Nanocarriers Loaded with Danshensu for Treating Ischemic Stroke by Reducing Oxidative Stress and Glial Overactivation.

Ischemic stroke is a complex health condition that can cause ischemia and necrosis of brain tissue. Subsequently, the excessive activation of glial cells can result in various inflammatory and oxidative stress reactions that exacerbate ischemic brain injury. In this paper, we propose the targeted self-assembly of a three-dimensional nanoparticle network containing Danshensu to rescue ischemic penumbra by reducing oxidative stress and glial overactivation. The network comprises nanoparticles composed of chitosan, thiol ketone, and carboxymethyl-ß-cyclodextrin as the core wrapped by the Pro-His-Ser-Arg-Asn (PHSRN) peptide sequence as the outer layer and loaded with Danshensu. The PHSRN-peptide-modified nanoparticles bind to integrin α5ß1 overexpressed on the damaged blood-brain barrier and accumulate in the damaged brain in a rat model of ischemia/reperfusion. When stimulated by reactive oxygen species, thiol ketone bonded to the nanoparticles was hydrolyzed, facilitating responsive drug release while consuming the reactive oxygen species. Subsequently, the released Danshensu scavenged the reactive oxygen species to prevent oxidative stress and inhibited the activation of astrocytes, thereby suppressing proinflammatory cytokine secretion, improving the inflammatory brain microenvironment and reducing neuronal apoptosis.

Development and validation of an interpretable machine learning for mortality prediction in patients with sepsis.

Introduction: Sepsis is a leading cause of death. However, there is a lack of useful model to predict outcome in sepsis. Herein, the aim of this study was to develop an explainable machine learning (ML) model for predicting 28-day mortality in patients with sepsis based on Sepsis 3.0 criteria. Methods: We obtained the data from the Medical Information Mart for Intensive Care (MIMIC)-III database (version 1.4). The overall data was randomly assigned to the training and testing sets at a ratio of 3:1. Following the application of LASSO regression analysis to identify the modeling variables, we proceeded to develop models using Extreme Gradient Boost (XGBoost), Logistic Regression (LR), Support Vector Machine (SVM), and Random Forest (RF) techniques with 5-fold cross-validation. The optimal model was selected based on its area under the curve (AUC). Finally, the Shapley additive explanations (SHAP) method was used to interpret the optimal model. Results: A total of 5,834 septic adults were enrolled, the median age was 66 years (IQR, 54-78 years) and 2,342 (40.1%) were women. After feature selection, 14 variables were included for developing model in the training set. The XGBoost model (AUC: 0.806) showed superior performance with AUC, compared with RF (AUC: 0.794), LR (AUC: 0.782) and SVM model (AUC: 0.687). SHAP summary analysis for XGBoost model showed that urine output on day 1, age, blood urea nitrogen and body mass index were the top four contributors. SHAP dependence analysis demonstrated insightful nonlinear interactive associations between factors and outcome. SHAP force analysis provided three samples for model prediction. Conclusion: In conclusion, our study successfully demonstrated the efficacy of ML models in predicting 28-day mortality in sepsis patients, while highlighting the potential of the SHAP method to enhance model transparency and aid in clinical decision-making.

Naringin attenuates Actinobacillus pleuropneumoniae-induced acute lung injury via MAPK/NF-κB and Keap1/Nrf2/HO-1 pathway.

Actinobacillus pleuropneumoniae (APP) causes porcine pleuropneumonia (PCP), which is clinically characterized by acute hemorrhagic, necrotizing pneumonia, and chronic fibrinous pneumonia. Although many measures have been taken to prevent the disease, prevention and control of the disease are becoming increasingly difficult due to the abundance of APP sera, weak vaccine cross-protection, and increasing antibiotic resistance in APP. Therefore, there is an urgent need to develop novel drugs against APP infection to prevent the spread of APP. Naringin (NAR) has been reported to have an excellent therapeutic effect on pulmonary diseases, but its therapeutic effect on lung injury caused by APP is not apparent. Our research has shown that NAR was able to alleviate APP-induced weight loss and quantity of food taken and reduce the number of WBCs and NEs in peripheral blood in mice; pathological tissue sections showed that NAR was able to prevent and control APP-induced pathological lung injury effectively; based on the establishment of an in vivo/in vitro model of APP inflammation, it was found that NAR was able to play an anti-inflammatory role through inhibiting the MAPK/NF-κB signaling pathway and exerting anti-inflammatory effects; additionally, NAR activating the Nrf2 signalling pathway, increasing the secretion of antioxidant enzymes Nqo1, CAT, and SOD1, inhibiting the secretion of oxidative damage factors NOS2 and COX2, and enhancing the antioxidant stress ability, thus playing an antioxidant role. In summary, NAR can relieve severe lung injury caused by APP by reducing excessive inflammatory response and improving antioxidant capacity.

