Objective·To investigate the role of interleukin-1β(IL-1β)in predicting the severity of oral and maxillofacial space infection(OMSI),and to explore the key mechanisms regulating IL-1β release,the critical immune cell subpopulations involved,and the intercellular communication networks among immune cells in OMSI patients.Methods·A total of 62 OMSI patients admitted to the Department of Oral Surgery,Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine,from January to November 2023 were enrolled,including 20 patients with moderate infection,21 with severe infection,and 21 with extremely severe infection.Logistic regression analysis was performed to identify risk factors for extremely severe infection,and receiver operating characteristic(ROC)curves were constructed to evaluate the ability of the above indicators to predict extremely severe infection.Peripheral blood mononuclear cells(PBMCs)from 2 patients in each group(moderate,severe and extremely severe)and 2 healthy controls(GSE224198)were analyzed using single-cell RNA sequencing(scRNA-seq)to identify key pro-inflammatory cell subtypes and genes,and to examine their changing trends with increasing infection severity.Cell-cell communication was assessed using CellChat.Quantitative real-time polymerase chain reaction(qPCR)and Western blotting were used to validate inflammasome activation levels in PBMCs.Results·Compared with patients with moderate and severe infections,levels of procalcitonin(PCT)(P<0.05)and IL-1β(P<0.05)were significantly elevated in patients with extremely severe infection.Logistic regression identified IL-1β as an independent risk factor for extremely severe infection(OR=1.814,95%CI 1.256?2.621,P=0.002).The area under the ROC curve(AUC)for the combined prediction of extremely severe infection using IL-1β and PCT was 0.943.scRNA-seq revealed continuous upregulation of NLRP3(NOD-like receptor family pyrin domain-containing 3)and IL1B gene expression in monocytes as infection severity increased,with intermediate monocytes being the main IL1B-expressing cell subtype.IL-1Β-IL-1R signaling,C-C motif chemokine ligand(CCL)and intercellular adhesion molecule(ICAM)signaling were significantly enhanced in monocytes.Macrophage migration inhibitory factor(MIF)signaling between T cells and monocytes also increased notably.With infection progression,the mRNA levels of NLRP3 and IL1B in peripheral blood rose steadily,and the protein levels of NLRP3,caspase-1 p20,apoptosis-associated speck-like protein containing a CARD(ASC)and IL-1β were persistently elevated.Conclusion·The combined levels of IL-1β and PCT at admission can effectively predict extremely severe OMSI.NLRP3 inflammasome activation is observed in PBMCs of OMSI patients.The elevation of IL-1β is closely associated with intermediate monocytes.Monocyte-mediated IL-1Β-IL-1R,CCL and ICAM signaling pathways,along with T cell-mediated MIF signaling pathways,collectively promote the inflammatory response.

