Objective:To compare the efficacy of neuroendoscopy-assisted small bone window craniotomy and large bone flap craniotomy for acute subdural hematoma (ASDH) evacuation in elderly patients.Methods:A retrospective cohort study was conducted to analyze the clinical data of 57 elderly patients with ASDH admitted to Chongqing University Fuling Hospital from November 2020 to November 2023, including 27 males and 30 females, aged 65-89 years [(75.0±7.0)years]. The preoperative Glasgow coma scale (GCS) ranged 8-15 points [11.0(11.0, 12.0)points]. Among them, 27 patients were treated with neuroendoscopy-assisted small bone window craniotomy to evacuate ASDH (small bone window group) and 30 received large bone flap craniotomy to evacuate ASDH (large bone flap group). The following parameters were compared between the two groups: surgical duration, intraoperative blood loss, and length of hospital stay; residual subdural hematoma volume before surgery and at 1 day after surgery; GCS before surgery, at 1 and 3 days after surgery; good rate of Glasgow outcome scale (GOS) at 7 days and 6 months after surgery; and postoperative complication rate.Results:All the patients were followed up for 6 months. The surgical duration, intraoperative blood loss, and length of hospital stay were 89.0(85.0, 96.0)minutes, 65.0(55.0, 85.0)ml, and 15.0(14.0, 16.0)days, respectively in the small bone window group, which were shorter or less than 135.0(127.5, 150.0)minutes, 332.0(308.0, 367.5)ml, and 18.5(16.0, 20.0)days in the large bone flap group ( P<0.01). There was no statistically significant difference in the residual subdural hematoma volume between the two groups before surgery and at 1 day after surgery ( P>0.05). No statistically significant difference was found in GCS scores between the two groups before surgery ( P>0.05), while the GCS scores in the small bone window group at 1 and 3 days after surgery [12.0(12.0, 13.0)points and 15.0(14.0, 15.0)points] were higher than 11.5(11.0, 12.0)points and 13.0(12.8, 14.0)points in the large bone flap group ( P<0.01). The good rate of GOS in the small bone window group at 7 days after surgery was 100% (27/27), higher than 77% (23/30) in the large bone flap group ( P<0.05), but no statistically significant difference was found in the good rate of GOS between the two groups at 6 months after surgery ( P>0.05). Two patients in the small bone window group had pulmonary infection after surgery, with a complication rate of 7% (2/27), while in the large bone flap group, four patients had pulmonary infection, two epidural hematoma, one intracranial infection, one delayed wound healing, one subcutaneous fluid accumulation, and one epilepsy after surgery, with a complication rate of 33% (10/30) ( P<0.05). Conclusion:Compared with the conventional large bone flap craniotomy, neuroendoscopy-assisted small bone window craniotomy can shorten the surgical duration and length of hospital stay, reduce the intraoperative bleeding volume, promote early functional recovery, improve prognosis, and reduce the complication rate in elderly patients with ASDH.

Methodological quality assessment is a pivotal link between primary studies and reliable evidence-based practice,and an essential pathway for operationalizing the core principles of the Guide on Methodological Standards in Pharmacoepidemiology(2nd edition).A prevalent challenge in practice,however,is the conflation of appraising methodological robustness(risk of bias assessment)with verifying reporting transparency(adherence to reporting guidelines).This paper systematically addresses this fundamental challenge,beginning with a clear distinction between the essence and boundaries of these two concepts.On this basis,the article provides a comprehensive review of mainstream quality assessment tools,covering the methodological features and evolutionary trajectory of numerous instruments for interventional(e.g.,RoB 2,ROBINS-I),observational(e.g.,NOS,the JBI/SIGN/NIH series),secondary(e.g.,AMSTAR 2),and other specific types of studies such as health economic evaluations.Furthermore,a complete case study is used to illustrate the practical application of the ROBINS-I tool.The paper's central thesis advocates for an"appraisal-informed design"philosophy,urging a conceptual shift from the retrospective critique of existing literature to the prospective quality control of new research by internalizing appraisal standards as design principles,while also exploring the emerging paradigm of artificial intelligence in assisting assessment.This paper provides a comprehensive methodological reference for researchers and practitioners to prudently select appropriate assessment tools and to conduct rigorous critical appraisals of pharmacoepidemiological evidence.

