PTK6) is implicated in promoting cancer growth, spread, and metastasis. Our review of The Cancer Genome Atlas database revealed PTK6 overexpression in KIRC, though its specific role in this cancer type was unclear. We investigated PTK6's cancer-promoting roles in KIRC using the database and confirmed our findings with patient-derived tissues. Our analysis showed that elevated PTK6 expression is linked to worse outcomes and higher levels of immune infiltration. It also correlates positively with neo-antigens (NEO) and DNA ploidy changes in KIRC. This research delves into PTK6's role in KIRC development, suggesting PTK6 as a possible biomarker for prognosis and treatment in KIRC.

Image detection of aortic dissection complications based on multi-scale feature fusion.

Background: Aortic dissection refers to the true and false two-lumen separation of the aortic wall, in which the blood in the aortic lumen enters the aortic mesomembrane from the tear of the aortic intima to separate the mesomembrane and expand along the long axis of the aorta. Purpose: In view of the problems of individual differences, complex complications and many small targets in clinical aortic dissection detection, this paper proposes a convolution neural network MFF-FPN (Multi-scale Feature Fusion based Feature Pyramid Network) for the detection of aortic dissection complications. Methods: The proposed model uses Resnet50 as the backbone for feature extraction and builds a pyramid structure to fuse low-level and high-level feature information. We add an attention mechanism to the backbone network, which can establish inter-dependencies between feature graph channels and enhance the representation quality of CNN. Results: The proposed method has a mean average precision (MAP) of 99.40% in the task of multi object detection for aortic dissection and complications, which is higher than the accuracy of 96.3% on SSD model and 99.05% on YoloV7 model. It greatly improves the accuracy of small target detection such as cysts, making it more suitable for clinical focus detection. Conclusions: The proposed deep learning model achieves feature reuse and focuses on local important information. By adding only a small number of model parameters, we are able to greatly improve the detection accuracy, which is effective in detecting small target lesions commonly found in clinical settings, and also performs well on other medical and natural datasets.

Engineering design and application of large-scale oil-based drilling cuttings treatment project.

Thermal phase separation technology is a new comprehensive treatment technology, which heats oil-based cuttings to a certain temperature to vaporize oil and water components. Based on a large oil-based drilling cuttings comprehensive utilization project, the engineering design and application effect of thermal phase separation technology were analysed. The practice shows that thermal phase separation technology can reduce the oil content of purified residue to 0.1-0.2%, the average recovery rate of base oil is 94.12% and the annual recovery of base oil is about 4800 t; the purified residue does not have corrosive, leaching toxicity and other dangerous characteristics, and can be used for making bricks or building materials. Thermal phase separation technology is a comprehensive utilization and treatment technology with excellent engineering and environmental benefits, which has a high promotion value.

Meta-analysis of the effectiveness and safety of robotic-assisted versus laparoscopic transabdominal preperitoneal repair for inguinal hernia.

BACKGROUND: Inguinal hernia is a common global disease. This study aims to investigate the effectiveness and safety of robot-assisted transabdominal preperitoneal repair (RTAPP) and laparoscopic transabdominal preperitoneal repair (LTAPP) for inguinal hernia. METHODS: We conducted a thorough search in Cochrane Library, Embase, and PubMed for relevant clinical studies. After applying inclusion and exclusion criteria, the quality of selected studies was assessed using the Jadad scale for randomized controlled studies and the Newcastle-Ottawa scale for observational studies. Meta-analysis was performed using RevMan 5.3 software. RESULTS: A total of ten studies were included, comprising two randomized controlled studies and eight non-randomized controlled studies. Meta-analysis results revealed no statistically significant differences between the RTAPP group and the LTAPP group regarding hospital stay [MD = 0.21 days, 95% CI (-0.09, 0.51), P = 0.17], incidence of seroma [OR = 0.85, 95% CI(0.45, 1.59), P = 0.61], overall complication rate [OR = 1.22, 95% CI(0.68, 2.18), P = 0.51], readmission rate [OR = 1.31, 95% CI(0.23, 7.47), P = 0.76], and recurrence rate [OR = 0.82, 95% CI(0.22, 3.07), P = 0.77]. However, the RTAPP group had longer operation time compared to the LTAPP group [MD = 14.02 minutes, 95% CI (6.65, 21.39), P = 0.0002], and the cost of the RTAPP procedure was higher than that of the LTAPP procedure [MD = $4.17 thousand, 95% CI (2.59, 5.76), P<0.00001]. CONCLUSION: RTAPP for inguinal hernia is a safe and feasible approach, however, it is associated with increased operation time and treatment costs.