Background and Aims:Acute inferior vena cava thrombosis(IVCT)commonly occurs secondary to inferior vena cava filter(VCF)implantation.If not promptly treated,it may lead to serious complications such as bilateral lower limb swelling and pulmonary embolism and can also reduce the likelihood of successful filter retrieval.Percutaneous mechanical thrombectomy(PMT)and catheter-directed thrombolysis(CDT)are currently the main interventional treatments for IVCT,but comparative studies evaluating their efficacy and safety remain limited.This study was to conduct a prospective randomized controlled trial to compare the clinical efficacy and safety of AngioJet mechanical thrombectomy versus conventional CDT in the treatment of acute IVCT and to explore factors influencing filter retrieval rates,thereby providing evidence-based guidance for clinical decision-making.Methods:From January 2022 to December 2024,patients diagnosed with acute IVCT following VCF implantation were prospectively enrolled at the Department of Vascular Surgery,Beijing Jishuitan Hospital,Capital Medical University.Patients were randomly assigned to either the CDT group(n=46)or the PMT group(n=48)according to the interventional procedure used.The two groups were compared in terms of filter retrieval rates,thrombus clearance outcomes,operative time,thrombolytic drug dosage,and incidence of complications.Logistic regression analysis was used to identify factors associated with primary filter retrieval.Results:A total of 94 patients were enrolled,with 46 in the CDT group and 48 in the PMT group.Compared to the CDT group,the PMT group demonstrated a significantly higher primary filter retrieval rate(77.1%vs.43.5%),grade Ⅲ thrombus clearance rate(70.8%vs.37.0%),and better postoperative thrombus scores.Additionally,the PMT group required lower urokinase doses and shorter thrombolysis duration(all P<0.05).The overall filter retrieval rate and 3-month IVC patency were similar between groups,both exceeding 93%.Regarding safety,the CDT group had a higher incidence of catheter-related infections and medical adhesive-related skin injury,while vagal reflex symptoms were more frequent in the PMT group.Logistic regression analysis identified thrombus clearance rate as an independent factor significantly associated with primary filter retrieval in the PMT group(OR=190.773,P<0.05).Conclusion:Compared to CDT,AngioJet mechanical thrombectomy combined with manual aspiration achieves higher thrombus clearance and primary filter retrieval rates in the treatment of acute IVCT while also reducing thrombolysis duration and drug dosage.However,attention should be paid to the increased risk of vagal reflex symptoms.There was no significant difference between the two groups in secondary filter retrieval rates or long-term IVC patency.The choice of intervention should be based on the patient's condition,timing of filter retrieval,and individualized clinical considerations.

Drug development encompasses multiple processes,wherein protein subcellular localization is essential.It promotes target identification,treatment development,and the design of drug delivery systems.In this research,a deep learning framework called LocPro is presented for predicting protein subcellular localization.Specifically,LocPro is unique in(a)combining protein representations from the pre-trained large language model(LLM)ESM2 and the expert-driven tool PROFEAT,(b)implementing a hybrid deep neural network architecture that integrates convolutional neural network(CNN),fully connected(FC)layer,and bidirectional long short-term memory(BiLSTM)blocks,and(c)developing a multi-label framework for predicting protein subcellular localization at multiple granularity levels.Additionally,a dataset was curated and divided using a homology-based strategy for training and validation.Compar-ative analyses show that LocPro outperforms existing methods in sequence-based multi-label protein subcellular localization prediction.The practical utility of this framework is further demonstrated through case studies on drug target subcellular localization.All in all,LocPro serves as a valuable complement to existing protein localization prediction tools.The web server is freely accessible at https://idrblab.org/LocPro/.

Drug development encompasses multiple processes, wherein protein subcellular localization is essential. It promotes target identification, treatment development, and the design of drug delivery systems. In this research, a deep learning framework called LocPro is presented for predicting protein subcellular localization. Specifically, LocPro is unique in (a) combining protein representations from the pre-trained large language model (LLM) ESM2 and the expert-driven tool PROFEAT, (b) implementing a hybrid deep neural network architecture that integrates convolutional neural network (CNN), fully connected (FC) layer, and bidirectional long short-term memory (BiLSTM) blocks, and (c) developing a multi-label framework for predicting protein subcellular localization at multiple granularity levels. Additionally, a dataset was curated and divided using a homology-based strategy for training and validation. Comparative analyses show that LocPro outperforms existing methods in sequence-based multi-label protein subcellular localization prediction. The practical utility of this framework is further demonstrated through case studies on drug target subcellular localization. All in all, LocPro serves as a valuable complement to existing protein localization prediction tools. The web server is freely accessible at https://idrblab.org/LocPro/.

