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

Objective:To investigate the clinicopathological characteristics, immunophenotypes, diagnostic criteria and differential diagnosis of atrophic kidney-like lesion (AKLL).Methods:Three cases of AKLL were collected from April 2021 to October 2023 at the Xiangya Hospital of Central South University, Changsha, Zhejiang Provincial People′s Hospital, Hangzhou and Ningbo Clinical Pathology Diagnosis Center, Ningbo, China. The clinical, morphological, and immunohistochemical characteristics were analyzed. Relevant literature was also reviewed. A targeted DNA-based next-generation sequencing (a panel of 150 genes) was performed on one of the three cases.Results:There were 1 female and 2 males, aged 30, 57, and 17 years (mean 34.6 years), respectively. The lesions were all incidentally identified during physical or imaging examination. Radiologically, they were all presented as a unilateral renal parenchymal mass. Grossly, the maximum diameters of the lesions were 1.8, 4.0, and 6.5 cm (mean 4.1 cm), respectively. The tumor cut-surfaces were sponge-like, multilocular cystic, and solid, respectively. At low magnification, the lesions were well-circumscribed, while a thick fibromuscular capsule was noted in cases 1 and 3. Cases 1 and 2 were composed of thin-walled cysts or follicular like structures of varying sizes, with the cyst wall lined by flattened and atrophic, or hobnail cells. The luminal spaces contained dense eosinophilic secretion and associated calcifications, while some cysts contained discohesive cells floating in the eosinophilic material. The tissue between the cysts showed predominantly small atrophic tubular structures. Case 3 was almost entirely composed of atrophic and collapsed tubular structures with focal cyst formation, imparting a solid sheets growth pattern under low magnification. Immunohistochemical staining revealed that the cyst lining cells and the intracystic floating cells were WT1 positive, PAX8 negative and CK7 negative, while the atrophic renal tubules were WT negative, PAX8 positive and CK7 positive. Targeted next-generation sequencing in case 1 showed no significant genetic abnormalities. All 3 patients underwent partial nephrectomy. No evidence of recurrence or metastasis was found with a follow-up of 17 to 36 months.Conclusions:AKLL is a rare and novel benign renal disease. It is easily misdiagnosed as a renal neoplasm grossly and histologically. Careful morphological observation combined with characteristic immunophenotypes can aid in its diagnosis and differential diagnosis.

Objective:Sort out the problems currently faced by Traditional Chinese Medicine(TCM)medical institutions in implementing the reform of medical insurance payment methods,and propose reform suggestions.Methods:Through literature analysis and field research,the reform practices of some cities that have implemented payment are summarize based on TCM dominant diseases.Results:Currently,payment by disease for TCM faces many problems and difficulties,such as the small number of dominant diseases of TCM carried out in various regions,the imperfect coding of TCM diagnoses and operations,and the unstable compensation mechanism for TCM medical institutions,which affect the development of dominant diseases of TCM.Conclusion:The payment for TCM dominant diseases requires the support and cooperation of multiple departments,scientifically and reasonably screening TCM dominant diseases,improving policies,refining management measures,and leveraging the unique advantages of traditional Chinese medicine.

