Liraglutide (Lira), a glucagon-like peptide-1 (GLP-1) receptor agonist approved for diabetes and obesity, has shown significant potential in treating metabolic dysfunction-associated steatotic liver disease (MASLD). However, its systematic molecular regulation and mechanisms remain underexplored. In this study, a mouse model of MASLD was developed using a high-fat diet (HFD), followed by Lira administration. Proteomics and glycoproteomics were analyzed using label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS), while potential molecular target analysis was conducted via quantitative real-time polymerase chain reaction (qPCR) and Western blotting. Our results revealed that Lira treatment significantly reduced liver weight and serum markers, including alanine aminotransferase (ALT) and others, with glycosylation changes playing a more significant role than overall protein expression. The glycoproteome identified 255 independent glycosylation sites, emphasizing the impact of Lira on amino acid, carbohydrate metabolism, and ferroptosis. Simultaneously, proteomic analysis highlighted its effects on lipid metabolism and fibrosis pathways. 21 signature molecules, including 7 proteins and 14 N-glycosylation sites (N-glycosites), were identified as potential targets. A Lira hydrogel formulation (Lira@fibrin (Fib) Gel) was developed to extend drug dosing intervals, offering enhanced therapeutic efficacy in managing chronic metabolic diseases. Our study demonstrated the importance of glycosylation regulation in the therapeutic effects of Lira on MASLD, identifying potential molecular targets and advancing its clinical application for MASLD treatment.

ObjectiveTo investigate the syndrome evolution patterns， characteristics of the used herbal medicinals， and efficacy variations across different stages of rheumatoid arthritis （RA） progression. MethodsBased on the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine （CERTAIN）， 2,506 RA patients were retrospectively enrolled and categorized into ＜6 months group （166 cases）， 6 months to ＜5 years group （1063 cases）， 5 to ＜20 years group （1067 cases）， and ≥20 years group （210 cases）. Syndromes were differentiated before and after traditional Chinese medicine （TCM） treatment， including damp-heat obstruction， wind-damp obstruction， cold-damp obstruction， blood stasis obstructed in the collaterals， phlegm-stasis obstruction， liver-kidney insufficiency， qi and blood deficiency， and qi-yin deficiency. The syndrome evolution rate was calculated for high-frequency syndromes before and after treatment. Analysis was conducted on top 20 frequently used Chinese herbs at the first diagnosis. Clinical efficacy of the 28-joint disease activity score based on erythrocyte sedimentation rate （DAS28-ESR） and 28-joint disease activity score based on C-reactive protein （DAS28-CRP） before and after treatment were assessed. A multivariate logistic regression analysis was performed to identify factors affecting the efficacy of TCM treatment. ResultsPatients with course of disease shorter than 6 months predominantly presented with cold-dampness obstruction syndrome （49/166， 29.5%）， wind-dampness obstruction syndrome （46/166， 27.7%）， and dampness-heat obstruction syndrome （43/166， 25.9%）. For patients with course of disease logner than 6 months and shorter than 5 years and those within 5 to 20 years， the dominant syndrome was dampness-heat obstruction syndrome （324/1063， 30.5% and 318/1067， 29.8%， respectively）. In patients with disease duration ≥20 years， liver-kidney insufficiency syndrome and dampness-heat obstruction syndrome both predominated， each accounting for 25.24% （53/210）. The syndromes with more than 100 cases before treatment and a syndrome evolution rate greater than 10% after treatment were dampness-heat obstruction （201/738， 27.2%）， liver-kidney insufficiency （119/367， 32.4%）， and phlegm-stasis obstruction syndromes （73/172， 42.4%）. These were classified as high-frequency syndromes. After treatment， damp-heat obstruction syndrome and liver-kidney insufficiency syndrome primarily evolved into wind-damp obstruction syndrome， while phlegm-stasis obstruction syndrome evolved into damp-heat obstruction and cold-damp obstruction syndrome. The top two commonly used Chinese herbs across all groups were Gancao （Radix et Rhizoma Glycyrrhizae） and Baishao （Radix Paeoniae Alba）. In the ＜6 months group and the 6 months to ＜5 years group， high-frequency herbs also included Fangfeng （Radix Saposhnikoviae）， Duhuo （Radix Angelicae Pubescentis）， Chuanxiong （Rhizoma Chuanxiong）， and Qianghuo （Radix et Rhizoma Notopterygii）. In the 5 to ＜20 years group and the ≥20 years group， the usage of Huangqi （Radix Astragali）， Fuling （Poria）， Niuxi （Radix Achyranthis Bidentatae）， and Danggui （Radix Angelicae Sinensis） increased， while the proportion of Fangfeng and Duhuo decreased. After treatment， the DAS28-ESR and DAS28-CRP scores in all groups significantly decreased （P＜0.05）. There were statistically significant differences in clinical efficacy based on DAS28-ESR and DAS28-CRP across all groups （P＜0.01）. Multivariate logistic regression revealed significantly reduced treatment efficacy in the 6 months-5 years group （OR=0.4）， 5~20 years group （OR=0.5）， and ≥20 years group （OR=0.4） compared to the ＜6 months group. ConclusionRA syndromes follow a progression pattern from excess to deficiency， with corresponding transition in herbal usage from pathogen-eliminating to healthy qi-reinforcing approaches. TCM intervention can significantly reduce disease activity of RA， with superior efficacy in patients with disease duration shorter than 6 months.

