Oropharyngeal squamous cell carcinoma(OPSCC)is a malignant tumor originating from the squamous epithelium of the oro-pharyngeal mucosa,accounting for more than 90％of oropharyngeal malignancies.In recent years,human papillomavirus(HPV)infec-tion has become one of the primary etiological factors of oropharyngeal squamous carcinoma.The incidence of HPV-associated oropharyn-geal squamous carcinoma has been rising annually,with a noticeable trend toward younger populations,posing a significant threat to hu-man health.Due to the distinct biological behavior and clinical characteristics of HPV-associated oropharyngeal squamous carcinoma com-pared to its non-HPV-related counterpart,the diagnostic and treatment strategies for oropharyngeal squamous carcinoma have undergone substantial changes.Prevention and screening for oropharyngeal squamous carcinoma are of critical importance.The diagnostic and treat-ment process involves multi-disciplinary collaboration,including oral and maxillofacial surgery,otolaryngology,head and neck surgery,oncology,radiology and pathology.Based on evidence from clinical practice,a comprehensive,integrated diagnostic and therapeutic ap-proach has been established,centered around the concept of"prevention,screening,diagnosis,treatment,and rehabilitation",covering the entire patient lifecycle and providing a valuable reference for clinical practice.

Objective To explore the impact of neurally adjusted ventilatory assist(NAVA)mode on the weaning outcomes of patients with severe cerebrovascular disease who have weaning difficulty from mechanical ventilation.Methods Patients with severe cerebrovascular disease who had weaning difficulty from mechanical ventilation and were admitted to the Intensive Care Unit(ICU)of Neurosurgery Departement,the First Affiliated Hospital of Wannan Medical College(Yijishan Hospital of Wannan Medical College)from November 2019 to November 2021 were prospectively and consecutively included.They were randomly divided into the NAVA group and the pressure support ventilation(PSV)group using a random number table,with 28 patients in each group.Baseline and clinical data of the two groups were collected,including gender,age,main diagnosis,past medical history(hypertension,stroke,respiratory diseases,diabetes,coronary heart disease),body mass index,acute physiology and chronic health evaluation(APACHE)Ⅱ score,Glasgow coma scale(GCS)score,types of difficult weaning(failure of the first spontaneous breathing trial[SBT],re-intubation within 48 h after the first weaning attempt),and mechanical ventilation time before randomization.SBT and weaning-related indicators after randomization were collected,including respiratory mechanics and parameters before SBT implementation after randomization(peak airway pressure,expiratory tidal volume,positive end-expiratory pressure,inspired oxygen concentration,minute ventilation,mean airway pressure,diaphragmatic electrical activity signal value,neural ventilation efficiency,neural mechanical efficiency),basic vital signs(mean arterial pressure,respiratory heart rate)before weaning after passing SBT,blood routine(white blood cells,hemoglobin)and biochemical tests(albumin,creatinine,troponin,B-type natriuretic peptide)within 48 h before weaning,and arterial blood gas within 30 min before weaning(pH,partial pressure of carbon dioxide,partial pressure of oxygen,bicarbonate ion,oxygenation index).The primary outcome measures included the time required for successful weaning from randomization to day 28(if the patient died or failed to wean successfully before day 28 after randomization,the time required for weaning was defined as 28 d),total mechanical ventilation time after randomization,total weaning success rate from randomization to day 28,total weaning-free time at 7,14,and 28 d after randomization,survival time at 28 d and 90 d after randomization,ICU length of stay,total hospital length of stay,and cumulative weaning success rate from randomization to day 28 in both groups.The secondary outcome measures included tracheotomy rate after randomization,ICU mortality rate,mortality rate at 28 d and 90 d after randomization,incidence of mechanical ventilation-related complications(ventilator-associated pneumonia,acute respiratory distress syndrome,pneumothorax,pleural effusion)during mechanical ventilation after randomization,and cumulative survival rate at 90 d after randomization.The human-machine coordination within 24 h after randomization was recorded in both groups including the number and index of ineffective triggering,false triggering,double triggering,premature switching from inspiration to expiration,delayed switching from inspiration to expiration,and triggering delay,as well as the total asynchrony index,with one record every 8 h,each record lasting for 1 min,for a total of 3 min.Results A total of 56 patients with severe cerebrovascular disease who had weaning difficulty from mechanical ventilation were included,with 28 patients in each of the PSV group and the NAVA group.There were no statistically significant differences between the two groups in terms of gender,age,main diagnosis,past medical history,body mass index,APACHE Ⅱ score,GCS score,types of difficult weaning,mechanical ventilation time before randomization,indicators before SBT implementation after randomization and after SBT before weaning(all P＞0.05).(1)The time required for successful weaning from randomization to day 28(9.00[7.00,15.50]d vs.15.50[10.25,22.75]d)and total mechanical ventilation time after randomization(8.50[7.00,12.75]d vs.13.50[10.00,20.00]d)were both lower in the NAVA group than those in the PSV group(all P＜0.05).The cumulative weaning success rate of the NAVA group was higher than that of the PSV group at 28 d after randomization(P=0.039),but there was no statistically significant difference in the total weaning success rate between the two groups from randomization to the day 28(92.9％[26/28]vs.85.7％[24/28],P=0.669).The NAVA group had longer periods without mechanical ventilation within 14 d(5.00[0.00,7.00]d vs.0.00[0.00,3.75]d)and within 28 d(18.00[9.25,20.75]d vs.10.50[0.25,17.75]d)after randomization compared with the PSV group(all P＜0.05),but there was no statistically significant difference in the period without mechanical ventilation within 7 d after randomization between the two groups(P=0.159).The ICU stay of the NAVA group was shorter than that of the PSV group(9.00[6.25,16.75]d vs.14.00[10.25,22.50]d,P=0.015),but there were no statistically significant difference in the total hospital stay and survival time within 28 d and 90 d after randomization between the two groups(all P＞0.05).(2)There was no statistically significant difference between the two groups in tracheotomy rate,ICU mortality rate,mortality rate at 28 d and 90 d after randomization,complications during mechanical ventilation after randomization,and cumulative survival rate at 90 d after randomization(all P＞0.05).(3)In terms of human-machine coordination,the NAVA group had lower frequencies and indices of false triggering(frequency:0.00[0.00,0.00]time/min vs.0.00[0.00,0.58]time/min;index:0.00[0.00,0.00]vs.0.00[0.00,0.02]),ineffective triggering(frequency:0.00[0.00,0.33]time/min vs.1.00[0.33,2.17]time/min;index:0.00[0.00,0.02]vs.0.05[0.02,0.09]),premature switching(frequency:0.00[0.00,0.33]time/min vs.0.33[0.33,1.00]time/min;index:0.00[0.00,0.01]vs.0.02[0.02,0.05]),delayed switching(frequency:0.00[0.00,0.00]time/min rs.1.17[0.00,5.67]time/min;index:0.00[0.00,0.00]rs.0.06[0.00,0.29]),and delayed triggering(frequency:0.00[0.00,0.58]time/min vs.0.67[0.33,1.67]time/min;index:0.00[0.00,0.02]vs.0.05[0.02,0.10])compared with the PSV group(all P＜0.01).The NAVA group had higher frequencies and indices of double triggering(frequency:1.17[0.33,2.00]time/min vs.0.00[0.00,0.00]time/min;index:0.06[0.02,0.11]vs.0.00[0.00,0.00];all P＜0.01),but the total asynchrony index of the NAVA group was lower than that of the PSV group(0.08[0.04,0.14]vs.0.24[0.19,0.51],P＜0.01).Conclusion The NAVA mode can shorten the weaning and mechanical ventilation time of patients with severe cerebrovascular disease who have weaning difficulty from mechanical ventilation,improve human-machine coordination,and has potential advantages in increasing the weaning success rate.