Objective The protective effect and molecular mechanism of electroacupuncture combined with massage on cartilage damage in knee Osteoarthritis rats were explored.Methods 50 SD rats were selected and divided into a control group,a model group,an electroacupuncture group,a massage group,and an electroacupuncture+massage group of 10 rats each using an odd even number method.The rats in the control group were not treated with modeling,and the rats in the other groups were injected with Papain into the articular cavity to build the right knee Osteoarthritis(KOA)model.The massage and electroacupuncture groups were intervened with electroacupuncture and massage for 2 weeks.The improved Le-quesne MG scale was used to evaluate the behavioral performance of rats.The pressure pain value and heat pain threshold of rats before and after intervention were calculated.After eight weeks,the rats were euthanized and abdominal aortic blood was collected.The serum levels of pain mediators(K+),5-hydroxytryptamine(5-HT),and dopamine(DA)were measured by ELISA in each group of rats.The right knee joint of rats was taken for HE staining Mankin score,TUNEL chondrocyte apoptosis analysis.Toluidine blue staining was used to observe the changes of cartilage matrix polysaccharide;Western blot was used to detect the concentration and expression of cartilage matrix factor type Ⅱ collagen(Collagen Ⅱ),C-terminal peptide(CTX Ⅱ),type Ⅱ collagen C-precursor peptide(CPⅡ),apoptosis related proteins Bax,Bcl-2,Cleared caspase-3,YAP,p-YAP in the knee joint tissues of rats in each group.Results After the establishment of the KOA model,the Lequesne MG score of rats increased significantly(P<0.05).Compared with the model group,the Lequesne MG scores of rats in the electroacupuncture group and massage group decreased significantly(P<0.05).The combination of the two can further reduce the Lequesne MG score significantly(P<0.05).Compared with the control group,the pain threshold(TWL,MWT)of the model group was downregulated significantly,and the levels of serum pain factors(K+,DA,5-HT)were upregulated significantly(P<0.05).Compared with the model group,the pain thresholds(TWL,MWT)of the electroacupuncture group and the massage group were upregulated significantly,while the levels of serum pain factors(K+,DA,5-HT)were downregulated significantly(P<0.05).The combination of the two reflected the highest pain threshold(TWL,MWT)and the lowest serum pain factor(K+,DA,5-HT)levels.The model group rats had significant joint cartilage fissures,cartilage matrix staining and staining area decreased,and Markin score and cell apoptosis ability were improved(P<0.05).Compared with the model group,the arrangement degree of the cartilage layer,staining degree of the cartilage matrix,and staining area of the electroacupuncture group and massage group were all improved,while the Markin score and cell apoptosis rate all decreased significantly(P<0.05).The combination can further reduce the Markin score and the degree of chondrocyte apoptosis(P<0.05).Compared with the control group,the expression of Collagen Ⅱ,CPⅡ,Bcl-2,and p-YAP proteins in the model group decreased significantly,while the expression of CTX Ⅱ,Bax,and Cleared caspase-3 proteins increased significantly(P<0.05).Conclusion The combination of electroacupuncture and massage intervention can significantly improve the pathological state of cartilage injury in rats with osteoarthritis,reduce knee joint pain,inhibit chondrocyte apoptosis,and play a protective role in cartilage injury.Its molecular mechanism may be related to the activation of Hippo YAP signaling pathway,which is worth further research in clinical practice.

Objective:To investigate the role of serotonergic (5-HT) neurons activation in the dorsal raphe nucleus (DRN) in heat-induced seizures and its influence on breathing patterns in Scn1a + /- mice. Methods:24-day-old male Scn1a + /- mice were used for experiments, and sudden unexpected death in epilepsy(SUDEP) model was established through heat induction for 5 consecutive days. (1) Fluoxetine intervention experiment: 20 male mice were randomly divided into model group( n=10) and fluoxetine group ( n=10) according the weight-matched method. The fluoxetine group received intraperitoneal injection of fluoxetine (10 mg/kg) 45 min before heat induction each day for 5 consecutive days, while the model group received equal volume of 0.9% NaCl solution. (2) Chemogenetic activation experiment: 20 male mice were randomly divided into vector control group( n=10) and chemogenetic activation group ( n=10) according the weight-matched method. Empty vector or rAAV-TPH2-hM3d(Gq)-EGFP-WPREs was stereotaxically injected into DRN 14 d prior to seizure induction, and deschloroclozapine (5 mg/kg) was intraperitoneally injected 30 min before heat induction. Seizure characteristics and survival were assessed through video monitoring, and respiratory parameters were monitored. Immunofluorescence was used to detect colocalization of tryptophan hydroxylase 2(TPH2) and c-Fos in DRN. Statistical analysis was performed using SPSS 24.0 and GraphPad Prism 9.0. The independent sample t-test or Mann-Whitney test was used for inter-group comparison. Results:(1) In the fluoxetine intervention experiment: the survival rates between the model group and fluoxetine group showed no statistically significant difference ( χ2=2.23, P>0.05). As for the frequency of grade Ⅳ seizures, the model group (1.50(1.25, 2.35)min) demonstrated higher frequency than the fluoxetine group (0.43(0.20, 0.67)min) ( t=-3.40, P<0.05).With respect to respiratory parameters, the model group demonstrated shorter expiratory time ((0.10±0.02) s) and inspiratory time ((0.15±0.02) s) compared to the fluoxetine group ((0.16±0.05) s, (0.19±0.04) s) ( t=-3.47, -3.73, both P<0.01). The respiratory rate in the model group ((269.96±44.84) times/min) was significantly higher compared to the fluoxetine group ((195.04±52.37) times/min) ( t=3.44, P<0.01). The tidal volume in the model group ((0.10±0.02) mL) was significantly lower than the fluoxetine group ((0.13±0.04) mL) ( t=-2.19, P<0.05).The number of TPH2+ /c-Fos+ co-expressing cells in the model group (11.00±4.00) was lower than that in the fluoxetine group (33.00±8.39)( t=-4.16, P<0.05). (2) In the chemogenetic activation experiment: compared to the vehicle group, the chemogenetic activation group demonstrated significantly enhanced survival rates ( χ2=5.83, P<0.05). As for the frequency of grade Ⅴ seizures, the vehicle group (2.11(1.62, 3.44) times/min) showed higher frequency compared to the chemogenetic activation group (0.81(0.00, 1.62) times/min) ( t=18.00, P<0.05). In terms of respiratory parameters, the vehicle group showed shorter expiratory time ((0.10±0.01) s) and inspiratory time ((0.14±0.01) s) compared to the chemogenetic activation group ((0.12±0.01) s, (0.15±0.01) s) ( t=-2.78, -2.50, both P<0.05). The respiratory rate in the vehicle group ((208.37±9.73) times/min) was significantly higher than the chemogenetic activation group ((191.85±8.83) times/min) ( t=3.98, P<0.01). The tidal volume in the vehicle group ((0.09±0.01) mL) was significantly lower than the chemogenetic activation group ((0.12±0.02) mL) ( t=-4.77, P<0.001).The number of TPH2+ /c-Fos+ co-expressing cells in the vehicle group (9.00±3.46) was lower than that in the chemogenetic activation group (43.00±11.02)( t=-5.20, P<0.01). Conclusion:Specific activation of serotonergic neurons in the DRN can ameliorate heat-induced epileptic symptoms, improve respiratory function, and prolong survival time in Scn1a + /- mice.