Recent advances in potential therapeutic targets of ferroptosis­associated pathways for the treatment of stroke (Review).

Stroke is a severe neurological disease that is associated with high rates of morbidity and mortality, and the underlying pathological processes are complex. Ferroptosis fulfills a significant role in the progression and treatment of stroke. It is well established that ferroptosis is a type of programmed cell death that is distinct from other forms or types of cell death. The process of ferroptosis involves multiple signaling pathways and regulatory mechanisms that interact with mechanisms inherent to stroke development. Inducers and inhibitors of ferroptosis have been shown to exert a role in the onset of this cell death process. Furthermore, it has been shown that interfering with ferroptosis affects the occurrence of stroke, indicating that targeting ferroptosis may offer a promising therapeutic approach for treating patients of stroke. Hence, the present review aimed to summarize the latest progress that has been made in terms of using therapeutic interventions for ferroptosis as treatment targets in cases of stroke. It provides an overview of the relevant pathways and molecular mechanisms that have been investigated in recent years, highlighting the roles of inducers and inhibitors of ferroptosis in stroke. Additionally, the intervention potential of various types of Traditional Chinese Medicine is also summarized. In conclusion, the present review provides a comprehensive overview of the potential therapeutic targets afforded by ferroptosis­associated pathways in stroke, offering new insights into how ferroptosis may be exploited in the treatment of stroke.

Insights into the history and tendency of glycosylation and digestive system tumor: A bibliometric-based visual analysis.

BACKGROUND: Glycosylation, a commonly occurring post-translational modification, is highly expressed in several tumors, specifically in those of the digestive system, and plays a role in various cellular pathophysiological mechanisms. Although the importance and detection methods of glycosylation in digestive system tumors have garnered increasing attention in recent years, bibliometric analysis of this field remains scarce. The present study aims to identify the developmental trends and research hotspots of glycosylation in digestive system tumors. AIM: To find and identify the developmental trends and research hotspots of glycosylation in digestive system tumors. METHODS: We obtained relevant literature from the Web of Science Core Collection and employed VOSviewer 1.6.19 and CiteSpace (version 6.1.R6) to perform bibliometric analysis. RESULTS: A total of 2042 documents spanning from 1978 to the present were analyzed, with the research process divided into three phases: the period of obscurity (1978-1990), continuous development period (1991-2006), and the rapid outbreak period (2007-2023). These documents were authored by researchers from 66 countries or regions, with the United States and China leading in terms of publication output. Reis Celso A had the highest number of publications, while Pinho SS was the most cited author. Co-occurrence analysis revealed the most popular keywords in this field are glycosylation, expression, cancer, colorectal cancer, and pancreatic cancer. Furthermore, the Journal of Proteome Research was the most prolific journal in terms of publications, while the Journal of Biological Chemistry had the most citations. CONCLUSION: The bibliometric analysis shows current research focus is primarily on basic research in this field. However, future research should aim to utilize glycosylation as a target for treating tumor patients.

[Circular RNA-Encoded Proteins in Gastrointestinal Cancer:A Review].

Circular RNAs(CircRNAs)are a class of non-coding RNAs with a covalently closed-loop structure,high stability,and tissue specificity,with the production mechanisms different from linear RNAs.Recent studies have discovered that some CircRNAs can encode proteins via cap-independent translation mechanisms such as internal ribosome entry site,N6-methyladenosine,and rolling loop translation.The encoded proteins regulate homologous linear proteins or downstream signaling pathways via protein bait or other mechanisms,thereby exerting biological functions.Studies have shown that CircRNAs play a role in various diseases,especially in tumor progression,proliferation,invasion,and metastasis and immune regulation.Therefore,by elucidating the expression and roles of proteins encoded by CircRNAs in tumorigenesis and development,this paper is expected to provide new tumor markers and potential targets for tumor diagnosis and treatment.

