In 2025, the European League Against Rheumatism(EULAR) and the European Respiratory Society(ERS) jointly released the first clinical practice guidelines for the management of connective tissue disease-associated interstitial lung disease (CTD-ILD), with a particular focus on systemic sclerosis-associated ILD(SSc-ILD). Based on evidence-based principles, the guidelines provide a comprehensive framework encompassing screening, progression assessment, therapeutic strategies, and follow-up. Notably, the guidelines emphasize the clinical value of combination therapy for patients at high risk or with rapidly progressive disease. This article summarizes and interprets the key recommendations, including HRCT-based screening, multi-dimensional assessment tools, stratified pharmacological strategies, classification of drug mechanisms, and risk-duration-based follow-up protocols. It aims to provide up-to-date international guidance for clinical decision-making and research in the management of SSc-ILD.

G protein-coupled receptor kinase 2 (GRK2) participates in the phosphorylation and desensitization of G protein-coupled receptor (GPCR), impacting various biological processes such as inflammation and cell proliferation. Dysregulated expression and activity of GRK2 have been reported in multiple cells in rheumatoid arthritis (RA). However, whether and how GRK2 regulates synovial hyperplasia and fibroblast-like synoviocytes (FLSs) proliferation is poorly understood. In this study, we investigated the regulation of GRK2 and its biological function in RA. We found that GRK2 transmembrane activity was increased in FLSs of RA patients and collagen-induced arthritis (CIA) rats. Additionally, we noted a positive correlation between high GRK2 expression on the cell membrane and serological markers associated with RA and CIA. Immunoprecipitation-mass spectrometry and pull-down analyses revealed tumor necrosis factor receptor-associated factor 2 (TRAF2) as a novel substrate of GRK2. Furthermore, surface plasmon resonance (SPR) and molecular docking assays determined that the C-terminus of GRK2 binds to the C-terminus of TRAF2 at the Gln340 residue. GRK2 knockdown and the GRK2 inhibitor CP-25 attenuated synovial hyperplasia and FLS proliferation in CIA both in vitro and in vivo by decreasing GRK2 membrane expression and activity. Mechanistically, increased GRK2 transmembrane activity contributed to the recruitment of TRAF2 on the cell membrane, promoting GRK2-TRAF2 interactions that facilitate the recruitment of the E3 ubiquitin ligase TRIM47 to TRAF2. This enhanced TRAF2 Lys63 polyubiquitylation and induced nuclear factor (NF)-κB activation, leading to synovial hyperplasia and abnormal proliferation of FLSs. Our study provides a mechanistic and preclinical rationale for further evaluation of GRK2 as a therapeutic target for RA.

Objective To develop a deep learning method for small sample multi-omics data using attention mechanism and Meta-learning for the establishment of autism diagnosis model.Methods MLAN(Meta-learning based attentive network)consisting of the omics feature pre-reduction module,the multi-omics data fusion and feature learning module,and the parameter optimization module was designed.Firstly,differential expression analysis was performed on high-dimensional multi-omics data to preliminarily screen out unimportant features.Secondly,a multi-channel attention mechanism was used to learn the importances of every set of omics data and to realize data fusion,and a two-layer fully connected network was constructed to further extract latent features and realize the diagnosis task.Finally,the Meta-learning algorithm Reptile was used to optimize the initial parameters of the above model to obtain the optimal parameters.A total of 58 children's saliva samples were collected,including 21 children diagnosed with autism,12 children with social disorders,and 25 healthy controls,and the protein and metabolomics data were detected by mass spectrometry.All data were randomly divided into training set and test set by 4∶1,and the training set was divided into training data and validation data in the same way for model training and validation.The test set was used for the final evaluation of the model effect.Five baseline models and three ablated models were constructed and evaluated along with MLAN based on metrics including multi-classification accuracy,F1-macro and F1-weighted scores.Results The constructed multi-classification autism diagnosis model MLAN achieved multi-classification accuracy,F1-macro and F1-weighted scores of 0.850±0.066,0.817±0.103 and 0.834±0.087.The values of all three indicators were better than those of baseline models and the ablated models.Conclusion The proposed MLAN can effectively deal with heterogeneous multi-omics data with small samples and achieve good results,which is expected to provide assistance for the clinical diagnosis of autism.

