Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

Hepatocellular carcinoma(HCC)expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming.Aldolase A(ALDOA)plays a prominent role in glycolysis;however,little is known about its role in HCC development.In the present study,we aim to explore how ALDOA is involved in HCC proliferation.HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout,which is consistent with ALDOA overexpression encouraging HCC prolifera-tion.Mechanistically,ALDOA knockout partially limits the glycolytic flux in HCC cells.Meanwhile,ALDOA translocated to nuclei and directly interacted with c-Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase;ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function.A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun,and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells.In HCC patients,the expression level of ALDOA was correlated with the phosphorylation level of c-Jun(Thr93)and poor prognosis.Remarkably,hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models,and the knockdown of Aldoa strikingly decreased HCC development in vivo.Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription,opening additional avenues for anti-cancer therapies.

Objective To explore the prognosis-related genes of lung adenocarcinoma(LUAD)and establish a prognostic prediction model for LUAD.Methods The differentially expressed genes of LUAD tissues and adjacent normal tissues in the GSE43458,GSE7670,and GSE140797 datasets were screened.The protein-protein interaction(PPI)network analysis,gene ontology(GO)function,Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analyses,least absolute shrinkage and selection operator for prognosis coefficient screening,disease-specific survival analysis,Cox regression analysis,and gene correlation analysis were performed.Independent prognostic genes of LUAD were screened from the differential genes,and a prognostic prediction model of LUAD was established.The expression of independent prognostic genes was analyzed,and the predictive model was evaluated by receiver operating characteristic(ROC)curve.The GSE68465 data set was used as an external validation set to verify the predictive model.Results There were 197 up-regulated differential genes and 77 down-regulated differential genes in LUAD and adjacent normal tissues common to the three datasets.Through stepwise screening,two genes,IL7R and SLC2A1,were identified as independent prognostic factors for LUAD.IL7R was an independent protective factor,while the SLC2A1 was an independent risk factor.A prediction model for curve was built with IL7R and SLC2A1.The prediction model for LUAD constructed with IL7R and SLC2A1 is as follows:Risk score=(-0.694)×expression level of IL7R+0.763×expression level of SLC2A1.Conclusion This study screened out IL7R as an independent prognostic protective factor for LUDA,and SLC2A1 as an independent prognostic risk factor for LUAD.The LUDA prediction model constructed based on these two genes has good predictive ability and generalization ability,which can provide references for the research and clinical individualized treatment of LUAD.

A dielectric barrier discharge ionization source with rapid evaporation and self-aspiration sampling(RE-SADBDI)was developed,integrating a rapid evaporation(RE)module and a dielectric barrier discharge ionization(DBDI)module.The sample was introduced into the RE module via a sampling swab and rapidly vaporized within it.The sealed design of the ionization source could enable the sample to be self-aspirated into the ionization region without the need of additional inert gas.All vaporized sample was efficiently directed into the ionization region due to the relatively enclosed environment for sample transfer and ionization,resulting in improved transfer and ionization efficiencies.Experimental results showed that the limit of detection(LOD)under ion isolation mode reached 0.05 ng/mL(caffeine),with a relative standard deviation(RSD)of 6.9%.Furthermore,when coupled with a miniaturized linear ion trap mass spectrometer,the source enabled real-time analysis of various sample types.The developed RE-SADBDI source was suitable for on-site analysis with miniaturized mass spectrometers.

Lentiviral vectors(LVs)are key gene delivery tools for integrating target genes into the host genome,but they may also pose risks of insertional mutagenesis.The vector copy number(VCN)in cells is critical for determining the safety of gene modification.However,the reliability and accuracy of its quantification process are influenced by multiple factors.Developing cell reference materials with specific vector copy numbers represents a viable approach to enhance the reliability and consistency of measurement results,enabling quality control of the quantification process and traceability of outcomes.However,the preparation of such reference materials faces challenges in cell sample design,preparation protocols,and advanced quantification techniques.In this study,T lymphocyte cell line Jurkat-based reference materials with LV gene copy numbers of 1 and 2 copy/cell were developed.A high-precision duplex digital polymerase chain reaction(dPCR)method was established to quantify the LV gene and endogenous genes simultaneously.Additionally,the results of dPCR were cross-validated through next-generation sequencing and flow cytometric analysis.Ultimately,confocal microscopy characterization results showed that the developed cell reference materials had intact morphology.The quantification result of VCN-1 was(1.07±0.11)copy/cell,and that of VCN-2 was(2.09±0.21)copy/cell.These cell reference materials demonstrated compliance with stability and homogeneity requirements,and could be applied for quality control throughout the VCN measurement workflow and metrological traceability,improving the accuracy,comparability,and validity of copy number measurements.