Finite element simulation and experimental test of normal coracoclavicular ligament and flexible reconstruction / 中国组织工程研究

BACKGROUND:For dislocation of acromioclavicular joint induced by coracoclavicular ligament fracture,single EndoButton Plate reconstruction and double EndoButton Plates reconstruction are common repair methods.Further study on the stress distribution and fracture risk of the two repair methods is of great significance. OBJECTIVE:To study the biomechanical properties of the coracoclavicular ligament,and compare the fixation effect,stress distribution and failure mode of single and double EndoButton Plates reconstruction. METHODS:(1)Finite element simulation analysis:Mimics,Wrap and SolidWorks were used to establish normal coracoclavicular ligament,single EndoButton Plate reconstruction and double EndoButton Plates reconstruction.Ansys software was used to analyze the stress and deformation of the scapula and clavicle of each model under vertical load.(2)Sample experiment:Fifteen intact scapular-clavicle specimens were randomly grouped into five groups,with three specimens in each group.In group A,the acromioclavicular ligament was severed and the coracoclavicular ligament remained intact.In group B,acromioclavicular ligaments and trapeoid ligaments were severed,leaving intact conical ligaments.In group C,acromioclavicular ligaments and conical ligaments were cut off,and the intact traprex ligaments were retained.In group D,acromioclavicular and coracoclavicular ligaments were severed,and coracoclavicular ligaments were repaired by single EndoButton Plate reconstruction.In group E,acromioclavicular and coracoclavicular ligaments were severed,and the coracoclavicular ligaments were repaired by double EndoButton Plates reconstruction.The mechanical experiment was carried out by a mechanical testing machine to analyze the biomechanical status,stress distribution and failure patterns of the scapular-clavicle and clavicle. RESULTS AND CONCLUSION:(1)Finite element simulation analysis:The average stress of coracoclavicular ligament attached specimens was the lowest,and the risk of coracoclavicular fracture was less than that of single and double EndoButton Plates reconstruction.The mean stress of the coracoid process was similar in single and double EndoButton Plates reconstruction,and the fracture risk was similar.(2)Sample experiment:In groups A,B,C,D and E,the stiffness of specimens was(26.4±3.5),(19.8±2.8),(21.3±3.2),(57.7±4.1),and(46.2±2.8)N/mm,respectively;the ultimate loads were(545.5±53.7),(360.1±42.1),(250.9±44.4),(643.5±39.1),and(511.9±31.7)N,respectively;global stiffness in groups D and E was higher than that in group A(P=0.000 06,0.000 3);ultimate load in group D was higher than that in group A(P<0.05);the ultimate load was not significantly different between the group E and group A(P>0.05).Ligament fracture was observed in groups A,B and C and coracoid process fracture was found in groups D and E.(3)These results suggest that from the biomechanical analysis,Single EndoButton Plate reconstruction and double EndoButton Plates reconstruction are effective treatment techniques for coracoclavicular ligament fracture in acromioclavicular joint dislocation,but increase the risk of fracture.The double EndoButton Plates reconstruction dispersed the stress of the steel plate and reduced the contact force between the steel plate and bone,but slightly reduced the ultimate bearing capacity.Single and double EndoButton Plates reconstruction should be selected according to the actual clinical situation.

Naringin alleviates pneumonia caused by Klebsiella pneumoniae infection by suppressing NLRP3 inflammasome.

Klebsiella pneumoniae (Kpn) is an important pathogen of hospital-acquired pneumonia, which can lead to sepsis and death in severe cases. In this study, we simulated pneumonia induced by Kpn infection in mice to investigate the therapeutic effect of naringin (NAR) on bacterial-induced lung inflammation. Mice infected with Kpn exhibited increases in white blood cells (WBC) and neutrophils in the peripheral blood and pathological severe injury of the lungs. This injury was manifested by increased expression of the inflammatory cytokines interleukin (IL)- 18, IL-1ß, tumor necrosis factor-α (TNF-α) and IL-6, and elevated the expression of NLRP3 protein. NAR treatment could decrease the protein expression of NLRP3, alleviate lung inflammation, and reduce lung injury in mice caused by Kpn. Meanwhile, molecular docking results suggest NAR could bind to NLRP3 and Surface Plasmon Resonance (SPR) analyses also confirm this result. In vitro trials, we found that pretreated with NAR not only inhibited nuclear translocation of nuclear factor (NF)-κB protein P65 but also attenuated the protein interaction of NLRP3, caspase-1 and ASC and inhibited the assembly of NLRP3 inflammasome in mice AMs. Additionally, NAR could reduce intracellular potassium (K+) efflux, inhibiting NLRP3 inflammasome activation. These results indicated that NAR could protect against Kpn-induced pneumonia by inhibiting the overactivation of the NLRP3 inflammasome signaling pathway. The results of this study confirm the efficacy of NAR in treating bacterial pneumonia, refine the mechanism of action of NAR, and provide a theoretical basis for the research and development of NAR as an anti-inflammatory adjuvant.