Background and Aims:Acute inferior vena cava thrombosis(IVCT)commonly occurs secondary to inferior vena cava filter(VCF)implantation.If not promptly treated,it may lead to serious complications such as bilateral lower limb swelling and pulmonary embolism and can also reduce the likelihood of successful filter retrieval.Percutaneous mechanical thrombectomy(PMT)and catheter-directed thrombolysis(CDT)are currently the main interventional treatments for IVCT,but comparative studies evaluating their efficacy and safety remain limited.This study was to conduct a prospective randomized controlled trial to compare the clinical efficacy and safety of AngioJet mechanical thrombectomy versus conventional CDT in the treatment of acute IVCT and to explore factors influencing filter retrieval rates,thereby providing evidence-based guidance for clinical decision-making.Methods:From January 2022 to December 2024,patients diagnosed with acute IVCT following VCF implantation were prospectively enrolled at the Department of Vascular Surgery,Beijing Jishuitan Hospital,Capital Medical University.Patients were randomly assigned to either the CDT group(n=46)or the PMT group(n=48)according to the interventional procedure used.The two groups were compared in terms of filter retrieval rates,thrombus clearance outcomes,operative time,thrombolytic drug dosage,and incidence of complications.Logistic regression analysis was used to identify factors associated with primary filter retrieval.Results:A total of 94 patients were enrolled,with 46 in the CDT group and 48 in the PMT group.Compared to the CDT group,the PMT group demonstrated a significantly higher primary filter retrieval rate(77.1%vs.43.5%),grade Ⅲ thrombus clearance rate(70.8%vs.37.0%),and better postoperative thrombus scores.Additionally,the PMT group required lower urokinase doses and shorter thrombolysis duration(all P<0.05).The overall filter retrieval rate and 3-month IVC patency were similar between groups,both exceeding 93%.Regarding safety,the CDT group had a higher incidence of catheter-related infections and medical adhesive-related skin injury,while vagal reflex symptoms were more frequent in the PMT group.Logistic regression analysis identified thrombus clearance rate as an independent factor significantly associated with primary filter retrieval in the PMT group(OR=190.773,P<0.05).Conclusion:Compared to CDT,AngioJet mechanical thrombectomy combined with manual aspiration achieves higher thrombus clearance and primary filter retrieval rates in the treatment of acute IVCT while also reducing thrombolysis duration and drug dosage.However,attention should be paid to the increased risk of vagal reflex symptoms.There was no significant difference between the two groups in secondary filter retrieval rates or long-term IVC patency.The choice of intervention should be based on the patient's condition,timing of filter retrieval,and individualized clinical considerations.

Objective·To investigate the role of interleukin-1β(IL-1β)in predicting the severity of oral and maxillofacial space infection(OMSI),and to explore the key mechanisms regulating IL-1β release,the critical immune cell subpopulations involved,and the intercellular communication networks among immune cells in OMSI patients.Methods·A total of 62 OMSI patients admitted to the Department of Oral Surgery,Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine,from January to November 2023 were enrolled,including 20 patients with moderate infection,21 with severe infection,and 21 with extremely severe infection.Logistic regression analysis was performed to identify risk factors for extremely severe infection,and receiver operating characteristic(ROC)curves were constructed to evaluate the ability of the above indicators to predict extremely severe infection.Peripheral blood mononuclear cells(PBMCs)from 2 patients in each group(moderate,severe and extremely severe)and 2 healthy controls(GSE224198)were analyzed using single-cell RNA sequencing(scRNA-seq)to identify key pro-inflammatory cell subtypes and genes,and to examine their changing trends with increasing infection severity.Cell-cell communication was assessed using CellChat.Quantitative real-time polymerase chain reaction(qPCR)and Western blotting were used to validate inflammasome activation levels in PBMCs.Results·Compared with patients with moderate and severe infections,levels of procalcitonin(PCT)(P<0.05)and IL-1β(P<0.05)were significantly elevated in patients with extremely severe infection.Logistic regression identified IL-1β as an independent risk factor for extremely severe infection(OR=1.814,95%CI 1.256?2.621,P=0.002).The area under the ROC curve(AUC)for the combined prediction of extremely severe infection using IL-1β and PCT was 0.943.scRNA-seq revealed continuous upregulation of NLRP3(NOD-like receptor family pyrin domain-containing 3)and IL1B gene expression in monocytes as infection severity increased,with intermediate monocytes being the main IL1B-expressing cell subtype.IL-1Β-IL-1R signaling,C-C motif chemokine ligand(CCL)and intercellular adhesion molecule(ICAM)signaling were significantly enhanced in monocytes.Macrophage migration inhibitory factor(MIF)signaling between T cells and monocytes also increased notably.With infection progression,the mRNA levels of NLRP3 and IL1B in peripheral blood rose steadily,and the protein levels of NLRP3,caspase-1 p20,apoptosis-associated speck-like protein containing a CARD(ASC)and IL-1β were persistently elevated.Conclusion·The combined levels of IL-1β and PCT at admission can effectively predict extremely severe OMSI.NLRP3 inflammasome activation is observed in PBMCs of OMSI patients.The elevation of IL-1β is closely associated with intermediate monocytes.Monocyte-mediated IL-1Β-IL-1R,CCL and ICAM signaling pathways,along with T cell-mediated MIF signaling pathways,collectively promote the inflammatory response.