AIM:To investigate the antitumor activity and targets of baicalein(Bai)in pancreatic cancer using network pharmacology combined with in vitro and in vivo experiments.METHODS:The targets of Bai and pancreatic can-cer were analyzed via multi-data screening.A protein-protein interaction network was constructed using STRING,and core targets were identified via Cytoscape.Functional enrichment was analyzed by Gene Ontology(GO)and Kyoto Ency-clopedia of Genes and Genomes(KEGG).Antitumor effects of Bai were assessed in pancreatic cancer cells Aspc-1 and Bxpc-3 using MTT and colony formation assays for proliferation,flow cytometry for apoptosis and cell cycle analysis,and Transwell assays for migration and invasion.A xenograft tumor model was established to evaluate tumor proliferation,im-munohistochemistry was performed to detect the protein expression of AKT in tumor tissues,and Western blot was used to analyze the expression levels of AKT,β-catenin,N-cadherin and Slug.RESULTS:A total of 108 overlapping targets were identified between Bai and pancreatic cancer.Among these,7 core targets were recognized,including proto-onco-gene tyrosine-protein kinase Src,heat shock protein 90 alpha family class A member 1(HSP90AA1),estrogen receptor 1(ESR1),tumor protein p53(TP53),epidermal growth factor receptor(EGFR),AKT1,and mitogen-activated protein ki-nase 3(MAPK3).The GO analysis revealed significant enrichment in oxidative stress response,protein phosphorylation,and serine/threonine kinase activity.The KEGG analysis primarily enriched the PI3K/AKT,MAPK and Ras signaling pathways.The MTT and colony formation assays showed that Bai inhibited the viability of Aspc-1 and Bxpc-3 cells in a dose-dependent manner(72 h IC50 values were 73.6 μmol/L and 83.4 μmol/L,respectively)and reduced cell colony for-mation(P<0.05 or P<0.01).Flow cytometry confirmed that Bai induced apoptosis of Aspc-1 and Bxpc-3 cells(P<0.01)and blocked the cell cycle at the G0/G1 phase(P<0.05 or P<0.01).Transwell experiments indicated that Bai inhibited the migration and invasion of Aspc-1 and Bxpc-3 cells(P<0.05 or P<0.01).In vivo,Bai significantly inhibited the growth of Aspc-1 cell xenograft tumors(P<0.01).Immunohistochemistry revealed a significant reduction in AKT expression in tu-mor tissues(P<0.01),and Western blot showed decreased expression of AKT,β-catenin,N-cadherin and Slug in both Aspc-1 and Bxpc-3 cells(P<0.01).CONCLUSION:Baicalein inhibits pancreatic cancer cell proliferation,migration,and invasion,potentially through down-regulation of AKT,β-catenin,N-cadherin,and Slug expression.

