Oral squamous cell carcinoma (OSCC) accounts for over 90% of oral malignancies, with more than 370 000 new cases and approximately 188 000 deaths annually worldwide. In China, there are roughly 65 000 new cases and 35 000 deaths each year, showing a significant upward trend compared with 2015 statistics. Despite continuous advancements in treatment modalities, the 5-year survival rate remains stagnant at 50%-60%, where tumor heterogeneity and therapy resistance persist as fundamental barriers to precision oncology. To address these critical challenges, this study established a standardized bioban-king protocol for OSCC patient-derived organoids (PDOs) (Patent: Method for constructing an oral squamous cell carcinoma organoid bank, ZL202311378598.3). Through groundbreaking optimization of culture media, enzymatic digestion kinetics, and stepwise cryopreservation, we achieved a biobanking success rate exceeding 95% and pioneered synchronous cultivation of matched primary tumors, lymph node metastases, and adjacent normal mucosa from individual patients, preserving spatial heterogeneity and stromal interactions. Leveraging this platform, we developed high-throughput drug screening: Quantified heterogeneity-driven differential chemoresponse using adenosine triphosphate (ATP)-based viability assays; We discovered resistance mechanisms: Identified sialylated cancer IgG (SIA-cIgG)-mediated cis-platin resistance (primary/secondary) through PTPN13 suppression, with anti-SIA-cIgG combination therapy demonstrating synergistic efficacy. Besides, we elucidated metastatic drivers: CRISPR-Cas9-edited organoids revealed WDR54 promoted metastasis via H3K4me3/H4K16ac epigenetic reprogramming, activating epithelial-mesenchymal plasticity (EMP) and inducing partial epithelial-mesenchymal transition (pEMT). This "holographic patient-mirroring" platform provided unprecedented resolution for OSCC precision therapy and had been formally incorporated into the Chinese Stomatological Association Technical Guidelines (Technical guideline for establishing patient-derived oral squamous cell carcinoma organoid banks, CHSA 2024-08). Future integration of immune-competent organoids, 3D-bioprinted vasculature, and multi-omics-AI systems will accelerate personalized oncology. These innovations will accelerate clinical translation of personalized therapeutic regimens, ultimately bridging the gap between bench research and bedside application.
Humans ; Organoids/pathology* ; Mouth Neoplasms/genetics* ; Carcinoma, Squamous Cell/pathology* ; Tissue Banks ; Biological Specimen Banks

Objective:To explore the clinical characteristics and prognoses of severe autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A).Methods:A retrospective analysis was performed. The clinical data of 12 patients with severe GFAP-A admitted to Department of Neurology, Guangdong 999 Brain Hospital from January 2018 to June 2023 were collected, including demography, clinical manifestations, MRI features, laboratory examination results (such as antibodies), treatments and prognoses.Results:Among the 12 patients, 9 were male and 3 were female, with an average onset age of (46.58±17.53) years. Primary symptoms included headache, limb weakness, limb numbness, mental disorder, epileptic seizure, and urinary and defecation disorder; 9 patients had fever before onset. With aggravated severe GFAP-A, 12 patients had impaired consciousness, 12 had respiratory failure, 6 had unstable blood pressure and heart rate, and 2 had status epilepticus. Cranial MRI indicated abnormal lesions in all 12 patients, including 10 with brainstem involvement (7 had involved medulla oblongata); 10 showed soft meningeal enhancement. In 8 patients received MRI of the whole spinal cord, 7 had abnormal spinal cord lesions; point-like enhancement of the whole spinal meninges was observed in 6 of the 7 patients. All 12 patients had positive cerebrospinal fluid GFAP-IgG, and 3 patients also had positive serum GFAP-IgG. All patients accepted glucocorticoids and immunoglobulin immunotherapy, and 1 patient was supplemented with mycophenolate mofetil; 8 patients had good prognosis, and 4 patients died. Pulmonary infection, hyponatremia, hypoproteinemia, and deep vein thrombosis were the common complications.Conclusion:Patients with severe GFAP-A mainly manifest as meningoencephalitis and meningoencephalomyelitis, and are likely involved medulla oblongata, enjoying rapid clinical progression; even with early immunotherapy, high mortality rate is still noted.

