Acute ischemic stroke is the most common type of stroke, characterized by high mortality, disability, and recurrence rates. Intravenous thrombolysis is the core treatment method. Among them, alteplase is effective as the standard drug, but it has limitations such as narrow time window, high risk of bleeding, and the need for continuous infusion. The new generation of improved drug tenecteplase has the advantages of single intravenous injection and higher fibrin specificity, making it a potential alternative drug to alteplase. In addition, endovascular therapy compensates for the low recanalization rate of large vessel occlusion on the basis of intravenous thrombolysis. This article reviews the clinical progress of teneplase in the treatment of acute ischemic stroke, aiming to provide reference for optimizing the treatment plan of acute ischemic stroke.

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.

The correlation between hearing loss (HL) and physical performance in patients receiving maintenance hemodialysis (MHD) remains poorly investigated. This study explored the association between HL and physical performance in patients on MHD. Methods: This multicenter cross-sectional study was conducted between July 2020 and April 2021 in seven hemodialysis centers in Shanghai and Suzhou, China. The hearing assessment was performed using pure-tone average (PTA). Physical performance was assessed using the Timed Up and Go Test (TUGT), handgrip strength, and gait speed. Results: Finally, 838 adult patients (male, 516 [61.6%]; 61.2 ± 2.6 years) were enrolled. Among them, 423 (50.5%) had mild to profound HL (male, 48.6% and female, 53.4%). Patients with HL had poorer physical performance than patients without HL (p < 0.001). TUGT was positively correlated with PTA (r = 0.265, p < 0.001), while handgrip strength and gait speed were negatively correlated with PTA (r = –0.356, p < 0.001 and r = –0.342, p < 0.001, respectively). Physical performance in patients aged <60 years showed significant dose-response relationships with HL. After adjusting for confounders, the odds ratios (95% confidence intervals) for HL across the TUGT quartiles (lowest to highest) were 1.00 (reference), 1.15 (0.73–1.81), 1.69 (1.07–2.70), and 2.87 (1.69–4.88) (p for trend = 0.005). Conclusion: Lower prevalence of HL was associated with a faster TUGT and a stronger handgrip strength in patients on MHD.

Objective:To explore the values of ultrasound, pathology combined with inflammatory indicators in predicting high nodal burden (HNB) in patients with early breast cancer and to construct a nomogram to provide reference for individualized diagnosis and treatment.Methods:The ultrasonographic, pathological features and preoperative inflammatory indicators of 378 female patients diagnosed with early breast cancer confirmed by pathology in the South Hospital of the Sixth People′s Hospital Affiliated to Shanghai Jiaotong University from January 2014 to July 2022 were retrospectively analyzed. They were randomly divided into training set ( n=302) and test set ( n=76) in a ratio of 8∶2, and the baseline data of the two groups were compared. The optimal cutoff values of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and lymphocyte to monocyte ratio (LMR) were obtained by ROC curve. In the training set, with axillary high lymph node load (≥3 metastatic lymph nodes) as the dependent variable, independent influencing factors of HNB were identified by univariate and multivariate Logistic regression analyses, and the nomogram was established. The test set data were used to verify the model. The discrimination, calibration and clinical applicability of the model were assessed by the area under the ROC curve (AUC), C-index, the calibration curve, Brier score and the decision curve analysis, respectively. Results:There were no significant differences in all variables between the training set and the test set (all P>0.05). ROC curve analysis results showed that AUCs of NLR, PLR and LMR were 0.578, 0.547 and 0.516, respectively, and the optimal cut-off values were 2.184, 150 and 3.042, respectively. Univariate Logistic regression analysis showed that age, pathological type, histological grade, Ki-67, lymphovascular invasion, NLR, PLR, ultrasonic characteristics (maximum diameter of primary tumor, shape, long/short diameter of lymph node, cortical thickness, cortical and medullary boundary, lymph node hilum, lymph node blood flow pattern) were correlated with HNB of early breast cancer (all P<0.05). Multivariate Logistic regression analysis showed that ultrasonic characteristics (maximum diameter of primary tumor >2 cm, effacement of lymph node hilum, non-lymphatic portal blood flow), lymphovascular invasion, Ki-67>14% and NLR>2.184 were independent risk factors for HNB in early breast cancer ( OR=7.258, 8.784, 6.120, 8.031, 3.394 and 3.767, respectively; all P<0.05) and were used to construct the nomogram model. The AUC of the training set was 0.914 (95% CI=0.878-0.949), C-index was 0.914; The AUC of the test set was 0.871 (95% CI=0.769-0.973), C-index was 0.871, indicating good discrimination. Calibration curve and Brier score were 0.090, indicating high calibration degree of the model. The clinical decision curve indicated good clinical benefit. Conclusions:The nomogram based on ultrasonic characteristics (maximum diameter of primary tumor, lymph node hilum, lymph node blood flow pattern), lymphovascular invasion, Ki-67 and NLR can effectively predict the risk of HNB in patients with early breast cancer, and provide a reference for precision diagnosis and treatment to avoid excessive or insufficient treatment.