Objective:To evaluate the sample preparation proficiency and storage proficiency of 11 clinical biobanks in Beijing through simulated experiments, and to establish an assessment method for the quality comparability of biological samples.Methods:An exploratory research design was adopted. In November 2023, artificial composite serum quality control materials containing six recombinant human protein markers—recombinant human alanine aminotransferase (rhALT), recombinant human aspartate aminotransferase (rhAST), recombinant human creatine kinase (rhCK), recombinant human creatine kinase-MB (rhCK-MB), recombinant human B-type natriuretic peptide (rhBNP), and recombinant human troponin I (rhTNI)—were distributed to 11 clinical biobanks in Beijing City. Sample preparation and storage followed the standardized operating procedures. Proficiency differences were assessed through statistical analysis.Results:Three-way repeated measures ANOVA revealed all six protein markers showed a declining trend over storage time in ultra-low-temperature environments ( F values 11.68-4 179.66, all P<0.01). However, neither long-term/temporary refrigerator types ( F values 0.01-1.23, all P>0.05)nor placement locations within refrigerators significantly affected the stability of these six proteins ( F valus 0.03-1.47, all P>0.05). The biases in detection results for rhALT, rhAST, rhTNI, and rhBNP at different storage time points were within the allowable bias limits for each item, supporting their use as markers for protein stability in biobank samples. All 11 institutions passed the storage proficiency assessment. In the preparation proficiency assessment, deviations were observed in post-preparation sample results, with a notably high out-of-control rate for rhCK (36.36%). Conclusion:Sample preparation proficiency can serve as a quality control metric for clinical biobanks. Future external quality assessment systems for biobanks should focus on sample preparation rather than storage processes.

Oral squamous cell carcinoma(OSCC)is a malignant lesion originating from the oral mucosal squamous epithelium,account-ing for over 80％of oral and maxillofacial malignancies.Key etiological factors include tobacco,alcohol abuse,and betel quid chewing.In China,its incidence has shown an overall upward trend,posing a significant threat to public health.OSCC exhibits high local invasive-ness,making early diagnosis critical for improving prognosis.Its clinical management requires close multidisciplinary collaboration among oral and maxillofacial surgery,head and neck surgery,radiation oncology,medical oncology,reconstructive surgery,radiology,patholo-gy,and nutritional support teams.Given the increasing disease burden of OSCC and rapid development of multidisciplinary collaborative models,an expert panel has formulated this integrated management consensus based on evidence-based medicine and extensive deliber-ation.Centered on the'Prevention-Screening-Diagnosis-Treatment-Rehabilitation'framework,the consensus provides comprehensive guidance for the entire disease course of OSCC patients,aiming to standardize clinical practice.

The NOD-like receptor protein 3 (NLRP3) inflammasome is essential in innate immune-mediated inflammation, with its overactivation implicated in various autoinflammatory, metabolic, and neurodegenerative diseases. Pharmacological inhibition of NLRP3 offers a promising treatment strategy for inflammatory conditions, although no medications targeting the NLRP3 inflammasome are currently available. This study demonstrates that clioquinol (CQ), a clinical drug with chelating properties, effectively inhibits NLRP3 activation, resulting in reduced cytokine secretion and cell pyroptosis in both human and mouse macrophages, with a half maximal inhibitory concentration (IC₅₀) of 0.478 μM. Additionally, CQ mitigates experimental acute peritonitis, gouty arthritis, sepsis, and colitis by lowering serum levels of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α). Mechanistically, CQ covalently binds to Arginine 335 (R335) in the NACHT domain, inhibiting NLRP3 inflammasome assembly and blocking the interaction between NLRP3 and its component protein. Collectively, this study identifies CQ as an effective natural NLRP3 inhibitor and a potential therapeutic agent for NLRP3-driven diseases.