Objective To evaluate the factors affecting urinary stone detection rate using virtual unenhanced(VUE)images obtained from triphasic dual-energy CT urography(DECTU)based on Logistic regression analysis.Methods For this study,150 patients who had suspected urinary stone and underwent triphasic DECTU were included.The true unenhanced(TUE)images were reconstructed as 120 kVp-like images,and VUE images at the portal venous phase[VUE(VP)]and excretory phase[VUE(EP)]were obtained using iodine removal technique from portal venous and excretory phase DECTU images,respectively.Two readers independently evaluated the above three types of images,and recorded the number of urinary stones,their anatomical locations,and whether there was residual iodine on the VUE images.Stone size and CT number were recorded only on the TUE images.Stone size,CT number,anatomical location,and iodine contrast agent were included in univariate and multivariate Logistic regression analyses to evaluate the factors affecting urinary stone detection rate using VUE images.Thresholds for detecting urinary stones on VUE images were determined using receiver operating characteristics(ROC)analysis.Results We detected 304 stones on TUE images,while the detection rates were 92.4％and 71.4％when using VUE(VP)and VUE(EP)images,respectively.Stone size and CT number were important factors influencing urinary stone detection rate using VUE(VP)and VUE(EP)images(P＜0.01).The area under curve(AUC)of using stone size and CT number for detecting stones using the VUE(VP)images was up to 0.96,and as threshold values,stones with size larger than 3.52 mm and CT number greater than 469 HU were found to have high accuracy.However,the AUC decreased to 0.88 when we combined stone size,CT number and anatomical location using the VUE(EP)images.In addition,different contrast agents did not affect the detection rate of stones on the VUE(EP)images(P=0.57).The stone detection rate in the kidney was significantly lower than those on the VUE(EP)images(P＜0.001).Conclusion VUE(VP)images provide better stone detection.Stone size and CT number have significant impacts on the stone detection rate using VUE images.The lower stone detection rate in the kidney on the VUE(EP)images is related to the residual iodine.

Objective:To explore the effect of free transplantation of composite tissue flap from the anterior lateral aspect of the femur in repairing head skin defects with artificial dural exposure infection.Methods:A retrospective study was conducted on 13 patients admitted to the First Affiliated Hospital of Air Force Military Medical University from April 2018 to August 2020 with craniotomy complications, including craniotomy skin and soft tissue defects combined with artificial dural exposure and infection. After preoperative anti infection treatment, the neurosurgery department participated in debridement and removed the artificial dura mater as much as possible during the operation. A composite tissue flap carrying the fascia lata was designed for the anterior lateral aspect of the thigh, and the flap artery and vein were anastomosed with the superficial temporal artery and superficial temporal vein/middle temporal vein respectively. The defect of the dura mater was repaired with the fascia lata with blood supply. The flap was used to seal the wound, and the donor site was directly sutured or transplanted with autologous medium thick skin graft. The postoperative blood supply and survival of the flap, the presence of cerebrospinal fluid leakage, and the healing of the donor site were observed; The observation of dural integrity and postoperative effects of skull reconstruction using cranial magnetic resonance imaging was followed up.Results:Among the 13 patients in this group, 11 patients had their artificial dura mater completely removed, while 2 patients were not completely removed due to severe adhesion. Among them, 1 patient had a residual area of 0.8 cm×1 cm, and the other had 3 residual areas, with a maximum area of 0.5 cm×0.7 cm; All transplanted skin flaps survived, with 12 cases achieving primary healing and 1 case of partial wound rupture after suture removal, which healed after conservative dressing change; All patients had no cerebrospinal fluid leakage; There was one case of partial necrosis of the graft in the donor site, which healed after supplementing the graft; Thirteen patients underwent cranial magnetic resonance imaging at 3-6 months postoperatively, all of which showed intact dura mater; Among them, 8 patients have completed skull reconstruction surgery, and all of them have healed well after reconstruction, with a good appearance of the surgical area.Conclusions:For wounds with head skin defects and exposed artificial dura mater infection, free transplantation of the anterior lateral composite tissue flap carrying the fascia lata can effectively cover the wound and repair the dura mater defect, achieve good function and appearance, and create favorable conditions for later skull reconstruction.