Renal outer medullary potassium (ROMK) channel is an important K⁺ excretion channel in the body, and K⁺ secreted by the ROMK channels is most or all source of urinary potassium. Previous studies focused on the ROMK channels of thick ascending limb (TAL) and collecting duct (CD), while there were few studies on the involvement of ROMK channels of the late distal convoluted tubule (DCT2) in K⁺ excretion. The purpose of the present study was mainly to record the ROMK channels current in renal DCT2 and observe the effect of high potassium diet on the ROMK channels by using single channel and whole-cell patch-clamp techniques. The results showed that a small conductance channel current with a conductance of 39 pS could be recorded in the apical membrane of renal DCT2, and it could be blocked by Tertiapin-Q (TPNQ), a ROMK channel inhibitor. The high potassium diet significantly increased the probability of ROMK channel current occurrence in the apical membrane of renal DCT2, and enhanced the activity of ROMK channel, compared to normal potassium diet (P < 0.01). Western blot results also demonstrated that the high potassium diet significantly up-regulated the protein expression levels of ROMK channels and epithelial sodium channel (ENaC), and down-regulated the protein expression level of Na⁺-Cl^- cotransporter (NCC). Moreover, the high potassium diet significantly increased urinary potassium excretion. These results suggest that the high potassium diet may activate the ROMK channels in the apical membrane of renal DCT2 and increase the urinary potassium excretion by up-regulating the expression of renal ROMK channels.
Potassium Channels, Inwardly Rectifying/metabolism* ; Kidney Tubules, Distal/metabolism* ; Potassium/metabolism* ; Epithelial Sodium Channels/metabolism* ; Diet

OBJECTIVES: To compare the application effect of microwave digestion - vacuum filtration - automated scanning electron microscopy (MD-VF-Auto SEM) method and plankton gene multiplex PCR system in the diagnosis of drowning. METHODS: Lung, liver and kidney tissue of 10 non-drowning cases and 50 drowning cases were prepared for further MD-VF-Auto SEM method analysis and plankton gene multiplex PCR system analysis. The positive detection rate of the two methods in each tissue was calculated. RESULTS: The positive rate of the MD-VF-Auto SEM method detecting diatoms in drowning cases was 100%, and few diatoms were detected in the liver and kidney tissues of 6 non-drowning cases. By using the plankton gene multiplex PCR system, the diatom positive rate of drowning cases was 84%, and all the non-drowning cases were negative. There were significant differences in the positive rate of the liver, kidney tissues between MD-VF-Auto SEM method and plankton gene multiplex PCR system (P<0.05), as well as the total positive rate of cases. However, no significant differences were found in the positive rates of lung tissues (P>0.05). CONCLUSIONS MD-VF-Auto SEM method is more sensitive than plankton gene multiplex PCR system in diatom test. But the plankton gene multiplex PCR system can also detect plankton other than diatoms. Combination of the two methods can provide a more reliable basis for the diagnosis of drowning.
Diatoms/genetics* ; Drowning/diagnosis* ; Humans ; Liver ; Lung ; Microscopy, Electron, Scanning ; Multiplex Polymerase Chain Reaction ; Plankton/genetics*