Objective To explore the correlation between the actual age and the pulp chamber volume(PCV)and pulp dentinal index(PDI)of the right first molars based on cone beam computed tomog-raphy(CBCT)technology,and to construct an accurate and convenient model for age estimation.Methods CBCT image data of 1 857 Han adults(883 males and 974 females)from the Department of Stomatology,Affiliated Hospital of North Sichuan Medical College were collected.The data were di-vided into training and validation sets at a ratio of 8∶2.A total of 1 485 training samples were used to construct the age estimation model,and 372 samples were used to validate the accuracy of the model.The Mimics 21.0 software was used to measure the PCV and calculate the PDI of the right first molars.Their correlations with age and the differences between different sexes and tooth positions were analyzed.Results Both the PCV and the PDI of the first molars showed strong negative correla-tions with the actual age(r values ranged from 0.82 to 0.89).The differences in PCV and PDI be-tween different sexes and tooth positions were statistically significant(P<0.05).The age estimation model based on PDI was superior to that based on PCV.The model based on the PDI values of the two right first molars(y=73.72-44.15 x3-28.27 x4,where x3 and x4 are the PDI values of the right maxil-lary and mandibular first molars,respectively)was the best,with the R2 of 0.79 and the mean abso-lute error of 4.90 years.Conclusion Both PCV and PDI of the first molars are effective indicators for age estimation.The age estimation model based on the PDI is more convenient and accurate than that based on the PCV,providing a more effective method for age estimation in forensic practice.