[Application of a low copper diet guidance based on food exchange portions in children with hepatolenticular degeneration]. / åŸºäºŽé£Ÿç‰©äº¤æ¢ä»½æ³•çš„ä½Žé“œé¥®é£ŸæŒ‡å¯¼åœ¨è‚è±†çŠ¶æ ¸å˜æ€§æ‚£å„¿ä¸­çš„åº”ç”¨æ•ˆæžœ.

OBJECTIVES: To study the efficacy of a low-copper diet guidance based on food exchange portions in children with hepatolenticular degeneration. METHODS: A self-controlled study was conducted from July 2021 to June 2022, including 30 children under the age of 18 who were diagnosed with hepatolenticular degeneration and poorly controlled with a low-copper diet. During the medical visit, personalized low-copper diet guidance was provided to the children and their parents using a copper-containing food exchange table and a copper food exchange chart. During home care, compliance with the low-copper diet of the children was improved by recording dietary diaries and conducting regular follow-ups. The changes in 24-hour urine copper level, liver function indicators, and the low-copper diet knowledge of the children's parents were observed before and after the intervention, with no change in the original drug treatment. RESULTS: After 8, 16, and 24 weeks of intervention, the 24-hour urine copper level decreased significantly compared to before intervention (P<0.05). When compared to 8-week intervention, the urine copper level decreased significantly after 16 and 24 weeks of intervention. The 24-hour urine copper level after 24 weeks of intervention decreased significantly compared to 16 weeks of intervention (P<0.05).After 24 weeks of intervention, the alanine aminotransferase and aspartate aminotransferase levels decreased significantly compared to before intervention (P<0.05). Additionally, in 16 of the cases (53%), alanine aminotransferase and aspartate aminotransferase returned to normal levels. Following 8 weeks of intervention, the low-copper diet knowledge of the children's parents increased significantly (P<0.05). CONCLUSIONS: A low-copper diet guidance based on food exchange portions can effectively decrease the urine copper level and improve liver function in children with hepatolenticular degeneration. Furthermore, it can increase the low-copper diet knowledge of the children's parents.

Differentiated Embryo-Chondrocyte Expressed Gene1 and Parkinson's Disease: New Insights and Therapeutic Perspectives.

Differentiated embryo-chondrocyte expressed gene1 (DEC1), an important transcription factor with a basic helix-loop-helix domain, is ubiquitously expressed in both human embryonic and adult tissues. DEC1 is involved in neural differentiation and neural maturation in the central nervous system (CNS). Recent studies suggest that DEC1 protects against Parkinson's disease (PD) by regulating apoptosis, oxidative stress, lipid metabolism, immune system, and glucose metabolism disorders. In this review, we summarize the recent progress on the role of DEC1 in the pathogenesis of PD and provide new insights into the prevention and treatment of PD and neurodegenerative diseases.

Unique mutation spectrum of progressive pseudorheumatoid dysplasia in the Chinese population: a retrospective genotype-phenotype analysis of 105 patients.

BACKGROUND: Progressive pseudorheumatoid dysplasia (PPRD) is a rare genetic disease with autosomal recessive inheritance. There was a lack of genotype-phenotype correlation data from the Chinese population. This study aimed to identify the genotype and phenotype characteristics of Chinese PPRD patients and to conduct a genotype-phenotype analysis of Chinese PPRD patients. METHODS: Genetic analysis was performed for suspected PPRD patients from Peking Union Medical College Hospital. Medical records were collected from the electronic medical record system and patient-held portable health records. Published Chinese PPRD cases were gathered from both international and Chinese local databases. We collected demographic information, genetic variants, clinical manifestations, and imaging characteristics for further analysis. RESULTS: We included 105 Chinese PPRD patients in the current study. Thirty-three variants, including nine novels and five hotspot variants, were identified, with 26/33 (79%) variants exclusively seen in the Chinese population. Chinese PPRD patients share a phenotype similar to that in international reports. Joint involvement may progress with age (R2 = 0.2541). Long bone shortening and severe deformities occur in three patients with biallelic null variants, of which at least one variant is located in exon 2. Among hotspot variants, c.624dupA (p.C209Mfs*21) were associated with later onset and more involved joints. Elbow joints were more likely to be affected in patients carrying c.624dupA (p.C209Mfs*21) and c.866dupA (p.S209Efs*13). Shoulder joints are more likely to be involved in patients with biallelic null variants (P = 0.027). CONCLUSIONS: Chinese PPRD patients share a unique mutation spectrum. Among the five hotspot variants, c.624dupA is associated with later onset of disease, more extensive joint involvement, and a tendency to affect elbow joints. Biallelic null variants with at least one variant in exon 2 could be a likely cause of long bone shortening and severe deformities.