Aim To explore the therapeutic effect and mechanism of Qingjie Huagong decoction in modulating PI3K/AKT/NF-κB signaling pathway in inflammatory response of acute pancreatitis(AP)mice.Methods Twenty-four mice were randomly divided into Blank group,Model group,Ustekin group,and Qingjie Hua-gong decoction group,with six mice in each group.The AP model was prepared by using rain frogin.Serum α-AMS,PNLP,IL-1β,IL-6,IL-8,IL-18,and TNF-α lev-els were detected by ELISA;the pancreatic pathology was detected by HE staining;the expressions of PI3K,AKT,and NF-κB-related proteins and mRNAs were de-tected by immunohistochemistry,Western blot,and RT-qPCR.Results Compared with the blank group,the model group showed obvious pathological damage to the pancreas,with significantly higher serum α-AMS,PN-LP,IL-1β,IL-6,IL-8,IL-18,and TNF-α levels(P＜0.01),and significantly higher levels of PI3K,AKT,and NF-κB-related proteins and mRNA expression(P＜0.01).Compared with the model group,both the Qingjie Huagong decoction group and the ustekin group improved the histopathological changes in the pancreas of AP mice,decreased the serum α-AMS,PNLP,IL-1β,IL-6,IL-8,IL-18,and TNF-α levels,and down-reg-ulated the expression levels of pancreatic PI3K,AKT,NF-κB-related proteins and mRNA(P＜0.05 or P＜0.01).Conclusion Qingjie Huagong decoction may inhibit the inflammatory response and protect pancreat-ic tissues by regulating the expression of PI3K/AKT/NF-κB signaling pathway.

Objective To investigate the incidence and types of patient-ventilator asynchrony(PVA)in mechanically ventilated patients within the intensive care unit(ICU),and to identify associated high-risk factors,thereby providing a basis for reducing PVA,enhancing mechanical ventilation efficiency,and refining ventilation strategies.Methods A prospective observational study was conducted among patients admitted to the general ICU of the Affiliated Hospital of Guizhou Medical University from October to December 2024 who were receiving mechanical ventilation.Inclusion criteria were as follows:age ≥18 years and mechanical ventilation duration ≥12 hours.Exclusion criteria included complete controlled mechanical ventilation,palliative care or do-not-resuscitate status,and lack of informed consent.Senior respiratory therapists performed daily bedside observations of ventilator waveforms for 10～15 minutes between 08:00 and 12:00.PVA was diagnosed based on pressure-time and flow-time waveforms,with the types of PVA being recorded.Demographic and clinical data,including age,sex,body mass index(BMI),primary diagnosis,comorbidities,APACHEⅡ score at ICU admission,blood gas analysis,ventila-tion mode and parameters,analgesia and sedation status,duration of mechanical ventilation,and length of ICU stay,were collected.The incidence and types of PVA during the observation period were analyzed.Univariate and multivariate logistic regression analyses were performed to identify high-risk factors for PVA.Clinical outcomes were compared between patients with and without PVA.Results A total of 105 patients and 453 episodes of assisted mechanical ventilation waveforms were analyzed.Among these,60.95％(64/105)experienced at least one episode of PVA.Of the 453 ventilation waveforms assessed,35.76％(162/453)demonstrated PVA.The types of PVA,ranked by incidence,were as follows:cycling mismatch(12.58％,57/453),double triggering(11.92％,54/453),ineffective triggering(9.49％,43/453),flow starvation(5.30％,24/453),and exhalation flow limitation(1.77％,8/453).The incidence of PVA varied significantly across different ventilation modes:45.7％in volume-assist/control ventilation(V-A/C),38.1％in pressure-assist/control ventilation(P-A/C),42.9％in synchronized intermittent mandatory ventilation(SIMV),and 16.7％in pressure support ventilation(PSV)(P<0.001).Multi-variate logistic regression analysis revealed that the mechanical ventilation mode[reference:PSV;V-A/C:OR=4.687,95％CI:2.140～10.263,P<0.001;P-A/C:OR=2.922,95％CI:1.489～5.734,P=0.002;SIMV:OR=4.682,95％CI:1.758～12.466,P=0.002]and actual respiratory rate(OR=1.07,95％CI:1.016～1.127,P=0.011)were significant high-risk factors for PVA.Patients with PVA had a significantly longer duration of mechanical ventilation[8.21(5.35,13.91)days vs.3.00(1.96,5.71)days,P<0.001]compared to those without PVA.Conclusions PVA is commonly observed in ICU patients receiving assisted invasive mechanical ventilation,with cycling mismatch,double triggering,and ineffective triggering being the most prevalent types.The incidence of PVA tends to be lower when using the PSV mode.Clinically,real-time monitoring of patient-ventilator synchrony via ventilator waveforms,along with the optimization of ventilator modes and parameters,should be employed to minimize the occurrence of PVA and enhance the efficiency of mechanical ventilation.

