ObjectiveTo explore the potential mechanism of Xianglian Huazhuo prescription （XLHZ） in treating chronic atrophic gastritis （CAG） by regulating cell cycle and inhibiting proliferation， using bioinformatics technology and animal experiments. MethodsDifferential expressed genes （DEGs） related to CAG were screened using GEO database and GEO2R tool. Weighted gene co-expression network analysis （WGCNA） was employed to search for hub genes of CAG. These hub genes were intersected with cell cycle proliferation based on GeneCards database. Eenrichment analysis of the intersecting genes was performed to obtain signaling pathways and biological processes related to CAG. Protein protein interaction （PPI） analysis of genes was conducted using the Protein Interaction Platform （STRING） database to search the super hub gene （hub 2.0）， and animal experiments were conducted for further validation. Fourteen of 70 male Wistar rats were randomly selected as the normal group， and the remaining 56 rats were prepared by the combined modeling method of "starvation disorder+N-methyl-N-nitro-N-nitrosoguanidine （MNNG） + sodium salicylate". The successfully modeled rats were randomly divided into the model group， XLHZ-H， XLHZ-M， and XLHZ-L groups （36， 18， 9 g·kg^-1， respectively）， and Morodan group （1.4 g·kg^-1）. Each group was given corresponding intervention for 60 days. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes of gastric mucosa in rats. The ultrastructure of gastric mucosal tissue cells was observed by transmission electron microscopy. The relative expression levels of TGF-β₁， Smad2 and Smad3 proteins， S/G₂/M phase marker geminin and proliferation marker MCM2 were detected by Western blot in gastric mucosal tissue， and Spearman correlation analysis was performed. ResultsA total of 15 hub 2.0 genes were identified， including TGF-β₁， suggesting the involvement of the TGF-β₁ signaling pathway in the CAG pathogenesis. Compared with the normal group， the expressions of TGF-β₁， Smad2， geminin and MCM2 proteins in the gastric mucosa tissue of the model group were increased （P<0.05）， and the expression of Smad3 protein was decreased （P<0.05）. Compared with the model group， the expressions of TGF-β₁ and geminin in the gastric mucosa were decreased in the drug groups （P<0.05）. The XLHZ-M group， XLHZ-H group and Morodan group had significantly decreased protein expression of Smad2 and MCM2 （P<0.05）. The protein expression of Smad3 was significantly increased in XLHZ-M， XLHZ-H， and Morodan groups （P<0.05）. Spearman correlation analysis showed that Smad3 was negatively correlated with other indicators， and positively correlated with other indicators （P<0.01）. ConclusionXLHZ may inhibit TGF-β₁/Smads signaling pathway， regulate cell cycle， and inhibit proliferation in the treatment of CAG.

ObjectiveTo explore the potential mechanism of Xianglian Huazhuo prescription （XLHZ） in treating chronic atrophic gastritis （CAG） by regulating cell cycle and inhibiting proliferation， using bioinformatics technology and animal experiments. MethodsDifferential expressed genes （DEGs） related to CAG were screened using GEO database and GEO2R tool. Weighted gene co-expression network analysis （WGCNA） was employed to search for hub genes of CAG. These hub genes were intersected with cell cycle proliferation based on GeneCards database. Eenrichment analysis of the intersecting genes was performed to obtain signaling pathways and biological processes related to CAG. Protein protein interaction （PPI） analysis of genes was conducted using the Protein Interaction Platform （STRING） database to search the super hub gene （hub 2.0）， and animal experiments were conducted for further validation. Fourteen of 70 male Wistar rats were randomly selected as the normal group， and the remaining 56 rats were prepared by the combined modeling method of "starvation disorder+N-methyl-N-nitro-N-nitrosoguanidine （MNNG） + sodium salicylate". The successfully modeled rats were randomly divided into the model group， XLHZ-H， XLHZ-M， and XLHZ-L groups （36， 18， 9 g·kg^-1， respectively）， and Morodan group （1.4 g·kg^-1）. Each group was given corresponding intervention for 60 days. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes of gastric mucosa in rats. The ultrastructure of gastric mucosal tissue cells was observed by transmission electron microscopy. The relative expression levels of TGF-β₁， Smad2 and Smad3 proteins， S/G₂/M phase marker geminin and proliferation marker MCM2 were detected by Western blot in gastric mucosal tissue， and Spearman correlation analysis was performed. ResultsA total of 15 hub 2.0 genes were identified， including TGF-β₁， suggesting the involvement of the TGF-β₁ signaling pathway in the CAG pathogenesis. Compared with the normal group， the expressions of TGF-β₁， Smad2， geminin and MCM2 proteins in the gastric mucosa tissue of the model group were increased （P<0.05）， and the expression of Smad3 protein was decreased （P<0.05）. Compared with the model group， the expressions of TGF-β₁ and geminin in the gastric mucosa were decreased in the drug groups （P<0.05）. The XLHZ-M group， XLHZ-H group and Morodan group had significantly decreased protein expression of Smad2 and MCM2 （P<0.05）. The protein expression of Smad3 was significantly increased in XLHZ-M， XLHZ-H， and Morodan groups （P<0.05）. Spearman correlation analysis showed that Smad3 was negatively correlated with other indicators， and positively correlated with other indicators （P<0.01）. ConclusionXLHZ may inhibit TGF-β₁/Smads signaling pathway， regulate cell cycle， and inhibit proliferation in the treatment of CAG.