Simultaneous determination of ten constituents in Jingfang Granules by HPLC-MS/MS / 中成药

AIM To establish an HPLC-MS/MS method for the simultaneous content determination of pulegone,prim-O-glucosylcimifugin,5-O-methylvisammioside,columbianadin,saikosaponin a,saikosaponin d,ferulic acid,naringin,liquiritin and glycyrrhizic acid in Jingfang Granules.METHODS The analysis of methanol extract of this drug was performed on a 30℃thermostatic ZORBAX Eclipse Plus C18 column(2.1 mm×150 mm,1.8 μm),with the mobile phase comprising of methanol-0.1%formic acid flowing at 0.3 mL/min in a gradient elution manner,and electron spray ionization source was adopted in positive and negative ion scanning with multiple reaction monitoring mode.RESULTS Ten constituents showed good linear relationships within their own ranges(r>0.996 5),whose average recoveries were 96.7%-98.8%with the RSDs of 0.9%-1.9%.CONCLUSION This rapid,simple,sensitive and specific method can be used for the quality control of Jingfang Granules.

Clinical observation on the efficacy and safety of dupilumab in the treatment of moderate to severe atopic dermatitis / 中华预防医学杂志

To investigate the clinical efficacy and safety of dupilumab in the treatment of moderate to severe atopic dermatitis (AD) in China. A small sample self-controlled study before and after treatment was conducted to retrospective analysis patients with moderate to severe AD treated with dupilumab in the department of dermatology of the First Affiliated Hospital of Chongqing Medical University from July 2020 to March 2022. Dupilumab 600 mg was injected subcutaneously at week 0, and then 300 mg was injected subcutaneously every 2 weeks. The condition was evaluated by SCORAD(severity scoring of atopic dermatitis), NRS(numerical rating scale), DLQI(dermatology life quality index) and POEM(patient-oriented eczema measure). The improvement of SCORAD, NRS, DLQI and POEM was analyzed by paired t test and non-parametric paired Wilcoxon. The results showed that a total of 67 patients with moderate to severe AD received dupilumab treatment, of which 41 patients (the course of treatment was more than 6 weeks) had reduced the severity of skin lesions, improved quality of life and reduced pruritus. A total of 23 patients completed 16 weeks of treatment. At 4, 8, 12 and 16 weeks, SCORAD, NRS, DLQI and POEM decreased compared with the baseline, and the differences were statistically significant. SCORAD (50.13±15.19) at baseline, SCORAD (36.08±11.96)(t=6.049,P<0.001) at week 4,SCORAD (28.04±11.10)(t=10.471,P<0.001) at week 8, SCORAD (22.93±9.72)(t=12.428,P<0.001) at week 12, SCORAD (16.84±7.82)(t=14.609,P<0.001) at week 16, NRS 7(6,8) at baseline, NRS 4(3,5)(Z=-3.861,P<0.001) at week 4, NRS 2(1,4)(Z=-4.088,P<0.001) at week 8, NRS 1(0,2)(Z=-4.206,P<0.001) at week 12, NRS 2(0,2)(Z=-4.222,P<0.001) at week 16, DLQI (13.83±5.71) at baseline, DLQI (8.00±4.02)(t=6.325,P<0.001) at week 4, DLQI (5.61±3.50)(t=8.060,P<0.001) at week 8, DLQI (3.96±1.99)(t=8.717,P<0.001) at week 12, DLQI (2.70±1.89)(t=10.355,P<0.001) at week 16, POEM (18.04±6.41) at baseline, POEM (9.70±4.70)(t=7.031,P<0.001) at week 4, POEM (7.74±3.48)(t=8.806,P<0.001) at week 8, POEM (6.35±3.33)(t=10.474,P<0.001) at week 12, POEM (4.26±2.51)(t=11.996,P<0.001) at week 16. In the 16th week, 100%(23 patients), 91.3%(21 patients), 34.8%(8 patients) and 8.7%(2 patients) of 23 patients reached SCORAD30, SCORAD50, SCORAD70, and SCORAD90 statuses, respectively. There were 82.6%(19 patients), 95.7%(22 patients) and 95.7%(22 patients) of 23 patients with NRS, DLQI and POEM improved by≥4 points compared with baseline. Twelve patients with AD who continued to receive dupilumab after 16 weeks showed further improvement in skin lesions. The adverse events were conjunctivitis and injection site reaction. In conclusion, dupilumab is an effective and safe treatment for moderate and severe AD. However, the longer-term efficacy and safety require further studies involving larger sample sizes and a longer follow-up time.

