Immune-stimulating antibody drug conjugate (ISAC) can not only effectively solve the defects of stimulator of interferon genes (STING) agonists by coupling antibodies with STING agonists through the targeting of antibodies, but also play a synergistic role with antibodies to further improve the efficacy of STING agonists. This review first provides a concise overview of the current research landscape of ISACs and STING agonists, systematically elaborates on evolving trends in STING agonist development, and subsequently summarizes the mechanistic advances in STING ISAC research. Special emphasis is placed on representative STING ISAC candidates in preclinical/clinical development. Finally, the future directions of STING ISACs are critically discussed with perspectives and recommendations, aiming to provide theoretical insights and practical guidance for future investigations.

OBJECTIVE To investigate the mechanism of Huangqin decoction in improving ulcerative colitis （UC） through the gut microbiota-tryptophan metabolism-aryl hydrocarbon receptor （AhR） axis. METHODS Mice were randomly divided into normal group （normal saline）， model group （normal saline）， microbiota depletion-model group （normal saline）， microbiota depletion-Huangqin decoction group （9.1 g/kg， by crude drug， similarly hereinafter）， Huangqin decoction group and mesalazine group （positive control group， 0.4 g/kg）， with 6 mice in each group. Microbiota depletion was achieved by providing free access to a mixed antibiotics for 10 days. The UC model was induced by administering 2.5% dextran sulfate sodium solution for 7 days. After successful modeling， each treatment group received corresponding drugs or normal saline intragastrically once daily for 10 days. After the final administration， body weight change ratio， disease activity index （DAI） score， and colon length were evaluated； colon pathological changes were observed； serum levels of interleukin-6 （IL-6）， IL-10， IL-22， and tumor necrosis factor-α （TNF-α） were measured； the expressions of Occludin， zonula occluden-1 （ZO-1）， and AhR in colon tissue were detected； fecal samples were subjected to high-throughput sequencing to analyze targeted tryptophan metabolomics. RESULTS Compared with the model group， Huangqin decoction group showed reduced infiltration of inflammatory cells in the colon tissue and restoration of the intestinal mucosal structure. Body weight change ratio， colon length， serum content of IL-10， the expressions of Occludin， ZO-1 and AhR in colon tissue and the contents of tryptophan metabolites indole-3-propionic acid （IPA）， N -acetylserotonin （NAS） and indole-3-acetic acid （IAA） were all significantly increased （ P ＜0.05）； DAI score， serum levels of IL-6， TNF-α， and IL-22 and the content of tryptophan metabolite indole-3-ethanol were significantly decreased （ P ＜0.05）； gut microbiota structure was improved， with increased relative abundances of beneficial bacteria such as Lactobacillus ， and decreased relative abundances of pathogenic bacteria such as Escherichia-Shigella . However， after antibiotic-induced microbiota depletion， although Huangqin decoction significantly increased the content of NAS in the feces of mice， the expression of AhR protein in colon tissue did not increase concurrently. CONCLUSIONS Huangqin decoction can repair the intestinal mucosal barrier in UC mice by regulating the gut microbiota and promoting the production of IPA and IAA， thereby activating AhR. This suggests that an intact gut microbiota is an important prerequisite for Huangqin decoction to exert its AhR-regulating effects.

Objective To propose a lightweight end-to-end neural network model for automated Korotkoff sound phase recognition and subsequent blood pressure (BP) measurement, aiming to improve measurement accuracy and population adaptability. Methods We developed a streamlined architecture integrating depthwise separable convolution (DSConv), multi-head attention (MHA), and bidirectional gated recurrent unit (BiGRU). The model directly processes Korotkoff sound time-series signals to identify auscultatory phases. Systolic BP (SBP) and diastolic BP (DBP) were determined using phase Ⅰ and phaseⅤdetections, respectively. Given the clinical relevance of phase Ⅳ for specific populations (e.g., children and pregnant women, denoted as DBPⅣ), BP values from this phase were also recorded.Results The study enrolled 106 volunteers with 70 males and 36 females at mean age of (40.0±12.0) years. The model achieved 94.25% phase recognition accuracy. Measurement errors were (0.1±2.5) mm Hg (SBP), (0.9±3.4) mm Hg (DBPⅣ), and (0.8±2.6) mm Hg (DBP). Conclusion Our method enables precise phase recognition and BP measurement, demonstrating potential for developing population-adaptive blood pressure monitoring systems.