Objective: QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer. Methods: This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment. Results: Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46).The median duration of response was 9.6 months (95% confidence interval [CI]=5.5–not estimable). The median progression-free survival was 8.1 months (95% CI=5.7–14.0). Fortyfive (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%). Conclusion QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can’t tolerate bevacizumab, which needs to be further verified in phase III confirmatory study.

ObjectiveTo investigate the clinical features and outcomes of critically ill pregnant and parturient women with chronic hepatitis B virus （HBV） infection， and to provide clinical experience for the rescue of critically ill pregnant and parturient women and the prevention and treatment of the severe exacerbation of liver disease. MethodsA total of 41 pregnant and parturient women with chronic HBV infection who were admitted to Department of Critical Care Medicine， Nanjing Second Hospital， from March 2013 to March 2023 were enrolled in this study， and their clinical data were collected through the electronic medical record system of hospital to summarize the main causes of transfer to the intensive care unit （ICU）， the causes of death， and treatment. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. The chi-square test was used for comparison of categorical data between two groups. ResultsAmong the 41 patients， 13 （31.71%） did not receive regular antenatal examination and 8 （19.51%） with a high viral load （HBV DNA ≥2×10⁵ IU/mL） did not receive antiviral therapy. Cesarean section was the main mode of delivery in 32 patients （78.05%）； 23 patients （56.10%） had premature delivery， and 5 patients died （12.20%）. The top three causes of transfer to the ICU were liver failure， postpartum hemorrhage， and hypertensive disorders of pregnancy. Liver failure mainly occurred in late pregnancy， with hepatic encephalopathy as the most common complication （28.57%） and intrahepatic cholestasis of pregnancy as the most common comorbidity （21.43%）； among the 14 patients with liver failure， 6 （42.86%） received regular antenatal examination， and 13 （92.86%） did not receive antiviral therapy before admission. The mean length of ICU stay was 3.31±1.65 days for the patients with postpartum hemorrhage， among whom the patients with severe liver disease had coagulation disorders before delivery， which were difficult to correct after 48 hours of treatment. ConclusionPregnant and parturient women with chronic HBV infection tend to have complex conditions and a relatively high mortality rate. For pregnant and parturient women with chronic HBV infection， assessment of liver status， regular antenatal examination， and timely antiviral therapy are of vital importance to reduce severe exacerbation and mortality rate.