Clinical observation on the efficacy and safety of dupilumab in the treatment of moderate to severe atopic dermatitis / 中华预防医学杂志

To investigate the clinical efficacy and safety of dupilumab in the treatment of moderate to severe atopic dermatitis (AD) in China. A small sample self-controlled study before and after treatment was conducted to retrospective analysis patients with moderate to severe AD treated with dupilumab in the department of dermatology of the First Affiliated Hospital of Chongqing Medical University from July 2020 to March 2022. Dupilumab 600 mg was injected subcutaneously at week 0, and then 300 mg was injected subcutaneously every 2 weeks. The condition was evaluated by SCORAD(severity scoring of atopic dermatitis), NRS(numerical rating scale), DLQI(dermatology life quality index) and POEM(patient-oriented eczema measure). The improvement of SCORAD, NRS, DLQI and POEM was analyzed by paired t test and non-parametric paired Wilcoxon. The results showed that a total of 67 patients with moderate to severe AD received dupilumab treatment, of which 41 patients (the course of treatment was more than 6 weeks) had reduced the severity of skin lesions, improved quality of life and reduced pruritus. A total of 23 patients completed 16 weeks of treatment. At 4, 8, 12 and 16 weeks, SCORAD, NRS, DLQI and POEM decreased compared with the baseline, and the differences were statistically significant. SCORAD (50.13±15.19) at baseline, SCORAD (36.08±11.96)(t=6.049,P<0.001) at week 4,SCORAD (28.04±11.10)(t=10.471,P<0.001) at week 8, SCORAD (22.93±9.72)(t=12.428,P<0.001) at week 12, SCORAD (16.84±7.82)(t=14.609,P<0.001) at week 16, NRS 7(6,8) at baseline, NRS 4(3,5)(Z=-3.861,P<0.001) at week 4, NRS 2(1,4)(Z=-4.088,P<0.001) at week 8, NRS 1(0,2)(Z=-4.206,P<0.001) at week 12, NRS 2(0,2)(Z=-4.222,P<0.001) at week 16, DLQI (13.83±5.71) at baseline, DLQI (8.00±4.02)(t=6.325,P<0.001) at week 4, DLQI (5.61±3.50)(t=8.060,P<0.001) at week 8, DLQI (3.96±1.99)(t=8.717,P<0.001) at week 12, DLQI (2.70±1.89)(t=10.355,P<0.001) at week 16, POEM (18.04±6.41) at baseline, POEM (9.70±4.70)(t=7.031,P<0.001) at week 4, POEM (7.74±3.48)(t=8.806,P<0.001) at week 8, POEM (6.35±3.33)(t=10.474,P<0.001) at week 12, POEM (4.26±2.51)(t=11.996,P<0.001) at week 16. In the 16th week, 100%(23 patients), 91.3%(21 patients), 34.8%(8 patients) and 8.7%(2 patients) of 23 patients reached SCORAD30, SCORAD50, SCORAD70, and SCORAD90 statuses, respectively. There were 82.6%(19 patients), 95.7%(22 patients) and 95.7%(22 patients) of 23 patients with NRS, DLQI and POEM improved by≥4 points compared with baseline. Twelve patients with AD who continued to receive dupilumab after 16 weeks showed further improvement in skin lesions. The adverse events were conjunctivitis and injection site reaction. In conclusion, dupilumab is an effective and safe treatment for moderate and severe AD. However, the longer-term efficacy and safety require further studies involving larger sample sizes and a longer follow-up time.

Early recombinant human growth hormone treatment improves mental development and alleviates deterioration of motor function in infants and young children with Prader-Willi syndrome.