Objective To explore the method for establishing a pig left lung orthotopic transplantation model. Methods A total of 4 male Yorkshire pigs weighing (40.0±2.5) kg underwent surgical procedures, including anesthesia, tracheal intubation, donor lung procurement, and recipient lung transplantation. Histological morphology and blood gas analysis of the transplanted lungs were assessed 2 hours after reperfusion to evaluate the histological changes and function of the transplanted lungs. Results The pigs underwent left lung in situ transplantation, effectively simulating conditions relevant to human lung transplantation. Two hours after the transplantation, arterial blood gas analysis showed that arterial partial pressure of oxygen was 155.4-178.6 mm Hg, arterial partial pressure of carbon dioxide was 53.1-62.4 mm Hg, and the oxygenation index was 310.8-357.2 mm Hg. Hematoxylin and eosin staining indicated a low degree of pulmonary edema and minimal cellular infiltration. Conclusion The pig left lung orthotopic transplantation model possesses strong operability and stability. Researchers can replicate this model according to the described methods and further conduct basic research and explore clinical translational applications.

BACKGROUND:Degenerative scoliosis is defined as a condition that occurs in adulthood with a coronal cobb angle of the spine>10° accompanied by sagittal deformity and rotational subluxation,which often produces symptoms of spinal cord and nerve compression,such as lumbar pain,lower limb pain,numbness,weakness,and neurogenic claudication.The finite element method is a mechanical analysis technique for computer modelling,which can be used for spinal mechanics research by building digital models that can realistically restore the human spine model and design modifications. OBJECTIVE:To review the application of finite element method in the etiology and treatment of degenerative scoliosis. METHODS:The literature databases CNKI,PubMed,and Web of Science were searched for articles on the application of finite element method in degenerative scoliosis published before October 2023.Search terms were"finite element analysis,biomechanics,stress analysis,degenerative scoliosis,adult spinal deformity"in Chinese and English.Fifty-four papers were finally included. RESULTS AND CONCLUSION:(1)The biomechanical findings from the degenerative scoliosis model constructed using the finite element method were identical to those from the in vivo experimental studies,which proves that the finite element method has a high practical value in degenerative scoliosis.(2)The study of the etiology and treatment of degenerative scoliosis by the finite element method is conducive to the prevention of the occurrence of the scoliosis,slowing down the progress of the scoliosis,the development of a more appropriate treatment plan,the reduction of complications,and the promotion of the patients'surgical operation.(3)The finite element method has gradually evolved from a single bony structure to the inclusion of soft tissues such as muscle ligaments,and the small sample content is increasingly unable to meet the research needs.(4)The finite element method has much room for exploration in degenerative scoliosis.

Brain tinnitus is a common clinical condition whose pathogenesis is not yet fully understood,and it still lacks effective therapies in clinical practice.Professor Liu Maocai believes that the clinical manifestations of brain tinnitus are usually characterized by deficiency syndrome,and sometimes are complicated excess syndrome.The disease is located in the brain and is closely related to the liver,spleen,and kidney.The treatment of brain tinnitus should be focused on tonifying the liver and kidney,and strengthening the spleen,and methods of calming the liver to extinguish wind,resolving phlegm to open the orifices,and activating blood circulation to unblock collaterals can be used for excess syndrome.In clinical practice,Professor Liu Maocai is skilled in using herb pairs such as Astragali Radix-Codonopsis Radix,Eucommiae Cortex-Achyranthis Bidentatae Radix,Paeoniae Radix Alba-Bupleuri Radix,Angelicae Sinensis Radix-Chuanxiong Rhizoma,Gastrodiae Rhizoma-Uncariae Ramulus cum Uncis,and Acori Tatarinowii Rhizoma-Polygalae Radix.Professor Liu Maocai's experience in treating brain tinnitus from the perspective of the liver,spleen,and kidney can provide valuable references for the clinical diagnosis and treatment of brain tinnitus with traditional Chinese medicine.