Identification of Novel, Selective Ataxia-Telangiectasia Mutated Kinase Inhibitors with the Ability to Penetrate the Blood-Brain Barrier: The Discovery of AZD1390.

The inhibition of ataxia-telangiectasia mutated (ATM) has been shown to chemo- and radio-sensitize human glioma cells in vitro and therefore might provide an exciting new paradigm in the treatment of glioblastoma multiforme (GBM). The effective treatment of GBM will likely require a compound with the potential to efficiently cross the blood-brain barrier (BBB). Starting from clinical candidate AZD0156, 4, we investigated the imidazoquinolin-2-one scaffold with the goal of improving likely CNS exposure in humans. Strategies aimed at reducing hydrogen bonding, basicity, and flexibility of the molecule were explored alongside modulating lipophilicity. These studies identified compound 24 (AZD1390) as an exceptionally potent and selective inhibitor of ATM with a good preclinical pharmacokinetic profile. 24 showed an absence of human transporter efflux in MDCKII-MDR1-BCRP studies (efflux ratio <2), significant BBB penetrance in nonhuman primate PET studies (Kp,uu 0.33) and was deemed suitable for development as a clinical candidate to explore the radiosensitizing effects of ATM in intracranial malignancies.

A multidimensional analysis of ZW10 interacting kinetochore protein in human tumors.

ZW10 interacting kinetochore protein (ZWINT), an essential part of the kinetochore complex, plays a crucial role in maintaining genome stability by correcting improper attachments between the kinetochore and microtubules. An initial analysis of The Cancer Genome Atlas and Gene Expression Omnibus databases revealed that ZWINT is significantly expressed across a diverse range of tumor types. We subsequently investigated the influence of ZWINT on clinical outcomes and potential signaling pathways. A multidimensional analysis of ZWINT revealed significant statistical associations between ZWINT expression and clinical outcomes, as well as the E2F1 oncogenic signature. Experimental validation confirmed the increased expression of ZWINT in both pancreatic cancer cell lines and pancreatic adenocarcinoma tissues. Furthermore, our findings indicate that ZWINT promotes the proliferation of PANC-1 cells through cell cycle regulation. This comprehensive analysis of ZWINT suggests a strong correlation between its expression and various types of tumors, especially pancreatic adenocarcinoma (PAAD), indicating its potential oncogenic role. These findings enhance our understanding of the function of ZWINT in carcinogenesis.

Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family in physiological and pathophysiological process and diseases.

Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family (PGC-1s), consisting of three members encompassing PGC-1α, PGC-1ß, and PGC-1-related coactivator (PRC), was discovered more than a quarter-century ago. PGC-1s are essential coordinators of many vital cellular events, including mitochondrial functions, oxidative stress, endoplasmic reticulum homeostasis, and inflammation. Accumulating evidence has shown that PGC-1s are implicated in many diseases, such as cancers, cardiac diseases and cardiovascular diseases, neurological disorders, kidney diseases, motor system diseases, and metabolic disorders. Examining the upstream modulators and co-activated partners of PGC-1s and identifying critical biological events modulated by downstream effectors of PGC-1s contribute to the presentation of the elaborate network of PGC-1s. Furthermore, discussing the correlation between PGC-1s and diseases as well as summarizing the therapy targeting PGC-1s helps make individualized and precise intervention methods. In this review, we summarize basic knowledge regarding the PGC-1s family as well as the molecular regulatory network, discuss the physio-pathological roles of PGC-1s in human diseases, review the application of PGC-1s, including the diagnostic and prognostic value of PGC-1s and several therapies in pre-clinical studies, and suggest several directions for future investigations. This review presents the immense potential of targeting PGC-1s in the treatment of diseases and hopefully facilitates the promotion of PGC-1s as new therapeutic targets.