Objective To develop a deep learning method for small sample multi-omics data using attention mechanism and Meta-learning for the establishment of autism diagnosis model.Methods MLAN(Meta-learning based attentive network)consisting of the omics feature pre-reduction module,the multi-omics data fusion and feature learning module,and the parameter optimization module was designed.Firstly,differential expression analysis was performed on high-dimensional multi-omics data to preliminarily screen out unimportant features.Secondly,a multi-channel attention mechanism was used to learn the importances of every set of omics data and to realize data fusion,and a two-layer fully connected network was constructed to further extract latent features and realize the diagnosis task.Finally,the Meta-learning algorithm Reptile was used to optimize the initial parameters of the above model to obtain the optimal parameters.A total of 58 children's saliva samples were collected,including 21 children diagnosed with autism,12 children with social disorders,and 25 healthy controls,and the protein and metabolomics data were detected by mass spectrometry.All data were randomly divided into training set and test set by 4∶1,and the training set was divided into training data and validation data in the same way for model training and validation.The test set was used for the final evaluation of the model effect.Five baseline models and three ablated models were constructed and evaluated along with MLAN based on metrics including multi-classification accuracy,F1-macro and F1-weighted scores.Results The constructed multi-classification autism diagnosis model MLAN achieved multi-classification accuracy,F1-macro and F1-weighted scores of 0.850±0.066,0.817±0.103 and 0.834±0.087.The values of all three indicators were better than those of baseline models and the ablated models.Conclusion The proposed MLAN can effectively deal with heterogeneous multi-omics data with small samples and achieve good results,which is expected to provide assistance for the clinical diagnosis of autism.

In 2025, the European League Against Rheumatism(EULAR) and the European Respiratory Society(ERS) jointly released the first clinical practice guidelines for the management of connective tissue disease-associated interstitial lung disease (CTD-ILD), with a particular focus on systemic sclerosis-associated ILD(SSc-ILD). Based on evidence-based principles, the guidelines provide a comprehensive framework encompassing screening, progression assessment, therapeutic strategies, and follow-up. Notably, the guidelines emphasize the clinical value of combination therapy for patients at high risk or with rapidly progressive disease. This article summarizes and interprets the key recommendations, including HRCT-based screening, multi-dimensional assessment tools, stratified pharmacological strategies, classification of drug mechanisms, and risk-duration-based follow-up protocols. It aims to provide up-to-date international guidance for clinical decision-making and research in the management of SSc-ILD.

Objective:To analyze the efficacy and feasibility of performing a new surgical procedure, tunnel esophagogastrostomy, to perform proximal gastrectomy.Methods:The study cohort comprised 10 consecutive patients who had undergone esophagogastrostomy by the tunnel technique in Jiangsu Cancer Hospital between October 2019 and July 2022. All patients were male. Their average age was (64.2±8.1) years and body mass index (25.5±3.2) kg/m2. Nine had upper gastric body adenocarcinoma, the remaining one having signet ring cell carcinoma. TNM staging of the tumors showed that seven were Stage IA, one Stage IB, one Stage IIA, and one Stage IIIA. Briefly, tunnel esophagogastrostomy is performed as follows: After performing a proximal gastrectomy, a rectangular seromuscular flap (3.0 cm × 3.5 cm) is created. The posterior esophageal wall is sutured to the gastric wall at the orad end of the seromuscular flap 5 cm from the stump with three to four stitches. Next, the stump of the esophagus is opened, the posterior esophageal wall is sutured to the gastric mucosa and submucosa, and the anterior esophageal wall is sutured to the full layer of the stomach. Finally, the caudad end of the seromuscular flap is closed. Data on surgical safety, postoperative morbidity, and postoperative reflux esophagitis were analyzed. All enrolled patients completed endoscopic follow-up 1 year and 2 years after surgery.Results:All procedures were completed. They comprised four cases of laparoscopic assisted surgery, four of DaVinci robotic surgery, and two of open surgery. The mean operation time was 212.7±33.2 mins, mean anastomosis time (51.6±5.3) minutes, mean tunnel preparation time (20.0±3.5) minutes, and mean operative blood loss (90.0±51.6) mL. The time to first postoperative passage of flatus was (64.8±11.5) hours. The mean hospital stay after surgery was (9.2±1.7) days. There were no postoperative complications above Clavien-Dindo Grade II. The mean preoperative Reflux Disease Questionnaire score was (3.3± 0.4) before the surgery, (3.8±1.0) 1 month postoperatively, and (3.3±0.4) 12 months postoperatively. All patients underwent endoscopic follow-up; no anastomotic stenoses were found. However, one patient had Grade A reflux esophagitis 1 year after surgery and another Grade B reflux esophagitis 2 years after surgery.Conclusion:Esophagogastrostomy by the tunnel technique is a safe and feasible means of performing proximal gastrectomy.