OBJECTIVE To explore the effects and potential mechanism of evodiamine on inflammatory response and apoptosis of epithelial cells in asthma model rats. METHODS SD rats were separated into control group， model group， evodiamine low-dose group （10 mg/kg）， evodiamine high-dose group （20 mg/kg）， dexamethasone group （positive control， 0.5 mg/kg）， epidermal growth factor （EGF） group [mitogen-activated protein kinase （MAPK） activator， 10 μg]， evodiamine high-dose+EGF group （20 mg/kg evodiamine+10 μg EGF）， with 10 rats in each group. Except for the control group， the other groups were sensitized by 3-point injection of 10% ovalbumin（OVA）-aluminium hydroxide mixture and stimulated by inhalation of 2%OVA nebulized liquid to establish an asthma model. The count of inflammatory cells （macrophages and lymphocytes） in bronchoalveolar lavage fluid （BALF） was detected in each group； pathological changes of lung tissue in rats were observed； the apoptosis of airway epithelial cells， the levels of serum inflammatory factors [tumor necrosis factor-α， interleukin-6 （IL-6） and IL-4]， the expressions of pathway-related proteins p38 MAPK， phosphorylated p38 MAPK （p-p38 MAPK）， signal transduction and transcription activating factor 1 （STAT1）] and apoptosis-related proteins [B cell lymphoma-2 （Bcl-2） and Bcl-2 associated X protein （Bax）] were all detected in lung tissue. RESULTS Compared with the control group， bronchial mucosal edema， thickening of alveolar septa and extensive infiltration of inflammatory cells were observed in the lung tissue of rats in the model group； the number of inflammatory cells， apoptosis rate of airway epithelial cells， the levels of inflammatory factors， p-38 MAPK/p-38 MAPK， and the protein expressions of Bax and STAT1 were increased significantly； the expressions of Bcl-2 protein and Bcl-2/Bax were reduced significantly （P＜0.05）. Compared with the model group， the pathological changes in lung tissues were alleviated to varying degrees in evodiamine low-dose and high-dose groups， and dexamethasone groups， and the above indicators were significantly reversed. However， the change trends of corresponding indicators in the EGF group were opposite to the above （P＜0.05）. EGF could significantly attenuate the effect of high-dose evodiamine on inflammatory response in asthmatic rats （P＜0.05）. CONCLUSIONS Evodiamine can relieve inflammatory reactions and inhibit the apoptosis of airway epithelial cells in asthmatic rats， the mechanism of which may be associated with inhibiting p38 MAPK/STAT1 signaling pathway.

OBJECTIVE To explore the effects and potential mechanism of evodiamine on inflammatory response and apoptosis of epithelial cells in asthma model rats. METHODS SD rats were separated into control group， model group， evodiamine low-dose group （10 mg/kg）， evodiamine high-dose group （20 mg/kg）， dexamethasone group （positive control， 0.5 mg/kg）， epidermal growth factor （EGF） group [mitogen-activated protein kinase （MAPK） activator， 10 μg]， evodiamine high-dose+EGF group （20 mg/kg evodiamine+10 μg EGF）， with 10 rats in each group. Except for the control group， the other groups were sensitized by 3-point injection of 10% ovalbumin（OVA）-aluminium hydroxide mixture and stimulated by inhalation of 2%OVA nebulized liquid to establish an asthma model. The count of inflammatory cells （macrophages and lymphocytes） in bronchoalveolar lavage fluid （BALF） was detected in each group； pathological changes of lung tissue in rats were observed； the apoptosis of airway epithelial cells， the levels of serum inflammatory factors [tumor necrosis factor-α， interleukin-6 （IL-6） and IL-4]， the expressions of pathway-related proteins p38 MAPK， phosphorylated p38 MAPK （p-p38 MAPK）， signal transduction and transcription activating factor 1 （STAT1）] and apoptosis-related proteins [B cell lymphoma-2 （Bcl-2） and Bcl-2 associated X protein （Bax）] were all detected in lung tissue. RESULTS Compared with the control group， bronchial mucosal edema， thickening of alveolar septa and extensive infiltration of inflammatory cells were observed in the lung tissue of rats in the model group； the number of inflammatory cells， apoptosis rate of airway epithelial cells， the levels of inflammatory factors， p-38 MAPK/p-38 MAPK， and the protein expressions of Bax and STAT1 were increased significantly； the expressions of Bcl-2 protein and Bcl-2/Bax were reduced significantly （P＜0.05）. Compared with the model group， the pathological changes in lung tissues were alleviated to varying degrees in evodiamine low-dose and high-dose groups， and dexamethasone groups， and the above indicators were significantly reversed. However， the change trends of corresponding indicators in the EGF group were opposite to the above （P＜0.05）. EGF could significantly attenuate the effect of high-dose evodiamine on inflammatory response in asthmatic rats （P＜0.05）. CONCLUSIONS Evodiamine can relieve inflammatory reactions and inhibit the apoptosis of airway epithelial cells in asthmatic rats， the mechanism of which may be associated with inhibiting p38 MAPK/STAT1 signaling pathway.