Objective:To explore the clinical effectiveness of a self-designed robot reduction system for femoral intertrochanteric fractures.Methods:A retrospective study was conducted to analyze the 57 patients with intertrochanteric fracture who had been treated at Department of Orthopedics, The Fourth Affiliated Central Hospital of Tianjin Medical University from June 2022 to February 2023. The patients were divided into a robot group (using the self-designed robot reduction system to assist intramedullary nailing) and a traction bed group (using a traction bed to assist intramedullary nailing) based on their fracture reduction method. The robot group: 31 patients, 11 males and 20 females, with an age of (78.7±9.3) years; 16 left and 15 right sides; 17 cases of type 31-A1, 12 cases of type 31-A2 and 2 cases of type 31-A3 by the AO/OTA classification. The traction bed group: 26 patients, 12 males and 14 females, with an age of (78.7±7.7) years; 13 left and 13 right sides; 16 cases of type 31-A1, 9 cases of type 31-A2 and 1 cases of type 31-A3 by the AO/OTA classification. The 2 groups were compared in terms of reduction and operation time, intraoperative blood loss, fluoroscopy frequency, reduction quality, and VAS and Harris score at preoperation, 1 week and 6 months postoperation.Results:The 2 groups were comparable due to insignificant differences in their preoperative general data ( P>0.05). The robot group was significantly better than the traction bed group in reduction time [(4.4±2.2) min versus (9.4±3.2) min], operation time [(29.0±13.5) min versus (49.3±13.3) min], intraoperative blood loss [(76.5±30.5) mL versus (115.0±38.4) mL], fluoroscopy frequency [(10.2±2.6) times versus (14.8±3.2) times], and good/excellent rate of reduction [80.6% (25/31) versus 50.0% (13/26)] ( P<0.05). All patients were followed up for (6.8±0.3) months. Respectively, the VAS scores at preoperation and 6 months postoperation was (6.2±1.3) and (2.4±0.8) points for the robot group, and (6.3±1.3) and (2.7±0.8) points for the traction bed group, showing no statistically significant differences between the 2 groups ( P>0.05). However, the VAS score was (3.3±1.2) points for the robotic group and (4.8±1.5) points for the traction bed group at 1 week postoperation, showing a statistically significant difference between the 2 groups ( P<0.001). Respectively, the Harris scores at preoperation and 6 months postoperation were (35.3±3.0) and (88.7±3.4) points for the robot group, and (35.6±2.9) and (87.2±3.5) points for the traction bed group, showing no statistically significant differences between the 2 groups ( P>0.05). However, the Harris score was (57.3±3.7) points for the robotic group and (46.7±2.8) points for the traction bed group at 1 week postoperation, showing a statistically significant difference between the 2 groups ( P<0.05). The patient satisfaction rates in the robot and traction bed groups were 96.8% (30/31) and 92.3% (24/26), respectively, showing no statistically significant difference ( P>0.05). Conclusion:Our self-designed robot reduction for femoral intertrochanteric fractures can effectively shorten reduction and operation time, reduce bleeding and fluoroscopy frequency, and enhance anatomical reduction.

Objective:The study retrospectively analyzed the etiology, clinical manifestations, emergency treatment and etiological treatment of a large sample of cases with hypercalcemic crisis.Methods:The clincial data of patients with hypercalcaemia cirisis who were administered in First Medical Center of Chinese PLA General Hospital from January 2009 to July 2022 were analyzed, inculding the general data, clinical manifestations, etiology, photographic examination, emergency treatment, etiological treatment, serological examination before and after treatment, pathological immunohistochemical findings and prognosis.Results:A total of 143 hypercalcaemia crisis patients(84 males and 59 females) with a mean age of 53.51±16.60 were enrolled. The most common disease was hyperparathyroidism(62/143), followed by solid malignancy(57/143) and multiple myeloma(12/143). Patients presented with digestive system symptoms at 76.91%, followed by neurological symptoms at 63.60%, urinary system symptoms at 58.76%, musculoskeletal symptoms at 55.23%, and cardiovascular system symptoms at 32.91%. After emergency calcium-lowering treatment, the remission rate of hypercalcemic crisis in 143 patients was 100%(143/143), and after etiological treatment, the remission rate of hypercalcemia was 85.31%(122/143).Conclusion:Early identification, emergency treatment and etiology treatment of hypercalcaemia crisis are essential. Effective treament with comprehensive calcium reduction can quickly relieve clinical symptoms and create opportunities for treatment for the cause. Targeted etiological interventions can lead to the correction or long-term remission of hypercalcemia.