Objective:To screen broadly neutralizing antibodies in human immunodeficiency virus-1（HIV-1）chronically infected individuals and characterize their molecular features and to provide new strategies for rational vaccine development and antibody-based therapeutics.Methods:A total of 34 treatment-na?ve individuals with chronic HIV-1 infection were enrolled. Plasma antibody binding levels were measured against two HIV-1 envelope proteins. Single antigen-specific memory B cells were sorted from high-binding samples，and antibody variable region genes were amplified by PCR for paired expression. The monoclonal antibodies were evaluated for neutralizing activity using pseudovirus assays，and their structural features were analyzed by integrating AlphaFold 3 prediction with Discovery Studio molecular docking.Results:Plasma samples showed strong binding to DU422-GP140 and BG505-GP140. Eight monoclonal antibodies were isolated from two donors. Among them，antibodies 0919-A4，0919-A9 and 0808-A2 could cross-react with GP140 from HIV-1 subtypes AE，BC and B. The monoclonal antibody 0919-A9 demonstrated potent neutralizing activity against SF162（Tier 1）and CH181（Tier 2）pseudoviruses，with somatic hypermutation rates of 13.27%（heavy chain）and 15.58%（light chain）. Structural modeling revealed its specific targeting of the V1V2 region on GP120.Conclusion:The isolated antibody 0919-A9 effectively neutralizes Tier 2 pseudoviruses. Its high somatic mutation frequency and V1V2-targeting property underlie its neutralizing activity，providing both a promising candidate and mechanistic insights for HIV vaccine development and antibody-based therapeutic strategies.

Instrument separation is a critical complication during root canal therapy, impacting treatment success and long-term tooth preservation. The etiology of instrument separation is multifactorial, involving the intricate anatomy of the root canal system, instrument-related factors, and instrumentation techniques. Instrument separation can hinder thorough cleaning, shaping, and obturation of the root canal, posing challenges to successful treatment outcomes. Although retrieval of separated instrument is often feasible, it carries risks including perforation, excessive removal of tooth structure and root fractures. Effective management of separated instruments requires a comprehensive understanding of the contributing factors, meticulous preoperative assessment, and precise evaluation of the retrieval difficulty. The application of appropriate retrieval techniques is essential to minimize complications and optimize clinical outcomes. The current manuscript provides a framework for understanding the causes, risk factors, and clinical management principles of instrument separation. By integrating effective strategies, endodontists can enhance decision-making, improve endodontic treatment success and ensure the preservation of natural dentition.
Humans ; Root Canal Therapy/adverse effects* ; Consensus ; Root Canal Preparation/adverse effects*