Objective To explore the clinical value of shear wave elastic imaging(SWE)for renal cortical elasticity in patients with hypertension.Methods According to the diagnostic criteria of 2020 International Society of Hypertension(ISH)Global Hypertension Practice Guidelines,44 patients with simple hypertension admitted to the Department of Cardiology of our hospital were selected and 46 healthy controls were selected for the same period.The general data and and renal function indicators of blood biochemical were recorded.All subjects were examined by two-dimensional ultrasound and SWE elasticity to obtain the conventional ultrasound parameters and the Young's modulus(YM)value of the right.The above parameters between the two groups were compared.The influence factors were analyzed by multiple linear regression among the YM value of the right renal cortex,the general data,conventional ultrasound indicators and renal function indicators in the simple hypertension group.Results The course,systolic blood pressure(SBP)and diastolic blood pressure(DBP)in the simple hypertension group was higher than those in the control group,and the difference was statistically significant(P＜0.05).The YM value of the right renal cortex in the simple hypertension group was higher than that in the control group,and the difference was statistically significant(P＜0.05).The correlation analysis showed that the YM value of the right renal cortex was positively correlated with the duration of hypertension(P＜0.05),but not with age,blood pressure,right renal volume,right renal cortex thickness,right renal artery trunk peak systolic flow velocity(PSV),right renal artery trunk resistance index(RI),blood urea nitrogen,blood creatinine,or uric acid(P＞0.05).Further simple linear regression analysis showed that the duration of hypertension was an independent factor affecting the YM value of the right renal cortex.Conclusion SWE may be used to find the variation in elasticity of renal cortex in patients with simple hypertension.

Astragalosides are the main active constituents of traditional Chinese medicine Huang-Qi, of which cycloastragenol-type glycosides are the most typical and major bioactive compounds. This kind of compounds exhibit various biological functions including cardiovascular protective, neuroprotective, etc. Owing to the limitations of natural sources and the difficulties encountered in chemical synthesis, re-engineering of biosynthetic machinery will offer an alternative and promising approach to producing astragalosides. However, the biosynthetic pathway for astragalosides remains elusive due to their complex structures and numerous reaction types and steps. Herein, guided by transcriptome and phylogenetic analyses, a cycloartenol synthase and four glycosyltransferases catalyzing the committed steps in the biosynthesis of such bioactive astragalosides were functionally characterized from Astragalus membranaceus. AmCAS1, the first reported cycloartenol synthase from Astragalus genus, is capable of catalyzing the formation of cycloartenol; AmUGT15, AmUGT14, AmUGT13, and AmUGT7 are four glycosyltransferases biochemically characterized to catalyze 3-O-xylosylation, 3-O-glucosylation, 25-O-glucosylation/O-xylosylation and 2'-O-glucosylation of cycloastragenol glycosides, respectively. These findings not only clarified the crucial enzymes for the biosynthesis and the molecular basis for the structural diversity of astragalosides in Astragalus plants, also paved the way for further completely deciphering the biosynthetic pathway and constructing an artificial pathway for their efficient production.

Objective:To explore clinical features, diagnosis, localization, and therapeutic strategy of migratory pharyngeal and cervical esophageal foreign bodies.Methods:A total 23 cases of pharyngeal and cervical esophageal migratory foreign bodies were admitted between January 2015 and December 2021. There were 14 females and 9 males with the age ranged from 35 to 82 (55.0±12.7)years. In all the cases, esophageal CT was taken to confirm the esophageal foreign body. Multiplanar reconstruction (MPR) was performed to locate the foreign body from the horizontal, coronal and sagittal dimensions as well as the corrected reconstructed MPR. According to the location of the foreign body, appropriate surgical method was selected.The symptoms, complications, types of foreign body, positioning, surgical methods, and relevant information were recorded.Data were analyzed using the descriptive method and SPSS 25.0 software.Results:The clinical symptoms of 23 migrating esophageal foreign bodies included pharyngodynia (20/23), foreign body sensation (6/23), hoarsenss (1/23), difficulty in turning neck(1/23), difficulty in opening mouth (1/23), fever (7/23), poor appetite (1/23), and abdominal pain (1/23). The foreign bodies included 19 fish bones, 2 wires, 1 embroidery needle and 1 chicken bone. There were 9 cases (39.1%) of foreign bodies located in extraluminal cervical esophagus, 2 cases (8.7%) of foreign bodies located in the muscular layer of the cervical esophagus and 12 cases (52.2%) of foreign bodies located in pharynx. Twenty-one cases of foreign bodies were removed by cervical lateral incision, in which 11 were removed by cervical lateral incision directly, 10 by the second lateral cervical incision after the foreign bodies were accurately located by MPR and/or corrected MPR, 1 foreign body was removed by incision of the pharyngeal mucosa under suspension laryngoscope, 1 foreign body was removed by tracheoscopy. Compared with patients with intraluminal foreign bodies ( n=308) treated in the same period, intake of fishbone [19 (19/23) vs. 133 (82.6% (43.2%, 133/308), OR=7.31] and first visit was more than 24 hours [20(87.0%, 20/23) vs. 77(25.0%, 77/308), OR=17.2] were the significant risk factors of migratory esophageal foreign bodies. Conclusions:MPR and the corrected MPR can accurately locate the migrating pharyngeal and cervical esophageal foreign bodies, by providing more intuitive imaging evidence for doctors, which provide imaging basis for formulation of surgical programs. Foreign bodies in pharyngeal and cervical esophagus need to be treated as soon as possible, otherwise they are easy to migrate, leading lead to serious complications.

