BACKGROUND: Severe stroke has high rates of mortality and morbidity. This study aimed to investigate the clinical course, causes of worsening, and outcomes of severe ischemic stroke. METHODS: This prospective, multicenter cohort study enrolled adult patients admitted ≤30 days after ischemic stroke from nine hospitals in China between September 2017 and December 2019. Severe stroke was defined as a score of ≥15 on the National Institutes of Health Stroke Scale (NIHSS). Clinical worsening was defined as an increase of 4 in the NIHSS score from baseline. Unfavorable functional outcome was defined as a modified Rankin scale score ≥3 at 3 months and 1 year after stroke onset, respectively. We performed Logistic regression to explore baseline features and reperfusion therapies associated with clinical worsening and functional outcomes. RESULTS: Among 4201 patients enrolled, 854 patients (20.33%) had severe stroke on admission. Of 3347 patients without severe stroke on admission, 142 (4.24%) patients developed severe stroke in hospital. Of 854 patients with severe stroke on admission, 33.95% (290/854) experienced clinical worsening (median time from stroke onset: 43 h, Q1-Q3: 20-88 h), with brain edema (54.83% [159/290]) as the leading cause; 24.59% (210/854) of these patients died by 30 days, and 81.47% (677/831) and 78.44% (633/807) had unfavorable functional outcomes at 3 months and 1 year respectively. Reperfusion reduced the risk of worsening (adjusted odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.12-0.49, P  <0.01), 30-day death (adjusted OR: 0.22, 95% CI: 0.11-0.41, P  <0.01), and unfavorable functional outcomes at 3 months (adjusted OR: 0.24, 95% CI: 0.08-0.68, P <0.01) and 1 year (adjusted OR: 0.17, 95% CI: 0.06-0.50, P  <0.01). CONCLUSIONS: Approximately one-fifth of patients with ischemic stroke had severe neurological deficits on admission. Clinical worsening mainly occurred in the first 3 to 4 days after stroke onset, with brain edema as the leading cause of worsening. Reperfusion reduced the risk of clinical worsening and improved functional outcomes. REGISTRATION ClinicalTrials.gov , NCT03222024.
Humans ; Male ; Female ; Prospective Studies ; Ischemic Stroke/mortality* ; Aged ; Middle Aged ; Aged, 80 and over ; Stroke ; Brain Ischemia

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Objective A model for studying oral ulcers induced by betel nut-extract was constructed in rats.Changes in the structure and diversity of oral flora were observed to explore the involvement of oral flora and local inflammatory factors in the pathogenesis of oral ulcers induced by betel nut-extract and to provide theoretical support for the prevention and treatment of oral ulcers in the clinic.Methods Thirty SD rats were randomly divided into normal,model and intervention groups(Guilin watermelon cream,8 mg/d for 7 days),with 10 rats/group.The oral mucosa of rats was subcutaneously injected with 10 g/mL of betel nut-extract to generate an oral ulcer model.The histomorphological changes were observed,and ulcer area and ulcer scores were assessed.Local oral tissue tumor necrosis factor-α(TNF-α),interleukin(IL)-2 and IL-8 levels were determined.Oral mucosal tissues were sampled for HE staining and analyzed for the structural distribution of oral flora and the diversity of microbial communities using high-throughput sequencing method.Results Compared with rats in the normal group,those in the model group had an increased ulcer area,significantly increased ulcer scores(P＜0.01),and significantly increased levels of TNF-α,IL-2 and IL-8 in the oral mucosal tissues(P＜0.01).The amount Streptococcus(P＜0.05)and Veillonella(P＜0.001)in the oral saliva of the model group rats was significantly reduced.The model group rats showed oral mucosal epithelial cell hyperplasia or focal necrosis,mucosal lamina propria edema,and hemorrhage accompanied by mass neutrophil and monocyte infiltration.Compared with the model group rats,the intervention group rats had significantly reduced ulcerated area(P＜0.05,P＜0.01)and ulcer scores(P＜0.05).And oral mucosal tissue levels of TNF-α(P＜0.01),IL-2(P＜0.05)and IL-8(P＜0.05),as well as significantly increased Streptococcus(P＜0.001)and Veillonella(P＜0.01)and significantly reduced Staphylococcus(P＜0.01)in the oral saliva.The degree of lesions in the oral mucosal tissues was significantly improved in the intervention group.Conclusions Betel nut-extract can be used to successfully reproduce a rat model of oral ulcer,and it is speculated that the development of oral ulcers after exposure to betel nut-extract may be related to an imbalance in the oral flora and local tissue inflammatory mediators.