BACKGROUND: Recombinant human growth hormone (rhGH) therapy has shown to improve height and body composition in children with Prader-Willi syndrome (PWS), the evidence of early rhGH treatment on motor and mental development is still accumulating. This study explored the time effect on psychomotor development, anthropometric indexes, and safety for infants and young children with PWS. METHODS: A phase 3, single-arm, multicenter, self-controlled study was conducted in six sites. Patients received rhGH at 0.5 mg/m2/day for first four weeks, and 1 mg/m2/day thereafter for up to 52 weeks. Motor development was measured using Peabody Developmental Motor Scales-second edition, mental development using Griffiths Development Scales-Chinese (GDS-C). Height standard deviation score (SDS), body weight SDS, and body mass index (BMI) SDS were also assessed. RESULTS: Thirty-five patients were enrolled totally. Significant improvements were observed in height, body weight, and BMI SDS at week 52; GDS-C score showed significant improvement in general quotient (GQ) and sub-quotients. In a linear regression analysis, total motor quotient (TMQ), gross motor quotient (GMQ), and fine motor quotient were negatively correlated with age; however, treatment may attenuate deterioration of TMQ and GMQ. Changes in GQ and locomotor sub-quotient in < 9-month group were significantly higher than ≥ 9-month group. Mild to moderate severity adverse drug reactions were reported in six patients. CONCLUSION: Fifty-two-week treatment with rhGH improved growth, BMI, mental development, and lessened the deterioration of motor function in infants and young children with PWS. Improved mental development was more pronounced when instituted in patients < 9 months old.

Long noncoding RNA negative regulator of antiviral response contributes to pancreatic ductal adenocarcinoma progression via targeting miR-299-3p.

BACKGROUND: Pancreatic ductal cancer (PDAC) has high malignancy and poor prognosis. Long noncoding RNAs (lncRNAs) are associated with high levels of malignancy, including PDAC. However, the biological and clinical significance of negative regulator of antiviral response (NRAV) in PDAC is unclear. AIM: To study the regulatory role of lncRNA NRAV in PDAC. METHODS: GEPIA analyzed lncRNA NRAV and miRNA (miR-299-3p) expression levels in PDAC tissues and measured them in PDAC cells by quantitative measurements in real time. The specific role of NRAV and miR-299-3p in cell proliferation and transfer potential was evaluated by cell formation analysis, Cell Counting Kit-8 and Transwell analysis. The relationship between NRAV and miR-299-3p was studied by predictive bioinformatics, RNA immunoassay, and fluorescence enzyme analysis. In vivo experiments included transplantation of simulated tumor cells under naked mice. RESULTS: The expression level of lncRNA NRAV was higher in both tumor tissues and cell lines of PDAC and was negatively associated with the clinical survival of PDAC patients. Functionally, overexpression of NRAV promoted cell proliferation and metastasis of PDAC cells, while knockdown of NRAV reversed these effects. Finally, NRAV was performed as a molecular sponge of miR-299-3p. Moreover, overexpression of miR-299-3p could reverse the promoting effects of NRAV on cell proliferation and metastasis of PDAC cells. CONCLUSION: NRAV facilitates progression of PDAC as a molecular sponge of miR-299-3p and may be a potential molecular marker for diagnosis and treatment of PDAC.

Correction to "Genome-wide CRISPR-Cas9 screening identifies that hypoxia-inducible factor-1a-induced CBX8 transcription promotes pancreatic cancer progression via IRS1/AKT axis".

[This corrects the article on p. 1709 in vol. 13, PMID: 34853645.].

Genome-wide CRISPR-Cas9 screening identifies that hypoxia-inducible factor-1a-induced CBX8 transcription promotes pancreatic cancer progression via IRS1/AKT axis.

