ObjectiveTo investigate whether Shixiaosan can improve neurological function and inhibit ferroptosis in rats with cerebral ischemia-reperfusion injury （CIRI） by regulating the nuclear factor E₂-related factor 2 （Nrf2）/solute carrier family 7 member 11 （SLC7A11）/glutathione peroxidase 4 （GPX4） pathway. MethodsA rat model of CIRI was established using the intraluminal filament method. Briefly， cervical blood vessels were separated， branches of the external carotid artery were ligated， and the common carotid artery and internal carotid artery were clamped. A nylon filament was inserted through the opening of the external carotid artery to the origin of the middle cerebral artery to block blood flow and induce cerebral ischemia. After 60-120 min of ischemia， the filament was withdrawn to restore blood flow， and the external carotid artery incision was ligated. The rats were divided into a CIRI group， a Shixiaosan low-dose （-L） group （intragastric administration of 1.26 g·kg^-1 Shixiaosan）， a Shixiaosan high-dose （-H） group （intragastric administration of 2.52 g·kg^-1 Shixiaosan）， a donepezil hydrochloride tablet （DON） group （intragastric administration of 0.45 mg·kg^-1 DON）， and a Shixiaosan -H + Nrf2 inhibitor （ML385） group （intragastric administration of 2.52 g·kg^-1 Shixiaosan combined with intraperitoneal injection of 30 mg·kg^-1 ML385）. An additional 12 rats underwent cervical artery separation followed by incision suturing and served as the control group. Equal volumes of double-distilled water were administered to the CIRI and control groups. Neurological function impairment was assessed using the modified Garcia JH score. Magnetic resonance imaging was used to determine the cerebral infarct volume ratio. Hematoxylin-eosin （HE） staining and Prussian blue staining were performed to observe neuronal injury and iron accumulation in the ischemic penumbra， respectively. Transmission electron microscopy was used to examine the ultrastructure of neuronal mitochondria in the ischemic penumbra. Commercial kits were used to measure ferrous iron （Fe²⁺）， malondialdehyde （MDA）， reduced glutathione （GSH） content， and reactive oxygen species （ROS） activity in the ischemic penumbra. The BODIPY （581/591） C11 fluorescent probe was used to detect intracellular lipid peroxidation levels. Western blot was performed to detect protein expression levels of Nrf2， SLC7A11， GPX4， transferrin receptor 1 （TFRC）， ferritin heavy chain （FHC）， and ferritin light chain （FLC） in the ischemic penumbra. ResultsCompared with the control group， the CIRI group exhibited neuronal injury in the ischemic penumbra， characterized by reduced neuron numbers， nucleolar shrinkage， and interstitial edema. Marked iron accumulation was observed in the tissue. Neuronal mitochondria showed atrophy and rupture， with reduced mitochondrial cristae and increased membrane density. The cerebral infarct volume ratio， Fe²⁺ content， MDA content， ROS activity， and lipid peroxidation levels were increased， whereas the modified Garcia JH score， GSH content， and protein expression levels of Nrf2， SLC7A11， GPX4， FHC， and FLC were decreased， and TFRC protein expression was increased （P<0.05）. Compared with the CIRI group， the Shixiaosan -L group， Shixiaosan -H group， and DON group showed attenuated neuronal injury in the ischemic penumbra， reduced iron accumulation， alleviated mitochondrial damage， decreased cerebral infarct volume ratio， Fe²⁺ and MDA contents， ROS activity， and lipid peroxidation levels， as well as increased modified Garcia JH scores， GSH content， and protein expression levels of Nrf2， SLC7A11， GPX4， FHC， and FLC， while TFRC protein expression was decreased （P<0.05）. The magnitude of changes in all indicators was greater in the Shixiaosan -H group than in the Shixiaosan -L group （P<0.05）. Compared with the Shixiaosan -H group， all measured indicators in the Shixiaosan -H + ML385 group showed opposite trends （P<0.05）. ConclusionShixiaosan may inhibit ferroptosis and restore neurological function in rats with CIRI by activating the Nrf2/SLC7A11/GPX4 pathway.

