[This corrects the article DOI: 10.1016/j.apsb.2021.07.004.].

Objective To investigate the role of poly(rC)-binding protein 1(PCBP1)in cadmium(Cd)-induced ferroptosis in mouse neuroblastoma Neuro-2a(N2A)cells.Methods N2A cells were exposed to a concentration gradient of CdCl?(0,1,2,4 μmol/L)for 72 h.Cell viability was assessed by trypan blue staining.Western blotting was employed to detect the expression of ferroptosis-related proteins(GPX4,HMOX1,ACSL4)and PCBP1.Intracellular Fe2? level and lipid peroxidation were detected using FerroOrange and BODIPY581/591 C11 probes,respectively.Ferrostatin-1(Fer-1),a ferroptosis inhibitor,was applied to confirm the critical role of ferroptosis in Cd-induced cytotoxicity.Molecular docking was performed to elucidate the interaction between PCBP1 and ferritin,as well as the binding sites of Cd2?.PCBP1 overexpression plasmid was further constructed for functional validation.Results Cd exposure suppressed cell viability in N2A cells in a dose-dependent manner(P<0.01),significantly down-regulated GPX4 expression(P<0.05),up-regulated HMOX1 expression(P<0.01),and induced Fe2? overload and lipid peroxidation(P<0.01).Molecular docking revealed that Cd2? directly bound to the KH2 domain of PCBP1 and then co-localized on the outer surface of ferritin heavy chain.Overexpression of PCBP1 markedly reversed Cd-induced Fe2? accumulation,GPX4 down-regulation,lipid peroxidation,and cell death.Conclusion Cd exposure disrupts PCBP1-mediated iron homeostasis via transcriptional suppression and competitive displacement of metal ions,and then synergistically drives Fe2? overload-triggered ferroptosis cascades,ultimately leading to neurotoxicity.Targeting PCBP1-mediated iron homeostasis can effectively mitigate Cd-induced neurotoxicity,and may serve as a novel therapeutic strategy.

Objective The aim is to utilize CRISPR/Cas9 gene editing technology to construct Dmd gene mutant mice with a point mutation in exon 23 of the Dmd gene. Subsequently, the phenotypic changes of the mice in muscles and immune systems are analyzed and verified, providing an evaluation model for Duchenne muscular dystrophy and other related diseases.MethodsBased on the sequence characteristics of exon 23 of the Dmd gene, small guide RNA (sgRNA) was designed and synthesized. Cas9 mRNA, sgRNA fragments, and oligo donor DNA were microinjected into fertilized eggs of C57BL/6J mice. After transferring the fertilized eggs to surrogate mice, F0 generation mice were born. After mating with F0 generation mice, offspring mice were obtained, and Dmd gene positive mutant (Dmd^Mu/+) mice were obtained after genotype identification. Male hemizygous Dmd^Mu/+(Dmd^Mu/Y) mice were selected for phenotype validation. The body weight of live 3- and 9-month-old mice were recorded. Muscle tension was evaluated through the grid test. Hearts and semitendinosus muscles were collected, and the histopathological changes were observed using HE staining. Further, the expression of Dmd protein in muscle tissue of 9-month-old mice was analyzed by Western blotting.An acute inflammation model was established in Dmd^Mu/Y mice using lipopolysaccharide induction. Peripheral blood from the submandibular vein was collected, and the changes in the proportion of neutrophils and monocytes were detected by flow cytometry.Results The results of genome sequencing and Western blotting confirmed the successful construction of Dmd gene point mutant mice (Dmd^Mu/+ mice). Dmd protein expression was not detected in skeletal muscle and myocardium of Dmd^Mu/+ mice, and it was significantly reduced compared to wild-type C57BL/6J mice (P<0.05). Compared with wild-type mice of the same background, Dmd^Mu/Y mice at 3 and 9 months of age showed significant weight loss (P<0.01) and decreased muscle tension (P<0.05). 9-month-old Dmd^Mu/Y mice exhibited significant pathological changes in skeletal muscle and myocardium, including widening of intermuscular space. Under normal condition, compared with wild-type mice, the proportion of neutrophils and monocytes in the peripheral blood of 3-month-old Dmd^Mu/Y mice was significantly lower than that of wild-type mice (P<0.01). After lipopolysaccharide stimulation, the proportion of neutrophils in peripheral blood of 3-month-old Dmd^Mu/Y mice remained significantly lower compared to that of wild-type mice (P<0.01). The proportion of neutrophils in peripheral blood of 9-month-old Dmd^Mu/Y mice significantly decreased after lipopolysaccharide induction (P<0.01), with a trend of change observed in monocytes between groups.Conclusion The successful construction of the Dmd gene mutant mouse model has confirmed the vital function of Dmd gene in maintaining normal muscle tissue morphology and muscle tone. It preliminarily indicated that Dmd gene deletion could significantly reduce the proportion of neutrophils in peripheral blood, offering a new perspective for the study of immune system alterations in Duchenne muscular dystrophy patients.