The Potential Value of Paraspinal Nerve Block (PVB) in Percutaneous Nephrolithotomy (PCNL) Compared with General Anesthesia and Epidural Anesthesia.

Objective: To analyze the potential value of paraspinal nerve block (PVB) in percutaneous nephrolithotomy (PCNL) and to compare it with general anesthesia and epidural anesthesia. Methods: 120 patients undergoing PCNL surgery in Shanghai Jiao Tong University Affiliated Sixth People's Hospital from January 2021 to June 2022 were selected and divided into PVB anesthesia group, general anesthesia group, and epidural anesthesia group according to different anesthesia methods, with 40 cases in each group. The anesthesia index (anesthesia operation time, anesthetic effect time, anesthesia time), the vital signs (heart rate, mean arterial pressure), postoperative pain [visual analog scale (VAS)], stress response index (cortisol and noradrenaline), the incidence of adverse reactions (nausea and vomiting, lethargy, dizziness, skin itching, bradycardia) were compared among the three groups. Results: The operation time of the anesthesia in the PVB anesthesia group was 5.72±1.25, which was significantly lower than that in the the general (7.95±1.15) and epidural anesthesia groups(8.23±1.43), and the differences were statistically significant (P = .000). The time of onset of anesthesia in the PVB anesthesia group was 6.63±1.87, which was significantly lower than that in the the general (9.84±2.41) and epidural anesthesia groups(10.14±2.89), and the differences were statistically significant (P = .000).The heart rate during percutaneous puncture and intraoperative lithotripsy in the PVB anesthesia group was statistically lower than in the general and epidural anesthesia groups (P < .05). The mean arterial pressure 20 minutes after anesthesia and at the end of operation in the PVB anesthesia group was higher than that in the general anesthesia group, and the mean arterial pressure during percutaneous puncture and intraoperative lithotomy was lower than that in the general anesthesia group (P < .05). The VAS scores of the PVB anesthesia group at 2, 6, 12, 24, and 48 hours after the operation were lower than those of general and epidural anesthesia groups (P < .05). The incidence of adverse reactions was 5.00% (2/40) in the PVB anesthesia group and 35.00% (14/40) in the general anesthesia group, which was lower than that of 27.50% (11/40) in the epidural anesthesia group. (P < .05). Conclusion: The potential value of PVB in PCNL is high is better than that of general anesthesia and epidural anesthesia, anesthesia can shorten operation time and work time, extend the time of anesthesia to maintain, and be helpful to the intraoperative vital signs in patients with stable, mild postoperative pain and stress, low incidence of adverse reactions, efficacy and safety are good, can be introduced.

Evaluation of diagnostic potential of CD38 in rickets.

BACKGROUND: Rickets occurs in infants and children (aged 2 months to 3 years), compromising their skeletal development and damaging nervous, hematopoietic, immune, and other system functions. This study aimed to explore the significance of CD38 in rickets. METHODS: The microarray dataset GSE22523 was analyzed to obtain differentially expressed genes in rickets patients. A total of 36 rickets patients and healthy controls were recruited for the study, and their blood samples were collected, followed by detecting mRNA levels of CD38 using quantitative real-time polymerase chain reaction (qRT-PCR). Moreover, the significance of CD38 in rickets patients was analyzed by receiver operating characteristic (ROC) analysis, while the correlation between CD38 and 25-hydroxy-vitamin D (25OHD)/parathyroid hormone (PTH) was analyzed with Pearson's correlation. RESULTS: Results showed that CD38 mRNA levels and PTH contents were significantly increased in the rickets patients while 25OHD contents were decreased. Correlation analysis indicated that CD38 was positively correlated with PTH and negatively correlated with 25OHD in both serum and plasma samples of rickets patients. Moreover, ROC analysis showed that serum CD38 was 0.9005 (95 % CI: 0.8313-0.9696), and the AUCs of plasma CD38 was 0.7215 (95 % CI: 0.6031-0.8398) in differentiating rickets patients from healthy persons, advocating serum CD38 had better diagnostic value. CONCLUSION: CD38 mRNA levels were upregulated in rickets patients and closely correlated with PTH and 25OHD contents, indicating CD38 might be a diagnostic marker of rickets patients. Further research on the diagnostic utility of CD38 is necessary for the diagnosis and treatment of ricketsin rickets in the future.