Objective Exploring the clinical efficacy of using autologous rib cartilage grafting to reconstruct finger hemiarticular defects.Methods From August 2022 to February 2024,for 6 patients with hemiarticular surface defects in the metacarpophalangeal joints and interphalangeal joints of 8 fingers,costal cartilage was used for joint remodeling and transplantation to reconstruct the hemiarticular surface defects of the fingers.All 8 joint transplants in 6 patients were two-stage surgeries.In the first stage,antibiotic bone cement was used to fill the space-occupying lesions,and in the second stage,costal cartilage joint remodeling was performed to reconstruct the finger joint defects.Postoperative follow-up and assessment of fracture healing according to Paley fracture healing scoring criteria.Outpatient and WeChat follow-up,upper limb function is evaluated according to the upper limb functional assessment standards of the Chinese Medical Association Hand Surgery Society.Record VAS pain score.Results In this group,there were a total of 6 patients with 8 cases of hemiarticular defects.Among them,2 patients had two joint surgical sites,while the remaining 4 patients had a single joint surgical site.There were 2 cases of metacarpophalangeal joint head defects,2 cases of proximal articular surface defects,3 cases of proximal articular head defects,and 1 case of thumb proximal articular head defect.After surgery,8 out of 6 patients'hand wounds healed successfully.All patients were followed up for 6-12 months postoperatively,with an average of 9 months.The VAS pain score(affected finger)for the last follow-up was 0-2 points,with an average of 0.6 points.According to Paley's scoring criteria,all 6 patients had excellent fracture healing.According to the evaluation criteria for upper limb functional assessment of the Chinese Medical Association Hand Surgery Society,3 cases were rated as excellent,3 cases were rated as good,and 2 cases were rated as fair.Conclusion For patients with half joint defects on one side of the finger,rib rib cartilage was used for joint reconstruction,which significantly improved the joint shape and function at the defect site,and reduced joint pain scores.

Objective:To evaluate the clinical effect of different types of aortic root replacement in adolescent patients with aortic root aneurysm by analyzing the perioperative and follow-up conditions of surgical treatment for adolescent aortic root aneurysm.Methods:The clinical data of patients aged ≤18 years who were admitted to the Beijing Anzhen Hospital from November 2012 to February 2025, diagnosed with aortic root aneurysm by ultrasound or aortic computed tomography angiography (CTA) and requiring surgical intervention, were collected retrospectively. They were divided into the valve-sparing aortic root replacement group (David operation group) and the aortic root replacement group (Bentall operation group) according to the surgical method. The perioperative results and long-term follow-up results of the two groups were analyzed. Kaplan-Meier survival curves were drawn to compare the reoperation intervention rate between the two groups.Results:A total of 25 patients were included in this study, including 17 in the Bentall group and 8 in the David group. There were no statistically significant differences in gender, age, blood routine, liver and kidney function, coagulation function, and electrolyte internal environment between the two groups (all P>0.05). There were no statistically significant differences in operation time and intensive care unit stay between the two groups (all P>0.05). Compared with the Bentall operation group, the intraoperative blood loss in the David operation group was more ( P<0.05). During the follow-up, no reoperation occurred in the Bentall operation group, while 3 patients in the David operation group had long-term re-intervention. The long-term reoperation intervention rate in the David operation group was higher than that in the Bentall group ( P=0.042), but there was no statistically significant difference in the aortic valve-related surgical intervention rate between the two groups ( P=0.15). Conclusions:For adolescent patients with aortic root aneurysm, although David operation may face long-term reoperation intervention, this intervention may not be due to the difference in surgical methods. Both Bentall operation and David operation are safe and reliable, with good perioperative results and stable medium and long-term prognosis.