Objectives:Interatrial block(IAB)is a conduction delay between the right and left atria,which is a phenomenon recognized as an electrocardiogram(ECG)feature of atrial fibrosis.This study aimed to investigate the relationship between advanced IAB and in-hospital new-onset atrial fibrillation(NOAF)in patients with ST-segment elevation myocardial infarction(STEMI). Methods:This single-center retrospective observational study consecutively enrolled 916 patients diagnosed with STEMI from September 2019 to June 2022,who underwent primary percutaneous coronary intervention within 24 hours of onset.ECG was recorded in all patients at the first medical contact,and the ECG was scanned and uploaded on the official China Chest Pain Center platform.The detection rate of IAB and the incidence of NOAF in STEMI patients were analyzed,and the possible associated factors of new-onset atrial fibrillation during hospitalization of STEMI patients were evaluated by logistic regression analysis. Results:IAB was detected in 269(29.4%)patients,57(21.2%)of these patients had advanced IAB.In-hospital NOAF was detected in 89(9.7%)patients.Multivariate analysis showed age(OR=1.070,95%CI:1.045-1.095,P<0.001),left ventricular ejection fraction(OR=0.929,95%CI:0.901-0.957,P<0.001),right coronary artery lesion(OR=1.672,95%CI:1.042-2.683,P=0.033),and advanced IAB(OR=4.007,95%CI:1.973-8.138,P<0.001)were independent determinants of in-hospital NOAF among STEMI patients.Integrated discrimination improvement(IDI)and net reclassification improvement(NRI)were improved significantly when advanced IAB was included in the NOAF risk model with a satisfactory C index(0.742). Conclusions:Advanced IAB is an independent risk marker for NOAF in patients with STEMI.Advanced IAB has incremental impact for improving the discriminatory accuracy of the NOAF predicting model.

Objective:To construction the risk factors associated with prolonged hospitalization in patients with severe acute pancreatitis (SAP) and develop a prediction model for assessing these risks.Methods:SAP patients admitted to the department of emergency of Hebei Province Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine from January 2015 to December 2023 were retrospectively selected as the study subjects. The 75% of hospital stay was used as the cut-off point, and the patients were categorized into a normal group and an extended group. Clinical indicators of patients were collected, and independent risk factors for prolonged hospital stay in SAP patients were analyzed using multifactor Logistic regression. A prediction model was established, and a nomogram was created. The efficiency of the prediction model was evaluated using a receiver operator characteristic curve (ROC curve). The accuracy of the model was assessed using Hosmer-Lemeshow goodness-of-fit test. Decision curve analysis (DCA) was employed to evaluate the clinical applicability of the model. Finally, internal validation of the model was conducted using Bootstrap method.Results:A total of 510 patients with SAP were included, and the length of hospital stay was 18 (6, 44) days, including 400 cases in the normal group (<24 days) and 110 cases in the extended group (≥24 days). Multivariate Logistic regression analysis showed that abdominal effusion [odds ratio ( OR) = 4.163, 95% confidence interval (95% CI) was 2.105-8.234], acute physiology and chronic health evaluation Ⅱ (APACHEⅡ; OR = 1.320, 95% CI was 1.185-1.470), C-reactive protein (CRP; OR = 1.006, 95% CI was 1.002-1.011), modified CT severity index (MCTSI; OR = 1.461, 95% CI was 1.213-1.758), procalcitonin (PCT; OR = 1.303, 95% CI was 1.095-1.550) and albumin ( OR = 0.510, 95% CI was 0.419-0.622) were independent risk factors for prolonged hospital stay in SAP patients (all P < 0.01). ROC curve analysis showed that the area under the curve (AUC) of the model was 0.922 (95% CI was 0.896-0.947), the optimal cut-off value was 0.726, the sensitivity was 87.3%, and the specificity was 85.3%. Hosmer-Lemeshow test showed that χ 2 = 5.79, P = 0.671. It showed that the prediction model had good prediction efficiency and fit degree. The DCA curve showed that the prediction probability of the model could bring more clinical benefits to patients at 0.1 to 0.7. Bootstrap internal verification showed that the model had a high consistency (AUC = 0.916). Conclusions:Abdominal effusion, high APACHEⅡ score, high CRP, high MCTSI, high PCT and low albumin level are significantly associated with prolonged hospital stay in SAP patients. The prediction model can help clinicians make more scientific clinical decisions for SAP patients.