BACKGROUND: Pancreatic cancer (PC) is one of the most lethal malignancies worldwide. It is known that the proliferation of PC cells is a critical process in the disease. Previous studies have failed to identify the key genes associated with PC cell proliferation, using bioinformatic analysis, genome-wide association studies, and candidate gene testing. AIM: To investigate the function of the chromobox 8 (CBX8)/receptor substrate 1 (IRS1)/AKT axis in PC. METHODS: A genome-wide CRISPR-Cas9 screening was performed to select genes that could facilitate PC cell proliferation. Quantitative reverse transcription-polymerase chain reaction was used to detect the expression of CBX8 in PC tissues and cells. The regulatory roles of CBX8 in cell proliferation, migration, and invasion were verified by in vivo and in vitro functional assays. RESULTS: CBX8 was upregulated in PC tissues and shown to drive PC cell proliferation. Higher expression of CBX8 was correlated with worse outcomes of PC patients from two independent cohorts comprising a total of 116 cases. CBX8 was also proved to serve as a promising therapeutic target for a PC xenograft model. We demonstrated that hypoxia-inducible factor (HIF)-1a induced CBX8 transcription by binding to the promoter of CBX8. CBX8 efficiently activated the PI3K/AKT signaling by upregulating insulin IRS1. CONCLUSION: CBX8 is a key gene regulated by HIF-1α, and activates the IRS1/AKT pathway, which suggests that targeting CBX8 may be a promising therapeutic strategy for PC.

Metabolomics and Transcriptomics Analysis on Metabolic Characteristics of Oral Lichen Planus.

OBJECTIVE: To explore metabolic biomarkers related to erosive and reticulated oral lichen planus (OLP) by non-targeted metabolomics methods and correlate metabolites with gene expression, and to investigate the pathological network pathways of OLP from the perspective of metabolism. METHODS: A total of 153 individuals were enrolled in this study, including 50 patients with erosive oral lichen planus (EOLP), 51 patients with reticulated oral lichen planus (ROLP), and 52 healthy controls (HC). The ultra-high-performance liquid chromatography quadrupole-Orbitrap high-resolution accurate mass spectrometry (UHPLC/Q-Orbitrap HRMS) was used to analyze the metabolites of 40 EOLP, 40 ROLP, and 40 HC samples, and the differential metabolic biomarkers were screened and identified. The regulatory genes were further screened through the shared metabolites between EOLP and ROLP, and cross-correlated with the OLP-related differential genes in the network database. A "gene-metabolite" network was constructed after finding the key differential genes. Finally, the diagnostic efficiency of the biomarkers was verified in the validation set and a diagnostic model was constructed. RESULT: Compared with HC group, a total of 19 and 25 differential metabolites were identified in the EOLP group and the ROLP group, respectively. A total of 14 different metabolites were identified between EOLP and ROLP. Two diagnostic models were constructed based on these differential metabolites. There are 14 differential metabolites shared by EOLP and ROLP. The transcriptomics data showed 756 differentially expressed genes, and the final crossover network showed that 19 differential genes were associated with 12 metabolites. Enrichment analysis showed that alanine, aspartate and glutamate metabolism were closely associated with the pathogenesis of OLP. CONCLUSION: The metabolic change of different types of OLP were clarified. The potential gene perturbation of OLP was provided. This study provided a strong support for further exploration of the pathogenic mechanism of OLP.

Long non-coding RNA TP73-AS1 promotes pancreatic cancer growth and metastasis through miRNA-128-3p/GOLM1 axis.

BACKGROUND: Previous studies have suggested that long non-coding RNAs (lncRNA) TP73-AS1 is significantly upregulated in several cancers. However, the biological role and clinical significance of TP73-AS1 in pancreatic cancer (PC) remain unclear. AIM: To investigate the role of TP73-AS1 in the growth and metastasis of PC. METHODS: The expression of lncRNA TP73-AS1, miR-128-3p, and GOLM1 in PC tissues and cells was detected by quantitative real-time polymerase chain reaction. The bioinformatics prediction software ENCORI was used to predict the putative binding sites of miR-128-3p. The regulatory roles of TP73-AS1 and miR-128-3p in cell proliferation, migration, and invasion abilities were verified by Cell Counting Kit-8, wound-healing, and transwell assays, as well as flow cytometry and Western blot analysis. The interactions among TP73-AS1, miR-128-3p, and GOLM1 were explored by bioinformatics prediction, luciferase assay, and Western blot. RESULTS: The expression of TP73-AS1 and miRNA-128-3p was dysregulated in PC tissues and cells. High TP73-AS1 expression was correlated with a poor prognosis. TP73-AS1 silencing inhibited PC cell proliferation, migration, and invasion in vitro as well as suppressed tumor growth in vivo. Mechanistically, TP73-AS1 was validated to promote PC progression through GOLM1 upregulation by competitively binding to miR-128-3p. CONCLUSION: Our results demonstrated that TP73-AS1 promotes PC progression by regulating the miR-128-3p/GOLM1 axis, which might provide a potential treatment strategy for patients with PC.