AKT,also known as Protein Kinase B(PKB),plays a critical role in cell proliferation and metabolism.There are three isoforms of AKT:AKT1,AKT2,and AKT3.The effects of these isoforms on the pluripotency and differentiation of mouse embryonic stem cells(mESCs)remain unclear.This study aims to explore the impact of three AKT isoform-specific knockouts on the self-renewal and differen-tiation of mouse embryonic stem cells.Using CRISPR/Cas9 gene-editing technology,AKT isoform-spe-cific knockout cell lines were established.The phenotypic and molecular changes were analyzed through Western blotting,flow cytometry,qRT-PCR,CCK-8 assays,Alkaline Phosphatase(AP)staining,and RNA-seq.The construction of AKT isoform-specific knockout cell lines was successful.The loss of AKT1 and AKT2 inhibited the proliferation of mESCs.The knockout of any single AKT isoform did not affect the expression of pluripotency genes at both mRNA or protein levels.However,during embryoid body forma-tion,the deletion of any of the three AKT isoforms affected the mRNA expression levels of genes in all three germ layers.Transcriptome analysis showed that compared to wild-type mESCs,995,547,and 429 differentially expressed genes(|log2FC|≧1,P＜0.05)were identified inAKT1,AKT2,and AKT3 isoform-specific knockout cells,respectively.There was some overlap in the differentially expressed genes regulated by these three isoforms.In conclusion,the independent knockout of AKT isoforms does not af-fect the maintenance of pluripotency in mouse embryonic stem cells,but they are crucial for differentia-tion.The three AKT isoforms can collectively regulate gene expression while retaining their own regulato-ry specificity.This study provides a foundation for understanding the unique and overlapping roles of AKT isoforms in stem cell biology,highlighting their importance in maintaining stem cell function and differen-tiation.

Objective Metabolomics combined with machine learning algorithms was used to systematically study the preoperative serum metabolites of patients with early postoperative cognitive dysfunction(POCD)after heart valve replacement,so as to screen biomarkers that may predict early POCD after heart valve replacement and explore the corresponding metabolic regulatory mechanisms.Methods A total of 60 patients underwent heart valve replacement under extracorporeal circulation were selected and divided into early-POCD group(group P)and non-POCD group(group N)according to whether POCD occurred or not.Metabolomic analysis was performed on preoperative serum samples of patients in group P and group N to screen the differential metabolites and metabolic pathways.The biomarkers related to early POCD were identified by random forest algorithm.Results A total of 532 differential metabolites were detected by metabonomics analysis,and 5 biomarkers were screened by random forest algorithm,namely quinoline,3'-sialyllactose,sphingomyelin(d18∶1/20∶0),lysophosphatidylcholine[P-18∶1(9Z)]and 25-hydroxycholesterol.Among them,the main metabolic pathways were phenylalanine metabolism,primary bile acid biosynthesis,ascorbic acid and aldonate metabolism,pentose and glucuronate interconversion,tryptophan metabolism,drug metabolism-cytochrome P450,porphyrin and chlorophyll metabolism.Conclusion Many metabolic pathways in patients with early POCD after heart valve replacement under extracorporeal circulation have changed before operation,which may lead to the occurrence of early POCD.Quinoline,3'-sialyllactose,sphingomyelin(d18∶1/20∶0),lysophosphatidylcholine[P-18∶1(9Z)]and 25-hydroxycholesterol may be biomarkers for predicting early POCD.