Two pediatric heart failure patients were treated with pulmonary artery banding(PAB)at Fuwai Hospital,from December 2021 to January 2022.In the first case,an 8-month-old patient presented with left ventricular non-compaction cardiomyopathy(LVNC),left ventricular systolic dysfunction,ventricular septal defect,and atrial septal defect.The second case was a 4-month-old patient with LVNC,left ventricular systolic dysfunction,and coarctation of the aorta.After PAB,the left ventricular function and shape of both patients were significantly improved,without serious surgery-related complications.In these individual cases of pediatric heart failure,pulmonary artery banding exhibited a more satisfactory efficacy and safety compared to pharmacological treatment,especially for those with unsatisfactory medication results.Future clinical data are needed to promote the rational and broader application of this therapeutic option for indicated patients.

Odontogenic maxillary sinusitis(OMS)is a subtype of maxillary sinusitis(MS).It is actually inflammation of the maxillary sinus that secondary to adjacent infectious maxillary dental lesion.Due to the lack of unique clinical features,OMS is difficult to distinguish from other types of rhinosinusitis.Besides,the characteristic infectious pathogeny of OMS makes it is resistant to conventional therapies of rhinosinusitis.Its current diagnosis and treatment are thus facing great difficulties.The multi-disciplinary cooperation between otolaryngologists and dentists is absolutely urgent to settle these questions and to acquire standardized diagnostic and treatment regimen for OMS.However,this disease has actually received little attention and has been underrepresented by relatively low publication volume and quality.Based on systematically reviewed literature and practical experiences of expert members,our consensus focuses on characteristics,symptoms,classification and diagnosis of OMS,and further put forward multi-disciplinary treatment decisions for OMS,as well as the common treatment complications and relative managements.This consensus aims to increase attention to OMS,and optimize the clinical diagnosis and decision-making of OMS,which finally provides evidence-based options for OMS clinical management.

BACKGROUND: Non-small cell lung cancer (NSCLC) is one of the most lethal malignancies worldwide. A novel Chinese medicine formula-01 (NCHF-01) has shown significant clinical efficacy in the treatment of NSCLC, but the mechanism of this formula in the treatment of NSCLC is not fully understood. The aim of this study is to investigate the molecular mechanism of NCHF-01 in inhibiting NSCLC. METHODS: Lewis lung cells (LLC) tumor bearing mice were established to detect the tumor inhibitory effect of NCHF-01. The morphological changes of tissues and organs in LLC tumor-bearing mice were detected by hematoxylin-eosin (HE) staining. NSCLC cells were treated by NCHF-01. The effects of cell viability and proliferation were detected by MTT and crystal violet staining experiment. Flow cytometry was used to detect cell cycle, apoptosis and reactive oxygen species (ROS). Network pharmacology was used to predict the mechanism of its inhibitory effect of NSCLC. Western blot and immunohistochemistry (IHC) were used to detect the expression of related proteins. RESULTS: NCHF-01 can inhibit tumor growth in LLC tumor-bearing mice, and has no obvious side effects on other tissues and organs. NCHF-01 could inhibit cell viability and proliferation, induce G2/M phase arrest and apoptosis, and promote the increase of ROS level. Network pharmacological analysis showed that NCHF-01 exerts anti-NSCLC effects through various biological processes such as oxidative stress and central carbon metabolism. NCHF-01 can reduce the protein expression and enzyme activity of the key enzymes 6-phosphate glucose dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) in the pentose phosphate pathway (PPP). CONCLUSIONS NCHF-01 can inhibit NSCLC through oxidative stress dependent on the PPP.
Animals ; Mice ; Carcinoma, Non-Small-Cell Lung/pathology* ; Lung Neoplasms/pathology* ; Reactive Oxygen Species/therapeutic use* ; Medicine, Chinese Traditional ; Pentose Phosphate Pathway ; Oxidative Stress ; Cell Line, Tumor ; Cell Proliferation ; Apoptosis