Objective To construct an aptamer-functionalized carboxylated graphene oxide(CGO)fluo-rescent sensor to achieve highly sensitive and specific detection of ketamine(KET)and its metabolite norketamine(NK)using an aptamer capable of simultaneously recognizing KET and NK.Methods A specific aptamer for simultaneous recognition of KET and NK was screened using graphene oxide-sys-tematic evolution of ligand by exponential enrichment(GO-SELEX)and molecular docking tech-niques.The aptamer,labeled with Cy5 fluorescence,was chemically conjugated to CGO to construct an aptamer-functionalized CGO fluorescent sensor.By optimizing detection conditions,including the mass concentration of CGO,aptamer concentration,reaction temperature,and incubation time,quantita-tive analysis of the target analytes was achieved using the ratio of fluorescence intensity changes be-fore and after target addition.The stability of the sensor in biological matrices was evaluated by moni-toring fluorescence intensity changes over incubation time in blank blood and urine,in comparison with the traditional physical adsorption-based CGO fluorescent sensor.Spiked recovery experiments in blank blood and urine were conducted to compare performance with that of HPLC-MS/MS.Results A specific aptamer A5 was selected and chemically conjugated with CGO to construct the aptamer-functionalized CGO fluorescent sensor.Under optimized conditions,the proposed fluorescent sensor ex-hibited a linear detection range of 1.0-5.0 ng/mL for KET,with a limit of detection(LOD)of 0.86 ng/mL;while for NK,the linear detection range was 1.0-5.0 ng/mL,with an LOD of 0.70 ng/mL.Com-pared with the CGO fluorescent sensor constructed via physical adsorption,this sensor demonstrated greater stability in blood and urine.The spiked recovery rates of KET and NK in blank blood and urine ranged from 81.50%to 110.03%,exhibiting detection performance comparable to that of HPLC-MS/MS.Conclusion The aptamer screening method offers a novel approach for selecting aptamers tar-geting drugs and their metabolites.The constructed aptamer-functionalized CGO fluorescent sensor pro-vides an efficient and reliable strategy for the high-performance detection of KET and NK.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective To evaluate the application value of fascial platform versus commercial platform in transumbilical single-port laparoscopic transabdominal preperitoneal repair(TAPP)for inguinal hernia.Methods One hundred patients with inguinal hernia admitted between January and December 2024 were prospectively enrolled and randomly assigned to either the fascial platform group(n=50)or the commercial platform group(n=50)by using a random number table.The following parameters were compared between the two groups:platform establishment time,operative time,intraoperative blood loss,incision suture time,operative difficulty score,camera manipulation difficulty score,postoperative 24-hour Visual Analogue Scale(VAS)score of pain,postoperative hospital stay,total hospitalization cost,comprehensive satisfaction score,and postoperative complications.Results The fascial platform group demonstrated significantly superior outcomes compared to the commercial platform group in platform establishment time[(3.4±1.0)min vs.(8.1±1.5)min,t=-18.389,P＜0.001],operative time[(67.5±7.9)min vs.(72.2±11.5)min,t=-2.380,P=0.019],intraoperative blood loss[(8.3±4.3)ml vs.(11.1±5.7)ml,t=-2.798,P=0.006],incision suture time[(7.0±1.4)min vs.(11.8±2.7)min,t=-11.212,P＜0.001],operative difficulty score(14.4±3.6 vs.23.1±4.1,t=-11.215,P＜0.001),camera manipulation difficulty score(11.4±2.6 vs.18.3±2.5,t=-13.370,P＜0.001),VAS score of postoperative 24-hour pain(2.4±1.0 vs.3.7±1.1,t=-6.139,P＜0.001),total hospitalization cost[(15.8±1.6)thousand yuan vs.(18.3±1.6)thousand yuan,t=-7.841,P＜0.001],and comprehensive satisfaction score(7.3±1.1 vs.6.3±1.0,t=5.271,P＜0.001).However,there were no statistically significant differences in postoperative hospital stay or postoperative complication between the two groups(P＞0.05).All the patients were followed up for 1-12 months postoperatively[(5.3±1.8)months vs.(5.7±2.0)months,t=-0.945,P=0.347],with no recurrence observed in either group.Conclusions Both fascial platform and commercial platform can be used for transumbilical single-port TAPP.The fascial platform offers advantages including shorter platform establishment time,reduced incision suture time,lower operative and camera manipulation difficulty,decreased cost,less postoperative pain,and higher patient satisfaction.

Objective:To explore the clinical efficacy of acupuncture therapy in treating post-stroke pulmonary(PSP)and its impact on diaphragm function based on the theory of liver ascending and lung descending.Methods:This study was a prospective study,70 PSP patients who were admitted to our hospital from April 2023 to August 2024 were selected,they were divided into control group and study group according to the random number table method,with 35 patients in each group.Both groups received routine treatment,the control group received respiratory training,while the study group received respiratory training combined with acupuncture therapy.Clinical efficacy,recovery time of signs,related scale scores[clinical pulmonary infection score(CPIS),National Institute of HealthStroke Scale(NIHSS)],blood gas and lung function indicators[(partial pressure of oxygen(PaO2),partial pressure of carbondioxide(PaCO2),forced expiratory volume in one second(FEV1),peak expiratory flow(PEF)]and diaphragm function between two groups were compared.Results:The total clinical effective rate of the study group was higher than that of the control group,and the time for fever resolution,relief of pulmonary infection,disappearance of pulmonary wet rales and disappearance of cough were shorter than those of the control group(P＜0.05).The CPIS scores,NIHSS scores and PaCO2 of the study group at 14 days after intervention were lower than those of the control group,FEV1,PEF,PaO2,thickening rate and activity of diaphragm were higher than those of the control group(P＜0.05).Conclusion:Acupuncture therapy in treating PSP patients based on the theory of liver ascending and lung descending,can shorten recovery time of signs,improve clinical treatment effectiveness,reduce the degree of infection and brain nerve damage,and improve patients' lung function and diaphragm function.