【Objective】 To investigate the prevalence and influencing factors of feeding difficulties in preterm infants at weaning and self-feeding transition stage, so as to provide a scientific basis for the management of feeding preterm infants. 【Methods】 Preterm infants at corrected age of 6 - 24 months were recruited from the Department of Child Health of five maternal and child health hospital of Chengdu from April to May 2021, and were surveyed by using the Chinese Version of the Montreal Children Hospital Feeding Scale (MCF-FS) and the self-designed questionnaire on the influencing factors of feeding difficulties. Then the status quo of feeding difficulties and its influencing factors were analyzed. 【Results】 The prevalence rate of feeding difficulties in 231 preterm infants was 32%. Among them, the prevalence rate of mild, moderate and severe feeding difficulties was 15.2%, 7.8% and 9.1%, respectively. Binary Logistic stepwise regression analysis indicated that food allergy (OR=4.253, 95%CI: 1.430 - 12.649), anxious mood of caregivers (OR=6.064, 95%CI: 2.998 - 12.268), tease or chase during eating(OR=2.873, 95%CI: 1.382 - 5.970), recreational activities at eating (OR=2.328, 95%CI: 1.115 - 4.860), and forced feeding (OR=2.772, 95%CI: 1.239 - 6.198) were positively associated with feeding difficulty of preterm infants(P<0.05). 【Conclusion】 Feeding difficulties in the weaning and self-feeding transition period of preterm infants are prevalent, so the guidance should focus on premature infants with food allergy, anxious caregivers and improper feeding behaviors, and appropriate interventions should be taken to promote scientific feeding.

Background:Recurrence after stone removal is common in patients with choledocholithiasis.Recent studies have indicated that dysbiosis in gut microbiota plays an important role in the formation of cholesterol gallstones.Aims:To explore the effect of probiotics supplementation on serum lipopolysaccharide(LPS)and the indicators of bile acid metabolism in patients with a high risk of cholesterol gallstone formation.Methods:Sixty choledocholithiasis patients undergoing ERCP lithotomy were recruited at the First Affiliated Hospital of Shihezi University from June 2021 to June 2023.Bile and stool samples were collected for bacterial culture.Then the patients were randomly allocated into two groups:patients in control group received conventional supportive therapy after calculus removal,while those in probiotics intervention group were given oral bifid triple viable enteric capsule 420 mg,twice a day for 6 months based on conventional therapy.Changes in serum levels of LPS,the cell wall component of Gram-negative bacteria,fibroblast growth factor 19(FGF19),the key molecule in bile acid metabolism,and cholesterol 7α-hydroxylase(CYP7A1),the rate-limiting enzyme of bile acid synthesis,were determined and compared between the two groups.Results:Escherichia coli and Klebsiella pneumoniae were the main pathogens in bile and stool of patients with choledocholithiasis.Six months after ERCP lithotomy,the serum levels of LPS and FGF19 were decreased,and the serum level of CYP7A1 was increased in both groups(all P<0.05),especially in probiotics intervention group(all P<0.05).Conclusions:Oral probiotics supplementation can reduce the serum LPS level and modulate the canonical pathway of enterohepatic circulation of bile acids--farnesoid X receptor(FXR)-FGF19 pathway in high-risk patients of cholesterol gallstone formation.These alterations reduce the cholesterol supersaturation in bile and inhibit the probability of cholesterol gallstone formation.