Objective:To investigate the incidence and risk factors of acute kidney injury in patients admitted to the resuscitation room of the Emergency Department.Methods:Patients were enrolled from the resuscitation room of our hospital from September to December 2018 by a retrospective cohort study. Patients were divided into AKI group and non-AKI group according to whether AKI occurred within seven days after admission. Demographic characteristics, APACHEⅡ score, whether to use nephrotoxic drugs,24-hour fluid volume, and patients survival time were collected. Multivariate regression analysis was used to explore the risk factors for AKI. Cox regression was used to study the effect of the occurrence of AKI on survival and to analyze the influence of AKI severity on the death risk of patients in the resuscitation room.Results:Among 238 critical patients who were finally included, 108 patients developed AKI(45.4%), 83 patients were in AKI stage 1 (34.9%), and 25 patients were in AKI stage 2-3 ( 10.5%).APACHEⅡ score>13( OR=1.11, 95% CI (1.08-1.16), P <0.01), vasoactive drugs ( OR=2.20, c95% CI (1.08-4.49), P=0.03), diabetes mellitus ( OR=2.33, 95% CI (1.23-4.42), P=0.01), and fluid load> 3 L( OR=3.10, 95% CI (1.17-8.25). P=0.02) were independent risk factors for AKI. After adjustment for APACHEⅡ score and age by multivariate COX regression, AKI remained an independent risk factor for death in emergency patients, and the severity of AKI significantly increased the risk of death in these patients(AKI 1: HR=1.45, 95% CI (1.08-2.03), P =0.04; AKI 2~3: HR=3.15, 95% CI (1.49-4.81), P=0.03). Conclusions:AKI occurred commonly in the resuscitation room of the emergency department. APACHE Ⅱ score>13, vasoactive drugs, diabetes, and fluid load>3 L were independent risk factors for AKI. The risk of death increased with the aggravation of AKI severity.

Objective:To analyze the changes of mean arterial pressure (MAP) and end expiratory carbon dioxide (ETCO 2) in patients after emergency endotracheal intubation (ETI). To explore the values of MAP and ETCO 2 monitoring in early prediction of severe cardiovascular collapse (CVC) after emergency ETI. Methods:The clinical data of adult patients who underwent ETI from March 2015 to May 2020 were collected consecutively in the emergency departments of Peking Union Medical College Hospital. The values of MAP and ETCO 2 were observed and recorded at 5, 10, 30, 60 and 120 min after intubation. According to whether severe CVC occurred after ETI, the patients were divided into the severe CVC group and non-severe CVC group. The values of MAP and ETCO 2 were compared at the same time points between the two groups and the adjacent time points within the groups. The correlation between MAP and ETCO 2 after ETI was also analyzed. ROC curve was used to analyze the ability of MAP and ETCO 2 at 5 min and 10 min after ETI to predict severe CVC. Results:Totally 116 patients were enrolled in this study, among them 75 (64.7%) cases had severe CVC after ETI. The majority were male and elderly patients in the severe CVC group. The values of MAP and ETCO 2 in 5, 10, 30, 60 and 120 min after ETI in severe CVC group were significantly lower than those in the non-severe CVC group. The values of MAP and ETCO 2 in the two groups showed simultaneous decrease from 5 min to 30 min after ETI, reached the lowest value at 30 min after ETI, and appeared the synchronous recover from then to 120 min after ETI. After ETI, the changes of MAP was correlated with that of ETCO 2 ( rs = 0.653, P<0.01). At 5 min after ETI, MAP could predict severe CVC (AUC=0.86, P<0.01), MAP≤72 mmHg was the best cutoff value (sensitivity 78.7%, specificity 87.8%); ETCO 2 could also predict severe CVC (AUC=0.85, P<0.01), and ETCO 2≤35 mmHg was the best cutoff value (sensitivity 77.3%, specificity 85.4%). At 10 min after ETI, MAP could predict severe CVC (AUC = 0.90, P<0.01), MAP≤67 mmHg was the best cutoff value (sensitivity 89.3%, specificity 85.4%), ETCO 2 could also predict severe CVC (AUC=0.87, P<0.01), and ETCO 2≤33 mmHg was the best cutoff value (sensitivity 81.3%, specificity 78.0%). There was no significant difference in the ability of prediction between any two indexes of the MAP and ETCO 2 at 5 min and 10 min after ETI ( P>0.05). Conclusions:Patients with severe CVC after ETI have early signs of decreased MAP and ETCO 2, but the delayed recognition and insufficient intervention may be related to the occurrence and development of severe CVC. MAP and ETCO 2 at the early stage after ETI have high accuracy in predicting severe CVC. MAP≤72 mmHg, ETCO 2≤35 mmHg at 5 min after intubation, MAP≤67 mmHg and ETCO 2≤33 mmHg at 10 minutes after intubation all suggest the possibility of severe CVC.