Objective To observe the efficacy and safety of neoadjuvant sintilimab combined with chemotherapy in the treatment of patients with locally advanced resectable esophageal squamous cell carcinoma (ESCC). Methods Clinical data were collected from patients with locally advanced resectable ESCC who received neoadjuvant immunotherapy combined with chemotherapy followed by surgical treatment at the Department of Thoracic Surgery of Jining No.1 People's Hospital from April 2020 to April 2022. The endpoints included major pathological response (MPR), pathological complete response (pCR), R0 resection rate, safety, and postoperative survival. Results A total of 43 patients with ESCC who received at least one cycle of neoadjuvant immunotherapy before surgery were included. Among them, there were 31 males and 12 females with a median age of 65 years (interquartile range: 58-69). All patients successfully completed the surgery without any surgical delays. The pCR rate was 14.0% (6/43), the MPR rate was 58.1% (25/43), and the R0 resection rate was 97.7% (42/43). Patients exhibited reliable safety during neoadjuvant therapy and postoperatively. The 2-year overall survival and disease-free survival rates were 90.7% and 81.4%, respectively. Kaplan-Meier survival analysis and log-rank test revealed lower recurrence rates and better survival in the MPR patients compared to the non-MPR patients. Conclusion The combination of neoadjuvant sintilimab and chemotherapy in the treatment of patients with locally advanced resectable ESCC has demonstrated significant clinical efficacy, while also being safe and reliable.

Objective:To investigate the prenatal echocardiographic features of fetuses diagnosed with Ebstein anomaly (EA), identify prognostic factors affect the fetal and neonatal mortality, and evaluate the clinical value of the Simpson Andrews Sharland prognostic score (SAS prognostic score).Methods:A retrospective cohort study was conducted on 37 fetuses diagnosed with EA via prenatal and postnatal echocardiography at Guangdong Provincial People′s Hospital from June 2012 to June 2024. The echocardiographic features of EA patients were summarized. According to the patients′ survival statuses during the fetal and neonatal periods, they were divided into survival group and death group for a comparative analysis of key echocardiographic parameters, as well as SAS prognostic score. Also, receiver operator characteristic (ROC) curve was employed to assess the predictive abilities of various indicators. Finally, based on the medium-and long-term prognostic outcomes of EA cases, the predictive value of the SAS system was evaluated. The t test, Mann-Whitney U test, and Fisher exact test were used for group comparison. Results:Regarding the 37 EA cases, the gestational age at the initial diagnosis was (29±4) weeks. All of EA fetuses exhibited echocardiographic characterized by tricuspid regurgitation (TR) originating below the native tricuspid annulus with the severity varied, accompanied by manifestations such as right atrial enlargement. Of all cases, 5 cases (14%) died prenatally, and 32 cases (86%) were born alive. Postnatally, 4 cases died preoperatively, 1 case died postoperatively, and 27 cases survived. Compared with the survival group, the death group had a significantly higher average SAS prognostic score (6.9±1.1 vs. 2.0±1.5, t=9.17, P<0.001), right atrium (RA) to left atrium (LA) transverse diameter ratio (2.0±0.5 vs. 1.3±0.2, t=4.87, P=0.001) and TR area to RA area ratio (0.8±0.2 vs. 0.4±0.2, t=5.27, P<0.001). According to the ROC analysis, the optimal predictive value indicators are RA to LA transverse diameter ratio (AUC=0.93, 95% CI 0.81-1.00) and the TR area-to-RA area ratio (AUC=0.93, 95% CI 0.85-1.00); the optimal cut-point values were 1.5 and 0.5, respectively. Of 32 born alive cases, 21 cases (66%) didn′t undergo surgery, 2 cases (6%) underwent bidirectional Glenn surgery, and one case (3%) underwent tricuspid valvuloplasty. All 17 cases with SAS score≤2 survived, while all 9 cases with SAS score≥6 died. Among the 11 cases with a score from 3 to 5, 8 cases achieved a biventricular outcome. Conclusions:The typical echocardiographic feature of EA fetuses is that the originating point of TR is below the native tricuspid annulus and the severity can vary. The SAS score is essential for tiered prognosis. When the SAS is 3-5, dynamic monitoring for TR and RA enlargement should be employed to help guide prenatal intervention and reduce fetal and neonatal mortality.

