ObjectiveTo explore the relationship between negative life events and depression severity in adolescent patients with depressive disorder， as well as the chain mediating role of insomnia symptoms and quality of life. Methods374 outpatient patients and hospitalized patients with adolescent depressive disorders were enrolled. The Adolescent Life Event Scale （ASLEC）， the Insomnia Severity Index （ISI）， the World Health Organization Quality of Life Questionnaire Short Form （WHOQOL-BREF）， and the Center for Epidemiology Depression Scale （CES-D） were used to evaluate the negative life event situation， insomnia symptoms， quality of life level and depression severity of the subjects， respectively. In addition， the PROCESS 4.0 macroprogram was used to analyze the chain mediating effect of insomnia symptoms and quality of life between negative life events and depression severity in patients with adolescent depressive disorder. ResultsThe results of correlation analysis showed that there was a significant correlation between negative life events and insomnia symptoms， quality of life， and depression severity （all P<0.05）. In addition， the results of chain mediation showed that negative life events had a significant direct effect on depression severity， with an effect size of 0.12 （P<0.001）. Insomnia symptoms and quality of life played a mediating role in the relationship between negative life events and depression severity in patients with adolescent depressive disorders， with indirect effect sizes of 0.062 （95%CI： 0.040-0.087） and 0.091 （95%CI： 0.059-0.123）， respectively. It could also play a chain mediation role， and the effect size was 0.039 （95%CI： 0.024-0.057）. ConclusionNegative life events experienced by patients with adolescent depressive disorder not only directly affect the severity of depressive symptoms， but may also indirectly exacerbate depression through insomnia symptoms and quality of life.

A 51-year-old male presented with nasal obstruction, followed by progressive hearing loss and blurred vision. Imaging identified space-occupying lesions in the paranasal sinuses, orbits, and paraspinal regions, while laboratory tests confirmed positive anti-proteinase 3 anti-neutrophil cytoplasmic antibody(PR3- ANCA) immunoglobulin G (IgG)and markedly elevated serum IgG4. Despite treatment with corticosteroids, immunosuppressants, and radiotherapy, the patient exhibited steroid dependency with relentless disease progression. Following multidisciplinary consultation, a diagnosis of inflammatory myofibroblastic tumor (IMT) coexisting with ANCA- associated vasculitis (AAV) was favored, though IgG4-related disease remained a critical differential. Ultimately, profound immunosuppression precipitated a severe herpesvirus infection, leading to disseminated intravascular coagulation and multiple organ dysfunction syndrome. This case underscores the rarity and diagnostic complexity of concurrent IMT and AAV, highlights the therapeutic dilemma of balancing primary disease control against fatal opportunistic infections, and emphasizes the critical role of multidisciplinary collaboration in the diagnosis and treatment of complex diseases.

Objective To establish a stable and reliable sepsis model of rat after liver transplantation (LT) for clinical translational research and analyze its characteristics. Methods The "two-sleeve method" was used to establish the in situ LT model of SD rats, and the sepsis model was constructed through cecal ligation and puncture (CLP) at 3 d after the operation. SD rats were randomly divided into 3 groups: sham operation group (Sham group), LT group, and LT + CLP group, with 6 rats in each group. The changes in body weight, rectal temperature and survival rate were compared, and the sepsis score was used for evaluation. The levels of blood biochemical indicators [alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea (Urea), creatinine (Cr), creatine kinase (CK), lactate dehydrogenase (LDH)] and inflammatory factors [interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor (TNF)-α] in each group were detected, and the pathological changes and cell apoptosis in different organs were observed. Results Compared with the Sham group, the body weight of the LT group and LT + CLP group decreased (all P<0.05). The rectal temperature of the LT + CLP group showed a continuous downward trend after the operation, the sepsis score increased sharply after the operation, and the survival rate dropped to 16.7%, and the differences between the Sham group, LT group and LT + CLP group were statistically significant (all P<0.05). The levels of ALT, AST, Urea, Cr, CK, LDH, and serum IL-1β, IL-6, IL-10 and TNF-α in the LT + CLP group were higher than those in the Sham group and LT group rats within 72 hours after the operation(all P<0.05). The pathological examination of the LT + CLP group showed severe tissue structure destruction, necrosis and infiltration of inflammatory cells in multiple organs, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining showed an increased level of cell apoptosis in multiple organs. Conclusions Using liver transplantation combined with CLP, a stable animal model of liver transplantation infection is successfully established, which exhibits a high mortality rate, significant multi-organ damage and intense inflammatory response, providing an ideal animal model for transplantation infection research.