Objective:To analyze the efficacy and feasibility of performing a new surgical procedure, tunnel esophagogastrostomy, to perform proximal gastrectomy.Methods:The study cohort comprised 10 consecutive patients who had undergone esophagogastrostomy by the tunnel technique in Jiangsu Cancer Hospital between October 2019 and July 2022. All patients were male. Their average age was (64.2±8.1) years and body mass index (25.5±3.2) kg/m2. Nine had upper gastric body adenocarcinoma, the remaining one having signet ring cell carcinoma. TNM staging of the tumors showed that seven were Stage IA, one Stage IB, one Stage IIA, and one Stage IIIA. Briefly, tunnel esophagogastrostomy is performed as follows: After performing a proximal gastrectomy, a rectangular seromuscular flap (3.0 cm × 3.5 cm) is created. The posterior esophageal wall is sutured to the gastric wall at the orad end of the seromuscular flap 5 cm from the stump with three to four stitches. Next, the stump of the esophagus is opened, the posterior esophageal wall is sutured to the gastric mucosa and submucosa, and the anterior esophageal wall is sutured to the full layer of the stomach. Finally, the caudad end of the seromuscular flap is closed. Data on surgical safety, postoperative morbidity, and postoperative reflux esophagitis were analyzed. All enrolled patients completed endoscopic follow-up 1 year and 2 years after surgery.Results:All procedures were completed. They comprised four cases of laparoscopic assisted surgery, four of DaVinci robotic surgery, and two of open surgery. The mean operation time was 212.7±33.2 mins, mean anastomosis time (51.6±5.3) minutes, mean tunnel preparation time (20.0±3.5) minutes, and mean operative blood loss (90.0±51.6) mL. The time to first postoperative passage of flatus was (64.8±11.5) hours. The mean hospital stay after surgery was (9.2±1.7) days. There were no postoperative complications above Clavien-Dindo Grade II. The mean preoperative Reflux Disease Questionnaire score was (3.3± 0.4) before the surgery, (3.8±1.0) 1 month postoperatively, and (3.3±0.4) 12 months postoperatively. All patients underwent endoscopic follow-up; no anastomotic stenoses were found. However, one patient had Grade A reflux esophagitis 1 year after surgery and another Grade B reflux esophagitis 2 years after surgery.Conclusion:Esophagogastrostomy by the tunnel technique is a safe and feasible means of performing proximal gastrectomy.

It is important to investigate the mechanical effects of morphology of prostatic urethra (PU) for benign prostatic hyperplasia (BPH). PU and bladder neck transverse diameter ratio (RPU-1), which related to vortex, and their influence on urine flow were observed by CFD. The results showed that vortexes appeared and expanded with increasing RPU on both sides of PU when RPU-1>0.79, and velocity of external urethral orifice decreased gradually. CFD is an available method for urodynamics research. The quantitative simulation of the relationship between RPU-1 and vortex was proposed for the first time, providing a new idea for advancing theory of PU lumen repair in BPH.