Objective To systematically evaluate the impact of cough enhancement techniques on weaning outcomes in adult patients under mechanical ventilation(MV).Methods Databases from the inception to 15th November,2024 were searched for randomised controlled trials(RCTs)on cough enhancement technique in MV patients.The searched databases were CNKI,Wanfang Data base,SinoMed,Vip,PubMed,Web of Science,Cochrane Library,Embase,and CINAHL.Literature and evidence quality were evaluated using Cochrane's evaluation tool for intervention research and the GRADE system,and data were extracted and analysed via Meta-analysis with Review Manager 5.3.Results A total of 27 studies were included,involving 2,322 patients(1,169 in the trial group and 1,153 in the control group).Compared with the control group,the trial group had shorter time of mechanical ventilation[MD=-1.40,95%CI(-1.83,-0.97),P<0.001],lower weaning failure rate[OR=0.48,95%CI(0.27,0.85),P=0.01],higher oxygenation index[MD=35.48,95%CI(21.53,49.43),P<0.001],lower pulmonary atelectasis incidence[OR=0.30,95%CI(0.18,0.49),P<0.001],greater sputum volume[MD=1.88,95%CI(0.76,3.01),P=0.001],shorter ICU stay[MD=-1.90,95%CI(-2.95,-0.85),P<0.001]and lower serum procalcitonin(PCT)[MD=-0.89,95%CI(-1.64,-0.14),P=0.02],all with statistically significant differences.However,there was no significant difference in the ventilator-associated pneumonia(VAP)between the two groups[OR=0.54,95%CI(0.21,1.35),P=0.19].Conclusion Cough enhancement techniques promote sputum discharge,improve infection and oxygenation,shorten mechanical ventilation and ICU stay,reduce weaning failure and atelectasis rates in MV patients.Further studies are required to reduce the incidence of VAP.

Objective To describe the significance of the pretreatment inflammatory indicators in predicting the prognosis of patients with esophageal squamous cell carcinoma (ESCC) after undergoing radical radiotherapy. Methods The data of 246 ESCC patients who underwent radical radiotherapy were retrospectively collected. Receiver operating characteristic (ROC) curves were drawn to determine the optimal cutoff values for platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR), and systemic immune-inflammation index (SII). The Kaplan-Meier method was used for survival analysis. We conducted univariate and multivariate analyses by using the Cox proportional risk regression model. Software R (version 4.2.0) was used to create the nomogram of prognostic factors. Results The results of the ROC curve analysis showed that the optimal cutoff values of PLR, NLR, and SII were 146.06, 2.67, and 493.97, respectively. The overall response rates were 77.6% and 64.5% in the low and high NLR groups, respectively (P<0.05). The results of the Kaplan-Meier survival analysis revealed that the prognosis of patients in the low PLR, NLR, and SII group was better than that of patients in the high PLR, NLR, and SII group (all P<0.05). The results of the multivariate Cox regression analysis showed that gender, treatment modalities, T stage, and NLR were independent factors affecting the overall survival (OS). In addition, T stage and NLR were independent factors affecting the progression-free survival (PFS) (all P<0.05). The nomogram models of OS and PFS prediction were established based on multivariate analysis. The C-index values were 0.703 and 0.668. The calibration curves showed excellent consistency between the predicted and observed OS and PFS. Conclusion The pretreatment values of PLR, NLR, and SII are correlated with the prognosis of patients with ESCC who underwent radical radiotherapy. Moreover, NLR is an independent factor affecting the OS and PFS of ESCC patients. The NLR-based nomogram model has a good predictive ability.

Objective : To investigate the diagnostic value of linear array endoscopic ultrasonography ( EUS) for common bile duct microlithiasis． Methods : Data of patients who attended in the hospital and diagnosed as common bile duct microlithiasis and biliary sludge by EUS were selected．A total of 85 patients with magnetic resonance cholangiopancreatography ( MRCP) examination and ERCP treatment during hospitalization were enrolled．The results of endoscopic retrograde cholangiopancreatography / endoscopic sphincterotomy ( ERCP / EST) were the gold standard for diagnosis．The results of EUS，MRCP，and diagnostic ERCP were compared with the gold standard， and the sensitivity，specificity，positive predictive value，negative predictive value，and diagnostic accuracy of the three methods were calculated，respectively．The chi-square test was used for comparison of the above indices． Results : Of all 85 patients，63 had positive EUS results，among whom 5 had false positive results; 22 had negative EUS results，among whom 1 had false negative results．Of all 85 patients，49 had positive MRCP results，among whom 4 had false positive results; 36 had negative MRCP results，among whom 14 had false negative results．Of all 85 patients，59 had positive diagnostic ERCP results，among whom 10 had false positive results; 26 had negative diagnostic ERCP results，among whom 10 had false negative results．The sensitivity，specificity，positive predictive value( PPV) ，negative predictive value ( NPV) ，and accuracy of EUS in diagnosing common bile duct microlithia- sis were 98. 3% ，80. 8% ，92. 1% ，95. 4% and 92. 9% ，respectively． For MRCP，these values were 76. 3% ， 84. 6% ，91. 8% ，61. 1% and 78. 8% ，respectively．For diagnostic ERCP，these values were 83. 1% ，61. 5% ， 83. 1% ，61. 5% and 76. 5% ，respectively．The EUS group had a significantly higher accuracy than the MRCP group ( χ2 = 6. 986，P ＜0. 05) and diagnostic ERCP group ( χ2 = 8. 900，P ＜0. 05) ．The areas under the ROC curves ( AUC) and 95% CI of EUS group，MRCP group and diagnostic ERCP were 0. 895 ( 95% CI: 0. 802 - 0. 988，P＜0. 001) ，0. 804 ( 95% CI: 0. 702 －0. 907，P ＜0. 001) and 0. 723 ( 95% CI: 0. 598 －0. 848，P = 0. 001) ，respectively． Conclusion EUS has a high diagnostic value in the diagnosis of common bile duct microli- thiasis and thus can be used as the preferred examination before therapeutic ERCP．