Aim To explore the therapeutic effect and mechanism of Qingjie Huagong decoction in modulating PI3K/AKT/NF-κB signaling pathway in inflammatory response of acute pancreatitis(AP)mice.Methods Twenty-four mice were randomly divided into Blank group,Model group,Ustekin group,and Qingjie Hua-gong decoction group,with six mice in each group.The AP model was prepared by using rain frogin.Serum α-AMS,PNLP,IL-1β,IL-6,IL-8,IL-18,and TNF-α lev-els were detected by ELISA;the pancreatic pathology was detected by HE staining;the expressions of PI3K,AKT,and NF-κB-related proteins and mRNAs were de-tected by immunohistochemistry,Western blot,and RT-qPCR.Results Compared with the blank group,the model group showed obvious pathological damage to the pancreas,with significantly higher serum α-AMS,PN-LP,IL-1β,IL-6,IL-8,IL-18,and TNF-α levels(P＜0.01),and significantly higher levels of PI3K,AKT,and NF-κB-related proteins and mRNA expression(P＜0.01).Compared with the model group,both the Qingjie Huagong decoction group and the ustekin group improved the histopathological changes in the pancreas of AP mice,decreased the serum α-AMS,PNLP,IL-1β,IL-6,IL-8,IL-18,and TNF-α levels,and down-reg-ulated the expression levels of pancreatic PI3K,AKT,NF-κB-related proteins and mRNA(P＜0.05 or P＜0.01).Conclusion Qingjie Huagong decoction may inhibit the inflammatory response and protect pancreat-ic tissues by regulating the expression of PI3K/AKT/NF-κB signaling pathway.

Objective To investigate the incidence and types of patient-ventilator asynchrony(PVA)in mechanically ventilated patients within the intensive care unit(ICU),and to identify associated high-risk factors,thereby providing a basis for reducing PVA,enhancing mechanical ventilation efficiency,and refining ventilation strategies.Methods A prospective observational study was conducted among patients admitted to the general ICU of the Affiliated Hospital of Guizhou Medical University from October to December 2024 who were receiving mechanical ventilation.Inclusion criteria were as follows:age ≥18 years and mechanical ventilation duration ≥12 hours.Exclusion criteria included complete controlled mechanical ventilation,palliative care or do-not-resuscitate status,and lack of informed consent.Senior respiratory therapists performed daily bedside observations of ventilator waveforms for 10～15 minutes between 08:00 and 12:00.PVA was diagnosed based on pressure-time and flow-time waveforms,with the types of PVA being recorded.Demographic and clinical data,including age,sex,body mass index(BMI),primary diagnosis,comorbidities,APACHEⅡ score at ICU admission,blood gas analysis,ventila-tion mode and parameters,analgesia and sedation status,duration of mechanical ventilation,and length of ICU stay,were collected.The incidence and types of PVA during the observation period were analyzed.Univariate and multivariate logistic regression analyses were performed to identify high-risk factors for PVA.Clinical outcomes were compared between patients with and without PVA.Results A total of 105 patients and 453 episodes of assisted mechanical ventilation waveforms were analyzed.Among these,60.95％(64/105)experienced at least one episode of PVA.Of the 453 ventilation waveforms assessed,35.76％(162/453)demonstrated PVA.The types of PVA,ranked by incidence,were as follows:cycling mismatch(12.58％,57/453),double triggering(11.92％,54/453),ineffective triggering(9.49％,43/453),flow starvation(5.30％,24/453),and exhalation flow limitation(1.77％,8/453).The incidence of PVA varied significantly across different ventilation modes:45.7％in volume-assist/control ventilation(V-A/C),38.1％in pressure-assist/control ventilation(P-A/C),42.9％in synchronized intermittent mandatory ventilation(SIMV),and 16.7％in pressure support ventilation(PSV)(P<0.001).Multi-variate logistic regression analysis revealed that the mechanical ventilation mode[reference:PSV;V-A/C:OR=4.687,95％CI:2.140～10.263,P<0.001;P-A/C:OR=2.922,95％CI:1.489～5.734,P=0.002;SIMV:OR=4.682,95％CI:1.758～12.466,P=0.002]and actual respiratory rate(OR=1.07,95％CI:1.016～1.127,P=0.011)were significant high-risk factors for PVA.Patients with PVA had a significantly longer duration of mechanical ventilation[8.21(5.35,13.91)days vs.3.00(1.96,5.71)days,P<0.001]compared to those without PVA.Conclusions PVA is commonly observed in ICU patients receiving assisted invasive mechanical ventilation,with cycling mismatch,double triggering,and ineffective triggering being the most prevalent types.The incidence of PVA tends to be lower when using the PSV mode.Clinically,real-time monitoring of patient-ventilator synchrony via ventilator waveforms,along with the optimization of ventilator modes and parameters,should be employed to minimize the occurrence of PVA and enhance the efficiency of mechanical ventilation.