Parkinson disease (PD) is a chronic progressive neurodegenerative disorder that typically leads to motor impairments (such as increased muscle tone, resting tremors, bradykinesia and postural instability) and various non-motor symptoms (including sleep disturbances, anxiety, depression, cognitive impairments and autonomic nervous system dysfunction). Currently, symptomatic treatment primarily relies on medication, but non-pharmacological approaches are also crucial, such as psychological interventions, rehabilitation therapies, neurostimulation techniques, biosensors and monitoring technologies. However, these are all symptomatic treatments, as PD cannot be completely cured at present and there are many limitations. Nevertheless, some promising new therapies such as optogenetics, drug delivery systems, stem cell therapy, gene therapy, immunotherapy, neuroprotection, and interventions to improve gut microbiota imbalance offer hope for alleviating PD symptoms and potentially making a cure for PD achievable in the future. This article provides an overview of the current status and recent advancements in both pharmacological and non-pharmacological treatments for Parkinson disease, as well as prospects for future promising therapeutic technologies.

Background:Acute lung injury(ALI)is the most common organ dysfunction in severe acute pancreatitis(SAP).Somatostatin analogue octreotide is a common used drug in acute pancreatitis.Aims:To explore the protective mechanism of octreotide on lung injury in SAP mice.Methods:In the first part,the experimental mice were randomly assigned into four groups.SAP model was induced by caerulin and lipopolysaccharide,and the mice were sacrificed 24 hours,48 hours and 72 hours after establishment.HE staining was used to observe the pathological score of pancreas and lung.Serum amylase and lung tissue myeloperoxidase(MPO)activity were detected.Real-time quantitative PCR was used to detect mRNA expressions of pyroptosis-related molecules apoptosis-associated speck-like protein containing a CARD(ASC),caspase-1,Gasdermin D(GSDMD),interleukin(IL)-1β,IL-18 and inflammatory factors IL-6,tumor necrosis factor(TNF)-α,high mobility group protein B1(HMGB1)in lung tissue.Western blotting was used to detect protein expressions of NOD-like receptor thermal protein domain associated protein 3(NLRP3),caspase-1,GSDMD and IL-1β in lung tissue.In the second part,mice were randomly divided into control group,SAP group,and octreotide group.HE staining was used to observe the pathological score of pancreas and lung.Serum amylase and lung tissue MPO activity were detected.Real-time quantitative PCR was used to detect mRNA expressions of pyroptosis-related molecules caspase-1,ASC,IL-1β,IL-18 and inflammatory factors IL-6,TNF-α,HMGB1.Immunofluorescence was used to detect protein expressions of NLRP3,caspase-1,GSDMD,ASC,IL-1β in lung tissue.Results:In the first part,compared with control group,pathological score of pancreas and lung tissue,serum amylase and MPO activity were significantly increased in SAP group(all P<0.05),mRNA expressions of pyroptosis-related molecules caspase-1,ASC,GSDMD,IL-1β,IL-18 and inflammatory factors IL-6,TNF-α,HMGB1 were significantly increased(all P<0.05),protein expressions of NLRP3,caspase-1,GSDMD and IL-1β in lung tissue were significantly increased(all P<0.05),especially in 24 hours after establishment group.In the second part,compared with SAP group,pathological score of pancreas and lung tissue,serum amylase were significantly decreased in octreotide group(all P<0.05),mRNA expressions of pyroptosis-related molecules caspase-1,ASC,IL-1β,IL-18 and inflammatory factors IL-6,TNF-α,HMGB1 were significantly decreased in lung tissue in octreotide group(all P<0.05),protein expressions of NLRP3,caspase-1,GSDMD,ASC and IL-1β in lung tissue were significantly decreased(all P<0.05).Conclusions:Cell pyroptosis is involved in the occurrence and development of lung injury in SAP mice,and octreotide may attenuate lung injury in SAP mice by inhibiting pyroptosis.