Proanthocyanidin B_2(PAC-B_2), a polyphenolic dimeric compound comprising two epicatechin molecules linked by a C-C bond, is extensively found in traditional Chinese medicines, with anti-tumor and anti-oxidant activities. Given the limited bioavailability, a thorough investigation and comprehensive understanding of PAC-B_2 metabolism in vivo are essential for elucidating therapeutic forms and mechanisms. In the present study, ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) in the negative ion mode was employed to acquire the MS/MS information of PAC-B_2 and metabolites in urine and feces samples of the rats administrated with PAC-B_2. Online energy-resolved MS(ER-MS) was applied as supplementary to obtain the full collision energy ramp-MS~2 spectra(FCER-MS~2) of isomers-of-interest, which implied comprehensive MS~2 information of targeted compounds. Finally, the possible metabolic pathways of PAC-B_2 in rats were proposed. The primary fragmentation behaviors of PAC-B_2 in the negative ion mode included quinone methide fission between C_4-C_8 bond, retro Diels-Alder cracking of F-ring, heterocyclic ring fission of C-ring, and neutral loss of small molecules such as H_2O. A total of 25 metabolites were tentatively elucidated in urine and feces samples of rats administrated with PAC-B_2 by fragmentation pattern and reported literature. Two groups of isomers, M3/M4/M5 and M9/M11, were confirmatively differentiated based on the relationships between optimal collision energy provided by FCER-MS~2 and bond properties, including bond length and bond dissociation energy. In addition to the ring-opening and methylation, PAC-B_2 could also be metabolized into epicatechin and low molecular weight phenolic acids, which were subsequently subjected to dehydroxylation, ring-opening, methylation, sulfation, and glucuronidation. The structural information provided by online ER-MS and FCER-MS~2 enabled the differentiation of isomers and improved the identification confidence. More importantly, the present study deeply analyzes the in vivo metabolic pathways of PAC-B_2, providing a basis for the research on the pharmacological mechanism of this compound.
Animals ; Proanthocyanidins/urine* ; Rats ; Male ; Drugs, Chinese Herbal/chemistry* ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry ; Chromatography, High Pressure Liquid ; Feces/chemistry* ; Molecular Structure

Severe open tibiofibular fractures account for approximately 28.1% of all open fractures. Among them, Gustilo-Anderson type IIIB/C fractures present significant clinical challenges due to associated bone and soft tissue defects, high infection rates, and risk of amputation. Inadequate preoperative assessment may lead to suboptimal emergency surgical planning or intraoperative complications. Historically, external fixation was often preferred, but this approach has been associated with limitations such as restricted joint mobility, delayed bone union, joint stiffness, and disuse osteoporosis, resulting in poor functional recovery. With advancements of debridement techniques, standardization of antibiotic use, and popularization of early soft tissue coverage, early internal fixation has gained broader acceptance. Nevertheless, controversies persist regarding the choice of fixation method, timing of definitive fixation, use of reamed versus unreamed intramedullary nailing, and necessity of fibular fixation. To standardize the diagnosis and early management of severe open tibiofibular fractures, reduce complication rates, and improve functional recovery, the Society of Microsurgery of the Chinese Medical Association organized a panel of domestic experts to develop the Evidence-based guideline for the diagnosis and early fixation of severe open tibiofibular fractures ( version 2025), using evidence-based methodology. The guidelines provided 12 recommendations covering diagnostic and early fixation strategies of severe open tibiofibular fractures, aiming to provide clinicians with scientifically grounded and standardized guidance.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

Severe open tibiofibular fractures account for approximately 28.1% of all open fractures. Among them, Gustilo-Anderson type IIIB/C fractures present significant clinical challenges due to associated bone and soft tissue defects, high infection rates, and risk of amputation. Inadequate preoperative assessment may lead to suboptimal emergency surgical planning or intraoperative complications. Historically, external fixation was often preferred, but this approach has been associated with limitations such as restricted joint mobility, delayed bone union, joint stiffness, and disuse osteoporosis, resulting in poor functional recovery. With advancements of debridement techniques, standardization of antibiotic use, and popularization of early soft tissue coverage, early internal fixation has gained broader acceptance. Nevertheless, controversies persist regarding the choice of fixation method, timing of definitive fixation, use of reamed versus unreamed intramedullary nailing, and necessity of fibular fixation. To standardize the diagnosis and early management of severe open tibiofibular fractures, reduce complication rates, and improve functional recovery, the Society of Microsurgery of the Chinese Medical Association organized a panel of domestic experts to develop the Evidence-based guideline for the diagnosis and early fixation of severe open tibiofibular fractures ( version 2025), using evidence-based methodology. The guidelines provided 12 recommendations covering diagnostic and early fixation strategies of severe open tibiofibular fractures, aiming to provide clinicians with scientifically grounded and standardized guidance.