Nasopharyngeal carcinoma (NPC) is a common malignant tumor in China. Radiotherapy is the first-line treatment. After appropriate radiotherapy, about 5%-15% patients experience recurrence. In view of the poor efficacy and high incidence of severe late toxicities associated with re-irradiation, salvage surgery by the transnasal endoscopic approach is recommended for recurrent NPC (rNPC). Compared with re-irradiation, endoscopic surgery can better prolong survival, improve the quality of life, and reduce complications and medical expenses of patients with rNPC. However, the complexity of the nasopharyngeal skull base enhances the difficulty and risk of surgery. Expanding the boundary of surgical resection remains a clinical challenge for otolaryngologists. In this regard, to help more advanced patients with rNPC, the surgical innovative system of NPC needs to be established by multi-disciplinary cooperation, involving skull base anatomy-based investigation, appropriate administration of the internal carotid artery (ICA), repair of skull base defect, and establishment of various types of endoscopic endonasal nasopharyngectomy.

OBJECTIVE: To study the trend of surgical type, surgical procedure and etiological distribution of upper urinary tract repair in recent 10 years. METHODS: The preoperative and perioperative variables and follow-up data of upper urinary tract reconstruction surgery in RECUTTER (Reconstruction of Urinary Tract: Technology, Epidemiology and Result) database from 2010 to 2021 were searched, collected and analyzed. The surgical type, surgical procedure, duration of hospitalization, time of operation, incidence of short-term complications, and proportion of the patients undergoing reoperations were compared between the two groups of 2010-2017 period and 2018-2021 period. RESULTS: A total of 1 072 patients were included in the RECUTTER database. Congenital factors and iatrogenic injuries were the main causes of upper urinary tract repair. Among them, 129 (12.0%) patients had open operation, 403 (37.6%) patients had laparoscopic surgery, 322 (30.0%) patients had robot-assisted laparoscopic surgery and 218 (20.3%) patients had endourological procedure. In the last decade, the total number of surgeries showed a noticeable increasing annual trend and the proportion of robot-assisted laparoscopic surgery in 2018-2021 was significantly higher than that in 2010-2017 (P < 0.001). The 1 072 patients included 124 (11.6%) cases of ileal ureter replacements, 440 (41.1%) cases of pyeloplasty, 229 (21.4%) cases of balloon dilation, 109 (10.2%) cases of ureteral reimplantation, 49 (4.6%) cases of boari flap-Psoas hitch surgery, 60 (5.6%) cases of uretero-ureteral anastomosis, 61 (5.7%) cases of lingual mucosal onlay graft ureteroplasty or appendiceal onlay flap ureteroplasty. Pyeloplasty and balloon dilatation had been the main types of surgery, while the proportion of lingual mucosal onlay graft ureteroplasty plus appendiceal onlay flap ureteroplasty had increased significantly in recent years (P < 0.05). In addition, the time of operation was significantly increased (P < 0.05) after 2018, which was considered to be related to the sharp increase in the proportion of robot-assisted laparoscopic surgery. We found that minimally invasive surgery (endourological procedure and robot-assisted laparoscopic surgery) as an independent risk factor (P=0.050, OR=0.472) could reduce the incidence of short-term post-operative complications. CONCLUSION We have justified the value of the RECUTTER database, created by the Institute of Urology, Peking University in data support for clinical research work, and provided valuable experience for the construction of other multi-center databases at home and abroad. In recent 10 years, we have observed that, in upper urinary tract reconstruction surgery, the surgery type tends to be minimally invasive and the surgery procedure tends to be complicated, suggesting the superiority of robot-assisted laparoscopic surgery.
Humans ; Laparoscopy/methods* ; Retrospective Studies ; Robotic Surgical Procedures ; Treatment Outcome ; Ureter/surgery* ; Ureteral Obstruction/surgery* ; Urologic Surgical Procedures/methods*