Objective:To investigate the diagnostic value of myocardial blood flow quantitative imaging with cadmium zinc telluride (CZT) SPECT in patients with high-risk coronary artery disease (CAD).Methods:A total of 148 patients (82 males, 66 females, age: (63.8±8.2) years) who successfully completed CZT SPECT dynamic acquisition and routine SPECT myocardial perfusion imaging (MPI) in TEDA International Cardiovascular Hospital from November 2018 to October 2020 were analyzed retrospectively. According to the results of coronary angiography (CAG), patients were divided into two groups: high-risk CAD group and low-to-medium-risk CAD group. At the case level, quantitative parameters (stress myocardial blood flow (sMBF), rest myocardial blood flow (rMBF) and myocardial flow reserve (MFR)), semi-quantitative parameters (summed stress score (SSS), summed rest score (SRS), summed difference score (SDS) and transient ischemic dilation (TID)) and left ventricular function parameters of two groups were compared. Diagnostic accuracy was evaluated by ROC curve analysis. At the vascular level, the correlation between the degree of coronary artery stenosis and some parameters was analyzed. Mann-Whitney U test, logistic regression, Spearman rank correlation analysis and DeLong test were used for statistical analysis. Results:Case level analysis showed that MFR and sMBF in high-risk CAD group were significantly lower than those in low-to-medium-risk CAD group (1.36(0.87, 1.64) vs 2.74(2.30, 3.33), 1.06(0.69, 1.48) vs 2.50(1.73, 2.95) ml·g -1·min -1; U values: 628.0 and 853.5, both P<0.001). MFR and SDS were independent predictors of high-risk CAD patients (odds ratio ( OR)=0.251(95% CI: 0.136-0.464), P<0.001; OR=1.188(95% CI: 1.026-1.375), P=0.021), and MFR was more capable of predicting high-risk CAD. MFR and sMBF had the highest accuracy in diagnosing high-risk CAD (AUCs: 0.885 and 0.844). Differences of AUCs between MFR and other parameters were statistically significant ( z values: 1.99-6.77, all P<0.05), and the best diagnostic cut-off value was ≤1.83 (sensitivity: 85.90%; specificity: 85.71%). Vascular level analysis showed that MFR and sMBF( R2 values: 0.39 and 0.35, both P<0.001) were negatively correlated with the degree of coronary stenosis, while SSS, SRS and SDS ( R2 values: 0.22, 0.12 and 0.14, all P<0.001) were positively correlated with the degree of coronary stenosis. Conclusion:Compared with conventional SPECT MPI, CZT SPECT myocardial blood flow quantitative imaging has better diagnostic efficacy and clinical value in patients with high-risk CAD.

Pancreatic adenocarcinoma (PAAD) is one of the most lethal malignancies. Although gemcitabine (GEM) is a standard treatment for PAAD, resistance limits its application and therapy. Secoemestrin C (Sec C) is a natural compound from the endophytic fungus Emericella, and its anticancer activity has not been investigated since it was isolated. Our research is the first to indicate that Sec C is a broad-spectrum anticancer agent and could exhibit potently similar anticancer activity both in GEM-resistant and GEM-sensitive PAAD cells. Interestingly, Sec C exerted a rapid growth-inhibiting effect (80% death at 6 h), which might be beneficial for patients who need rapid tumor shrinkage before surgery. Liquid chromatography/mass spectrometry and N-acetyl-l-cysteine (NAC) reverse assays show that Sec C sulfates cysteines to disrupt disulfide-bonds formation in endoplasmic reticulum (ER) proteins to cause protein misfolding, leading to ER stress and disorder of lipid biosynthesis. Microarray data and subsequent assays show that ER stress-mediated ER-associated degradation (ERAD) ubiquitinates and downregulates YAP to enhance ER stress via destruction complex (YAP-Axin-GSK-βTrCP), which also elucidates a unique degrading style for YAP. Potent anticancer activity in GEM-resistant cells and low toxicity make Sec C a promising anti-PAAD candidate.

Objective:To construct an automatic recognition system for PD patients with freezing of gait (FOG) based on mobile phone videos by recording the gait videos of PD patients with FOG.Methods:Forty-nine PD patients with FOG, admitted to our hospital from December 2020 to May 2021, were chosen in our study. Their clinical data were collected. The processes of these patients accepted "3-meter-round trip" and "3-meter-round trip through narrow (0.6 m)" were recorded and 87 valid gait videos were extracted. Position signals of key points in the video were extracted, and featured data were extracted after signal preprocessing. From the featured data, action recognition model, straight FOG recognition model and turn FOG recognition model were established respectively, and finally end-to-end FOG recognition model was formed. Leave-one-subject-out (LOSO) method was used to evaluate the performance of the above models.Results:A total of 22 066 non-FOG window samples and 3815 FOG window samples were obtained from 87 valid videos, which constituted the training sample pool of this study. LOSO method showed that the motion recognition model enjoyed 83.27% sensitivity, 91.38% specificity, and 89.28% accuracy; the straight FOG recognition model enjoyed 57.69% sensitivity and 88.12% specificity; the turn FOG recognition model enjoyed 61.54% sensitivity and specificity 98.72%; and the end-to-end FOG recognition model enjoyed 85.71% sensitivity and 75.73% specificity.Conclusion:The automatic recognition system for PD patients with FOG based on mobile phone videos has relatively high sensitivity and specificity, which can realize remote assessment and is convenient for screening and follow-up of PD patients with FOG.