Objective To explore the mechanism of action of Huaier (Vanderbylia robiniophila) against pancreatic cancer. Methods The chemical components and targets of Huaier (Vanderbylia robiniophila) were searched through the Herb database. Pancreatic cancer-related targets were screened from GeneCards, NCBI, and DisGeNET online databases, and a Venn diagram was drawn to obtain the intersection targets of drugs and diseases. The protein-protein interaction (PPI) network was constructed using the String platform, and a series of network diagrams were drawn using Cytoscape 3.8.0 software to screen core targets and perform GO analysis and KEGG pathway enrichment analysis on the target genes. Finally, the key active components were molecularly docked with potential target genes using AutoDock software. The KEGG enrichment top 20 pathways and the whole-genome association analysis data of pancreatic cancer were used to further validate the results using the Open GWAS database through Mendelian randomization analysis. Results A total of 4 effective components of Huaier (Vanderbylia robiniophila) were identified, 112 drug-disease intersection targets, the main active components were kaempferol, rutin, genistein, and glucuronic acid, and the core targets were mitogen-activated protein kinase 8 (MAPK8), uridine diphosphate(UDP)-glucuronic acid transferase 1 family peptide A1 (UGT1A1), and superoxide dismutase 2 (SOD2). The mechanism of action may be related to pancreatic cancer, tumor necrosis factor(TNF) signaling pathway, and interleukin(IL)-17 signaling pathway. The molecular docking showed that the main active components had good docking activity with the key targets. After screening, 73 genes were retained, and 24,195,229 single nucleotide polymorphism(SNP) were used for two-sample Mendelian randomization analysis. The analysis results showed that MAPK8 may be an important therapeutic target for pancreatic cancer. Conclusions Huaier (Vanderbylia robiniophila) may exert an anti-pancreatic cancer effect by acting on MAPK8, providing initial theoretical evidence for further verifying the mechanism of action of Huaier in treating pancreatic cancer.

Lung cancer is the cancer with the highest incidence of morbidity and mortality in the world, and the number of lung cancer cases in China is also increasing year by year, which seriously threatens the life and health of human beings. Circulating tumor cells (CTCs) refer to the tumor cell that falls off from primary tumor tissue or metastatic focus into the peripheral blood, which is the key to tumor metastasis. Currently, there are various methods for CTCs testing, each with its own advantages and disadvantages. In recent years, there have been numerous studies on the application of CTCs in lung cancer around the world. Further exploration of the progress of clinical application of CTCs in lung cancer can provide a new basis for the role of CTCs in early diagnosis, efficacy assessment and prognostic monitoring of lung cancer.

[This corrects the article DOI: 10.1016/j.apsb.2019.01.013.].

Reach-to-grasp movements require integrating information on both object location and grip type, but how these elements are planned and to what extent they interact remains unclear. We designed a new experimental paradigm in which monkeys sequentially received reach and grasp cues with delays, requiring them to retain and integrate both cues to grasp the goal object with appropriate hand gestures. Neural activity in the dorsal premotor cortex (PMd) revealed that reach and grasp were similarly represented yet not independent. Upon receiving the second cue, the PMd continued encoding the first, but over half of the neurons displayed incongruent modulations: enhanced, attenuated, or even reversed. Population-level analysis showed significant changes in encoding structure, forming distinct neural patterns. Leveraging canonical correlation analysis, we identified a shared subspace preserving the initial cue's encoding, contributed by both congruent and incongruent neurons. Together, these findings reveal a novel perspective on the interactive planning of reach and grasp within the PMd, providing insights into potential applications for brain-machine interfaces.
Animals ; Motor Cortex/physiology* ; Hand Strength/physiology* ; Macaca mulatta ; Psychomotor Performance/physiology* ; Neurons/physiology* ; Male ; Cues ; Movement/physiology* ; Gestures