Objective To evaluate the clinical value of a modified Cancer and Aging Research Group(CARG)model in guiding anticancer drug dose adjustments for elderly cancer patients in China.Methods This prospective study enrolled patients aged≥65 years with solid tumors at the Department of Oncology,Peking Union Medical College Hospital from September 1,2022 to October 29,2023.All patients underwent comprehensive geriatric assessment(CGA)and CARG risk scoring,and were stratified into low-,intermediate-,and high-risk groups.Anti-cancer drug doses(including chemotherapy,targeted therapy or immunotherapy)were reduced proportionally based on CARG risk stratification and treatment intent(curative vs.palliative).Treatment outcomes and adverse events(AEs)were recorded regularly.Fisher's Exact Test compared AE incidence between the CARG-guided dose adjust-ment group(experimental)and the physician-experience-guided dose adjustment group(control).Receiver operating characteristic(ROC)curve analysis was used to assess the predictive value of the CARG model for severe toxicity.Results Among 166 enrolled patients(median age:71 years[range:65-90];78.3%were male;68.7%had gastro-intestinal cancers;69.3%had stageⅣ),95 were assigned to the experimental group(CARG low-risk:24[25.3%],intermediate-risk:51[53.7%],high-risk:20[21.0%])and 71 were included into the control group.By December 31,2024,81 patients experienced disease progression and 10 patients died.Overall AE rates was 92.6%in the ex-perimental group and 94.4%in the control group,while grade≥3 AEs were recorded in 45.3%vs.43.7%,respec-tively(both P＞0.05).Conclusions The modified CARG model-guided dose adjustment strategy achieved comparable safety to empirical dose adjustment,which is in line with the individualized treatment paradigm for elderly cancer pa-tients,representing a structured framework for optimizing therapeutic decision-making in geriatric oncology.

In the current process of talent cultivation in biology majors,some challenges like teaching content that lags behind the forefront of scientific research,instructional models that deviate from the principles of effective knowledge transmission,and evaluation systems that lack dimensions reflecting scientific innovation.As a strategy of tackling challenges,the Genetic Engineering teaching team,drawing on theoretical analysis and extensive teaching practice,has explored a reform of the instructional model from the perspective of integrating theory with practice.This effort led to the development of a research-oriented teaching model characterized by four iterative stages:knowledge instruction,thinking exercises,practical operation,and feedback evaluation.This model is ground-ed in five core elements of scientific thinking:criticality,coherence,simplicity,logic,and integrity.Imple-mentation follows the four-step framework,emphasizing structured knowledge delivery,cultivation of analytical thinking,hands-on experimentation,and comprehensive feedback.After one semester of application,it was found that through reconstructed knowledge systems,immersive simulations of research contexts,realistic problem-solving of technical bottlenecks and all-round feedback,this teaching model effectively fosters scientific thinking among both instructors and students,significantly enhances students'scientific research ca-pabilities and improves overall teaching effectiveness.