The important studies in the field of extracorporeal life support (ECLS) in 2024 focused on the application of cardiac support technologies in acute myocardial infarction (AMI) with cardiogenic shock (CS): veno-arterial extracorporeal membrane oxygenation (V-A ECMO) has not shown advantages in either short- or long-term outcomes and may increase the risk of bleeding and vascular complications; in contrast, micro-axial flow pumps demonstrate potential in improving mortality. The effects of veno-venous extracorporeal membrane oxygenation (V-V ECMO) combined with prone positioning on severe acute respiratory distress syndrome (ARDS) remain uncertain. The survival benefit of extracorporeal cardiopulmonary resuscitation (ECPR) in out-of-hospital cardiac arrest (OHCA) patients has been further validated. The potential benefits of extracorporeal carbon dioxide removal (ECCO2R) require further investigation. Additionally, new guidelines released in 2024 focus on Neurological monitoring and management during ECMO, as well as the Definition and management of right ventricular injury during veno-venous ECMO. ECMO management requires more refined strategies, including optimized oxygenation targets, anticoagulation, blood transfusion, and weaning strategies to improve patient outcomes.
Humans ; Extracorporeal Membrane Oxygenation/methods* ; Shock, Cardiogenic/therapy* ; Cardiopulmonary Resuscitation ; Myocardial Infarction/therapy*

Objective:To investigate the value of biparametric-MRI (bpMRI) based peritumoral radiomics for preoperative prediction of extraprostatic extension (EPE) in prostate cancer (PCa).Methods:In this cross-sectional study, consecutive bpMRI of patients undergoing prostatectomy for PCa were retrospectively collected from the First Medical Center (center 1) and the Third Medical Center (center 2) of Chinese PLA General Hospital. A total of 274 patients were finally enrolled. Patients at center 1 from January 2020 to December 2022 were randomly divided into a training set (149 cases) and an internal validation set (63 cases) by stratified random sampling. Patients at center 2 from January 2023 to March 2024 were assigned to the external test set (62 cases). Patients were categorized into EPE-positive group and EPE-negative group according to pathological assessment postoperatively. In the training set, there were 49 cases in EPE-positive group and 100 cases in EPE-negative group. In the internal validation set, there were 26 cases in EPE-positive group and 37 cases in EPE-negative group. In the external test set, there were 22 cases in EPE-positive group and 40 cases in EPE-negative group. Axial T 2WI and apparent diffusion coefficient (ADC) images were manually annotated to obtain index lesion regions of interest (ROIs), with the peritumoral ROIs subsequently delineated by semi-automatic segmentation technique. Radiomics features were extracted from intra-tumoral, peri-tumoral, and intra-tumoral plus peri-tumoral ROIs. The training set data was employed to select and optimize features to build the radiomics models. The logistic regression analysis was used to develop radiomics, clinical, and integrated models. The predictive performance was assessed by the area under the receiver operating characteristic curve (AUC) in the external test set, and compared by the DeLong test. The sensitivity and specificity were compared by the exact McNemar test. Results:In the external test set, the peri-tumoral radiomics model based on bpMRI showed the highest performance in evaluating EPE, with an AUC of 0.739 (95% CI 0.611-0.842), which was identified as the optimal radiomics model. EPE grade ( OR=6.151, 95% CI 3.371-11.226, P<0.001) was incorporated into the clinical model, with an AUC of 0.780 (95% CI 0.657-0.875) in the external test set. The integrated model had an AUC of 0.817 (95% CI 0.698-0.904) in the external test set. There was no statistically significant difference in comparisons of AUCs among the three models (all P>0.05). The sensitivity of the integrated model (68.2%) showed no significant difference from those of the clinical model and the optimal radiomics model (77.3% and 86.4%, respectively; P=0.500 and P=0.289). However, the specificity of the integrated model (85.0%) was significantly higher than those of the clinical model (67.5%, P=0.016) and the optimal radiomics model (50.0%, P<0.001). Conclusion:A bpMRI-based peritumoral radiomics integrating clinical model demonstrates high performance for preoperative prediction of EPE in PCa.