OBJECTIVE To investigate the improvement effect and mechanism of processed Oxytropis falcata on renal fibrosis （RF） in rats. METHODS RF model was induced by adenine. After modeling， the rats were divided into the model group， positive control group （colchicine， 0.45 mg/kg）， and processed O. falcata low-， medium- and high-dose groups （0.5， 1， 2 g/kg）， respectively. Additionally， a blank group without modeling was set up， with 8 rats in each group. The positive control group and the various dosage groups of processed O. falcata were given the corresponding medicinal solutions intragastrically， while the blank group and model group were given equal volume of normal saline intragastrically， once daily for 28 consecutive days. The appearance and histopathological morphology of the rats’ kidneys were observed. Serum levels of renal function indexes [bl ood urea nitrogen （BUN）， creatinine （Cr） ] and inflammatory factors [interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） ] in rats were detected. Protein expressions of fibronectin （FN）， α -smooth muscle actin （ α -SMA） and collagen type Ⅰ （Col-Ⅰ） in renal tissue of rats were determined. mRNA expressions of transforming growth factor-β 1 （TGF-β 1 ）， Smad3 and extracellular signal-regulated kinase 1/2 （ERK1/2） in renal tissues were measured. Protein expression of TGF-β 1 and phosphorylation levels of Smad3 and ERK1/2 in renal tissues were detected. RESULTS Compared with the blank group， the rats in the model group exhibited enlarged kidneys with pale color， rough and uneven surface. There was a significant infiltration of inflammatory cells and vacuolated cells in the renal tubules， along with marked proliferation of collagen fibers. Serum levels of BUN， Cr， IL-6 and TNF-α， protein expressions of α -SMA， Col-Ⅰ and FN in renal tissues， mRNA expressions of TGF-β 1 ， Smad3， ERK1 and ERK2 and protein expression of TGF-β 1 as well as phosphorylation levels of Smad3 and ERK1/2 in renal tissues were increased significantly （ P ＜0.05）. Compared with the model group， renal pathological changes of rats were alleviated in processed O. falcata groups， with reduced infiltration of inflammatory cells and proliferation of collagen fibers. The levels of the aforementioned quantitative indicators were all significantly reversed （ P ＜0.05）. CONCLUSIONS Processed O. falcata can improve renal function in RF rats， alleviate inflammatory responses， and reduce abnormal collagen fiber deposition. Its mechanism of action may be related to the inhibition of the activity of the TGF-β 1 /Smad signaling pathway.

The application of immunosuppressants has significantly reduced the incidence rate of rejection reaction after liver transplantation， but the clinical efficacy of immunosuppressants is greatly affected by individual differences between patients. This article systematically reviews the recent research advances in the interaction between immunosuppressants and gut microbiota， with a focus on the regulatory role and mechanism of intestinal microflora communities on the efficacy of immunosuppressants. Studies have shown that intestinal microbiome is one of the key factors influencing the efficacy of immunosuppressive therapy after liver transplantation. This review aims to provide a theoretical basis for in-depth research in this field and provide new insights for developing individualized immunosuppressive treatment regimens based on the regulation of intestinal microflora.