OBJECTIVE To establish the estimation model for the exposure of mycophenolic acid （MPA） in early renal transplant recipients [calculated by the area under the plasma concentration-time curve with 12 h （AUC0－12 h）]. METHODS Twenty kidney transplant recipients， who received triple immunosuppressive therapy of mycophenolate mofetil （MMF）+tacrolimus+ methylprednisolone， were selected and given MMF dispersible tablets （750 mg， q12 h） on the 15th day after the operation； the blood samples were collected from the patients before and 0.5， 1.0， 1.5， 2.0， 3.0， 4.0， 6.0， 8.0， 12.0 hours after the administration， respectively. The blood concentration of MPA was determined， and the pharmacokinetic parameters of MPA were calculated. The multivariate linear stepwise regression analysis method was used to fit an estimation formula for the finite sampling method suitable for MPA-AUC0－12 h of the recipients. Bland-Altman analysis was used to evaluate the agreement between the estimation formula and the classical pharmacokinetic method. RESULTS The main pharmacokinetic parameters of MPA in 20 renal transplant recipients： c0 was （1.53±0.84） μg/mL， cmax was （12.07±5.97） μg/mL， t1/2 was （5.41±3.67） h， tmax was （1.58±0.75） h， and the average AUC0－12 h calculated by the classical pharmacokinetic method was （33.95±13.40） μg·h/mL. MPA-AUC0－12 h was estimated with sampling points of “4.0， 8.0， 12.0 h”； the simplified calculation formula was AUC0－12 h＝12.058+2.819c4.0+7.045c8.0+ 3.879c12.0 （R 2＝0.934）. The predicted value had a good correlation and consistency with the measured value， and 95.0% of predicted values did not exceed the x±1.96SD （standard deviation） range. CONCLUSIONS The estimation model is established successfully for the exposure of MPA in early renal transplant recipients； the model has better prediction accuracy and fewer sampling points.

Objective:To construct the prediction model of SAP complicated with intra-abdominal hypertension (IAH), and evaluate the prediction efficiency of the model.Methods:The clinical data of 322 SAP patients admitted to the emergency department of Cangzhou Hospital of Integrated Chinese and Western Medicine in Hebei Province from January 2017 to December 2021 were retrospectively analyzed. They were divided into IAH group ( n=153) and control group ( n=169) according to whether they had IAH complications or not. The clinical characteristics and laboratory test results of the two groups were compared. Multifactor logistic step-up regression was used to analyze the risk factors of SAP patients complicated with IAH. A nomogram model for predicting SAP complicated with IAH was established by using R software. The receiver operating characteristic curve (ROC) of the model was plotted, and the area under the curve (AUC) was calculated to evaluate its prediction efficiency. Calibration chart, Hosmer-Lemesshow test and decision curve analysis were used to evaluate the prediction accuracy and clinical application value of the model. The Bootstrap method was applied to verify the model internally. Results:In IAH group, cases with body mass index, CRP, procalcitonin (PCT), WBC, acute physiological and chronic health assessmentⅡ (APACHEⅡ) score, modified CT Severity Index score (MCTSI), incidence of complications (abdominal effusion, abdominal infection, gastrointestinal dysfunction, shock, multiple organ dysfunction syndrome), mechanical ventilation, the number of high-volume fluid reactivation (24 h≥4 L) were more than those in control group; serum albumin and serum calcium in IAH group were lower than those in control group, and the differences were statistically significant (all P value <0.05). Multivariate logistic regression analysis showed that serum albumin ( OR=0.815, 95% CI 0.710-0.937), CRP ( OR=1.005, 95% CI 1.002-1.008), MCTSI ( OR=2.043, 95% CI 1.695-2.463), complication of gastrointestinal dysfunction ( OR=4.179, 95% CI 2.170-8.049), and high-volume fluid resuscitation ( OR=4.265, 95% CI 2.269-8.015) were independent risk factors for IAH in SAP.The Nomogram prediction model was established using the five factors above as parameters, and the AUC value for predicting IAH complication was 0.886. The Hosmer-Lemesshow test showed a high consistency between the prediction results and the actual clinical observation results ( P=0.189). The results of decision curve analysis showed that the prediction probability of the model was between 10% and 85%, which could bring more benefits to patients. Conclusions:The early prediction model of SAP with concurrent IAH is successfully established, which can better predict the risk of SAP with concurrent IAH.