Objective To explore the new mechanism of Escin inhibiting the progression of breast cancer cells.Methods Escin treatment groups with different concentrations(0,10,20,30,40μg/ml)were set up,and BC cells were treated with corresponding concentrations of Escin,then CCK8,clonal formation,flow cytometry,transmission electron microscopy and protein immunoblotting were used to evaluate the cell phenotype and possible mechanisms.Control group,Escin group and Escin+VX-765 group were set up,to determine the role of Caspase-1/GSDMD signaling pathway in Escin-induced pyroptosis of BC cells,cells were pretreated with Caspase-1 inhibitor VX-765.The cells in control group,Escin group and Escin+NAC group were pretreated with the reactive oxygen species(ROS)scavher N-Acetylcysteine(NAC),to determine the role of ROS in Escin induced pyroptosis of BC cells.Results Compared with the control group,different concentrations of Escin inhibited the proliferation and colony formation of BC cells in a concentration dependent manner(P＜0.05).Compared with the control group,the ROS and pyroptosis rate were increased in Escin-treated group(P＜0.05).The protein expression levels of FL-GSDMD and pro-Caspase-1 were significantly decreased in the Escin-treated group,while N-GSDMD,cleaved Caspase-1 and IL-18 protein expression were significantly increased(P＜0.05).Compared with the Escin-treated group,the proliferation rate of Escin+VX-765 group was increased(P＜0.05),and the expression of pyroptosis protein was decreased(P＜0.05).Compared with the Escin-treated group,the proliferation rate of Escin+NAC group was increased(P＜0.05),and the ROS,pyroptosis rate and pyroptosis protein expression were decreased(P＜0.05).Conclusion The inhibitory effect of Escin on the progression of breast cancer cells may be related to its regulation of ROS/Caspase-1/GSDMD signaling pathway to promote cell pyroptosis.

Objective:To observe the changes in choroidal morphology and blood perfusion in patients with macular edema secondary to retinal vein occlusion (RVO) after intravitreal injections of ranibizumab.Methods:A cohort study was performed.A total of 157 patients (157 eyes) with macular edema secondary to monocular acute retinal vein occlusion (RVO) were enrolled in the Third People's Hospital of Dalian from January 2022 to March 2023.There were 66 cases (66 eyes) with central retinal vein occlusion (CRVO) and 91 cases (91 eyes) with branch retinal vein occlusion (BRVO).All patients were treated with 3+ pro re nata (PRN) regimen of ranibizumab.Before and 1 month after each injection, the central retinal thickness of the macula was measured by optical coherence tomography (OCT).Clear images of the choroid were obtained using the OCT enhanced depth scan mode.Subfoveal choroidal thickness (SFCT), the nasal choroidal thickness at 1 500 μm of macula (CT N1.5 mm), the temporal choroidal thickness at 1 500 μm of macula (CT T1.5 mm) were measured and mean macular thickness (CT Mean) was calculated.Binarization of choroidal images processed by ImageJ software was used to analyze luminal area (LA), stromal area (SA) and total choroidal area (TCA), and choroidal vascularity index (CVI) was calculated.This study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of the Third People's Hospital of Dalian (No.2023-145-001).Results:SFCT, CT T1.5 mm, CT N1.5 mm, CT Mean, LA, SA, TCA and CVI of RVO eyes were higher than those of the contralateral eyes and the differences were statistically significant (all P<0.01).CT Mean in CRVO group was (326.99±64.92)μm, which was higher than (299.80±73.08)μm in BRVO group, with a statistically significant difference ( t=2.41, P=0.02).Baseline CVI values in CRVO group and BRVO group were (72.50±5.62)% and (72.33±5.85)%, respectively, with no significant difference ( t=0.187, P=0.85).In eyes with RVO, CRVO and BRVO, SFCT, CT T1.5 mm, CT N1.5 mm, CT Mean, LA, SA, TCA and CVI after every injection were lower than the baseline and the differences were statistically significant (all P<0.05).In eyes with CRVO, there was no significant difference in LA and CVI between first and second injections (both P>0.05), and SFCT, CT T1.5 mm, CT N1.5 mm, CT Mean, SA and TCA after second injection were lower than those after first injection with statistically significant differences (all P<0.05).In eyes with BRVO, there was no significant difference in SA and CVI between first and second injections (both P>0.05), and SFCT, CT T1.5 mm, CT N1.5 mm, CT Mean, LA and TCA after second injection were lower than those after first injection with statistically significant differences (all P<0.05).In eyes with RVO, CRVO and BRVO, there was no significant difference in SFCT, CT T1.5 mm, CT N1.5 mm, CT Mean, SA, TCA and CVI between second and third injections (all P>0.05). Conclusions:After intravitreal injection of ranibizumab, the choroidal thickness becomes thinner and CVI decreases in eyes with macular edema secondary to RVO, and remain relatively stable after the second injection.