Background/Aims: The pathophysiology of refractory gastroesophageal reflux disease (RGERD), which differs from proton pump inhibitor dependent gastroesophageal reflux disease (DGERD), remains incompletely elucidated. This study aims to compare esophageal motility patterns, transdiaphragmatic pressure gradients (TPG), and reflux profiles between RGERD and DGERD patients, and to delineate dynamic pressure gradient-esophagogastric junction (EGJ) interactions in these patients. Methods: In this retrospective study, 274 patients who underwent 24-hour impedance-pH monitoring and high-resolution manometry, along with an assessment of proton pump inhibitor responsiveness, were classified as RGERD (32.5%), DGERD (54.4%), or non-GERD (13.1%). Clinical characteristics, TPG, esophageal motility, and reflux metrics were compared between RGERD and DGERD patients. Subgroup analysis excluding hiatal hernia (HH) was conducted to investigate the pathophysiology of RGERD. Results: The RGERD group exhibited a significantly higher proportion of chest pain compared to the DGERD group. Regarding reflux profiles, RGERD patients without HH (RGERDHH- group) experienced increased weakly acidic reflux (P < 0.001) and prolonged bolus exposure (P = 0.006) compared to their counterparts (DGERDHH- group). Mechanistically, the RGERDHH- group showed reduced lower esophageal sphincter basal pressure (P = 0.010) and EGJ contractile integral (P = 0.005). Notably, following a wet-swallow, the RGERDHH- group experienced the significant elevation in gastric pressure and TPG. Correlation analyses revealed weakly acidic reflux and bolus exposure were positively correlated with gastric pressure variation, and inversely correlated with lower esophageal sphincter basal pressure. Conclusions Transient gastric pressure elevation and compromised EGJ barrier function drive weakly acidic reflux and esophageal bolus exposure. This pressure gradient-barrier mismatch underpins the refractoriness of RGERD.

Objective:To develop a deep learning model based on 3D super-resolution reconstruction technology and to analyze its feasibility and effectiveness in predicting paraglottic space invasion in hypopharyngeal cancer.Methods:A retrospective study was conducted involving 382 patients with hypopharyngeal squamous cell carcinoma treated at Qilu Hospital of Shandong University between January 2014 and December 2020. The cohort included 364 males and 18 females, with a mean age of 62±7 years. Patients were divided into a training set ( n=300) and a test set ( n=82) based on enrollment time. A generative adversarial network was used to perform 3D super-resolution reconstruction on contrast-enhanced CT images, improving spatial resolution by 16 times. A 2.5D deep learning strategy was employed to construct Resnet-NR and Resnet-SR models based on conventional and super-resolution images, respectively, to predict whether the paraglottic space was invaded. Model performance was evaluated using receiver operating characteristic (ROC) curves and area under the curve (AUC). A multi-reader multi-case study was conducted to assess the impact of the artificial intelligence (AI) model on clinicians′ diagnostic capabilities. Results:The super-resolution model Resnet-SR achieved the highest accuracy in both the training set (AUC=0.87, 95% CI: 0.84-0.90) and the test set (AUC=0.88, 95% CI: 0.81-0.96), significantly outperforming traditional clinical indicators (T stage, N stage, tumor diameter, and pathological differentiation degree) (AUC range: 0.55-0.70, all P<0.05). In comparison, the conventional-resolution model Resnet-NR achieved AUCs of 0.81 (95% CI: 0.77-0.84, P=0.005) and 0.80 (95% CI: 0.71-0.89, P=0.184) in the training and test sets, respectively. Using Resnet-SR to assist clinical decision-making improved the diagnostic accuracy of junior physicians (AUC=0.793 without AI assistance vs. AUC=0.871 with AI assistance, P=0.012) and significantly reduced diagnosis time for clinicians of all experience levels (86.5 s without AI assistance vs. 82.5 s with AI assistance, t=2.01, P=0.032). Conclusion:This study successfully develops a deep learning model based on 3D super-resolution reconstruction technology, which can assist in preoperative prediction of paraglottic space invasion in hypopharyngeal cancer. The AI-assisted tool improves diagnostic accuracy for junior physicians and enhances diagnostic efficiency for clinicians across all experience levels.

Pannexin 1(PANX1)interacts with purinergic receptors through regulating immune responses,relea-sing adenosine triphosphate(ATP),and the NLRP3/caspase-1/interleukin(IL)-1β signaling pathway,then influ-ences the activation of immune cells and promotes the production of reactive oxygen species(ROS),thus causing in-flammation and tissue damage which exacerbates infection.This research group has synthesized new polypeptides named QE20 and EE20,which can specifically inhibit the opening of PANX1 channels under inflammatory stimula-tion,offering advantages such as reducing cellular ATP release,inhibiting inflammatory factor secretion,and pre-venting hepatocyte pyroptosis,et al.This review summarizes the roles and mechanisms of PANX1 in various infec-tious diseases,and predicts the feasibility of PANX1 as a potential therapeutic target in the future.