AKT,also known as Protein Kinase B(PKB),plays a critical role in cell proliferation and metabolism.There are three isoforms of AKT:AKT1,AKT2,and AKT3.The effects of these isoforms on the pluripotency and differentiation of mouse embryonic stem cells(mESCs)remain unclear.This study aims to explore the impact of three AKT isoform-specific knockouts on the self-renewal and differen-tiation of mouse embryonic stem cells.Using CRISPR/Cas9 gene-editing technology,AKT isoform-spe-cific knockout cell lines were established.The phenotypic and molecular changes were analyzed through Western blotting,flow cytometry,qRT-PCR,CCK-8 assays,Alkaline Phosphatase(AP)staining,and RNA-seq.The construction of AKT isoform-specific knockout cell lines was successful.The loss of AKT1 and AKT2 inhibited the proliferation of mESCs.The knockout of any single AKT isoform did not affect the expression of pluripotency genes at both mRNA or protein levels.However,during embryoid body forma-tion,the deletion of any of the three AKT isoforms affected the mRNA expression levels of genes in all three germ layers.Transcriptome analysis showed that compared to wild-type mESCs,995,547,and 429 differentially expressed genes(|log2FC|≧1,P＜0.05)were identified inAKT1,AKT2,and AKT3 isoform-specific knockout cells,respectively.There was some overlap in the differentially expressed genes regulated by these three isoforms.In conclusion,the independent knockout of AKT isoforms does not af-fect the maintenance of pluripotency in mouse embryonic stem cells,but they are crucial for differentia-tion.The three AKT isoforms can collectively regulate gene expression while retaining their own regulato-ry specificity.This study provides a foundation for understanding the unique and overlapping roles of AKT isoforms in stem cell biology,highlighting their importance in maintaining stem cell function and differen-tiation.

Objective Metabolomics combined with machine learning algorithms was used to systematically study the preoperative serum metabolites of patients with early postoperative cognitive dysfunction(POCD)after heart valve replacement,so as to screen biomarkers that may predict early POCD after heart valve replacement and explore the corresponding metabolic regulatory mechanisms.Methods A total of 60 patients underwent heart valve replacement under extracorporeal circulation were selected and divided into early-POCD group(group P)and non-POCD group(group N)according to whether POCD occurred or not.Metabolomic analysis was performed on preoperative serum samples of patients in group P and group N to screen the differential metabolites and metabolic pathways.The biomarkers related to early POCD were identified by random forest algorithm.Results A total of 532 differential metabolites were detected by metabonomics analysis,and 5 biomarkers were screened by random forest algorithm,namely quinoline,3'-sialyllactose,sphingomyelin(d18∶1/20∶0),lysophosphatidylcholine[P-18∶1(9Z)]and 25-hydroxycholesterol.Among them,the main metabolic pathways were phenylalanine metabolism,primary bile acid biosynthesis,ascorbic acid and aldonate metabolism,pentose and glucuronate interconversion,tryptophan metabolism,drug metabolism-cytochrome P450,porphyrin and chlorophyll metabolism.Conclusion Many metabolic pathways in patients with early POCD after heart valve replacement under extracorporeal circulation have changed before operation,which may lead to the occurrence of early POCD.Quinoline,3'-sialyllactose,sphingomyelin(d18∶1/20∶0),lysophosphatidylcholine[P-18∶1(9Z)]and 25-hydroxycholesterol may be biomarkers for predicting early POCD.