Purpose To identify the distinct MRI findings of gastric-type endocervical adenocarcinoma(GEA)that can help differentiate it from usual-type endocervical adenocarcinoma(UEA)and reveal the radiologic-pathologic correlation.Materials and Methods All consecutive patients with cervical GEA(27 cases)and UEA(45 cases)treated at Shanghai First Maternity and Infant Hospital from January 2015 to August 2023 were included retrospectively.All patients underwent enhanced pelvic MRI examination.The clinical characteristics,tumor location,tumor shape,presence and size of cysts,and presence of hydrometra were evaluated between the two groups.Results The clinical characteristics included vaginal discharge in 12 cases of GEA and one case of UEA,vaginal bleeding in seven cases of GEA and 28 cases of UEA(P=0.048).Additionally,there were two cases of Peutz-Jeghers syndrome in GEA.Among the 27 GEA cases,the lesion was in the upper cervix in nine cases and involved the entire cervix in 16 cases;among the 45 UEA cases,the lesions were in the upper,lower and entire cervix in 12,29 and four cases,respectively(P=0.023).Regarding the tumor growth pattern,in the GEA group,there were nine cases of mass-forming growth pattern and 18 cases of diffuse infiltrative pattern;in the UEA group,there were 35 cases of mass-forming growth pattern and ten cases of diffuse infiltrative pattern,with a statistically significant difference(χ2=10.718,P=0.014).In 27 GEA cases,14 cases had observed intrauterine fluid,while in 45 UEA cases,eight cases had observed intrauterine fluid(χ2=12.657,P=0.002).Among the GEA cases,five had no cysts,12 had microcysts and ten had macrocysts;among the UEA cases,14 had no cysts,31 had microcysts and macrocysts were not observed(P=0.001).The maximum diameter of the GEA masses was(4.030±0.375)cm,and that of UEA masses was(2.315±0.769)cm,with a statistically significant difference(t=7.134,P<0.001).Conclusion By integrating multiple MRI features of the diffuse infiltrative growth pattern(such as the predominant location in the upper or entire cervix,frequent association with uterine cavity effusion or larger cysts,and a maximum mass diameter≥4 cm),it aids in distinguishing GEA from UEA.

Objective:To investigate the value of biparametric-MRI (bpMRI) based peritumoral radiomics for preoperative prediction of extraprostatic extension (EPE) in prostate cancer (PCa).Methods:In this cross-sectional study, consecutive bpMRI of patients undergoing prostatectomy for PCa were retrospectively collected from the First Medical Center (center 1) and the Third Medical Center (center 2) of Chinese PLA General Hospital. A total of 274 patients were finally enrolled. Patients at center 1 from January 2020 to December 2022 were randomly divided into a training set (149 cases) and an internal validation set (63 cases) by stratified random sampling. Patients at center 2 from January 2023 to March 2024 were assigned to the external test set (62 cases). Patients were categorized into EPE-positive group and EPE-negative group according to pathological assessment postoperatively. In the training set, there were 49 cases in EPE-positive group and 100 cases in EPE-negative group. In the internal validation set, there were 26 cases in EPE-positive group and 37 cases in EPE-negative group. In the external test set, there were 22 cases in EPE-positive group and 40 cases in EPE-negative group. Axial T 2WI and apparent diffusion coefficient (ADC) images were manually annotated to obtain index lesion regions of interest (ROIs), with the peritumoral ROIs subsequently delineated by semi-automatic segmentation technique. Radiomics features were extracted from intra-tumoral, peri-tumoral, and intra-tumoral plus peri-tumoral ROIs. The training set data was employed to select and optimize features to build the radiomics models. The logistic regression analysis was used to develop radiomics, clinical, and integrated models. The predictive performance was assessed by the area under the receiver operating characteristic curve (AUC) in the external test set, and compared by the DeLong test. The sensitivity and specificity were compared by the exact McNemar test. Results:In the external test set, the peri-tumoral radiomics model based on bpMRI showed the highest performance in evaluating EPE, with an AUC of 0.739 (95% CI 0.611-0.842), which was identified as the optimal radiomics model. EPE grade ( OR=6.151, 95% CI 3.371-11.226, P<0.001) was incorporated into the clinical model, with an AUC of 0.780 (95% CI 0.657-0.875) in the external test set. The integrated model had an AUC of 0.817 (95% CI 0.698-0.904) in the external test set. There was no statistically significant difference in comparisons of AUCs among the three models (all P>0.05). The sensitivity of the integrated model (68.2%) showed no significant difference from those of the clinical model and the optimal radiomics model (77.3% and 86.4%, respectively; P=0.500 and P=0.289). However, the specificity of the integrated model (85.0%) was significantly higher than those of the clinical model (67.5%, P=0.016) and the optimal radiomics model (50.0%, P<0.001). Conclusion:A bpMRI-based peritumoral radiomics integrating clinical model demonstrates high performance for preoperative prediction of EPE in PCa.