Objectives:To explore the morphological changes of the superficial and deep thoraolumbar paraspinal muscles on both convex and concave sides during rest and contraction states in patients with mod-erate adolescent idiopathic scoliosis(AIS),and their effects on scoliosis angle,to analyze the relations between scoliosis angle and the morphological changes of paraspinal muscles.Methods:21 AIS patients(thoracic Cobb angle 20°-45°,S-shaped with the main curve in thoracic segment,4 males and 17 females,aged 13.9±1.6 years old)treated in our hospital from July 2020 to December 2023 and 21 healthy subjects(7 males and 14 females,aged 14.6±1.4 years old)were prospectively enrolled.The morphological data of thoracolumbar paraspinal muscles were collected with musculoskeletal ultrasound,including the resting thickness and thick-ness during maximum voluntary isometric contraction(MVIC)of superficial erector spinae(ES)and multifidus(MF)muscles of AIS patients on both convex and concave sides(left and right sides of healthy controls).The differences in resting thickness,contraction thickness,change rate of contraction thickness,and total resting thickness and total contraction thickness(ES+MF)of superficial and deep thoracolumbar paravertebral muscles between the two groups were analyzed,and the structural characteristics of the thoracolumbar paravertebral muscles on the convex and concave sides of AIS were analyzed.The correlation between Cobb angle in tho-racolumbar segment and morphological indexes(resting thickness,contraction thickness change rates)of ES and MF muscles was analyzed,and the influence of scoliosis severity on the morphology of superficial and deep paravertebral muscle was further analyzed.Results:In AIS patients,the mean thoracic Cobb angle were 31.62°±7.68°,and mean lumbar Cobb angle were 19.52°±6.48°.Comparing with healthy controls,patients with AIS were significantly different in resting thickness,contraction thickness and thickness change rates of tho-racic paraspinal muscles on both convex and concave sides,and the resting thickness of ES in thoracic seg-ment on concave side was less than that on the convex side,which of MF was less on the convex side than on the concave side(P＜0.01).The contraction thickness of thoracic MF muscles on the convex and concave sides in S-type AIS patients was smaller than that in healthy controls(P＜0.05),while the contraction thickness of thoracic ES muscles on the convex and concave side wasn't statistically different from that of healthy con-trols,and the contraction thickness change rate of ES muscles on the convex and MF on the concave side of thoracic segment in AIS patients was significantly decreased(P＜0.05).There was no significant difference in the total resting thickness of thoracic(convex and concave)paravertebral muscles(ES+MF)between AIS patients and the corresponding segments(left and right)of control group(P＞0.05),and there was no statistically signifi-cant difference in the total resting thickness of thoracic paravertebral muscle between the convex and concave sides of AIS patients(P＞0.05).The total contraction thickness of thoracic paravertebral muscle(ES+MF)in AIS patients was lower than that in control group(P＜0.05).Compared with the control group,the resting thickness,contraction thickness and thickness change rate of lumbar MF muscle on the convex and concave sides in AIS patients were significantly reduced(P＜0.05),and the contraction thickness change rate of the lumbar ES muscle on the concave side was less than that of the control group(P＜0.05).There were no significant differ-ences in resting thickness and contraction thickness between the convex and concave paravertebral muscles in AIS patients(P＞0.05).The total resting thickness(ES+MF)and total contraction thickness(ES+MF)of lumbar(convex and concave)paraspinal muscles in AIS patients were lower than those in control group(P＜0.05).There was a significant negative correlation between the Cobb angle of the main thoracic curve and the rest-ing thickness of the thoracic MF muscle on the concave and the change rate of the contraction thickness of the thoracic ES muscle on the convex in S-type AIS patients(r=-0.53/-0.45,P＜0.05).There was no signifi-cant correlation between the Cobb angle of lumbar segment and the change rates of the resting thickness and contraction thickness of ES and MF muscles on both convex and concave sides(P＞0.05).Conclusions:In pa-tients with moderate S-type AIS,there are different muscle morphological changes in the paraspinal muscles on both convex and concave sides of the main thoracic curve,and the concave paravertebral muscle is more affected by scoliosis;The contraction function of the bilateral deep core stabilizing muscles in the lumbar re-gion is markedly decreased.Different patterns of superficial and deep muscle atrophy and contractility decline may be a key cause of spinal movement disorder and scoliosis progression in AIS patients.