Objective     To systematically evaluate the safety, efficacy, and economics of intracardiac echocardiography (ICE) versus transesophageal echocardiography (TEE) in left atrial appendage occlusion (LAAO). Methods     PubMed, EMbase, The Cochrane Library, CBM, CNKI, VIP and WanFang Database were systematically  searched to collect relevant studies on comparing ICE and TEE-guided LAAO from inception to June 15th, 2022. Two reviewers independently screened the literatures, extracted the data, and assessed the risk of bias of the included studies. Meta-analyses were performed using RevMan 5.3 and R 4.0.3. Retrospective cohort studies were excluded for sensitivity analysis. Subgroup analyses were performed based on the types of occluder and ICE catheter. Results     A total of 14 studies with 6 599 patients were included. Meta-analyses showed no statistical differences in technical success rate, overall complications, device embolization, peri-device leakage, device-related thrombus, stroke, vascular complications, bleeding, operation time, fluoroscopy time, or contrast agent volume between the ICE and TEE-guided LAAO. The total in-room time (MD=–33.47 min, 95%CI –41.20 to –25.73, P<0.000 01) and radiation dosage (MD=–170.20 mGy, 95%CI –309.79 to –30.62, P=0.02) were lower in the ICE group than those in the TEE group, whereas the incidence of pericardial effusion/tamponade was higher than the TEE group (RR=1.57, 95%CI 1.01 to 2.45, P=0.048). Except for pericardial effusion/tamponade, subgroup analyses and sensitivity analysis showed similar results. The analysis based on the cost data from the United States showed comparable or even lower total costs for ICE versus TEE, but comparative domestic cost studies were lacking. Conclusion     Current evidence suggests that ICE-guided LAAO can reduce radiation dosage and total in-room time, and there is no statistical difference in the overall complication rate between the two groups. Owing to the limitations of sample size and quality of the included studies, the conclusion still needs to be verified by large sample size and high-quality randomized controlled trials.

Objective:To investigate the relationship between prolonged PR interval and carotid atherosclerosis(CAS)in middle-aged and elderly patients with type 2 diabetes mellitus(T2DM).Methods:A total of 537 middle-aged and elderly inpatients with T2DM in the Southern Branch of the Sixth People′s Hospital of Shanghai Jiaotong University from January 2019 to January 2021 were selected as the research objects. Color Doppler ultrasound was used to detect bilateral carotid artery intima-media thickness(CIMT). The subjects were divided into carotid atherosclerosis group(CAS group, n=352)and non-carotid atherosclerosis group(NCAS group, n=185). The difference in the PR interval of ECG between the two groups was compared. Pearson or Spearman rank correlation analysis was used for evaluating the correlation of PR interval and CAS lesions with various clinical index. The relationship between PR interval and CAS lesions was adopted by multivariate logistic regression analysis. Results:The average PR interval of middle-aged and elderly patients with T2DM was(164.57±23.02)ms. The average PR interval in CAS group was significantly higher than that in NCAS group [(169.76±24.28) vs (154.70±16.42)ms, P<0.01]. The results of multifactorial logistic regression analysis showed that age, low density lipoprotein-cholesterol, serum osteocalcin, and PR interval were independent factors influencing the development of CAS lesions in middle-aged and elderly patients with T2DM( OR=1.079, 1.936, 0.879, 1.039, respectively, P<0.05 or P<0.01)where each 1 ms increase in PR interval was associated with a 3.9% increase in the risk of CAS in middle-aged and elderly patients with T2DM( OR=1.039, 95% CI 1.006-1.073, P=0.020). Multivariate logistic regression analysis showed that middle-aged and elderly type 2 diabetic patients with PR interval≥158 ms were 4.072 times more likely to have CAS lesions than those with PR interval<158 ms( OR=4.072, 95% CI 1.417-11.702, P<0.01). Conclusion:The PR interval of electrocardiogram is correlated with CAS lesions in middle-aged and elderly patients with T2DM. Middle-aged and elderly type 2 diabetic patients with significantly prolonged PR interval should be reminded to screen for CAS lesions early.