Purpose To identify the distinct MRI findings of gastric-type endocervical adenocarcinoma(GEA)that can help differentiate it from usual-type endocervical adenocarcinoma(UEA)and reveal the radiologic-pathologic correlation.Materials and Methods All consecutive patients with cervical GEA(27 cases)and UEA(45 cases)treated at Shanghai First Maternity and Infant Hospital from January 2015 to August 2023 were included retrospectively.All patients underwent enhanced pelvic MRI examination.The clinical characteristics,tumor location,tumor shape,presence and size of cysts,and presence of hydrometra were evaluated between the two groups.Results The clinical characteristics included vaginal discharge in 12 cases of GEA and one case of UEA,vaginal bleeding in seven cases of GEA and 28 cases of UEA(P=0.048).Additionally,there were two cases of Peutz-Jeghers syndrome in GEA.Among the 27 GEA cases,the lesion was in the upper cervix in nine cases and involved the entire cervix in 16 cases;among the 45 UEA cases,the lesions were in the upper,lower and entire cervix in 12,29 and four cases,respectively(P=0.023).Regarding the tumor growth pattern,in the GEA group,there were nine cases of mass-forming growth pattern and 18 cases of diffuse infiltrative pattern;in the UEA group,there were 35 cases of mass-forming growth pattern and ten cases of diffuse infiltrative pattern,with a statistically significant difference(χ2=10.718,P=0.014).In 27 GEA cases,14 cases had observed intrauterine fluid,while in 45 UEA cases,eight cases had observed intrauterine fluid(χ2=12.657,P=0.002).Among the GEA cases,five had no cysts,12 had microcysts and ten had macrocysts;among the UEA cases,14 had no cysts,31 had microcysts and macrocysts were not observed(P=0.001).The maximum diameter of the GEA masses was(4.030±0.375)cm,and that of UEA masses was(2.315±0.769)cm,with a statistically significant difference(t=7.134,P<0.001).Conclusion By integrating multiple MRI features of the diffuse infiltrative growth pattern(such as the predominant location in the upper or entire cervix,frequent association with uterine cavity effusion or larger cysts,and a maximum mass diameter≥4 cm),it aids in distinguishing GEA from UEA.

Objective:To screen broadly neutralizing antibodies in human immunodeficiency virus-1（HIV-1）chronically infected individuals and characterize their molecular features and to provide new strategies for rational vaccine development and antibody-based therapeutics.Methods:A total of 34 treatment-na?ve individuals with chronic HIV-1 infection were enrolled. Plasma antibody binding levels were measured against two HIV-1 envelope proteins. Single antigen-specific memory B cells were sorted from high-binding samples，and antibody variable region genes were amplified by PCR for paired expression. The monoclonal antibodies were evaluated for neutralizing activity using pseudovirus assays，and their structural features were analyzed by integrating AlphaFold 3 prediction with Discovery Studio molecular docking.Results:Plasma samples showed strong binding to DU422-GP140 and BG505-GP140. Eight monoclonal antibodies were isolated from two donors. Among them，antibodies 0919-A4，0919-A9 and 0808-A2 could cross-react with GP140 from HIV-1 subtypes AE，BC and B. The monoclonal antibody 0919-A9 demonstrated potent neutralizing activity against SF162（Tier 1）and CH181（Tier 2）pseudoviruses，with somatic hypermutation rates of 13.27%（heavy chain）and 15.58%（light chain）. Structural modeling revealed its specific targeting of the V1V2 region on GP120.Conclusion:The isolated antibody 0919-A9 effectively neutralizes Tier 2 pseudoviruses. Its high somatic mutation frequency and V1V2-targeting property underlie its neutralizing activity，providing both a promising candidate and mechanistic insights for HIV vaccine development and antibody-based therapeutic strategies.