Objective To construct a prediction model for the risk of peripherally inserted central venous catheter(PICC)-related bloodstream infection(CRBSI)in preterm infants,and evaluate the effect of the model.Methods 1 295 preterm infants admitted to the neonatal intensive care unit(NICU)in a hospital and received PICC intrave-nous infusion from January 2019 to October 2023 were selected as the study subjects,including 1 080 preterm in-fants from January 2019 to December 2022 in the modeling set and 215 premature infants from January to October 2023 in the validation set.Risk factors of cases were analyzed based on 24 clinical characteristics,optimized charac-teristics was selected by LASSO regression,independent risk factors for CRBSI of preterm infants during PICC in-dwelling period were identified by multiple logistic regression analysis,and nomogram model was constructed with R software.Discrimination and fitting of the model were evaluated by the area under the curve(AUC)of the receiver operating characteristic(ROC)as well as Hosmer-Lemeshow test and calibration curve,and clinical practicality of the model was evaluated by decision curve analysis(DCA).Results Multivariate logistic analysis showed that birth weight ≥1 500 g,sterile protection during catheter maintenance,and sterile cloth wrapped joints were protective factors for CRBSI during PICC indwelling period in preterm infants(OR=0.172,0.187,0.063,respectively,all P＜0.05),while puncture frequency＞2 times,catheter indwelling period＞14 days,and use of tees were inde-pendent risk factors for CRBSI during PICC indwelling period in premature infants(OR=2.533,14.128,13.256,respectively,all P＜0.05).The AUC of ROC of the modeling set was 0.953(95％CI:0.936-0.969),and that of the validation set was 0.930(95％CI:0.885-0.974),indicating good discriminability of the model.The calibra-tion curve and Hosmer-Lemeshow goodness of fit test showed that the model had good accuracy and consistency,with high net profit value,indicating that the predictive value of the model was high and with good clinical practica-lity.The statistical test result in the rationality analysis of the model was P＜0.001.Conclusion The nomogram model based on the general clinical characteristics of preterm infants as well as the basic prevention and control measures of the catheter can provide a visual and simple evaluation tool for early identification of high risk factors for CRBSI in preterm infants.

Objective To compare image quality and clinical usefulness between single breath-hold three-dimensional magnetic resonance cholangiopancreatography with compressed sensing(3D BH-CS-MRCP)and with gradient and spin-echo(3D BH-GRASE-MRCP)and conventional three-dimensional breath-triggered magnetic resonance cholangiopancreatography(3D RT-MRCP).Methods A retrospective analysis was performed in 48 patients(26 males and 22 females,mean age of 53.14±15.19 years),who underwent 3D BH-GRASE-MRCP,3D BH-CS-MRCP and 3D RT-MRCP from September to December 2023.Pancreaticobiliary duct visibility,motion artifacts,background suppression,and overall image quality were scored on a 5-point scale by two radiologists.The relative contrast ratio of three bile duct segmentations(common bile duct,left and right intrahepatic bile ducts)were calculated,and the acquisition time of the three sequences was recorded.Friedman test with a post-hoc test was performed to compare image acquisition time,qualitative and quantitative results.Results The acquisition time was significantly shorter in the two breath-hold groups than for conventional 3D RT-MRCP(P＜0.001).There were no significant differences in overall image quality,motion artifacts,common bile duct and primary branch of intrahepatic bile duct among the three groups.The relative contrast ratio,intrahepatic biliary secondary branch visibility and background suppression score of 3D RT-MRCP and BH-CS-MRCP were significantly higher than those of BH-GRASE-MRCP(P＜0.01).The pancreatic duct(proximal,middle,distal)visibility score of 3D RT-MRCP was significantly better than that of BH-GRASE-MRCP(P=0.002,0.043,0.001),but the gallbladder and gallbladder duct visibility score of BH-GRASE-MRCP was higher than that of 3D RT-MRCP(P=0.036).There was no significant difference between 3D RT-MRCP and BH-CS-MRCP scores except for the middle and distal pancreatic duct visibility.Conclusion Breath-hold 3D MRCP with GRASE and CS can give us feasible options for pancreaticobiliary diagnosis,which significantly shortens the acquisition time without reducing the overall image quality.Compared with BH-GRASE-MRCP,BH-CS-MRCP has better consistency in pancreaticobiliary duct visibility and background suppression.

Acute gallstone pancreatitis (AGP) represents an acute inflammatory condition of the pancreas, of which etiology and prevention require systematic understanding from the molecular mechanisms of onset, combined with the foundations of pathological anatomy and pathophysiological processes. Main pancreatic duct obstruction and bile acid reflux are the primary causes of AGP. The duration of the obstruction is particularly crucial to its progression, and early intervention in pancreatic duct obstruction is key to preventing severe cases. The management strategy for AGP in its early stages includes endoscopic ultrasound, endoscopic retrograde cholangiopancreatography, and endoscopic sphincterotomy. The core of diagnosis and treatment involves promptly identifying the cause, relieving bile and pancreatic duct obstruction, reducing pressure in the pancreatic duct, implementing common bile duct drainage, and evaluating the effect of pancreatic duct stenting. Since gallstones are the only controllable factor, early cholecystectomy is the safest choice for preventing AGP. However, the timing and methods of etiological prevention and treatment of AGP still require further research. This article synthesizes insights into anatomical factor management, gallstone prevention, interruption of the onset process, and coordination of prevention mechanisms, aiming to provide a reference for AGP prevention and treatment.