Objective To explore the method and clinical value of sentinel lymph node biopsy for penile carcinoma guided by multispectral separate-merge guided surgery device (MGS).Methods The clinical data of 7 patients with sentinel lymph node biopsy of penile cancer guided by MGS from April 2017 to April 2018 were analyzed retrospectively at First Hospital of Shanxi Medical University.They were 62-78 years old,with an average age of 65 years.All of carcinoma was located in the glans or coronal sulcus,which diameter was 1.0-3.5 cm,with an average of 2.5 cm.Three cases of inguinal lymph nodes could be non-palpable and the others palpable.All patients were injected 0.25 ml (2.5 mg/ml) of indocyanine greensolution with 1 ml syringe at 12,4,6 and 9 points in the proximal normal skin of penile tumors.Immediately,the imaging probe was aligned with the injection point to observe the dynamic changes of fluorescence image on MGS display.Results There were 14 sides of groin in 7 patients,except for 1 side without images,other 13 sides developed well.The images displayed by MGS include visible image,fluorescent image and merged image,and the merged image was green pseudo color.According to the dynamic changes of the image,it could be divided into five parts:injection point,penile body,pubic symphysis,inguinal region and sentinel lymph node.In 13 well-developed sides,fluorescence gradually disappeared in other parts about 15 minutes after injection,and the location of sentinel lymph nodes was determined in vitro by gradually consolidating and fixing the fluorescence images in the inguinal region.The lymph node-like tissue with strong fluorescence intensity was observed immediately after the skin incision.There was a clear boundary between the lymph node-like tissue and the surrounding tissue.Along this boundary,lymph nodes were separated,ligated,excised.No lymph nodes were found on the undetected side.Postoperative pathology confirmed that lymph nodes were located by fluorescence imaging in vitro and traced by fluorescence imaging in vivo,the coincidence rate was 100％.There were residual fluorescent tissues on three sides and lymphatic vessels were removed.Conclusions MGS-assisted intraoperative fluorescence imaging could improve the doctor's visual depth so that physicians can real-time,dynamic,accurate in vitro location and in vivo tracking of sentinel lymph nodes of penile cancer.

BACKGROUNDThe prognosis of R1-resection at the bronchial stump in patients with non-small cell lung cancer (NSCLC) remains unclear. This study intends to identify the prognostic factors and to optimize treatments for these patients under update conditions.

METHODSThe data of 124 NSCLC patients who underwent R1-resection at the bronchial stump was reviewed. There were 41 patients in the surgery group (S), 21 in the postoperative radiotherapy (PORT) group (S+R), 30 in the postoperative chemotherapy (POCT) group (S+C), and 32 in the PORT plus POCT group (S+R+C). The constitute proportion in different groups was tested using the χ(2) method, univariate analysis was performed using the Kaplan-Meier and log-rank method, and multivariate analysis was done using the Cox hazard regression with entry factors including age, sex, pathological type and stage, classification of the residual disease, and treatment procedure. The process was performed stepwise backward with a maximum iteration of 20 and an entry possibility of 0.05 as well as an excluded possibility of 0.10 at each step.

RESULTSIn univariate analysis, survival was more favorable for patients with squamous cell carcinoma, early pathological T or N stage, and chemotherapy or radiotherapy. There was no significant difference in the survival for patients with different types of the residual disease, except for the difference between patients with carcinoma in situ and lymphangiosis carcinomatosa (P = 0.030). The survival for patients receiving chemoradiotherapy was superior to that for those undergoing surgery alone (P = 0.016). In multivariate analysis, the pathological type (HR 2.51, 95% CI 1.59 to 3.96, P = 0.000), pathological T (HR 1.29, 95% CI 1.04 to 1.60, P = 0.021) or N stage (HR 2.04, 95% CI 1.40 to 2.98, P = 0.000), and chemotherapy (HR 0.24, 95% CI 0.13 to 0.43, P = 0.000) were independent prognostic factors.

CONCLUSIONPatients with squamous cell carcinoma, early pathological T or N stage, or receiving chemotherapy had a more favorable prognosis.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; radiotherapy ; surgery ; Female ; Humans ; Lung Neoplasms ; drug therapy ; pathology ; radiotherapy ; surgery ; Male ; Middle Aged ; Prognosis