Objective:To investigate the clinical significance of the primary tumor size in patients with endometrial carcinoma (EC).Methods:A total of 385 patients with EC admitted to Peking University People's Hospital from January 2006 to December 2016 with complete follow up data were selected, whose tumor size data before biopsy were retrospectively studied.Results:(1) The mean diameter of the primary tumor was (3.6±1.8) cm (range: 1-15 cm). And 48 cases were 0-<2 cm, 78 cases were 2-<3 cm, 92 cases were 3-<4 cm, 73 cases were 4-<5 cm, 94 cases were ≥5 cm. The diameter of the tumor was associated with age <60 years old, premenopause, CA 125≥35 kU/L, non-parturition, poor differentiation, stage Ⅲ-Ⅳ, depth of myometrial infiltration ≥1/2, cervical interstitial involvement, adnexal metastasis and lymph node metastasis (all P<0.05), but not associated with body mass index, hypertension, diabetes mellitus, pathology, lymph-vascular space invasion (all P>0.05). (2) Among the 334 patients underwent lymphadenectomy, 45 (13.5%, 45/334) cases with lymph node metastasis were observed. Stratified analysis showed that lymph node metastasis and recurrence rate of patients with EC gradually increased with the increase of tumor size ( P<0.05). Adopting 2, 3, 4 and 5 cm as cut-off values of tumor size, there were significant differences in the rate of lymph node metastasis and recurrence among them observed ( P<0.05), except for lymph node metastasis rate and recurrence rate when the cut-off value was 2 cm ( P>0.05). (3) An receiver operating characteristic (ROC) curve analysis showed that a tumor diameter of 4.25 cm was the cut-off prognostic value to predict lymph node metastasis and recurrence of EC. Conclusions:Tumor diameter is significantly correlated with lymph node metastasis and recurrence in patients with EC. Tumor size should be considered in determining the scope of surgery and adjuvant therapy.

Objective: Aimed to construct an immune-related risk signature and nomogram predicting endometrial cancer (EC) prognosis. Methods: An immune-related risk signature in EC was constructed using the least absolute shrinkage and selection operator regression analysis based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A nomogram integrating the immune-related genes and the clinicopathological characteristics was established and validated using the Kaplan-Meier survival curve and receiver operating characteristic (ROC) curve to predict the overall survival (OS) of EC patients. The Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) R tool was used to explore the immune and stromal scores. Results: CCL17, CTLA4, GPI, HDGF, HFE2, ICOS, IFNG, IL21R, KAL1, NR3C1, S100A2, and S100A9 were used in developing an immune-related risk signature evaluation model. The Kaplan-Meier curve indicated that patients in the low-risk group had better OS (p<0.001).The area under the ROC curve (AUC) values of this model were 0.737, 0.764, and 0.782 for the 3-, 5-, and 7-year OS, respectively. A nomogram integrating the immune-related risk model and clinical features could accurately predict the OS (AUC=0.772, 0.786, and 0.817 at 3-, 5-, and 7-year OS, respectively). The 4 immune cell scores were lower in the high-risk group. Forkhead box P3 (FOXP3) and basic leucine zipper ATF-like transcription factor (BATF) showed a potential significant role in the immune-related risk signature. Conclusion Twelve immune-related genes signature and nomogram for assessing the OS of patients with EC had a good practical value.

Objective:To promote emergency airway management from the perspective of training and to explore the training mode of emergency airway management based on clinical procedures.Methods:Airway management training courses were designed according to the clinical treatment principle centered on patient safety in combination with actual clinical procedures. The course took the CHANNEL process of airway management as the main line and focused on artificial ventilation, oxygen therapy and rapid induction of intubation techniques. During the teaching, we took the clinical handling process as the main line, and adopted methods of equipment display, video presentation and on-site explanation. Courses were freely registered or oriental enrollment. Online questionnaires were used to collect feedback from the students after class and were then analyzed.Results:A total of 15 training sessions were held in 13 cities across the country, with 566 participants, and 185 questionnaire responses were received. About the content of single course, participants thought that the first three parts were difficult to understand, including oxygen therapy (48, 25.9%), CHANNEL process explanation and practice (48, 25.9%) and rapid induction of intubation process (47, 25.4%). After class, 41 participants (22.2%) changed work procedures of emergency airway management, 140 (75.7%) partially changed work procedures of emergency airway management, and 4 (2.2%) still used the original work procedure.Conclusion:The course of emergency airway management based on clinical procedures meets the current clinical needs and can better improve the training of clinical competency.