Objectives:To explore the morphological changes of the superficial and deep thoraolumbar paraspinal muscles on both convex and concave sides during rest and contraction states in patients with mod-erate adolescent idiopathic scoliosis(AIS),and their effects on scoliosis angle,to analyze the relations between scoliosis angle and the morphological changes of paraspinal muscles.Methods:21 AIS patients(thoracic Cobb angle 20°-45°,S-shaped with the main curve in thoracic segment,4 males and 17 females,aged 13.9±1.6 years old)treated in our hospital from July 2020 to December 2023 and 21 healthy subjects(7 males and 14 females,aged 14.6±1.4 years old)were prospectively enrolled.The morphological data of thoracolumbar paraspinal muscles were collected with musculoskeletal ultrasound,including the resting thickness and thick-ness during maximum voluntary isometric contraction(MVIC)of superficial erector spinae(ES)and multifidus(MF)muscles of AIS patients on both convex and concave sides(left and right sides of healthy controls).The differences in resting thickness,contraction thickness,change rate of contraction thickness,and total resting thickness and total contraction thickness(ES+MF)of superficial and deep thoracolumbar paravertebral muscles between the two groups were analyzed,and the structural characteristics of the thoracolumbar paravertebral muscles on the convex and concave sides of AIS were analyzed.The correlation between Cobb angle in tho-racolumbar segment and morphological indexes(resting thickness,contraction thickness change rates)of ES and MF muscles was analyzed,and the influence of scoliosis severity on the morphology of superficial and deep paravertebral muscle was further analyzed.Results:In AIS patients,the mean thoracic Cobb angle were 31.62°±7.68°,and mean lumbar Cobb angle were 19.52°±6.48°.Comparing with healthy controls,patients with AIS were significantly different in resting thickness,contraction thickness and thickness change rates of tho-racic paraspinal muscles on both convex and concave sides,and the resting thickness of ES in thoracic seg-ment on concave side was less than that on the convex side,which of MF was less on the convex side than on the concave side(P＜0.01).The contraction thickness of thoracic MF muscles on the convex and concave sides in S-type AIS patients was smaller than that in healthy controls(P＜0.05),while the contraction thickness of thoracic ES muscles on the convex and concave side wasn't statistically different from that of healthy con-trols,and the contraction thickness change rate of ES muscles on the convex and MF on the concave side of thoracic segment in AIS patients was significantly decreased(P＜0.05).There was no significant difference in the total resting thickness of thoracic(convex and concave)paravertebral muscles(ES+MF)between AIS patients and the corresponding segments(left and right)of control group(P＞0.05),and there was no statistically signifi-cant difference in the total resting thickness of thoracic paravertebral muscle between the convex and concave sides of AIS patients(P＞0.05).The total contraction thickness of thoracic paravertebral muscle(ES+MF)in AIS patients was lower than that in control group(P＜0.05).Compared with the control group,the resting thickness,contraction thickness and thickness change rate of lumbar MF muscle on the convex and concave sides in AIS patients were significantly reduced(P＜0.05),and the contraction thickness change rate of the lumbar ES muscle on the concave side was less than that of the control group(P＜0.05).There were no significant differ-ences in resting thickness and contraction thickness between the convex and concave paravertebral muscles in AIS patients(P＞0.05).The total resting thickness(ES+MF)and total contraction thickness(ES+MF)of lumbar(convex and concave)paraspinal muscles in AIS patients were lower than those in control group(P＜0.05).There was a significant negative correlation between the Cobb angle of the main thoracic curve and the rest-ing thickness of the thoracic MF muscle on the concave and the change rate of the contraction thickness of the thoracic ES muscle on the convex in S-type AIS patients(r=-0.53/-0.45,P＜0.05).There was no signifi-cant correlation between the Cobb angle of lumbar segment and the change rates of the resting thickness and contraction thickness of ES and MF muscles on both convex and concave sides(P＞0.05).Conclusions:In pa-tients with moderate S-type AIS,there are different muscle morphological changes in the paraspinal muscles on both convex and concave sides of the main thoracic curve,and the concave paravertebral muscle is more affected by scoliosis;The contraction function of the bilateral deep core stabilizing muscles in the lumbar re-gion is markedly decreased.Different patterns of superficial and deep muscle atrophy and contractility decline may be a key cause of spinal movement disorder and scoliosis progression in AIS patients.