Idiopathic pulmonary fibrosis(IPF)is a chronic progressive interstitial lung disease of unknown etiology,with a rapid disease course,poor prognosis,and the absence of effective therapeutic drugs.Mitochondrial dys-function is one of the crucial causes of inducing IPF.Silent information regulator 3(SIRT3)can restore mitochondrial ho-meostasis by inhibiting mitochondrial oxidative stress,repairing mitochondrial DNA damage,and ameliorating abnormal mitochondrial lipid metabolism.This paper summarizes the role and mechanism of SIRT3 in attenuating mitochondrial dys-function based on delineating the relationship between mitochondrial dysfunction and IPF,aiming to provide references for finding effective treatment methods for IPF.

As a classic prescription for invigorating spleen and replenishing qi, Sijunzi Decoction has a good clinical efficacy in the treatment of gastric cancer. It can improve chemotherapy resistance, reduce the toxic and side effects of chemotherapy, promote postoperative recovery, enhance immunity, improve the nutritional status of patients, improve the quality of life of patients and prevent precancerous lesions. Network pharmacology studies have shown that Sijunzi Decoction exerts anti-gastric cancer effects through multiple active ingredients, multiple targets and multiple pathways, and quercetin may be the main active component in Sijunzi Decoction to exert anti-gastric cancer effects. The main mechanisms of Sijunzi Decoction in the treatment of gastric cancer include regulating the expression of cell cycle and apoptosis-related gene proteins, and inhibiting the proliferation, migration, invasion and gastric cancer stem cell characteristics of gastric cancer cells.

Kupffer cells(KC),an important subset of immune cells in the liver,are essential for maintaining tissue homeostasis and responding quickly to liver damage.The complement receptor of the immuno-globulin superfamily(CRIg)is a receptor protein on the KC membrane.CRIg can not only capture pathogens in the blood flowing through the liver by complement binding but also mediate immune responses by regulating im-mune cells in the liver.Recent studies have confirmed the role of CRIg in regulating liver immunity.This article reviews the main modes of action of CRIg and the research progress of CRIg in regulating liver immunity.

Objective:To investigate the effect of cumulative serum uric acid (cumSUA) on early-onset ischemic stroke in young adults.Methods:A prospective cohort study was conducted. A total of 15 607 Kailuan workers who participated in at least two physical check-ups in 2006 and 2008 and at the time of the last physical check-up before 2014 were selected as subjects. Cumulative uric acid exposure during the follow-up period was calculated. The subjects were divided into three groups according to the quantile of cumSUA: the first quantile group was cumSUA<1 563 μmol/L·year, the second quantile group was: 1 563 μmol/L·year≤cumSUA<1 996 μmol/L·year, the third group was cumSUA≥1 996 μmol/L·year. The time of the last physical check-up was regarded as the starting point of follow-up, and early-onset ischemic stroke was regarded as the end event. Kaplan-Meier was used to calculate the incidence of early-onset ischemic stroke in different groups, and Log-rank method was used to calculate the differences in the incidence of early-onset ischemic stroke among different groups. Multivariate Cox regression model was used to analyze the risk of early-onset ischemic stroke in different groups. A four-node (5th, 25th, 75th, 95th percentile) restricted cubic spline plot was used to assess the dose-response relationship between cumSUA and early-onset ischemic stroke.Results:A total of 15 607 subjects were followed up for (7.3±1.1) years. 100 cases with early-onset ischemic stroke were observed with an average age of (46±4) years old. The number of events in the first, second, and third quartile groups was 18, 35, and 47, respectively, and the cumulative incidence rates in the first, second, and third quartile groups were 0.40%, 0.77%, and 1.07%, respectively. The difference in cumulative incidence of endpoint events between the groups was statistically significant by Log-rank test ( χ2=14.96, P=0.003). The results of Cox regression analysis showed that after correcting for confounders, the HR(95% CI) for early-onset ischemic stroke in the second and third quartile groups was [1.67(0.92,3.00), P=0.090; 2.05(1.48,3.69), P=0.020]. Restricted cubic spline results showed a nonlinear correlation between cumSUA and early-onset ischemic stroke after adjysted for confounders. Conclusion:Cumulative serum uric acid is positively correlated with the risk of early-onset ischemic stroke in young adults.